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Zhang S, Cao Y, Huang Y, Zhang X, Mou C, Qin T, Chen Z, Bao W. Abortive PDCoV infection triggers Wnt/β-catenin pathway activation, enhancing intestinal stem cell self-renewal and promoting chicken resistance. J Virol 2025; 99:e0013725. [PMID: 40135895 PMCID: PMC11998530 DOI: 10.1128/jvi.00137-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 02/28/2025] [Indexed: 03/27/2025] Open
Abstract
Porcine deltacoronavirus (PDCoV) is an emerging coronavirus causing economic losses to swine industries worldwide. PDCoV can infect chickens under laboratory conditions, usually with no symptoms or mild symptoms, and may cause outbreaks in backyard poultry and wildfowl, posing a potential risk of significant economic loss to the commercial poultry industry. However, the reasons for such a subdued reaction after infection are not known. Here, using chicken intestinal organoid monolayers, we found that although PDCoV infects them nearly as well as porcine intestinal organoid monolayers, infection did not result in detectable amounts of progeny virus. In ex vivo and in vivo experiments using chickens, PDCoV infection failed to initiate interferon and inflammatory responses. Additionally, infection did not result in a disrupted intestinal barrier nor a reduced number of goblet cells and mucus secretion, as in pigs. In fact, the number of goblet cells increased as did the secreted mucus, thereby providing an enhanced protective barrier. Ex vivo PDCoV infection in chicken triggered activation of the Wnt/β-catenin pathway with the upregulation of Wnt/β-catenin pathway genes (Wnt3a, Lrp5, β-catenin, and TCF4) and Wnt target genes (Lgr5, cyclin D1, and C-myc). This activation stimulates the self-renewal of intestinal stem cells (ISCs), accelerating ISC-mediated epithelial regeneration by significant up-regulation of PCNA (transiently amplifying cells), BMI1 (ISCs), and Lyz (Paneth cells). Our data demonstrate that abortive infection of PDCoV in chicken cells activates the Wnt/β-catenin pathway, which facilitates the self-renewal and proliferation of ISCs, contributing to chickens' resistance to PDCoV infection.IMPORTANCEThe intestinal epithelium is the main target of PDCoV infection and serves as a physical barrier against pathogens. Additionally, ISCs are charged with tissue repair after injury, and promoting rapid self-renewal of intestinal epithelium will help to re-establish the physical barrier and maintain intestinal health. We found that PDCoV infection in chicken intestinal organoid monolayers resulted in abortive infection and failed to produce infectious virions, disrupt the intestinal barrier, reduce the number of goblet cells and mucus secretion, and induce innate immunity, but rather increased goblet cell numbers and mucus secretion. Abortive PDCoV infection activated the Wnt/β-catenin pathway, enhancing ISC renewal and accelerating the renewal and replenishment of shed PDCoV-infected intestinal epithelial cells, thereby enhancing chicken resistance to PDCoV infection. This study provides novel insights into the mechanisms underlying the mild or asymptomatic response to PDCoV infection in chickens, which is critical for understanding the virus's potential risks to the poultry industry.
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Affiliation(s)
- Shuai Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Yanan Cao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Yanjie Huang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Xueli Zhang
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Chunxiao Mou
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Tao Qin
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Zhenhai Chen
- College of Veterinary Medicine, Yangzhou University, Yangzhou, China
| | - Wenbin Bao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
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Zhao Z, Wang S, Wang K, Ji X, Chen D, Shen Q, Yu Y, Cui S, Wang J, Chen Z, Tang G. Transcriptome analysis of liver and ileum reveals potential regulation of long non-coding RNA in pigs with divergent feed efficiency. Anim Biosci 2025; 38:588-599. [PMID: 39483020 PMCID: PMC11917451 DOI: 10.5713/ab.24.0434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/23/2024] [Accepted: 09/18/2024] [Indexed: 11/03/2024] Open
Abstract
OBJECTIVE Long non-coding RNA (LncRNA) plays a significant role in regulating feed efficiency. This study aims to explore the key lncRNAs, associated genes, and pathways in pigs with extreme feed efficiencies. METHODS We screened pigs with extremely high and low residual feed intake through a 12-week animal growth trial and then conducted transcriptome analysis on their liver and ileum tissues. We analyzed the differential expressed lncRNAs, microRNAs (miRNAs), and messenger RNAs through target gene prediction and functional analysis. And we identified key lncRNAs and their potential regulatory genes associated with feed efficiency through the construction of competitive endogenous RNA network. RESULTS Differentially expressed lncRNAs were pinpointed in the liver, revealing 23 crucial target genes primarily associated with guanosine triphosphate metabolism and glycolipid biosynthesis. In the ileum, a screening identified 92 pivotal target genes, mainly linked to lipid and small molecule metabolism. Moreover, LOC106504303 and LOC102160805 emerged as potentially significant lncRNAs respectively, playing roles in mitochondrial oxidative phosphorylation in the liver, and lipid and cholesterol metabolism in the ileum. CONCLUSION The lncRNAs regulate energy metabolism and biosynthesis in the liver, and the digestive absorption capacity in the small intestine, affecting the feed efficiency of pigs.
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Affiliation(s)
- Zhenjian Zhao
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Shujie Wang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Kai Wang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Xiang Ji
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Dong Chen
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Qi Shen
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Yang Yu
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Shendi Cui
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Junge Wang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Ziyang Chen
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
| | - Guoqing Tang
- Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130,
China
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130,
China
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Lee BJ, Flood TR, Russell SL, McCormick JJ, King KE, Fujii N, Amano T, Notley S, Kenny GP. Intestinal epithelial injury and inflammation after physical work in temperate and hot environments in older men with hypertension or type 2 diabetes. Exp Physiol 2025. [PMID: 40159416 DOI: 10.1113/ep092567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 02/27/2025] [Indexed: 04/02/2025]
Abstract
We tested whether older adults with well-controlled type 2 diabetes or hypertension, compared with age-matched adults without chronic disease, exhibit greater intestinal damage, microbial translocation and inflammation during exertional heat stress. Twelve healthy men (age 59 years, SD 4 years), nine with type 2 diabetes (age 60 years, SD 5 years) and nine with hypertension (age 60 years, SD 4 years) walked for 180 min at 200 W/m2 in temperate conditions (wet-bulb globe temperature 16°C) and high-heat stress conditions (wet-bulb globe temperature 32°C). Serum intestinal fatty acid binding protein (IFABP), plasma soluble cluster of differentiation 14, lipopolysaccharide-binding protein (LBP), interleukin-6 and tumour necrosis factor-alpha were measured pre- and postexercise and after 60 min recovery. Total exercise duration was lower in men with hypertension and diabetes (p ≤ 0.049), but core temperature did not differ. All markers increased more in heat versus temperate conditions (p < 0.002). In the heat, individuals with type 2 diabetes had greater postexercise increases in IFABP [+545 pg/mL (95% confidence interval: 222, 869)] and LBP [+3.64 µg/mL (1.73, 5.56)] relative to healthy control subjects (p < 0.048), but these resolved after recovery. Despite reduced exercise duration, hypertensive individuals showed similar increases in IFABP and LBP to control subjects. Our findings suggest that older workers with well-controlled type 2 diabetes or hypertension might have greater vulnerability to heat-induced gastrointestinal barrier disturbance and downstream inflammatory responses when compared with otherwise healthy, age-matched adults during prolonged exercise in the heat.
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Affiliation(s)
- Ben J Lee
- Occupational and Environmental Physiology Group, Centre for Physical Activity, Sport and Exercise Sciences, Coventry University, Coventry, UK
| | - Tessa R Flood
- Institute of Sport, Manchester Metropolitan University, Manchester, UK
| | - Sophie L Russell
- Occupational and Environmental Physiology Group, Centre for Physical Activity, Sport and Exercise Sciences, Coventry University, Coventry, UK
| | - James J McCormick
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Quebec, Canada
| | - Kelli E King
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Quebec, Canada
| | - Naoto Fujii
- Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan
| | - Tatsuro Amano
- Laboratory for Exercise and Environmental Physiology, Faculty of Education, Niigata University, Niigata, Japan
| | - Sean Notley
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Quebec, Canada
| | - Glen P Kenny
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Quebec, Canada
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Severo JS, da Silva ACA, dos Santos BLB, Reinaldo TS, de Oliveira AM, Lima RSP, Torres-Leal FL, dos Santos AA, da Silva MTB. Physical Exercise as a Therapeutic Approach in Gastrointestinal Diseases. J Clin Med 2025; 14:1708. [PMID: 40095789 PMCID: PMC11899784 DOI: 10.3390/jcm14051708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 03/19/2025] Open
Abstract
Background/Objectives: Physical exercise can have significant consequences for the gastrointestinal tract, which is why there have been studies into its influence on the treatment of conditions such as colorectal cancer, inflammatory bowel diseases (IBD), and irritable bowel syndrome (IBS), being that there is epidemiological evidence that exercise has a protective effect against colon cancer. This review aims to demonstrate the mechanisms of action of physical exercise in the gastrointestinal tract, as well as the benefits of exercise in diseases associated with the digestive system, in addition to gathering training recommendations in treating different gastrointestinal diseases. Results: Physical exercise modulates gastrointestinal motility, permeability, immune responses, and microbiota composition, with both beneficial and adverse effects depending on intensity and duration. Regular moderate exercise is associated with improved quality of life in IBD and IBS, reduced colorectal cancer risk, and potential symptom relief in constipation. However, high-intensity exercise may exacerbate gastroesophageal reflux symptoms and increase the risk of gastrointestinal bleeding. While aerobic exercise has been extensively studied, the effects of resistance training on gastrointestinal health remain underexplored. Conclusions: New methodologies and techniques, such as molecular biology and the study of gastric receptors, have led to advances in understanding the gastrointestinal changes associated with physical exercise. These advances cover different exercise intensities and are being investigated in both experimental models and clinical studies.
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Affiliation(s)
- Juliana Soares Severo
- Graduate Program in Food Sciences and Nutrition, Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Laboratory of Metabolic Diseases Glauto Tuquarre, Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina 64049-550, PI, Brazil; (J.S.S.); (A.M.d.O.); (R.S.P.L.); (F.L.T.-L.)
| | | | | | - Thiago Sousa Reinaldo
- Multicenter Postgraduate Program in Physiological Sciences in Association with the Brazilian Society of Physiology, Federal University of Piauí, Teresina 64049-550, PI, Brazil;
| | - Aureliano Machado de Oliveira
- Graduate Program in Food Sciences and Nutrition, Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Laboratory of Metabolic Diseases Glauto Tuquarre, Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina 64049-550, PI, Brazil; (J.S.S.); (A.M.d.O.); (R.S.P.L.); (F.L.T.-L.)
| | - Rodrigo Soares Pereira Lima
- Graduate Program in Food Sciences and Nutrition, Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Laboratory of Metabolic Diseases Glauto Tuquarre, Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina 64049-550, PI, Brazil; (J.S.S.); (A.M.d.O.); (R.S.P.L.); (F.L.T.-L.)
| | - Francisco Leonardo Torres-Leal
- Graduate Program in Food Sciences and Nutrition, Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Laboratory of Metabolic Diseases Glauto Tuquarre, Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina 64049-550, PI, Brazil; (J.S.S.); (A.M.d.O.); (R.S.P.L.); (F.L.T.-L.)
| | - Armênio Aguiar dos Santos
- Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-270, CE, Brazil;
| | - Moisés Tolentino Bento da Silva
- Graduate Program in Pharmacology, Federal University of Piauí, Teresina 64049-550, PI, Brazil;
- Laboratory of Physiology, (MedInUP/RISE-Health)—Department of Immunophysiology and Pharmacology, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
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5
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Hawley JA, Forster SC, Giles EM. Exercise, the Gut Microbiome and Gastrointestinal Diseases: Therapeutic Impact and Molecular Mechanisms. Gastroenterology 2025:S0016-5085(25)00329-4. [PMID: 39978410 DOI: 10.1053/j.gastro.2025.01.224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 01/16/2025] [Accepted: 01/25/2025] [Indexed: 02/22/2025]
Abstract
The benefits of regular physical activity (PA) on disease prevention and treatment outcomes have been recognized for centuries. However, only recently has interorgan communication triggered by the release of "myokines" from contracting skeletal muscles emerged as a putative mechanism by which exercise confers protection against numerous disease states. Cross-talk between active skeletal muscles and the gut microbiota reveal how regular PA boosts host immunity, facilitates a more diverse gut microbiome and functional metabolome, and plays a positive role in energy homeostasis and metabolic regulation. In contrast, and despite the large interindividual variation in the human gut microbiome, reduced microbial diversity has been implicated in several diseases of the gastrointestinal (GI) tract, systemic immune diseases, and cancers. Although prolonged, intense, weight-bearing exercise conducted in extreme conditions can increase intestinal permeability, compromising gut-barrier function and resulting in both upper and lower GI symptoms, these are transient and benign. Accordingly, the gut microbiome has become an attractive target for modulating many of the positive effects of regular PA on GI health and disease, although the precise dose of exercise required to induce favourable changes in the microbiome and enhance host immunity is currently unknown. Future efforts should concentrate on gaining a deeper understanding of the factors involved in exercise-gut interactions through the generation of functional 'omics readouts (ie, metatranscriptomics, metaproteomics, and metabolomics) that have the potential to identify functional traits of the microbiome that are linked to host health and disease states, and validating these interactions in experimental and preclinical systems. A greater understanding of how PA interacts with the GI tract and the microbiome may enable targeted therapeutic strategies to be developed for individuals and populations at risk for a variety of GI diseases.
