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Coutinho LL, Femino EL, Gonzalez AL, Moffat RL, Heinz WF, Cheng RYS, Lockett SJ, Rangel MC, Ridnour LA, Wink DA. NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer. Int J Mol Sci 2024; 25:6103. [PMID: 38892290 PMCID: PMC11173351 DOI: 10.3390/ijms25116103] [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: 02/28/2024] [Revised: 05/24/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.
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Affiliation(s)
- Leandro L. Coutinho
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
- Center for Translational Research in Oncology, ICESP/HC, Faculdade de Medicina da Universidade de São Paulo and Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo 01246-000, SP, Brazil;
| | - Elise L. Femino
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
| | - Ana L. Gonzalez
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
| | - Rebecca L. Moffat
- Optical Microscopy and Analysis Laboratory, Office of Science and Technology Resources, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA;
| | - William F. Heinz
- Optical Microscopy and Analysis Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (W.F.H.); (S.J.L.)
| | - Robert Y. S. Cheng
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
| | - Stephen J. Lockett
- Optical Microscopy and Analysis Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; (W.F.H.); (S.J.L.)
| | - M. Cristina Rangel
- Center for Translational Research in Oncology, ICESP/HC, Faculdade de Medicina da Universidade de São Paulo and Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo 01246-000, SP, Brazil;
| | - Lisa A. Ridnour
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
| | - David A. Wink
- Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; (L.L.C.); (E.L.F.); (A.L.G.); (R.Y.S.C.)
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Vitale G, Dicitore A, Barrea L, Sbardella E, Razzore P, Campione S, Faggiano A, Colao A, Albertelli M, Altieri B, Bottiglieri F, De Cicco F, Di Molfetta S, Fanciulli G, Feola T, Ferone D, Ferraù F, Gallo M, Giannetta E, Grillo F, Grossrubatscher E, Guadagno E, Guarnotta V, Isidori AM, Lania A, Lenzi A, Calzo FL, Malandrino P, Messina E, Modica R, Muscogiuri G, Pes L, Pizza G, Pofi R, Puliani G, Rainone C, Rizza L, Rubino M, Ruggieri RM, Sesti F, Venneri MA, Zatelli MC. From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell? Rev Endocr Metab Disord 2021; 22:511-525. [PMID: 32935263 PMCID: PMC8346435 DOI: 10.1007/s11154-020-09589-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/04/2020] [Indexed: 02/06/2023]
Abstract
Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host's metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host's immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.
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Affiliation(s)
- Giovanni Vitale
- Istituto Auxologico Italiano IRCCS, Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Cusano Milanino, MI, Italy.
- Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
| | - Alessandra Dicitore
- Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy
| | - Luigi Barrea
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Emilia Sbardella
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Paola Razzore
- Endocrinology Unit, A.O. Ordine Mauriziano, Turin, Italy
| | | | | | - Annamaria Colao
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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Wei X, Feng XP, Wang LY, Huang YQ, Liang LL, Mo XQ, Wei HY. Improved method for inducing chronic atrophic gastritis in mice. World J Gastrointest Oncol 2019; 11:1115-1125. [PMID: 31908717 PMCID: PMC6937435 DOI: 10.4251/wjgo.v11.i12.1115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 09/27/2019] [Accepted: 10/02/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) is a common disease of the digestive system with pathological characteristics of a decreasing number, or disappearance, of inherent glands of the gastric mucosa. CAG has been defined as a precancerous condition of gastric cancer. Intestinal metaplasia or intraepithelial neoplasia accompanying atrophied glands of the stomach is regarded as one of the most important precancerous lesions of gastric cancer. As a common malignant tumour, gastric cancer remains without a satisfactory therapy and its pathogenesis remains unclear, seriously threatening human life. Therefore, some scholars have proposed to prevent the incidence of gastric cancer by avoiding precancerous lesions. If CAG can be reversed, the incidence of gastric cancer can be substantially reduced. To reverse and prevent CAG and study its pathogenesis and therapy, it is necessary to develop an ideal, safe, stable, animal model.
AIM To study a rapid, stable, and safe method of establishing a mouse model of human CAG.
METHODS Six-week-old Kunming mice were divided into a phosphate buffered solution control group, a Helicobacter pylori (H. pylori) group, an N-methyl-N'-nitroguanidine (MNNG) group, an ammonia water group, and a group combining H. pylori, MNNG, and ammonia water (hereinafter referred to as the combined group). The mice were administrated with drinking water containing ammonia or infected with H. pylori through gavage. At the 30th, 60th, 90th, and 120th day after the last H. pylori infection, mice were selected randomly to collect their gastric mucosa for hematoxylin eosin staining, terminal nick-end labelling staining detection, and immunohistochemical staining for Bax and Bcl-2. In addition, H. pylori was isolated, cultured, and identified, and its extent of colonisation calculated. Blood was collected to detect inflammatory factors interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α and immune function markers CD4 and CD8 to confirm successful establishment of the CAG model.
RESULTS The combined group showed slight CAG at the 90th day and moderate CAG at the 120th day, while other groups did not show CAG at that time.