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Affiliation(s)
- John A Hawley
- The Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia; Department of Sport and Exercise Sciences, Manchester Metropolitan University Institute of Sport, Manchester, United Kingdom.
| | - Samuel C Forster
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia
| | - Edward M Giles
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Paediatrics, Monash University, Clayton, Victoria, Australia
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Gibson OR, Laitano O, Watanabe K, González-Alonso J. Differential intestinal injury and unchanged systemic inflammatory responses to leg and whole-body passive hyperthermia in healthy humans. Exp Physiol 2025. [PMID: 39937620 DOI: 10.1113/ep092389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/22/2025] [Indexed: 02/14/2025]
Abstract
Hyperthermia can cause intestinal injury, facilitating endotoxin translocation and an inflammatory response that has been associated with heat illness. However, the potential occurrence of these responses has been incompletely reported during passive hyperthermia, and the independent effect of hyperthermia is equivocal. Furthermore, passive hyperthermia is a feature of heat therapy interventions, with mechanistic understanding developing. This experiment quantified the changes in intestinal fatty acid binding protein (iFABP), a marker of intestinal injury, and cytokine, chemokine and growth factor responses during three different prolonged passive hyperthermia protocols. Eight healthy males visited the laboratory on four counterbalanced occasions to undertake 2.5 h of rest (CON), one-leg heating (OLH), two-leg heating (TLH) and whole-body heating (WBH) via a garment circulating water at 50°C. Plasma concentrations of iFABP and 38 cytokines, chemokines and growth factors were quantified periodically, and core temperature (Tcore) was measured continuously. The Tcore increased from baseline in OLH, TLH and WBH (+0.4°C ± 0.2°C, +0.7°C ± 0.2°C and +2.3°C ± 0.4°C, respectively; P < 0.05) but remained unchanged in CON. iFABP increased from baseline in WBH only (∆587 ± 651 pg ml-1) and was different from CON and OLH in WBH after 2 h (P < 0.05). Increased iFABP (∆1085 ± 572 pg ml-1) was observed in 50% of participants at the end of WBH, with the other 50% demonstrating no change (∆89 ± 19 pg ml-1). All chemokines, cytokines and growth factors were unchanged in all protocols. These data indicate that passive whole-body hyperthermia, but not lower-limb hyperthermia, can cause intestinal injury in some individuals without a systemic inflammatory response.
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Affiliation(s)
- Oliver R Gibson
- Division of Sport, Health and Exercise Sciences, Department of Life Sciences, Brunel University of London, Uxbridge, UK
- Centre for Physical Activity in Health and Disease (CPAHD), Brunel University of London, Uxbridge, UK
| | - Orlando Laitano
- College of Health and Human Performance, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA
| | - Kazuhito Watanabe
- Division of Sport, Health and Exercise Sciences, Department of Life Sciences, Brunel University of London, Uxbridge, UK
- Faculty of Education and Human Studies, Department of School Education, Akita University, Akita, Japan
| | - José González-Alonso
- Division of Sport, Health and Exercise Sciences, Department of Life Sciences, Brunel University of London, Uxbridge, UK
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Feng Y, Zeng N, Bordbar F, Lu Z, Gao C. Dietary fermented mixed ingredient product enhances growth performance and intestinal stem cell-mediated epithelial regeneration through Wnt/β-catenin pathway in layer chicks. Poult Sci 2025; 104:104821. [PMID: 39854967 PMCID: PMC11803830 DOI: 10.1016/j.psj.2025.104821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/12/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
This study aimed to investigate the effects of dietary supplements of fermented mixed ingredient product (FMIP) on the growth performance, intestinal health, and immune performance of layer hens during the brooding period. Four hundred eighty healthy one-day-old layer chicks were randomly divided into four groups (six replicates/group, twenty hens/replicate) and were fed with different experimental diets for eight weeks (from day 1 to day 56): (1) Corn-soybean-base diet (CON); (2) Chlortetracycline group (CTC; CON diet supplemented with 0.5g/kg chlortetracycline); (3) 4 % fermented mixed ingredient product (4 % FMIP); (4) 8 % fermented mixed ingredient product (8 % FMIP). The results showed that, compared with the CON group, feeding with CTC, 4 % or 8 % FMIP increased the average daily feed intake (ADFI), average daily gain (ADG), immune organs index, serum IgA, IgM, and IgG levels, as well as the apparent metabolic rates of dry matter, crude protein, crude fiber, and crude ash (P < 0.05). Meanwhile, FMIP supplementation improved jejunal morphology and barrier function, as reflected by increased villus height and transepithelial electrical resistance, decreased DAO activity in serum, and up-regulated Occludin protein expression (P < 0.05). Additionally, FMIP supplementation significantly increased protein expression of the stem cell markers (SOX9 and Lgr5), proliferative cell marker (PCNA), and differentiated absorptive cell marker (Villin) (P < 0.05). The immunofluorescence results were consistent with the above results, and FMIP groups have the same effects as the CTC group. Furthermore, the CTC or 4 % FMIP treatment group resulted in a remarkable increase in Wnt/β-catenin signaling proteins (including β-catenin, TCF4, c-Myc, and Cyclin-D1) compared with the CON group (P < 0.05). In conclusion, dietary supplementation of 4 % FMIP improves growth and immune performance, and promotes the intestinal stem cell expansion of layer chicks through Wnt/β-catenin pathway activation.
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Affiliation(s)
- Yuqing Feng
- College of Animal Science, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China
| | - Nan Zeng
- College of Animal Science, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China
| | - Farhad Bordbar
- College of Animal Science, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China
| | - Zhujin Lu
- College of Animal Science, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China
| | - Chunqi Gao
- College of Animal Science, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangdong Laboratory for Lingnan Modern Agriculture, State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China.
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Barekatain R, Inhuber V, Sharma N, Nowland T, Van TTH, Moore RJ, Cadogan D. Intestinal barrier function, caecal microbiota and growth performance of thermoneutral or heat stressed broiler chickens fed reduced crude protein diets supplemented with guanidinoacetic acid. Poult Sci 2025; 104:104792. [PMID: 39805251 PMCID: PMC11770507 DOI: 10.1016/j.psj.2025.104792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/16/2025] Open
Abstract
The effectiveness of guanidinoacetic acid (GAA) in reduced protein (RP) diets on performance and gut health of broilers under heat stress is largely unknown. A 35-d experiment was conducted using four dietary treatments: a standard protein diet (SP, 22.1 and 20.7% CP in grower and finisher), a RP diet (20.1 and 18.7% in grower and finisher), a RP diet with 0.092% GAA per kg diet substituting 50% of supplemented arginine (GAA50) at one-to-one ratio and a RP diet with the same amount of GAA added on top (GAAtop). Day-old male Ross 308 chicks were assigned to 64 pens (10 birds each) in two rooms. In each room, each diet was replicated 8 times. From d 25 to 35, birds in one room were subjected to a cyclic heat stress (32±1 °C for 8 h). There was no interaction between diets and heat stress for any of the studied parameters. GAA50 followed by GAAtop significantly decreased the feed intake during the finisher phase (P<0.01) and from d 10 to 35 (P<0.001), compared with SP diet. Heat stress reduced (P<0.0001) feed intake and body weight gain at all stages of the study but did not impact FCR. The GAA50 tended to reduce FCR from d 24 to 35 (P=0.086) and d 10 to 35 (P=0.082) compared with SP and RP. Heat stress increased (P<0.05) intestinal permeability whereas diets had no effect. The gene expression of IL1β was downregulated (P<0.01) by GAA50 but diet had no effect on other selected genes. Heat stress upregulated the expression of several genes including Claudin 2, Claudin 3, GPX-1, HSP70, IL1β, SOD-1 and AMPK-α1. Caecal microbiota composition remained unaffected. The results indicate that replacing 50% of supplemented arginine with GAA tends to improve FCR by reducing the feed intake under both thermoneutral and heat stress conditions without any interaction. Supplementation of GAA or two percentage points reduction of dietary protein had no demonstrable effects on parameters of intestinal health.
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Affiliation(s)
- Reza Barekatain
- South Australian Research and Development Institute, Roseworthy Campus, Roseworthy, SA, Australia; School of Animal and Veterinary Sciences, Roseworthy Campus, University of Adelaide, Roseworthy, SA, Australia.
| | | | - Nishchal Sharma
- School of Environmental and Rural Science, University of New England, Armidale, NSW, Australia
| | - Tanya Nowland
- South Australian Research and Development Institute, Roseworthy Campus, Roseworthy, SA, Australia; School of Animal and Veterinary Sciences, Roseworthy Campus, University of Adelaide, Roseworthy, SA, Australia
| | - Thi Thu Hao Van
- School of Science, RMIT University, Bundoora West Campus, Bundoora, VIC, Australia
| | - Robert J Moore
- School of Science, RMIT University, Bundoora West Campus, Bundoora, VIC, Australia
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Liu J, Wei F, Liu J, Sun W, Liu S, Chen S, Zhang D, Xu B, Ma S. Protective effects and mechanisms of HuDiChangRong capsule on TNBS-induced ulcerative colitis in mice. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118879. [PMID: 39369923 DOI: 10.1016/j.jep.2024.118879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 10/08/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE UC, characterized by chronic inflammation primarily affecting the colon and rectum, follows a protracted relapsing course marked by inflammation and an abundance of free radicals at the onset. Hudichangrong Capsule (HDCRC), a traditional Chinese medicinal formula, has long been employed in the treatment of UC and chronic bacillary dysentery, exhibiting positive therapeutic outcomes and a high rate of cure in clinical practice. AIM OF THE STUDY The precise mechanism underlying its efficacy for UC remains elusive. Our objective was to investigate the anti-inflammatory effect and underlying mechanisms of HDCRC on TNBS-induced UC. MATERIALS AND METHODS Here, we introduced HDCRC and induced UC using TNBS. SPF BALB/c mice were divided into 6 groups as follows: control group, colitis model group, colitis treated with sulfasalazine (400 mg/kg) group, and colitis treated with HDCRC (156, 312, and 624 mg/kg) groups. To assess the effects of HDCRC on colitis, we measured body weight loss, disease activity index (DAI), colon length, tissue damage, degree of inflammation, immune capacity, and oxidative stress. Additionally, we evaluated the TLR-4/MyD88 pathway and its downstream signaling using immunohistochemistry, real-time qPCR, and Western blot. Network pharmacology was used for main target prediction. 16s rRNA was employed for gut microbiota detechtion and UPLC-QTOF-MS was used for its and its metabonomics. RESULTS HDCRC significantly slowed weight loss, ameliorated DAI, restored colon length, alleviated TNBS-induced tissue damage. It exerted the therapeutic effects via reducing oxidative stress, restoring immune balance, normalizing the inflammatory mediator levels and restoring intestinal barrier integrity. Furthermore, HDCRC mainly alleviate UC via suppressing the TLR-4/MyD88 pathway and its downstream signaling. The key components of the downstream pathway, including TLR-4, MyD88, NF-κB p65, ERK, p-JNK, p38, p-JAK1, JAK1, p-STAT3, and STAT3, were improved, thereby ameliorating the TNBS-induced injury. In addition, HDCRC could regulate gut microbiota (eg. Erysipelaloclostridium,etc.) and its metabonomics (eg. Vitamin B6 metabolism) in UC mice. CONCLUSIONS In conclusion, HDCRC exerts a protective effect against TNBS-induced UC in mice by inhibiting the TLR-4/MyD88 pathway and its downstream signaling, and partially JAK1/STAT3, suppressing oxidative stress, regulating immunity, restoring intestinal barrier integrity, and regulating gut microbiota and its metabonomics.
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Affiliation(s)
- Jingjing Liu
- National Institutes for Food and Drug Control, Beijing, 100050, China
| | - Feng Wei
- National Institutes for Food and Drug Control, Beijing, 100050, China
| | - Jing Liu
- National Institutes for Food and Drug Control, Beijing, 100050, China
| | - Wenbin Sun
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Shusen Liu
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Shengnan Chen
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Dongqi Zhang
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Beilei Xu
- School of Pharmacy, Harbin University of Commerce, Harbin, 150076, China; Engineering Research Center of Natural Anti-cancer Drugs, Ministry of Education, Harbin, 150076, China; Engineering Research Center of Chinese Medicine Production and New Drug Development, Beijing, 102488, China.
| | - Shuangcheng Ma
- Chinese Pharmacopoeia Commission, Beijing, 100061, China.
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10
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McKenna ZJ, Atkins WC, Wallace T, Jarrard CP, Crandall CG, Foster J. Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults. Exp Physiol 2025; 110:79-92. [PMID: 39417775 DOI: 10.1113/ep092204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 09/30/2024] [Indexed: 10/19/2024]
Abstract
We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32 ± 3 years) and nine older (72 ± 3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11 ± 0.11), but the excretion of sucrose was increased only in older adults (Δ1.7 ± 1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65 ± 0.89 µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08 ± 0.07 mg/dL), cystatin C (group-wide: Δ0.16 ± 0.18 mg/L) and urinary IGFBP7 × TIMP-2 [group-wide: Δ0.64 ± 0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age.
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Affiliation(s)
- Zachary J McKenna
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Whitley C Atkins
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Department of Health, Exercise and Sports Sciences, University of New Mexico, Albuquerque, New Mexico, USA
| | - Taysom Wallace
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
| | - Caitlin P Jarrard
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
- Applied Clinical Research Department, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Craig G Crandall
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Josh Foster
- Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, Texas, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Centre for Human and Applied Physiological Sciences, King's College London, London, UK
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11
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Wei J, Liu Q, Yuen HY, Lam ACH, Jiang Y, Yang Y, Liu Y, Zhao X, Xiao L. Gut-bone axis perturbation: Mechanisms and interventions via gut microbiota as a primary driver of osteoporosis. J Orthop Translat 2025; 50:373-387. [PMID: 40171106 PMCID: PMC11960541 DOI: 10.1016/j.jot.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 09/27/2024] [Accepted: 11/12/2024] [Indexed: 04/03/2025] Open
Abstract
A growing number of studies have highlighted the significance of human gut microbiota (GM) as a potential target for osteoporosis. In this review, we discuss the effect of GM to bone metabolism focusing on two aspects: the local alterations of the human gut permeability that modify how the GM interact with the gut-bone axis (e.g., intestinal leakage, nutrient absorption), and the alterations of the GM itself (e.g., changes in microbiota metabolites, immune secretion, hormones) that modify the events of the gut-bone axis. We then classify these changes as possible therapeutic targets of bone metabolism and highlight some associated promising microbiome-based therapies. We also extend our discussions into combinatorial treatments that incorporate conservative treatments, such as exercise. We anticipate our review can provide an overview of the current pathophysiological and therapeutic paradigms of the gut-bone axis, as well as the prospects of ongoing clinical trials for readers to gain further insights into better microbiome-based treatments to osteoporosis and other bone-degenerative diseases. The translational potential of this article: This paper reviewed the potential links between gut microbiota and osteoporosis, as well as the prospective therapeutic avenues targeting gut microbiota for osteoporosis management, presenting a thorough and comprehensive literature review.
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Affiliation(s)
- Jingyuan Wei
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
- Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Qi Liu
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Ho-Yin Yuen
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Avery Chik-Him Lam
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Yuanyuan Jiang
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
| | - Yuhe Yang
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Yaxiong Liu
- Jihua Laboratory, Foshan, Guangdong, 528000, China
| | - Xin Zhao
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
| | - Long Xiao
- Translational Medical Innovation Center, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, China
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12
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Lee BJ, Meade RD, Davey SL, Thake CD, McCormick JJ, King KE, Kenny GP. Effect of brief ambient cooling on serum stress biomarkers in older adults during a daylong heat exposure: a laboratory-based heat wave simulation. Appl Physiol Nutr Metab 2025; 50:1-8. [PMID: 40036754 DOI: 10.1139/apnm-2024-0476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
Visiting an air-conditioned location during heat exposure reduces physiological strain; however, the effects on gastrointestinal barrier dysfunction and renal ischemia remain unexplored. We compared serum protein responses during a 9 h heat exposure (40.3 °C, 9.3% relative humidity) in 17 older adults without cooling (control) and 19 older adults with a cooling break (∼23 °C) during hours 5 and 6 (cooling). IFABP and sCD14 increased similarly across groups. NGAL was 3.2 pg/mL [1.9, 6.1] lower in the cooling group during heat exposure. A 2 h cooling centre exposure did not ameliorate gastrointestinal barrier dysfunction, but did a reduce a surrogate marker of renal ischemia. ClinicalTrials.gov identifier: NCT04353076.
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Affiliation(s)
- Ben J Lee
- Occupational and Environmental Physiology Group, Centre for Physical Activity, Sport, Exercise Sciences, Coventry University, Coventry, United Kingdom
| | - Robert D Meade
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Sarah L Davey
- Occupational and Environmental Physiology Group, Centre for Physical Activity, Sport, Exercise Sciences, Coventry University, Coventry, United Kingdom
| | - Charles D Thake
- Occupational and Environmental Physiology Group, Centre for Physical Activity, Sport, Exercise Sciences, Coventry University, Coventry, United Kingdom
| | - James J McCormick
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Kelli E King
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
| | - Glen P Kenny
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, ON, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada
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13
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Zhou X, Wei C, Chen Z, Xia X, Wang L, Li X. Potential mechanisms of ischemic stroke induced by heat exposure. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 952:175815. [PMID: 39197783 DOI: 10.1016/j.scitotenv.2024.175815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 08/04/2024] [Accepted: 08/24/2024] [Indexed: 09/01/2024]
Abstract
Recent decades of epidemiological and clinical research have suggested that heat exposure could be a potential risk factor for ischemic stroke. Despite climate factors having a minor impact on individuals compared with established risk factors such as smoking, their widespread and persistent effects significantly affect public health. The mechanisms by which heat exposure triggers ischemic stroke are currently unclear. However, several potential mechanisms, such as the impact of temperature variability on stroke risk factors, inflammation, oxidative stress, and coagulation system changes, have been proposed. This article details the potential mechanisms by which heat exposure may induce ischemic stroke, aiming to guide the prevention and treatment of high-risk groups in hot climates and support public health policy development.
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Affiliation(s)
- Xiao Zhou
- Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Chanjuan Wei
- Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Zhuangzhuang Chen
- Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xiaoshuang Xia
- Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Lin Wang
- Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xin Li
- Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China; Department of Geriatrics, The Second Hospital of Tianjin Medical University, Tianjin, China.
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14
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Soliman MG, Martinez-Serra A, Antonello G, Dobricic M, Wilkins T, Serchi T, Fenoglio I, Monopoli MP. Understanding the role of biomolecular coronas in human exposure to nanomaterials. ENVIRONMENTAL SCIENCE. NANO 2024; 11:4421-4448. [PMID: 39263008 PMCID: PMC11382216 DOI: 10.1039/d4en00488d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/17/2024] [Indexed: 09/13/2024]
Abstract
Nanomaterials (NMs) are increasingly used in medical treatments, electronics, and food additives. However, nanosafety-the possible adverse effects of NMs on human health-is an area of active research. This review provides an overview of the influence of biomolecular coronas on NM transformation following various exposure routes. We discuss potential exposure pathways, including inhalation and ingestion, describing the physiology of exposure routes and emphasising the relevance of coronas in these environments. Additionally, we review other routes to NM exposure, such as synovial fluid, blood (translocation and injection), dermal and ocular exposure, as well as the dose and medium impact on NM interactions. We emphasize the need for an in-depth characterisation of coronas in different biological media, highlighting the need and opportunity to study lung and gastric fluids to understand NM behaviour and potential toxicity. Future research aims to predict better in vivo outcomes and address the complexities of NM interactions with biological systems.
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Affiliation(s)
- Mahmoud G Soliman
- Chemistry Department, RCSI (Royal College of Surgeons in Ireland) 123 St Stephen Green Dublin 2 Ireland
- Physics Department, Faculty of Science, Al-Azhar University Cairo Egypt
| | - Alberto Martinez-Serra
- Chemistry Department, RCSI (Royal College of Surgeons in Ireland) 123 St Stephen Green Dublin 2 Ireland
| | - Giulia Antonello
- Department of Chemistry, University of Torino 10125 Torino Italy
| | - Marko Dobricic
- Chemistry Department, RCSI (Royal College of Surgeons in Ireland) 123 St Stephen Green Dublin 2 Ireland
| | - Terence Wilkins
- School of Chemical & Process Innovation, University of Leeds Engineering Building Leeds LS2 9JT UK
| | - Tommaso Serchi
- Environmental Research and Innovation Department (Luxembourg Institute of Science and Technology) 41, Rue du Brill L4422 Belvaux GD Luxembourg
| | - Ivana Fenoglio
- Department of Chemistry, University of Torino 10125 Torino Italy
| | - Marco P Monopoli
- Chemistry Department, RCSI (Royal College of Surgeons in Ireland) 123 St Stephen Green Dublin 2 Ireland
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15
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Das S, Preethi B, Kushwaha S, Shrivastava R. Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management. Histol Histopathol 2024; 39:1395-1425. [PMID: 38497338 DOI: 10.14670/hh-18-730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.
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Affiliation(s)
- Shreya Das
- Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, India
| | - B Preethi
- Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, India
| | - Sapana Kushwaha
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Lucknow, India.
| | - Richa Shrivastava
- Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, India.
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16
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Sun M, Li Q, Zou Z, Liu J, Gu Z, Li L. The mechanisms behind heatstroke-induced intestinal damage. Cell Death Discov 2024; 10:455. [PMID: 39468029 PMCID: PMC11519599 DOI: 10.1038/s41420-024-02210-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 10/04/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024] Open
Abstract
With the frequent occurrence of heatwaves, heatstroke (HS) is expected to become one of the main causes of global death. Being a multi-organized disease, HS can result in circulatory disturbance and systemic inflammatory response, with the gastrointestinal tract being one of the primary organs affected. Intestinal damage plays an initiating and promoting role in HS. Multiple pathways result in damage to the integrity of the intestinal epithelial barrier due to heat stress and hypoxia brought on by blood distribution. This usually leads to intestinal leakage as well as the infiltration and metastasis of toxins and pathogenic bacteria in the intestinal cavity, which will eventually cause inflammation in the whole body. A large number of studies have shown that intestinal damage after HS involves the body's stress response, disruption of oxidative balance, disorder of tight junction proteins, massive cell death, and microbial imbalance. Based on these damage mechanisms, protecting the intestinal barrier and regulating the body's inflammatory and immune responses are effective treatment strategies. To better understand the pathophysiology of this complex process, this review aims to outline the potential processes and possible therapeutic strategies for intestinal damage after HS in recent years.
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Affiliation(s)
- Minshu Sun
- Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
- Academy of Orthopedics·Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qin Li
- Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
- Academy of Orthopedics·Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhimin Zou
- Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
- Academy of Orthopedics·Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jian Liu
- Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
- Academy of Orthopedics·Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhengtao Gu
- Department of Treatment Center For Traumatic Injuries, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.
- Academy of Orthopedics·Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Li Li
- Department of Intensive Care Unit, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
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17
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Xie K, Qi J, Deng L, Yu B, Luo Y, Huang Z, Mao X, Yu J, Zheng P, Yan H, Li Y, Li H, He J. Protective effect of dihydromyricetin on intestinal epithelium in weaned pigs upon enterotoxigenic Escherichia coli challenge. Int Immunopharmacol 2024; 140:112806. [PMID: 39098232 DOI: 10.1016/j.intimp.2024.112806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/17/2024] [Accepted: 07/23/2024] [Indexed: 08/06/2024]
Abstract
Dihydromyricetin (DMY), a natural flavonoid compound, are believed to prevent inflammatory response, dealing with pathogens and repairing the intestinal barrier. The objective of this study was to investigate whether DMY supplementation could attenuate intestinal damage in the context of enterotoxigenic Escherichia coli K88 (ETEC F4+) infection. After weaning, different litters of pigs were randomly assigned to one of the following treatments: (1) non-challenged control (CON, fed with basal diet); (2) ETEC-challenged control (ECON, fed with basal diet); and (3) ETEC challenge + DMY treatment (EDMY, fed with basal diet plus 300 mg kg-1 DMY). We observed a significant reduction in fecal Escherichia coli shedding and diarrhea incidence, but an increase in ADG in pigs of EDMY group compared to the pigs of ECON group. Relative to the pigs of ECON group, dietary DMY treatment decreased (P < 0.05) concentrations of the serum D-xylose, D-lactate and diamine oxidase (DAO), but increased the abundance of zonula occludens-1 (ZO-1) in the jejunum of pigs. In addition, DMY also decreased (P < 0.05) the number of S-phase cells and the percentage of total apoptotic epithelial cells of jejunal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Furthermore, DMY decreased the mRNA expression levels of critical immune-associated genes TLR4, NFκB, Caspase3, Caspase9, IL-1β, IL-6, TNF-α and the protein p-NFκB and p-IκBα expressions of intestinal epithelium in pigs of the EDMY group compared to the pigs of the ECON group. Compared to the ECON group, DMY elevated (P < 0.05) the expression levels of β-defensins PBD1, PBD2, PBD3, PBD129, as well as the abundance of secreted IgA in intestinal mucosae of the EDMY group. Thus, our results indicate that DMY may relieve intestinal integrity damage due to Escherichia coli F4.
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Affiliation(s)
- Kunhong Xie
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Jiawen Qi
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Lili Deng
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, PR China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Zhiqing Huang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Yan Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Hua Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, PR China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, PR China.
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18
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Yuan L, Li W, Hu S, Wang Y, Wang S, Tian H, Sun X, Yang X, Hu M, Zhang Y. Protective effects of ginsenosides on ulcerative colitis: a meta-analysis and systematic review to reveal the mechanisms of action. Inflammopharmacology 2024; 32:3079-3098. [PMID: 38977646 DOI: 10.1007/s10787-024-01516-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 06/07/2024] [Indexed: 07/10/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. METHODS Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. RESULTS Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5-200 mg/kg with an intervention time of 7-28 days were relatively effective. CONCLUSIONS Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC.
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Affiliation(s)
- Lingling Yuan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuangyuan Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yingyi Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shaofeng Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Huai'e Tian
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuhui Sun
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuli Yang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mengyun Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yi Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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19
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AlZaabi A, Younus HA, Al-Reasi HA, Al-Hajri R. Could environmental exposure and climate change Be a key factor in the rising incidence of early onset colorectal cancer? Heliyon 2024; 10:e35935. [PMID: 39258208 PMCID: PMC11386049 DOI: 10.1016/j.heliyon.2024.e35935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 08/02/2024] [Accepted: 08/06/2024] [Indexed: 09/12/2024] Open
Abstract
The emergence of early onset colorectal cancer (EOCRC) is believed to result from the complex interplay between external environmental factors and internal molecular processes. This review investigates the potential association between environmental exposure to chemicals and climate change and the increased incidence of EOCRC, focusing on their effects on gut microbiota (GM) dynamics. The manuscript explores the birth cohort effect, suggesting that individuals born after 1950 may be at higher risk of developing EOCRC due to cumulative environmental exposures. Furthermore, we also reviewed the impact of environmental pollution, including particulate matter and endocrine disrupting chemicals (EDCs), as well as global warming, on GM disturbance. Environmental exposures have the potential to disrupt GM composition and diversity, leading to dysbiosis, chronic inflammation, and oxidative stress, which are known risk factors associated with EOCRC. Particulate matter can enter the gastrointestinal tract, modifying GM composition and promoting the proliferation of pathogenic bacteria while diminishing beneficial bacteria. Similarly, EDCs, can induce GM alterations and inflammation, further increasing the risk of EOCRC. Additionally, global warming can influence GM through shifts in gut environmental conditions, affecting the host's immune response and potentially increasing EOCRC risk. To summarize, environmental exposure to chemicals and climate change since 1950 has been implicated as contributing factors to the rising incidence of EOCRC. Disruptions in gut microbiota homeostasis play a crucial role in mediating these associations. Consequently, there is a pressing need for enhanced environmental policies aimed at minimizing exposure to pollutants, safeguarding public health, and mitigating the burden of EOCRC.