CONCLUSION The combination of H. pylori, MNNG, and ammonia is an effective method of developing a mouse model of human CAG.
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Affiliation(s)
- Xian Wei
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Xue-Ping Feng
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Lu-Yao Wang
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yan-Qiang Huang
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Ling-Ling Liang
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Qiang Mo
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Hong-Yu Wei
- Breeding Base of Microbial Infection Key Laboratory in the West Guangxi, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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Lee YI, Kim JS, Cho JS, Kim HK, Hussain A. Standardized Combined Plant Extract, RUG-com, Reduces Bacterial Levels and Suppresses Acute and Chronic Inflammation in Balb/c Mice Infected with CagA + Helicobacter pylori.. Prev Nutr Food Sci 2019; 24:426-433. [PMID: 31915638 PMCID: PMC6941731 DOI: 10.3746/pnf.2019.24.4.426] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Accepted: 08/23/2019] [Indexed: 01/20/2023] Open
Abstract
Helicobacter pylori are etiological agents in the development of gastritis, gastroduodenal ulcers, gastric cancer, and mucosa-associated lymphoid tumors. Our previous investigations demonstrated that standardized combined plants extracts (Rubus crataegifolius and Ulmus macrocarpa) inhibit the growth of H. pylori in in vitro experiments. Also, we demonstrated that Gardenia jasminoides is effective in preventing gastritis and gastric ulcers in animal experiments. In the present work, we tested the standardized combined three plant extract (RUG-com) on the mouse model of H. pylori infectious disease to examine the effects of RUG-com on both the prevention and curing on the stomachs of infected mice. After the final administrations, biopsy samples of gastric mucus were assayed for bacterial numbers, biochemical analysis, inflammatory scores, and histology. Treatment with standardized plants extracts, single or combined, reduced the H. pylori load compared with the control. Treatment also significantly (P<0.05) reduced both acute and chronic mucosal and subacute inflammation, and epithelial cell degeneration and erosion induced by H. pylori infection. Further investigations demonstrated that H. pylori-induced inflammation was decreased by RUG-com extracts via down regulating cyclooxygenase-2 and inducible nitric oxide synthase pro-inflammatory gene expression. Our results suggest that RUG-com is useful to prevent H. pylori infection, H. pylori-induced inflammation and associated gastric damage.
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Affiliation(s)
| | - Jong Seok Kim
- Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365,
Korea
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Tiwari SK, Shaik AS, Shaik AP, Alyousef AA, Bardia A, Habeeb MA, Khan AA. Gene expression patterns of COX-1, COX-2 and iNOS in H. Pylori infected histopathological conditions. Microb Pathog 2019; 135:103634. [PMID: 31325568 DOI: 10.1016/j.micpath.2019.103634] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 07/17/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Research indicates that Helicobacter pylori can inflict severe histological damage through the modulation of host-related genes. The current study investigated the effect of H. pylori genotypes in the outcome of disease, and the expression of anti-apoptotic related genes, COX-1, COX-2, and iNOS genes in benign, pre-malignant, and malignant lesions of gastric carcinogenesis. MATERIALS AND METHODS Tissue samples from H. pylori positive patients were graded based on the genotype of the infected H. pylori strain. Expression of COX-1, COX-2 and iNOS was assessed using a combination of real-time PCR and immunohistochemistry. RESULTS Gene expression studies confirmed that COX-2 and iNOS expression was highly and selectively induced in epithelium with premalignant changes such as atrophic conditions, metaplasia and dysplasia, suggesting an important role of these genes in the sequence to gastric carcinoma of the intestinal type. Furthermore, the expression of COX-2 and iNOS was also dependent on the genotype of H. pylori and subjects with genotype-1 exhibited significantly higher expressions of COX-2 and iNOS compared to other genotypes. Comparison of the expression levels among infected and uninfected individuals demonstrated significant difference in the expression pattern of COX-2 gene whereas iNOS expression was found only in subjects infected H. pylori (p < 0.001). Immunohistochemical staining showed 1.5619 folds higher propensity of COX-2 and 3.2941 folds higher intensity of iNOS expression in subjects infected with H. pylori genotype 1. CONCLUSION The up-regulation of COX-2 and iNOS was associated with the genotype of the H. pylori strain and the presence of certain genotype may greatly affect early events during carcinogenesis.
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Affiliation(s)
- Santosh K Tiwari
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Asma Sultana Shaik
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abjal Pasha Shaik
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abdullah A Alyousef
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Avinash Bardia
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Md Aejaz Habeeb
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India
| | - Aleem A Khan
- Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana, India.
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Park HS, Wijerathne CUB, Jeong HY, Seo CS, Ha H, Kwun HJ. Gastroprotective effects of Hwanglyeonhaedok-tang against Helicobacter pylori-induced gastric cell injury. JOURNAL OF ETHNOPHARMACOLOGY 2018; 216:239-250. [PMID: 29410309 DOI: 10.1016/j.jep.2018.01.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 01/18/2018] [Accepted: 01/19/2018] [Indexed: 06/07/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1β, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.