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Affiliation(s)
- Adhari AlZaabi
- College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman
| | - Hussein A Younus
- Nanotechnology Research Center, Sultan Qaboos University, PO Box 17, Al-Khoud, PC 123 Oman
| | - Hassan A Al-Reasi
- Department of Biology, College of Science, Sultan Qaboos University, PO Box 36, PC 123, Al-Khoud, Muscat, Oman
- Faculty of Education and Arts, Sohar University, PO Box 44, PC 311, Sohar, Oman
| | - Rashid Al-Hajri
- Department of Petrolleum and Chemical Engineering, College of Engineering, Sultan Qaboos University, P. O. Box 33, Al Khoud, Muscat, PC 123, Oman
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20
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Qi J, Yu B, Hu Y, Luo Y, Zheng P, Mao X, Yu J, Zhao X, He T, Yan H, Wu A, He J. Protective Effect of Coated Benzoic Acid on Intestinal Epithelium in Weaned Pigs upon Enterotoxigenic Escherichia coli Challenge. Animals (Basel) 2024; 14:2405. [PMID: 39199939 PMCID: PMC11350680 DOI: 10.3390/ani14162405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/14/2024] [Accepted: 08/18/2024] [Indexed: 09/01/2024] Open
Abstract
The study was designed to investigate the protective effect of dietary supplementation with coated benzoic acid (CBA) on intestinal barrier function in weaned pigs challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two pigs were randomized to four treatments and given either a basal diet or a basal diet supplemented with 3.0 g/kg CBA, followed by oral administration of ETEC or culture medium. The results showed that CBA supplementation increased the average daily weight gain (ADWG) in the ETEC-challenged pigs (p < 0.05). CBA also increased the serum activity of total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), as it decreased the serum concentrations of endotoxin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the ETEC-challenged pigs (p < 0.05). Interestingly, the CBA alleviated the ETEC-induced intestinal epithelial injury, as indicated by a reversal of the decrease in D-xylose absorption and a decrease in the serum levels of D-lactate and diamine oxidase (DAO) activity, as well as a decrease in the quantity of apoptotic cells in the jejunal epithelium following ETEC challenge (p < 0.05). Moreover, CBA supplementation significantly elevated the mucosal antioxidant capacity and increased the abundance of tight junction protein ZO-1 and the quantity of sIgA-positive cells in the jejunal epithelium (p < 0.05). Notably, CBA increased the expression levels of porcine beta defensin 2 (PBD2), PBD3, and nuclear factor erythroid-2 related factor 2 (Nrf-2), while downregulating the expression of toll-like receptor 4 (TLR4) in the jejunal mucosa (p < 0.05). Moreover, CBA decreased the expression levels of interleukin-1β (IL-1β), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) in the ileal mucosa upon ETEC challenge (p < 0.05). These results suggest that CBA may attenuate ETEC-induced damage to the intestinal epithelium, resulting in reduced inflammation, enhanced intestinal immunity and antioxidant capacity, and improved intestinal epithelial function.
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Affiliation(s)
- Jiawen Qi
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Youjun Hu
- Nuacid Nutrition Co., Ltd., Qingyuan 511500, China; (Y.H.); (X.Z.); (T.H.)
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Xiaonan Zhao
- Nuacid Nutrition Co., Ltd., Qingyuan 511500, China; (Y.H.); (X.Z.); (T.H.)
| | - Taiqian He
- Nuacid Nutrition Co., Ltd., Qingyuan 511500, China; (Y.H.); (X.Z.); (T.H.)
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Aimin Wu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.Q.); (B.Y.); (Y.L.); (P.Z.); (X.M.); (J.Y.); (H.Y.); (A.W.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
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21
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Yang H, Zhou C, Nie S, Xu S, Li M, Yu Q, Wei Y, Wang X. Anti-ulcerative colitis effect of rotating magnetic field on DSS-induced mice by modulating colonic inflammatory deterioration. Mol Immunol 2024; 172:23-37. [PMID: 38865801 DOI: 10.1016/j.molimm.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/15/2024] [Accepted: 05/29/2024] [Indexed: 06/14/2024]
Abstract
Ulcerative colitis (UC) is a prevalent inflammatory disorder that emerges in the colon and rectum, exhibiting a rising global prevalence and seriously impacting the physical and mental health of patients. Significant challenges remain in UC treatment, highlighting the need for safe and effective long-term therapeutic approaches. Heralded as a promising physical treatment, the rotating magnetic field (RMF) demonstrates safety, stability, manageability, and efficiency. This study delves into RMF's potential in mitigating DSS-induced UC in mice, assessing disease activity indices (DAI) and pathological alterations such as daily body weight, fecal occult blood, colon length, and morphological changes. Besides, several indexes have been detected, including serum concentrations of pro-inflammatory cytokines (IL6, IL-17A, TNF-α, IFN-γ) and anti-inflammatory cytokines (TGF-β, IL-4, IL-10), the ratio of splenic CD3+, CD4+, and CD8+ T cells, the rate of apoptotic colonic cells, the expression of colonic inflammatory and tight junction-associated proteins. The results showed that RMF had beneficial effects on the decrease of intestinal permeability, the restoration of tight junctions, and the mitigation of mitochondrial respiratory complexes (MRCs) by attenuating inflammatory dysfunction in colons of DSS-induced UC model of mice. In conclusion, this study demonstrates that RMF attenuates colonic inflammation, enhances colonic tight junction, and alleviates MRCs impairment by regulating the equilibrium of pro-inflammatory and anti-inflammatory cytokines in UC mice, suggesting the potential application of RMF in the clinical treatment of UC.
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Affiliation(s)
- Hua Yang
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China; International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China
| | - Cai Zhou
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Shenglan Nie
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Shuling Xu
- School of Pharmacy, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Mengqing Li
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Qinyao Yu
- School of Pharmacy, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China
| | - Yunpeng Wei
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
| | - Xiaomei Wang
- Department of Physiology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China; International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China; School of Pharmacy, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
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22
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Chen X, Xuan Y, Chen Y, Yang F, Zhu M, Xu J, Chen J. Polystyrene nanoplastics induce intestinal and hepatic inflammation through activation of NF-κB/NLRP3 pathways and related gut-liver axis in mice. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 935:173458. [PMID: 38796000 DOI: 10.1016/j.scitotenv.2024.173458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 02/01/2024] [Accepted: 05/20/2024] [Indexed: 05/28/2024]
Abstract
Nanoplastics (NPs) present in food and water poses a genuine risk of their accumulation in humans through the diet. Preferential contact between ingested NPs and the intestine as well as the liver has the potential to induce enteritis and hepatitis. However, there is still a lack of comprehensive understanding regarding the inter-organ crosstalk between the intestine and liver when exposed to NPs, as well as the underlying signaling pathways involved. In this study, we employed a 21-day mice exposure model to investigate the accumulation profile of PS-NPs and elucidate the mechanism of intestinal and hepatic inflammation induced by NPs. After exposure, notable fluorescent signals originating from PS-NPs were detected not only in the stomach and intestine but also in other organs such as liver, lung, kidney, brain, and testes. Histopathological analysis along with routine blood tests both revealed an acute inflammatory reaction in mice. Further mechanistic investigations demonstrated that PS-NPs activated inflammatory NF-κB/NLRP3 pathways and induced the expression of cytokines IL-1β and IL-18 in the intestine, which recruited macrophages and neutrophils into the intestine. Concurrently, a significant decrease in the expression levels of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1) was observed, resulting in an increase in intestinal permeability and elevated endotoxin (LPS) levels. The high levels of LPS further activated TLR4/NF-κB/NLRP3/GSDMD pathways in the liver, inducing liver inflammation and hepatocyte pyroptosis. The impairment of liver function was positively correlated with intestinal inflammation and barrier disruption. These findings underscore that exposure to NPs can instigate enteritis and hepatitis while emphasizing the crucial role played by the indirect gut-liver axis in elucidating the potential mechanism underlying NP-induced liver pathogenesis.
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Affiliation(s)
- Xuanwei Chen
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China
| | - Yang Xuan
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China
| | - Yawen Chen
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China
| | - Fanfan Yang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China
| | - Mengying Zhu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China
| | - Jian Xu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China.
| | - Jin Chen
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hang Zhou 310053, China.
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23
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Rashwan AG, Assar DH, Salah AS, Liu X, Al-Hawary II, Abu-Alghayth MH, Salem SMR, Khalil K, Hanafy NAN, Abdelatty A, Sun L, Elbialy ZI. Dietary Chitosan Attenuates High-Fat Diet-Induced Oxidative Stress, Apoptosis, and Inflammation in Nile Tilapia ( Oreochromis niloticus) through Regulation of Nrf2/Kaep1 and Bcl-2/Bax Pathways. BIOLOGY 2024; 13:486. [PMID: 39056682 PMCID: PMC11273726 DOI: 10.3390/biology13070486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 06/20/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024]
Abstract
Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.
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Affiliation(s)
- Aya G. Rashwan
- Department of Fish Processing and Biotechnology, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; (A.G.R.); (I.I.A.-H.)
| | - Doaa H. Assar
- Clinical Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
| | - Abdallah S. Salah
- Department of Aquaculture, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
- Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK
| | - Xiaolu Liu
- Single-Cell Center, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, CAS Key Laboratory of Biofuels, Chinese Academy of Sciences, Qingdao 266101, China;
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Ibrahim I. Al-Hawary
- Department of Fish Processing and Biotechnology, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; (A.G.R.); (I.I.A.-H.)
| | - Mohammed H. Abu-Alghayth
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, P.O. Box 255, Bisha 67714, Saudi Arabia;
| | - Shimaa M. R. Salem
- Department of Animal Nutrition and Nutritional Deficiency Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura 33516, Egypt;
| | - Karim Khalil
- Department of Veterinary Medicine, College of Applied & Health Sciences, A’Sharqiyah University, P.O. Box 42, Ibra 400, Oman;
| | - Nemany A. N. Hanafy
- Group of Molecular Cell Biology and Bionanotechnology, Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
| | - Alaa Abdelatty
- Pathology Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt;
| | - Luyang Sun
- Single-Cell Center, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology, CAS Key Laboratory of Biofuels, Chinese Academy of Sciences, Qingdao 266101, China;
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Zizy I. Elbialy
- Department of Fish Processing and Biotechnology, Faculty of Aquatic and Fisheries Sciences, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; (A.G.R.); (I.I.A.-H.)
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24
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Liu X, Zhou Y, Zhang Y, Cui X, Yang D, Li Y. Octreotide attenuates intestinal barrier damage by maintaining basal autophagy in Caco2 cells. Mol Med Rep 2024; 29:90. [PMID: 38577927 PMCID: PMC11019401 DOI: 10.3892/mmr.2024.13214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 03/12/2024] [Indexed: 04/06/2024] Open
Abstract
The intestinal mucosal barrier is of great importance for maintaining the stability of the internal environment, which is closely related to the occurrence and development of intestinal inflammation. Octreotide (OCT) has potential applicable clinical value for treating intestinal injury according to previous studies, but the underlying molecular mechanisms have remained elusive. This article is based on a cell model of inflammation induced by lipopolysaccharide (LPS), aiming to explore the effects of OCT in protecting intestinal mucosal barrier function. A Cell Counting Kit‑8 assay was used to determine cell viability and evaluate the effectiveness of OCT. Gene silencing technology was used to reveal the mediated effect of somatostatin receptor 2 (SSTR2). The changes in intestinal permeability were detected through trans‑epithelial electrical resistance and fluorescein isothiocyanate‑dextran 4 experiments, and the alterations in tight junction proteins were detected using immunoblotting and reverse transcription fluorescence‑quantitative PCR technology. Autophagosomes were observed by electron microscopy and the dynamic changes of the autophagy process were characterized by light chain (LC)3‑II/LC3‑I conversion and autophagic flow. The results indicated that SSTR2‑dependent OCT can prevent the decrease in cell activity. After LPS treatment, the permeability of monolayer cells decreased and intercellular tight junctions were disrupted, resulting in a decrease in tight junction protein zona occludens 1 in cells. The level of autophagy‑related protein LC3 was altered to varying degrees at different times. These abnormal changes gradually returned to normal levels after the combined application of LPS and SSTR2‑dependent OCT, confirming the role of OCT in protecting intestinal barrier function. These experimental results suggest that OCT maintains basal autophagy and cell activity mediated by SSTR2 in intestinal epithelial cells, thereby preventing the intestinal barrier dysfunction in inflammation injury.
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Affiliation(s)
- Xiaoli Liu
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
| | - Yan Zhou
- Department of Gastrointestinal Surgery, Yantai Mountain Hospital, Yantai, Shandong 264003, P.R. China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China
| | - Xigang Cui
- Department of Gastrointestinal and Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Donglin Yang
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
| | - Yuling Li
- School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong 264003, P.R. China
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25
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Lin Q, Tu X, Li X, Gou F, Ding L, Lu Z, Feng J, Ying Y, Hu C. Effects of electrolyte balance on intestinal barrier, amino acid metabolism, and mTORC1 signaling pathway in piglets fed low-protein diets. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2024; 17:408-417. [PMID: 38812495 PMCID: PMC11134538 DOI: 10.1016/j.aninu.2024.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 05/31/2024]
Abstract
A proper dietary electrolyte balance (dEB) is essential to ensure optimal growth performance of piglets. In the low-protein diet, this balance may be affected by the reduction of soybean meal and the inclusion of high levels of synthetic amino acids. The objective of this experiment was to evaluate the optimal dEB of low-protein diets and its impact on the growth performance of piglets. A total of 108 piglets (initial age of 35 d) were randomly divided into 3 groups with 6 replicates of 6 pigs each as follows: low electrolyte diet (LE group; dEB = 150 milliequivalents [mEq]/kg); medium electrolyte diet (ME group; dEB = 250 mEq/kg); high electrolyte diet (HE group; dEB = 350 mEq/kg). Results indicated that the LE and HE diet significantly decreased the average daily gain, average daily feed intake, and crude protein digestibility (P < 0.05) in piglets. Meanwhile, LE diets disrupted the structural integrity of the piglets' intestines and decreased jejunal tight junction protein (occludin and claudin-1) expression (P < 0.05). Additionally, the pH and HCO3- in the arterial blood of piglets in the LE group were lower than those in the ME and HE groups (P < 0.05). Interestingly, the LE diet significantly increased lysine content in piglet serum (P < 0.05), decreased the levels of arginine, leucine, glutamic acid, and alanine (P < 0.05), and inhibited the mammalian target of rapamycin complex 1 (mTORC1) pathway by decreasing the phosphorylation abundance of key proteins. In summary, the dietary electrolyte imbalance could inhibit the activation of the mTORC1 signaling pathway, which might be a key factor in the influence of the dEB on piglet growth performance and intestinal health. Moreover, second-order polynomial (quadratic) regression analysis showed that the optimal dEB of piglets in the low-protein diet was 250 to 265 mEq/kg.
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Affiliation(s)
- Qian Lin
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Xiaodian Tu
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Xin Li
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Feiyang Gou
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Lin Ding
- Animal Husbandry Technology Promotion and Breeding Livestock and Poultry Monitoring Station of Zhejiang Province, Hangzhou 310000, China
| | - Zeqing Lu
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Jie Feng
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
| | - Yongfei Ying
- Animal Husbandry Technology Promotion and Breeding Livestock and Poultry Monitoring Station of Zhejiang Province, Hangzhou 310000, China
| | - Caihong Hu
- College of Animal Sciences, Zhejiang University, Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China
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Wang H, Zhu W, Hong Y, Wei W, Zheng N, He X, Bao Y, Gao X, Huang W, Sheng L, Li M, Li H. Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155492. [PMID: 38479258 DOI: 10.1016/j.phymed.2024.155492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 02/02/2024] [Accepted: 02/26/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PURPOSE This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. METHODS In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. RESULTS APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. CONCLUSION APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.
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Affiliation(s)
- Hao Wang
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Weize Zhu
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ying Hong
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wenjing Wei
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ningning Zheng
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaofang He
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yiyang Bao
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xinxin Gao
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Wenjin Huang
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lili Sheng
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Mingxiao Li
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Houkai Li
- Functional Metabolomics and Gut Microbiome Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Ribeiro JL, Santos TA, Garcia MT, Carvalho BFDC, Esteves JECS, Moraes RM, Anbinder AL. Heat-killed Limosilactobacillus reuteri ATCC PTA 6475 prevents bone loss in ovariectomized mice: A preliminary study. PLoS One 2024; 19:e0304358. [PMID: 38820403 PMCID: PMC11142514 DOI: 10.1371/journal.pone.0304358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 05/11/2024] [Indexed: 06/02/2024] Open
Abstract
Osteoporosis is an important health problem that occurs due to an imbalance between bone formation and resorption. Hormonal deficiency post-menopause is a significant risk factor. The probiotic Limosilactobacillus reuteri has been reported to prevent ovariectomy (Ovx)-induced bone loss in mice and reduce bone loss in postmenopausal women. Despite the numerous health benefits of probiotics, as they are live bacteria, the administration is not risk-free for certain groups (e.g., neonates and immunosuppressed patients). We evaluated the effects of L. reuteri (ATCC PTA 6475) and its heat-killed (postbiotic) form on Ovx-induced bone loss. Adult female mice (BALB/c) were randomly divided into four groups: group C-control (sham); group OVX-C-Ovx; group OVX-POS-Ovx + heat-killed probiotic; group OVX-PRO-Ovx + probiotic. L. reuteri or the postbiotic was administered to the groups (1.3x109 CFU/day) by gavage. Bacterial morphology after heat treatment was accessed by scanning electron microscopy (SEM). The treatment started one week after Ovx and lasted 28 days (4 weeks). The animals were euthanized at the end of the treatment period. Bone microarchitecture and ileum Occludin and pro-inflammatory cytokines gene expression were evaluated by computed microtomography and qPCR techniques, respectively. The Ovx groups had lower percentage of bone volume (BV/TV) and number of bone trabeculae as well as greater total porosity compared to the control group. Treatment with live and heat-killed L. reuteri resulted in higher BV/TV and trabecular thickness than the Ovx group. The heat treatment caused some cell surface disruptions, but its structure resembled that of the live probiotic in SEM analysis. There were no statistical differences in Occludin, Il-6 and Tnf-α gene expression. Both viable and heat-killed L. reuteri prevented bone loss on ovariectomized mice, independently of gut Occludin and intestinal Il-6 and Tnf-α gene expression.
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Affiliation(s)
- Jaqueline Lemes Ribeiro
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
| | - Thaís Aguiar Santos
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
| | - Maíra Terra Garcia
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
| | - Bruna Fernandes do Carmo Carvalho
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
| | | | - Renata Mendonça Moraes
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
| | - Ana Lia Anbinder
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology of São José dos Campos (São Paulo State University–Unesp), São José dos Campos, São Paulo, Brazil
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Guo H, Xie W, Ji Z, Wang B, Ren W, Gao W, Yuan B. Oyster Peptides Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis via Modulating the Gut Microbiota and Inhibiting the TLR4/NF-κB Pathway. Nutrients 2024; 16:1591. [PMID: 38892524 PMCID: PMC11175164 DOI: 10.3390/nu16111591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/20/2024] [Accepted: 05/21/2024] [Indexed: 06/21/2024] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease with an increasing prevalence year over year, and the medications used to treat patients with UC clinically have severe side effects. Oyster peptides (OPs) have anti-inflammatory and antioxidant properties as functional foods that can alleviate a wide range of inflammatory conditions. However, the application of oyster peptides in ulcerative colitis is not well studied. In this work, an animal model of acute colitis was established using 3% dextran sulfate sodium (DSS), and the impact of OP therapy on colitis in mice was examined. Supplementing with OPs prevented DSS-induced colitis from worsening, reduced the expression of oxidative stress and inflammatory markers, and restored the intestinal barrier damage caused by DSS-induced colitis in mice. The 16S rDNA results showed that the OP treatment improved the gut microbiota structure of the UC mice, including increasing microbial diversity, increasing beneficial bacteria, and decreasing harmful bacteria. In the UC mice, the OP therapy decreased the relative abundance of Family_XIII_AD3011_group and Prevotella_9 and increased the relative abundance of Alistipes. In conclusion, OP treatment can inhibit the TLR4/NF-κB pathway and improve the intestinal microbiota in UC mice, which in turn alleviates DSS-induced colitis, providing a reference for the treatment of clinical UC patients.
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Affiliation(s)
- Haixiang Guo
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wenyin Xie
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Zhonghao Ji
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
- Department of Basic Medicine, Changzhi Medical College, Changzhi 046000, China
| | - Bingbing Wang
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wenzhi Ren
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Wei Gao
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
| | - Bao Yuan
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (H.G.); (W.X.); (Z.J.); (B.W.); (W.R.)
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Mora-Rodriguez R, Moreno-Cabañas A, Alvarez-Jimenez L, Mora-Gonzalez D, Ortega JF, Morales-Palomo F. A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals. Am J Physiol Endocrinol Metab 2024; 326:E648-E662. [PMID: 38568152 DOI: 10.1152/ajpendo.00312.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 03/01/2024] [Accepted: 03/24/2024] [Indexed: 05/01/2024]
Abstract
We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating carbohydrate oxidation and glycogen use would increase the disposal of an ingested glucose load [i.e., oral glucose tolerance test (OGTT); 75 g of glucose]. Separated by at least 1 wk, nine young healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58 ± 5% V̇o2max either in a thermoneutral (21 ± 1°C; NEUTRAL) or in a hot environment (33 ± 1°C; HEAT) eliciting similar energy expenditure (503 ± 101 kcal). These two trials were compared with a no-exercise trial (NO EXER). Twenty minutes after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149 ± 35 vs. 124 ± 31 µmol·kg-1·min-1, P = 0.010). However, during the following OGTT, glucose Rd was similar in HEAT and NEUTRAL trials (i.e., 25.1 ± 3.6 vs. 25.2 ± 5.3 µmol·kg-1·min-1, P = 0.981). Insulin sensitivity (i.e., ISIndexMATSUDA) only improved in NEUTRAL compared with NO EXER (10.1 ± 4.6 vs. 8.8 ± 3.7 au; P = 0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.NEW & NOTEWORTHY Exercise in the heat increases estimated muscle glycogen use. Reduced muscle glycogen after exercise in the heat could increase insulin-mediated glucose uptake during a subsequent oral glucose tolerance test (OGTT). However, plasma glucose kinetics are not improved during the OGTT in response to a bout of exercise in the heat, and insulin sensitivity worsens. Heat stress activates glucose counterregulatory hormones whose actions may linger during the OGTT, preventing increased glucose uptake.
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Affiliation(s)
| | - Alfonso Moreno-Cabañas
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
- Centre for Nutrition, Exercise and Metabolism, University of Bath, Bath, United Kingdom
- Department for Health, University of Bath, Bath, United Kingdom
| | | | - Diego Mora-Gonzalez
- Department of Nursing, Physiotherapy, and Occupational Therapy, University of Castilla-La Mancha, Toledo, Spain
| | - Juan Fernando Ortega
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
| | - Felix Morales-Palomo
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
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Lee BJ, Flood TR, Galan-Lopez N, McCormick JJ, King KE, Fujii N, Kenny GP. Changes in surrogate markers of intestinal epithelial injury and microbial translocation in young and older men during prolonged occupational heat stress in temperate and hot conditions. Eur J Appl Physiol 2024; 124:1049-1062. [PMID: 37815618 DOI: 10.1007/s00421-023-05329-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/16/2023] [Indexed: 10/11/2023]
Abstract
PURPOSE Exertional heat stress can cause damage to the intestinal epithelium and disrupt gastrointestinal barrier integrity, leading to microbial translocation (MT) linked to the development of heat stroke. This study aimed to assess age-related differences in markers of intestinal epithelial injury and MT following non-heat stress and high-heat stress exercise in healthy young and older men. METHODS Markers of intestinal epithelial injury (intestinal fatty acid-binding protein-'IFABP') and MT (soluble cluster of differentiation 14-'sCD14'; and lipopolysaccharide-binding protein-'LBP') were assessed in healthy young (18-30 y, n = 13) and older (50-70 y) men (n = 12). Blood samples were collected before, after 180 min of moderate-intensity (metabolic rate: 200 W/m2) walking and following 60 min recovery in either a non-heat stress [temperate: 21.9 °C, 35% relative humidity (RH)] or high-heat stress (hot: 41.4 °C, 35% RH) environment. RESULTS There were no differences in IFABP and sCD14 between the young and older groups in the temperate condition, while LBP was greater in the older group (+ 0.66 ug/mL; + 0.08 to + 1.24 ug/mL). In the hot condition, the older group experienced greater increases in IFABP compared to the young group (+ 712 pg/mL/hr; + 269 to + 1154 pg/mL/hr). However, there were no clear between-group differences for sCD14 (+ 0.24 ug/mL/hr, - 0.22 to + 0.70 ug/mL/hr) or LBP (+ 0.86 ug/mL/hr, - 0.73 to + 2.46 ug/mL/hr). CONCLUSION While older men may experience greater intestinal epithelial injury following exercise in the heat; this did not lead to a greater magnitude of microbial translocation relative to their younger counterparts.
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Affiliation(s)
- Ben J Lee
- Occupational and Environmental Physiology Group, Centre for Sport, Exercise, and Life Sciences, Coventry University, Coventry, UK
| | - Tessa R Flood
- Institute of Sport, Manchester Metropolitan University, Manchester, UK
| | - Natalia Galan-Lopez
- Occupational and Environmental Physiology Group, Centre for Sport, Exercise, and Life Sciences, Coventry University, Coventry, UK
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - James J McCormick
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University Ave., Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada
| | - Kelli E King
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University Ave., Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada
| | - Naoto Fujii
- Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan
| | - Glen P Kenny
- Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, 125 University Ave., Room 367, Montpetit Hall, Ottawa, ON, K1N 6N5, Canada.