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Affiliation(s)
- Hee-Seon Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Charith U B Wijerathne
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Hye-Yun Jeong
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
| | - Chang-Seob Seo
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyekyung Ha
- K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea..
| | - Hyo-Jung Kwun
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea..
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Zhang J, Zhao X, Jiang Y, Zhao W, Guo T, Cao Y, Teng J, Hao X, Zhao J, Yang Z. Antioxidant status and gut microbiota change in an aging mouse model as influenced by exopolysaccharide produced by Lactobacillus plantarum YW11 isolated from Tibetan kefir. J Dairy Sci 2017; 100:6025-6041. [PMID: 28551178 DOI: 10.3168/jds.2016-12480] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 03/30/2017] [Indexed: 12/21/2022]
Abstract
This study investigated the effect of exopolysaccharide (EPS) produced by Lactobacillus plantarum YW11 on the oxidative status and gut microbiota in an aging mouse model induced with d-galactose. The in vitro assay of the antioxidant activity of the EPS showed concentration-dependent (0.25-3.0 mg/mL) activities. At 3.0 mg/mL, the EPS reached the highest scavenging activities with half maximal inhibitory concentration values against hydroxyl radicals at 75.10% and 1.22 mg/mL, superoxide anion at 62.71% and 1.54 mg/mL, 2, 2-diphenyl-1-picrylhydrazyl at 35.11% and 0.63 mg/mL, and the maximal chelating rate on ferrous ion and the half-maximal chelating concentration of the EPS at 41.09% and 1.07 mg/mL, respectively. High doses of EPS (50 mg/kg per day) effectively relieved the oxidative stress in the aging mice with increased levels of glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity in mice serum by 21.55, 33.14, 61.09, and 38.18%, respectively, and decreased malondialdehyde level from 11.69 to 5.89 mmol/mL compared with those in the untreated aging mice model. The analysis of pyrosequencing sequence data from the gut microbiota revealed that the EPS could recover the microbiota diversity and phylotypes decreased or eliminated by the d-galactose treatment. The EPS could selectively decrease the abundance of Flexispira (37.5 fold), and increase the abundance of Blautia (36.5 fold) and Butyricicoccus (9.5 fold), which correspondingly decreased the content of nitrogen oxides to 9.87% and increased the content of short-chain fatty acids by 2.23 fold, thereby improving the oxidative and health conditions of the host intestinal tract. Further correlation analysis of core-microbiota variation induced by different treatments showed a strong correlation with oxidative phenotypes [catalase, goodness of prediction (Q2) = 0.49; total antioxidant capacity, Q2 = 0.45; nitrogen oxides, Q2 = 0.67; short-chain fatty acids, Q2 = 0.55]. The fermented milk with L. plantarum YW11 containing EPS also showed favorable antioxidant and gut microbiota regulating activities. The present finding provided new insights into the functional mechanism of probiotics bioactivity.
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Affiliation(s)
- Jian Zhang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Xiao Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Yunyun Jiang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Wen Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Ting Guo
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Yongqiang Cao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Junwei Teng
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Xiaona Hao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Juan Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China
| | - Zhennai Yang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China.
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Lin ZL, Zheng GW, Zhang L, Zheng JT, Chen H. RETRACTED: Effect of transplantation of BMMSCs on pathological change of gastric precancerous lesions of rats. ASIAN PAC J TROP MED 2015; 8:1060-1063. [PMID: 26706680 DOI: 10.1016/j.apjtm.2015.11.006] [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: 09/15/2015] [Revised: 10/20/2015] [Accepted: 11/03/2015] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVE To build the rat model of gastric precancerous lesions and discuss the effect of transplantation of mesenchymal stem cells (BMMSCs) on the pathological change. METHODS The rat model of gastric precancerous lesions was built using N-methyl-N'-nitro-N'-nitrosoguanidine. After the intravenous transplantation of BMMSCs, the migration and colonization location was then observed, as well as its effect on the related factors of gastric precancerous lesions, including VEGF, IL-10 and IFN-γ. RESULTS BMMSCs were mainly colonized in the gastric body and gastric antrum, which could be differentiated into the epithelial and interstitial cells. The expression of VEGF in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05); while the expression of VEGF in the transplantation group was significantly higher than that in the non-transplantation group (t = 3.88, P < 0.001). The expression of serum IL-10 and IFN-γ in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05), while the expression of IL-10 and IFN-γ in the transplantation group was significantly lower than that in the non-transplantation group (t = 3.03, P = 0.004; t = 3.80, P < 0.001). CONCLUSIONS BMMSCs can be directionally differentiated into the epithelial and interstitial cells and can also regulate the related growth factors and inflammatory factors to reduce the injury of inflammation, relieve or reverse the process of gastric precancerous lesions.
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Affiliation(s)
- Zhen-Lv Lin
- Department of Emergency Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China
| | - Guang-Wei Zheng
- Department of Emergency Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China
| | - Lin Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China.
| | - Jian-Tao Zheng
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China
| | - Hui Chen
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, China
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