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Cao J, Zhang D, Li W, Yuan W, Luo G, Xie S. Azilsartan improves urinary albumin excretion in hypertension mice. Aging (Albany NY) 2024; 16:4138-4148. [PMID: 38462692 PMCID: PMC10968693 DOI: 10.18632/aging.205271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 05/31/2023] [Indexed: 03/12/2024]
Abstract
Hypertension is one of the most important risk factors for chronic kidney diseases, leading to hypertensive nephrosclerosis, including excessive albuminuria. Azilsartan, an angiotensin II type 1 receptor blocker, has been widely used for the treatment of hypertension. However, the effects of Azilsartan on urinary albumin excretion in hypertension haven't been reported before. In this study, we investigated whether Azilsartan possesses a beneficial property against albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Compared to the control group, the ANG/HS group had higher blood pressure, oxidative stress, and inflammatory response, all of which were rescued by Azilsartan dose-dependently. Importantly, the ANG/HS-induced increase in urinary albumin excretion and decrease in the expression of occludin were reversed by Azilsartan. Additionally, it was shown that increased fluorescence intensity of FITC-dextran, declined trans-endothelial electrical resistance (TEER) values, and reduction of occludin and krüppel-like factor 2 (KLF2) were observed in ANG/HS-treated human renal glomerular endothelial cells (HrGECs), then prevented by Azilsartan. Moreover, the regulatory effect of Azilsartan on endothelial monolayer permeability in ANG/HS-treated HrGECs was abolished by the knockdown of KLF2, indicating KLF2 is required for the effect of Azilsartan. We concluded that Azilsartan alleviated diabetic nephropathy-induced increase in Uterine artery embolization (UAE) mediated by the KLF2/occludin axis.
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Affiliation(s)
- Jun Cao
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
| | - Dandan Zhang
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
| | - Wenfeng Li
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
| | - Wenjin Yuan
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
| | - Gang Luo
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
| | - Shaofeng Xie
- Department of Nephrology, People’s Hospital of Ganzhou, Ganzhou 341001, Jiangxi Province, China
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Takami M, Aoi W, Matsumoto K, Kato Y, Kobayashi Y, Kuwahata M. High-intensity exercise impairs intestinal barrier function by generating oxidative stress. J Clin Biochem Nutr 2024; 74:136-140. [PMID: 38510689 PMCID: PMC10948349 DOI: 10.3164/jcbn.23-96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/07/2023] [Indexed: 03/22/2024] Open
Abstract
The intestine functions as a barrier preventing the entry of extrinsic factors into the body. This barrier function is disrupted by oxidative damage along with an impaired mucosal layer. Excessive exercise can generate oxidative stress in the intestinal tissue; however, the effect of exercise-induced oxidative stress on intestinal permeability is unclear. In this study, we examined the involvement of oxidative stress in barrier function of the ileum of mice following high-intensity exercise. Male ICR mice (12-week-old) were divided into sedentary and exercise groups. Mice in the exercise group underwent a single bout of treadmill running, and the ileum was collected for histological and biochemical analyses. Plasma fluorescence intensity level after oral administration of fluorescein isothiocyanate-dextran gradually increased until 30 min after exercise in response to intensity of exercise. Relatively high levels of oxidative proteins and low level of claudin-1, a tight-junction protein, were observed in the exercise group. Treatment with a xanthine oxidase inhibitor suppressed exercise-induced increases in intestinal permeability. Moreover, excessive exercise training for two weeks led to relatively high intestinal permeability at rest. These results suggest that high-intensity exercise increases intestinal permeability and tight junction damage, which may be mediated by oxidative stress.
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Affiliation(s)
- Maki Takami
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto 606-8522, Japan
| | - Wataru Aoi
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto 606-8522, Japan
| | - Karin Matsumoto
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto 606-8522, Japan
| | - Yoji Kato
- Laboratory of Free Radical and Food Function, School of Human Science and Environment, University of Hyogo, 1-1-12 Shinzaikehon-cho, Himeji, Hyogo 670-0092, Japan
| | - Yukiko Kobayashi
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto 606-8522, Japan
| | - Masashi Kuwahata
- Laboratory of Nutrition Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto 606-8522, Japan
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Li Y, Ling P, Li Y, Wang Y, Li G, Qiu C, Wang J, Gong K. miR-138-5p ameliorates intestinal barrier disruption caused by acute superior mesenteric vein thrombosis injury by inhibiting the NLRP3/HMGB1 axis. PeerJ 2024; 12:e16692. [PMID: 38406274 PMCID: PMC10893868 DOI: 10.7717/peerj.16692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/28/2023] [Indexed: 02/27/2024] Open
Abstract
Background Acute superior mesenteric venous thrombosis (ASMVT) decreases junction-associated protein expression and intestinal epithelial cell numbers, leading to intestinal epithelial barrier disruption. Pyroptosis has also recently been found to be one of the important causes of mucosal barrier defects. However, the role and mechanism of pyroptosis in ASMVT are not fully understood. Methods Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). Gene expression levels were determined by RNA extraction and reverse transcription-quantitative PCR (RT-qPCR). Western blot and immunofluorescence staining analysis were used to analyze protein expression. H&E staining was used to observe the intestinal tissue structure. Cell Counting Kit-8 (CCK-8) and fluorescein isothiocyanate/propidine iodide (FITC/PI) were used to detect cell viability and apoptosis, respectively. Dual-luciferase reporter assays prove that miR-138-5p targets NLRP3. Results miR-138-5p expression was downregulated in ASMVT-induced intestinal tissues. Inhibition of miR-138-5p promoted NLRP3-related pyroptosis and destroyed tight junctions between IEC-6 cells, ameliorating ASMVT injury. miR-138-5p targeted to downregulate NLRP3. Knockdown of NLRP3 reversed the inhibition of proliferation, apoptosis, and pyroptosis and the decrease in tight junction proteins caused by suppression of miR-138-5p; however, this effect was later inhibited by overexpressing HMGB1. miR-138-5p inhibited pyroptosis, promoted intestinal epithelial tight junctions and alleviated ASMVT injury-induced intestinal barrier disruption via the NLRP3/HMGB1 axis.
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Affiliation(s)
- Yuejin Li
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Ping Ling
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Yu Li
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Yongzhi Wang
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Guosan Li
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Changtao Qiu
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Jianghui Wang
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
| | - Kunmei Gong
- The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China
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Zhang Y, Fang H, Wang T, Zhang Z, Zhu T, Xiong L, Hu H, Liu H. Lactobacillus acidophilus-Fermented Jujube Juice Ameliorates Chronic Liver Injury in Mice via Inhibiting Apoptosis and Improving the Intestinal Microecology. Mol Nutr Food Res 2024; 68:e2300334. [PMID: 38150643 DOI: 10.1002/mnfr.202300334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 09/28/2023] [Indexed: 12/29/2023]
Abstract
SCOPE Chronic liver diseases are clinically silent and responsible for significant morbidity and mortality worldwide. Jujube has displayed various biological activities. Here, the therapeutic effect of Lactobacillus acidophilus (L. acidophilus)-fermented jujube juice (FJJ) and the possible mechanism against chronic liver injury (CLI) in mice are further studied. METHODS AND RESULTS After the CCl4 -induced CLI mice are separately treated with L. acidophilus (LA), unfermented jujube juice (UFJJ), and FJJ, FJJ but not LA or UFJJ suppresses the liver index. By using H&E staining, immunofluorescence staining, RT-PCR, and western blotting, it is shown that LA, UFJJ, and FJJ intervention ameliorate hepatocyte necrosis, inhibit the mRNA levels of pro-inflammatory (NLRP3, Caspase-1, IL-1β, and TNF-α) and fibrosis-associated factors (TGF-β1, LXRα, and MMP2). Also, FJJ displays significant protection against mucosal barrier damage in CLI mice. Among the three interventions, FJJ exhibits the best therapeutic effect, followed by UFJJ and LA. Furthermore, FJJ improves dysbiosis in CLI mice. CONCLUSIONS This study suggests that FJJ exhibits a protective effect against CCl4 -induced CLI mice by inhibiting apoptosis and oxidative stress, regulating liver lipid metabolism, and improving gut microecology. Jujube juice fermentation with L. acidophilus can be a food-grade supplement in treating CLI and related liver diseases.
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Affiliation(s)
- Yu Zhang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
| | - Haitian Fang
- Ningxia Key Laboratory for Food Microbial-Applications Technology and Safety Control, College of Food and Wine, Ningxia University, Yinchuan, 750021, P. R. China
| | - Tong Wang
- Ningxia Key Laboratory for Food Microbial-Applications Technology and Safety Control, College of Food and Wine, Ningxia University, Yinchuan, 750021, P. R. China
| | - Zhigang Zhang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
| | - Tianxiang Zhu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
| | - Lei Xiong
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
| | - Haiming Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan, 430065, P. R. China
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Li Y, Lu Y, Yu B, Huang Z, Luo Y, Zheng P, Mao X, Yu J, Luo J, Yan H, He J. Effect of cordyceps militaris on growth performance, antioxidant capacity, and intestinal epithelium functions in weaned pigs. J Anim Sci 2024; 102:skae194. [PMID: 39001695 PMCID: PMC11322740 DOI: 10.1093/jas/skae194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 07/13/2024] [Indexed: 08/15/2024] Open
Abstract
To explore the effects of cordyceps militaris (CM) on growth performance and intestinal epithelium functions, 180 weaned pigs were randomly assigned into 5 treatments with 6 replicate pens per treatment (6 pigs per pen). Pigs were fed with basal diet (control) or basal diet supplemented with 100, 200, 400, and 800 mg/kg CM. The trial lasted for 42 d, and pigs from the control and optimal-dose groups (based on growth performance) were picked for blood and tissue collection (n = 6). Results showed that CM elevated the average daily gain (ADG) and decreased the ratio of feed intake to gain (F:G) in the weaned pigs (P < 0.05). CM supplementation at 100 mg/kg improved the digestibilities of dry matter (DM), crude protein (CP), and gross energy (GE) (P < 0.05). CM not only increased the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) but also increased the concentration of interleukin-10 (IL-10) in serum (P < 0.05). The serum concentrations of malondialdehyde (MDA), d-lactate, and diamine oxidase (DAO) were reduced by CM (P < 0.05). Interestingly, CM elevated the villus height and the ratio of villus height to crypt depth in the duodenum and jejunum and increased the activities of duodenal sucrase and maltase (P < 0.05). Moreover, CM elevated the expression levels of tight-junction proteins ZO-1, claudin-1, and occluding, as well as critical functional genes such as the fatty acid transport protein (FATP1), cationic amino acid transporter 1 (CAT1), and NF-E2-related factor 2 (Nrf2) in the duodenum and jejunum (P < 0.05). Importantly, CM increased the concentrations of acetic acid and butyric acid, and elevated the abundances of Bacillus and Lactobacillus in the cecum and colon, respectively (P < 0.05). These results indicated potential benefits of CM in improving the growth of weaned pigs, and such effect may be tightly associated with improvement in antioxidant capacity and intestinal epithelium functions.
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Affiliation(s)
- YanPing Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Yang Lu
- Institute of Animal Husbandry and Veterinary Sciences, Shanghai Academy of Agricultural Sciences, Shanghai, People’s Republic of China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Zhiqing Huang
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Junqiu Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Sichuan Province, Chengdu 611130, People’s Republic of China
- Key Laboratory of Animal Disease-resistant Nutrition, Sichuan Province, Chengdu 611130, People’s Republic of China
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Pedrosa de Menezes AL, Bloem BR, Beckers M, Piat C, Benarroch EE, Savica R. Molecular Variability in Levodopa Absorption and Clinical Implications for the Management of Parkinson's Disease. JOURNAL OF PARKINSON'S DISEASE 2024; 14:1353-1368. [PMID: 39240647 PMCID: PMC11492115 DOI: 10.3233/jpd-240036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Indexed: 09/07/2024]
Abstract
Levodopa is the most widely used medication for the symptomatic treatment of Parkinson's disease and, despite being an "old" drug, is still considered the gold standard for offering symptomatic relief. The pharmacokinetic and pharmacodynamics of levodopa have been studied extensively. Our review explores the molecular mechanisms that affect the absorption of this drug, focusing on the large intra- and interindividual variability of absorption that is commonly encountered in daily clinical practice, and on the interaction with other medications. In addition, we will explore the clinical implications of levodopa absorption variability and address current and future strategies for researchers and clinicians.
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Affiliation(s)
| | - Bastiaan R. Bloem
- Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Radboud University Medical Center, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Milan Beckers
- Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Donders Institute for Brain, Radboud University Medical Center, Cognition and Behaviour, Nijmegen, The Netherlands
| | - Capucine Piat
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | | | - Rodolfo Savica
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
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Yang Y, Zhang Y, Song J, Li Y, Zhou L, Xu H, Wu K, Gao J, Zhao M, Zheng Y. Bergamot polysaccharides relieve DSS-induced ulcerative colitis via regulating the gut microbiota and metabolites. Int J Biol Macromol 2023; 253:127335. [PMID: 37820919 DOI: 10.1016/j.ijbiomac.2023.127335] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 09/16/2023] [Accepted: 10/08/2023] [Indexed: 10/13/2023]
Abstract
This study aimed to explore the efficacy of polysaccharides from bergamot (BP) in alleviating DSS-induced colitis. Results showed that BP was primarily composed of two components, BP-1 and BP-2, with similar monosaccharide compositions to BP (mainly glucose and xylose) and molecular weights (Mw) of 4.50 × 105 and 2.35 × 105 Da. This study found BP relieved disease symptoms such as weight loss and colon shortening in mice with colitis. Gut microbiota and metabolomics analysis revealed that the BP could also promote the proliferation of beneficial bacteria such as Bifidobacteria, Butyrivibrio, and Blautia, resulting in increased levels of SCFAs and L-phenylalanine, which were associated with phenylalanine, tyrosine, and tryptophan metabolism pathways. Further analysis validated the inflammatory activity of L-phenylalanine. Hence, BP may relieve colitis symptoms by regulating the gut microbiota and metabolism, which reduced inflammation and enhanced the expression of tight junctional proteins (TJ proteins) and mucin in the intestine.
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Affiliation(s)
- Yiren Yang
- Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521031, China; School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Yuwei Zhang
- Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521031, China; School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Jiangping Song
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Yaqian Li
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Liuyang Zhou
- Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521031, China; School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Hongtao Xu
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Kaizhang Wu
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Jie Gao
- School of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
| | - Mouming Zhao
- Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521031, China; School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
| | - Yang Zheng
- Chaozhou Branch of Chemistry and Chemical Engineering Guangdong Laboratory, Chaozhou 521031, China; School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
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Zhu L, Dou Z, Wu W, Hou Q, Wang S, Yuan Z, Li B, Liu J. Ghrelin/GHSR Axis Induced M2 Macrophage and Alleviated Intestinal Barrier Dysfunction in a Sepsis Rat Model by Inactivating E2F1/NF- κB Signaling. Can J Gastroenterol Hepatol 2023; 2023:1629777. [PMID: 38187112 PMCID: PMC10769719 DOI: 10.1155/2023/1629777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 10/20/2023] [Accepted: 12/11/2023] [Indexed: 01/09/2024] Open
Abstract
Sepsis is an inflammatory reaction disorder state that is induced by infection. The activation and regulation of the immune system play an essential role in the development of sepsis. Our previous studies have shown that ghrelin ameliorates intestinal dysfunction in sepsis. Very little is known about the mechanism of ghrelin and its receptor (GHSR) on the intestinal barrier and the immune function of macrophage regulation. Our research is to investigate the regulatory effect and molecular mechanism of the ghrelin/GHSR axis on intestinal dysfunction and macrophage polarization in septic rats. A rat model of sepsis was established by cecal ligation and puncture (CLP) operation. Then, the sepsis rats were treated with a ghrelin receptor agonist (TZP-101) or ghrelin inhibitor (obestatin). The results suggested that TZP-101 further enhanced ghrelin and GHSR expressions in the colon and spleen of septic rats and obestatin showed the opposite results. Ghrelin/GHSR axis ameliorated colonic structural destruction and intestinal epithelial tight junction injury in septic rats. In addition, the ghrelin/GHSR axis promoted M2-type polarization of macrophages, which was characterized by the decreases of IL-1β, IL-6, and TNF-α, as well as the increase of IL-10. Mechanistically, the ghrelin/GHSR axis promoted E2F2 expression and suppressed the activation of the NF-κB signaling pathway in septic rats. Collectively, targeting ghrelin/GHSR during sepsis may represent a novel therapeutic approach for the treatment of intestinal barrier injury.
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Affiliation(s)
- Lei Zhu
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Zhimin Dou
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Wei Wu
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Qiliang Hou
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Sen Wang
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Ziqian Yuan
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Bin Li
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Jian Liu
- Department of Intensive Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, China
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Dou W, Xu H, Feng S, Liu T, Xiao L, Wu Y, Chen S, Pan Y, Wang X. The Alleviating Effects and Mechanisms of Betaine on Dextran Sulfate Sodium-Induced Colitis in Mice. Mol Nutr Food Res 2023; 67:e2300376. [PMID: 37815169 DOI: 10.1002/mnfr.202300376] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/17/2023] [Indexed: 10/11/2023]
Abstract
SCOPE Ulcerative colitis (UC) is an intestinal disease that is becoming increasingly prevalent and is often overlooked in early stages, and its pathogenesis is often closely related to inflammatory processes. Betaine is a natural product with anti-inflammatory effects that exists in a wide range of plants and animals. METHODS AND RESULTS In this study, the protective effects of betaine are investigated on intestinal barrier function in a mouse model, a dextran sulfate sodium-induced ulcerative colitis and its mechanism of action in the inflammatory context. FITC-dextran 4000 Da (FD-4) flux, disease activity index, histopathological scores, and inflammatory factor levels in sera are determined across different groups. In addition, Caco-2 cell monolayer barrier function is evaluated by transepithelial resistance and FD-4 flux. The expression levels and distribution of tight junction proteins are determined using Western blot and immunofluorescence, respectively. Activation of the NF-κBp65/MLCK/p-MLC signaling pathway is detected by Western blot. Chromatin immunoprecipitation is performed to examine the binding of NF-κB to the MLCK gene promoter. The results indicated that betaine inhibits NF-κB-mediated activation of the MLCK/p-MLC signaling pathway to protect the intestinal barrier function of mice with UC. CONCLUSION Betaine can be used as a potential candidate drug to improve intestinal barrier dysfunction in patients with UC.
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Affiliation(s)
- Weidong Dou
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Hao Xu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Shuo Feng
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Tao Liu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Lin Xiao
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Yingchao Wu
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Shanwen Chen
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Yisheng Pan
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Peking University, 8 Xi ShiKu Street, Beijing, 100034, P. R. China
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Niu X, Hu C, Chen S, Wen J, Liu X, Yong Y, Yu Z, Ma X, Li C, Warda M, Abd El-Aty AM, Gooneratne R, Ju X. Chitosan-gentamicin conjugate attenuates heat stress-induced intestinal barrier injury via the TLR4/STAT6/MYLK signaling pathway: In vitro and in vivo studies. Carbohydr Polym 2023; 321:121279. [PMID: 37739521 DOI: 10.1016/j.carbpol.2023.121279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 08/06/2023] [Accepted: 08/08/2023] [Indexed: 09/02/2023]
Abstract
Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly (P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin, claudin1, and claudin2. However, pretreatment with CS-GT significantly increased (P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4. In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo. This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury.
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Affiliation(s)
- Xueting Niu
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China
| | - Canying Hu
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China
| | - Shengwei Chen
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China
| | - Jiaying Wen
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China
| | - Xiaoxi Liu
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Yanhong Yong
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Zhichao Yu
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Xingbin Ma
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China
| | - Chengpeng Li
- College of Chemistry and Environment Science, Guangdong Ocean University, Zhanjiang 524088, China
| | - Mohamad Warda
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
| | - A M Abd El-Aty
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum 25240, Turkey
| | - Ravi Gooneratne
- Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647, New Zealand
| | - Xianghong Ju
- College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China; Marine Medical Research and Development Centre, Shenzheng Institute of Guangdong Ocean University, Shenzheng 518120, China.
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Liu Y, Li Y, Deng Z, Zhao Y, Yuan R, Yang M, Wang L, Fang Y, Ding D, Zhou F, Kang H. Protective and immunomodulatory effects of mesenchymal stem cells on multiorgan injury in male rats with heatstroke. J Therm Biol 2023; 118:103696. [PMID: 37871397 DOI: 10.1016/j.jtherbio.2023.103696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/01/2023] [Accepted: 08/25/2023] [Indexed: 10/25/2023]
Abstract
Heatstroke (HS) causes multiple organ dysfunction syndrome (MODS) with a mortality rate of 60% after hospitalization. Currently, there is no effective and targeted approach for the treatment of HS. Despite growing evidence that mesenchymal stem cells (MSCs) may reduce multiorgan damage and improve survival through immunomodulatory effects in several diseases, no one has tested whether MSCs have immunomodulatory effects in heatstroke. The present study focused on pathological changes and levels of the cytokines and immunoglobulins to investigate the mechanisms underlying the protective effect and the anti-inflammatory effects of MSCs. We found that MSCs treatment significantly reduced the 28-day mortality rate (P < 0.05), the levels of hepatic and renal function markers on day 1 (P < 0.01) and the pathological lesion scores of multiple organs in HS rats. The levels of IgG1, IgM, and IgA of the HS + MSC group was significantly higher than that in HS group on days 3 and 28(P < 0.05). In conclusion, MSCs contribute to protecting against multiorgan injury, reducing pro-inflammatory cytokines, stabilizing immunoglobulins, and reducing the mortality rate of HS rats.
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Affiliation(s)
- Yuyan Liu
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yun Li
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Zihui Deng
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Basic Medicine, Graduate School, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yan Zhao
- Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Rui Yuan
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Mengmeng Yang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Lu Wang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yuan Fang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Dengfeng Ding
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Laboratory Animal Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China
| | - Feihu Zhou
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Laboratory Animal Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, PR China
| | - Hongjun Kang
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China; Department of Critical Care Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
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Morella I, Negro M, Dossena M, Brambilla R, D'Antona G. Gut-muscle-brain axis: Molecular mechanisms in neurodegenerative disorders and potential therapeutic efficacy of probiotic supplementation coupled with exercise. Neuropharmacology 2023; 240:109718. [PMID: 37774944 DOI: 10.1016/j.neuropharm.2023.109718] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 09/13/2023] [Accepted: 09/16/2023] [Indexed: 10/01/2023]
Abstract
Increased longevity is often associated with age-related conditions. The most common neurodegenerative disorders in the older population are Alzheimer's disease (AD) and Parkinson's disease (PD), associated with progressive neuronal loss leading to functional and cognitive impairments. Although symptomatic treatments are available, there is currently no cure for these conditions. Gut dysbiosis has been involved in the pathogenesis of AD and PD, thus interventions targeting the "gut-brain axis" could potentially prevent or delay these pathologies. Recent evidence suggests that the skeletal muscle and the gut microbiota can affect each other via the "gut-muscle axis". Importantly, cognitive functions in AD and PD patients significantly benefit from physical activity. In this review, we aim to provide a comprehensive picture of the crosstalk between the brain, the skeletal muscle and the gut microbiota, introducing the concept of "gut-muscle-brain axis". Moreover, we discuss human and animal studies exploring the modulatory role of exercise and probiotics on cognition in AD and PD. Collectively, the findings presented here support the potential benefits of physical activity and probiotic supplementation in AD and PD. Further studies will be needed to develop targeted and multimodal strategies, including lifestyle changes, to prevent or delay the course of these pathologies.
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Affiliation(s)
- Ilaria Morella
- Neuroscience and Mental Health Innovation Institute, School of Biosciences, Cardiff University, Cardiff, UK
| | - Massimo Negro
- Centro di Ricerca Interdipartimentale Nelle Attività Motorie e Sportive (CRIAMS)-Sport Medicine Centre, University of Pavia, Voghera, Italy
| | - Maurizia Dossena
- Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Riccardo Brambilla
- Neuroscience and Mental Health Innovation Institute, School of Biosciences, Cardiff University, Cardiff, UK; Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Giuseppe D'Antona
- Centro di Ricerca Interdipartimentale Nelle Attività Motorie e Sportive (CRIAMS)-Sport Medicine Centre, University of Pavia, Voghera, Italy; Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy.
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Knipping K, Kartaram SW, Teunis M, Zuithoff NPA, Buurman N, M’Rabet L, van Norren K, Witkamp R, Pieters R, Garssen J. Salivary concentrations of secretory leukocyte protease inhibitor and matrix metallopeptidase-9 following a single bout of exercise are associated with intensity and hydration status. PLoS One 2023; 18:e0291297. [PMID: 37992002 PMCID: PMC10664895 DOI: 10.1371/journal.pone.0291297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/25/2023] [Indexed: 11/24/2023] Open
Abstract
AIM To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status. METHODS Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5). Saliva samples were collected before (T0) and immediately after exercise (T1), and at several time points after exercise (2 hours (T3), 3 hours (T4), 6 hours (T5) and 24 hours (T6)). Secretory Leukocyte Protease Inhibitor (SLPI), Matrix Metallopeptidase-9 (MMP-9) and lactoferrin was analyzed using a commercial ELISA kit, a panel of 22 cytokines and chemokines were analyzed using a commercial multiplex immunoassay. Data was analyzed using a multilevel mixed linear model, with multiple test correction. RESULTS Among a panel of 25 inflammatory markers, SLPI concentrations were significantly elevated immediately after exercise in all protocols compared to rest and higher concentrations reflected the intensity of exercise and hydration status. MMP-9 showed a significant increase in the 70% Wmax dehydrated, 50% Wmax and intermittent protocols. CONCLUSIONS Salivary concentrations of SLPI and MMP-9 seem associated with exercise intensity and hydration status and may offer non-invasive biomarkers to study (local) inflammatory responses to different exercise intensities in human studies.
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Affiliation(s)
- Karen Knipping
- Danone Nutricia Research, Utrecht, The Netherlands
- Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Shirley W. Kartaram
- Research Group Innovative Testing in Life Sciences and Chemistry, University of Applied Sciences Utrecht, Utrecht, The Netherlands
| | - Marc Teunis
- Research Group Innovative Testing in Life Sciences and Chemistry, University of Applied Sciences Utrecht, Utrecht, The Netherlands
| | - Nicolaas P. A. Zuithoff
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | | | - Laura M’Rabet
- Research Group Innovative Testing in Life Sciences and Chemistry, University of Applied Sciences Utrecht, Utrecht, The Netherlands
| | - Klaske van Norren
- Nutritional Biology, Division Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Renger Witkamp
- Nutritional Biology, Division Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Raymond Pieters
- Research Group Innovative Testing in Life Sciences and Chemistry, University of Applied Sciences Utrecht, Utrecht, The Netherlands
- Institute for Risk Assessment Sciences, Immunotoxicology (IRAS), Utrecht University, Utrecht, The Netherlands
| | - Johan Garssen
- Danone Nutricia Research, Utrecht, The Netherlands
- Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
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Yu S, Guo H, Ji Z, Zheng Y, Wang B, Chen Q, Tang H, Yuan B. Sea Cucumber Peptides Ameliorate DSS-Induced Ulcerative Colitis: The Role of the Gut Microbiota, the Intestinal Barrier, and Macrophage Polarization. Nutrients 2023; 15:4813. [PMID: 38004208 PMCID: PMC10674221 DOI: 10.3390/nu15224813] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/14/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
The incidence of ulcerative colitis (UC) is increasing annually. There are few treatments for UC patients, and some drugs have serious side effects. Sea cucumber peptide (SCP) has anti-inflammatory, antioxidant and other biological activities, and various sea cucumber species are in pharmaceutical development. However, relevant studies on the effects of SCP on UC progression are still lacking. In this study, a mouse model of acute colitis was induced by 3% dextran sulfate (DSS), and the effect of 500 mg/kg SCP on colitis was investigated. The results showed that SCP can alleviate DSS-induced colon damage and intestinal barrier damage. SCP significantly inhibited the expression of inflammatory factors and oxidative stress in UC mice. SCP reversed the intestinal microbiota dysregulation induced by DSS, inhibited the growth of Sutterella, Prevotella_9 and Escherichia-Shigella harmful bacteria, and increased the abundance of Lachnospiraceae_NK4A136_group. At the same time, SCP treatment significantly inhibited the LPS-induced polarization of M1 macrophages, which may be mediated by two monopeptides, IPGAPGVP and TGPIGPPGSP, via FPR2. In conclusion, SCP can protect against colitis by modulating the intestinal microbiota composition and the intestinal barrier and inhibiting the polarization of M1 macrophages.
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Affiliation(s)
- Song Yu
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Haixiang Guo
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Zhonghao Ji
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
- Department of Basic Medicine, Changzhi Medical College, Changzhi 046000, China
| | - Yi Zheng
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Bingbing Wang
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Qingqing Chen
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Hongyu Tang
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
| | - Bao Yuan
- Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China; (S.Y.); (H.G.); (Z.J.); (Y.Z.); (B.W.); (Q.C.)
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Cheng J, Liu D, Huang Y, Chen L, Li Y, Yang Z, Fu S, Hu G. Phlorizin Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota and Inhibiting Ferroptosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:16043-16056. [PMID: 37856155 DOI: 10.1021/acs.jafc.3c01497] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2023]
Abstract
Phlorizin (PHZ) is the main active component of apple peel and presents a potential application value. In the past few years, some reports have suggested that PHZ may have antioxidant and anti-inflammatory effects. Herein, we have attempted to assess the protective effects of PHZ on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the underlying molecular mechanisms. Our results suggested that early intervention with PHZ (20, 40, and 80 mg/kg) significantly reduced the severity of DSS-induced colitis in mice, as presented by a longer colon, improved tight junction protein, decreased disease activity index, and attenuated inflammatory factors. Additionally, early intervention with + (20, 40, and 80 mg/kg) significantly inhibited ferroptosis by decreasing the surrogate ferroptosis marker levels (MDA and Iron Content). Additionally, PHZ (80 mg/kg) increased the diversity of intestinal flora in colitic mice by elevating the levels of beneficial bacteria (Lactobacillaceae and Muribaculaceae) and reducing the levels of harmful bacteria (Lachnospiraceae). This indirectly led to an increase in the amount of short-chain fatty acids. A fecal microbial transplantation (FMT) test was conducted to show that PHZ (80 mg/kg) ameliorated ulcerative colitis (UC) by regulating gut dysbiosis. In conclusion, early intervention with PHZ decreased DSS-induced colitis in mice by preserving their intestinal barrier and regulating their intestinal flora.
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Affiliation(s)
- Ji Cheng
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Dianfeng Liu
- College of Animal Science, Jilin University, Changchun 130062, China
| | - Yaping Huang
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Lisha Chen
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Ying Li
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Zhanqing Yang
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Shoupeng Fu
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Guiqiu Hu
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
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Yang W, Jiang F, Yu B, Huang Z, Luo Y, Wu A, Zheng P, Mao X, Yu J, Luo J, Yan H, He J. Effect of Different Dietary Lipid Sources on Growth Performance, Nutrient Digestibility, and Intestinal Health in Weaned Pigs. Animals (Basel) 2023; 13:3006. [PMID: 37835612 PMCID: PMC10571906 DOI: 10.3390/ani13193006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
To investigate the effects of lipid sources on growth performance and intestinal health, 72 weaned pigs were randomly allocated to three treatments. Pigs were fed with a corn-soybean meal diet containing 2% soybean oil (SO), or fish-palm-rice oil mixture (FPRO), or coconut-palm-rice oil mixture (CPRO). The trial lasted for 28 days; blood and intestinal tissue samples were collected. The results showed that the crude fat digestibility of the FPRO group was higher than that of the SO and CPRO groups (p < 0.05). The FPRO group also had higher digestibility of dry matter, ash, and gross energy than the SO group (p < 0.05); compared to the SO group, the serum interlukin-6 (IL-6) concentration was decreased. Interestingly, the FPRO and CPRO groups had higher villus height than the SO group in the jejunum and ileum, respectively (p < 0.05). Moreover, the FPRO group had higher Lactobacillus abundance than the SO group in the colon and cecum (p < 0.05). Importantly, the expression levels of tight junction protein ZO-1, Claudin-1, and Occludin in the duodenal and ileal mucosa were higher in the FPRO group than in the SO and CPRO groups (p < 0.05). The expression levels of nutrient transporters such as the CAT-1, PepT1, FATP1, and SGLT1 were higher in the FPRO group than in the SO group (p < 0.05). The improved digestibility and intestinal epithelium functions, as well as the reduced inflammatory cytokines, in the FPRO and CPRO group suggest that a mixed lipid source such as the FPRO deserves further attention.
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Affiliation(s)
- Wenjuan Yang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Fei Jiang
- Singao Agribusiness Development Co., Ltd., Longyan 361000, China;
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Zhiqing Huang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Aimin Wu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Junqiu Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (W.Y.); (B.Y.); (Z.H.); (Y.L.); (A.W.); (P.Z.); (X.M.); (J.Y.); (J.L.); (H.Y.)
- Key Laboratory of Animal Disease-Resistant Nutrition, Chengdu 611130, China
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Abaidullah M, La S, Liu M, Liu B, Cui Y, Wang Z, Sun H, Ma S, Shi Y. Polysaccharide from Smilax glabra Roxb Mitigates Intestinal Mucosal Damage by Therapeutically Restoring the Interactions between Gut Microbiota and Innate Immune Functions. Nutrients 2023; 15:4102. [PMID: 37836386 PMCID: PMC10574425 DOI: 10.3390/nu15194102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 09/09/2023] [Accepted: 09/13/2023] [Indexed: 10/15/2023] Open
Abstract
Smilax glabra Roxb (S. glabra) is a conventional Chinese medicine that is mainly used for the reliability of inflammation. However, bioactive polysaccharides from S. glabra (SGPs) have not been thoroughly investigated. Here, we demonstrate for the first time that SGPs preserve the integrity of the gut epithelial layer and protect against intestinal mucosal injury induced by dextran sulfate sodium. Mechanistically, SGPs mitigated colonic mucosal injury by restoring the association between the gut flora and innate immune functions. In particular, SGPs increased the number of goblet cells, reduced the proportion of apoptotic cells, improved the differentiation of gut tight junction proteins, and enhanced mucin production in the gut epithelial layer. Moreover, SGPs endorsed the propagation of probiotic bacteria, including Lachnospiraceae bacterium, which strongly correlated with decreased pro-inflammatory cytokines via the blocking of the TLR-4 NF-κB and MyD88 pathways. Overall, our study establishes a novel use of SGPs for the treatment of inflammatory bowel disease (IBD)-associated mucosal injury and provides a basis for understanding the therapeutic effects of natural polysaccharides from the perspective of symbiotic associations between host innate immune mechanisms and the gut microbiome.
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Affiliation(s)
- Muhammad Abaidullah
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Shaokai La
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
| | - Mengqi Liu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
| | - Boshuai Liu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Yalei Cui
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Zhichang Wang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Hao Sun
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Sen Ma
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
| | - Yinghua Shi
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450002, China; (M.A.); (S.L.); (M.L.); (B.L.); (Y.C.); (Z.W.); (H.S.); (S.M.)
- Henan Key Laboratory of Innovation and Utilization of Grassland Resources, Zhengzhou 450002, China
- Henan Forage Engineering Technology Research Center, Zhengzhou 450002, China
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Du L, Zhu L, Lu X, Yu Y, Liu P, Pan J. Inhibition of the MLCK/MLC2 pathway protects against intestinal heat stroke-induced injury in rats. J Therm Biol 2023; 116:103655. [PMID: 37506522 DOI: 10.1016/j.jtherbio.2023.103655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 06/08/2023] [Accepted: 07/04/2023] [Indexed: 07/30/2023]
Abstract
Intestinal barrier dysfunction often exists in the heat stroke (HS) pathological process, which increases intestinal permeability and induces endotoxemia. The upregulation of MLCK is a crucial player affecting intestinal permeability. This study aimed to explore whether inhibiting myosin light chain kinase (MLCK) can improve HS-induced intestinal injury in rats. Twelve-week-old Wistar male rats were divided into three groups: the control group, the HS model group, and the treatment group [HS model + ML-7 (MLCK inhibitor)]. HS impaired the tight junctions in the rat gut and increased permeability. Additionally, increased inflammatory factors in serum, activation of apoptosis, and downregulation of tight junction proteins were observed in intestinal cells. ML-7 significantly inhibited the MLCK/p-MLC2 signaling pathway, increased the expression of tight junction proteins, reduced intestinal permeability, reduced apoptosis and alleviated the intestinal damage caused by HS. ML-7 inhibited HS-induced apoptosis of intestinal epithelial cells by regulating the ERK/p38/HSP70 axis. Furthermore, inhibition of MLCK upregulated HSP70 expression through activation of the ERK pathway and inhibited cell apoptosis by abolishing the p38 MAPK pathway. In conclusion, inhibiting the MLCK/p-MLC2 signaling pathway reduces HS-induced intestinal permeability and protects the intestinal mucosal barrier.
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Affiliation(s)
- Liwen Du
- Department of Emergency, Ningbo No.2 Hospital, Ningbo, 315010, China
| | - Leilei Zhu
- Department of Emergency, Ningbo No.2 Hospital, Ningbo, 315010, China
| | - Xiaozhen Lu
- Department of Emergency, Ningbo No.2 Hospital, Ningbo, 315010, China
| | - Yuezhou Yu
- Department of Emergency, Ningbo No.2 Hospital, Ningbo, 315010, China
| | - Peng Liu
- Department of Emergency, Ningbo No.2 Hospital, Ningbo, 315010, China
| | - Jianneng Pan
- Department of Intensive Care Unit, Ningbo No.2 Hospital, Ningbo, 315010, China.
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49
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Enichen E, Adams RB, Demmig-Adams B. Physical Activity as an Adjunct Treatment for People Living with HIV? Am J Lifestyle Med 2023; 17:502-517. [PMID: 37426740 PMCID: PMC10328202 DOI: 10.1177/15598276221078222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/02/2023] Open
Abstract
This review evaluates physical activity as a candidate for an adjunct treatment, in conjunction with antiretroviral therapy (ART), for people living with HIV (PLWH). Evidence is summarized that chronic, non-resolving inflammation (a principal feature of immune system dysfunction) and a dysfunctional state of the gut environment are key factors in HIV infection that persist despite treatment with ART. In addition, evidence is summarized that regular physical activity may restore normal function of both the immune system and the gut environment and may thereby ameliorate symptoms and non-resolving inflammation-associated comorbidities that burden PLWH. Physicians who care for PLWH could thus consider incorporating physical activity into treatment plans to complement ART. It is also discussed that different types of physical activity can have different effects on the gut environment and immune function, and that future research should establish more specific criteria for the design of exercise regimens tailored to PLWH.
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Affiliation(s)
- Elizabeth Enichen
- Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA, (EE, BDA); Physical Therapy of Boulder, Boulder, CO, USA, (RBA)
| | - Robert B. Adams
- Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA, (EE, BDA); Physical Therapy of Boulder, Boulder, CO, USA, (RBA)
| | - Barbara Demmig-Adams
- Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA, (EE, BDA); Physical Therapy of Boulder, Boulder, CO, USA, (RBA)
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50
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Peng S, Shen L, Yu X, Zhang L, Xu K, Xia Y, Zha L, Wu J, Luo H. The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis. Front Immunol 2023; 14:1200111. [PMID: 37359553 PMCID: PMC10285877 DOI: 10.3389/fimmu.2023.1200111] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/22/2023] [Indexed: 06/28/2023] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, the incidence of which has been on the rise in recent years. Nuclear factor erythroid 2-related factor 2 (Nrf2), known for its key function as a transcription factor, is pivotal in inducing antioxidant stress and regulating inflammatory responses. Numerous investigations have demonstrated the involvement of the Nrf2 pathway in maintaining the development and normal function of the intestine, the development of UC, and UC-related intestinal fibrosis and carcinogenesis; meanwhile, therapeutic agents targeting the Nrf2 pathway have been widely investigated. This paper reviews the research progress of the Nrf2 signaling pathway in UC.
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Affiliation(s)
- Shuai Peng
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
| | - Lei Shen
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
| | - Xiaoyun Yu
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li Zhang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ke Xu
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuan Xia
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
| | - Lanlan Zha
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
| | - Jing Wu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
| | - Hesheng Luo
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Digestive Diseases, Wuhan, China
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