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1
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Petrilli JD, Estevão P, De Araújo LE, Muller I, Yoshinaga MY, Ramos PIP, Chaves-Filho AB, Horta T, Sorgi CA, Miyamoto S, Riley L, Arruda S, Queiroz A. Immunoregulatory macrophages induced by mycobacterial nonpolar lipids. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2025:vkae058. [PMID: 40280187 DOI: 10.1093/jimmun/vkae058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 12/16/2024] [Indexed: 04/29/2025]
Abstract
The capacity of Mycobacterium tuberculosis (Mtb) to establish long-term survival is attributed to its ability to subvert host defense mechanisms, especially macrophages. Although Mtb lipids are believed to play a role in this host-pathogen crosstalk, how mycobacterial lipids drive this complex interaction is poorly characterized. Here, we cultured macrophages with nonpolar cell wall Mtb lipids and applied high-throughput expression profiling (RNA sequencing), mass spectrometry-based targeted eicosanoid, and untargeted lipidomics analysis. This system-level analysis revealed that Mtb nonpolar lipid triggered the expression of phenotypic markers for classically and alternatively activated macrophages, a state previously referred as immunoregulatory. Specifically, under lipid stimulation, macrophages expressed high levels of proinflammatory markers, activated components of the interleukin-1 family, underwent an imbalance in lipid metabolism, and shifted the eicosanoid synthesis pathway toward the prostaglandin axis. Taken together, these results suggest an intricate mechanism of Mtb-driven macrophage immunomodulation that may favor its long-term survival.
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Affiliation(s)
- Jéssica Dias Petrilli
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
| | - Paulo Estevão
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
| | | | - Igor Muller
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
| | - Marcos Yukio Yoshinaga
- Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, Brazil
| | | | | | - Thainá Horta
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
| | - Carlos Arterio Sorgi
- Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Sayuri Miyamoto
- Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, Brazil
| | - Lee Riley
- Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, United States
| | - Sérgio Arruda
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
| | - Adriano Queiroz
- Advanced Laboratory of Public Health, Gonçalo Moniz Institute/Fiocruz, Salvador, Brazil
- Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, United States
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2
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Yao M, Zhu X, Chen YC, Yang GH, Ao P. Exploring Multi-Target Therapeutic Strategies for Glioblastoma via Endogenous Network Modeling. Int J Mol Sci 2025; 26:3283. [PMID: 40244148 PMCID: PMC11989339 DOI: 10.3390/ijms26073283] [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: 01/14/2025] [Revised: 03/25/2025] [Accepted: 03/29/2025] [Indexed: 04/18/2025] Open
Abstract
Medical treatment of glioblastoma presents a significant challenge. A conventional medication has limited effectiveness, and a single-target therapy is usually effective only in the early stage of the treatment. Recently, there has been increasing focus on multi-target therapies, but the vast range of possible combinations makes clinical experimentation and implementation difficult. From the perspective of systems biology, this study conducted simulations for multi-target glioblastoma therapy based on dynamic analysis of previously established endogenous networks, validated with glioblastoma single-cell RNA sequencing data. Several potentially effective target combinations were identified. The findings also highlight the necessity of multi-target rather than single-target intervention strategies in cancer treatment, as well as the promise in clinical applications and personalized therapies.
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Affiliation(s)
- Mengchao Yao
- Shanghai Center for Quantitative Life Sciences and Physics Department, Shanghai University, Shanghai 200444, China;
| | - Xiaomei Zhu
- Shanghai Key Laboratory of Modern Optical System, School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai 200444, China
| | - Yong-Cong Chen
- Shanghai Center for Quantitative Life Sciences and Physics Department, Shanghai University, Shanghai 200444, China;
| | - Guo-Hong Yang
- Department of Physics, Shanghai University, Shanghai 200444, China;
| | - Ping Ao
- College of Biomedical Engineering, Sichuan University, Chengdu 610065, China
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3
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Wu N, Wang S, Zhang Y, Wang S. Research Progress on Anti-Inflammatory Mechanism of Inula cappa. Int J Mol Sci 2025; 26:1911. [PMID: 40076538 PMCID: PMC11900443 DOI: 10.3390/ijms26051911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/14/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
The incidence of various inflammatory diseases has remained high. Inula cappa is a kind of Chinese herbal medicine with a wide range of pharmacological uses and application value. It has anti-inflammatory, antibacterial, antioxidant, hepatoprotective and other pharmacological activities. The monomeric compounds that have been confirmed to have anti-inflammatory effects are luteolin, chrysoerilol, artemetin, chlorogenic acid, neochlorogenic acid, cryptchlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C and 1,3-O-dicaffeoylquinic acid. This article introduces the relationship between Inula cappa and inflammation, the anti-inflammatory components of I. cappa, the modulation of each component on the inflammatory transduction signal pathway, and the TLR2/MyD88/NF-KB anti-inflammatory signaling pathway, providing a theoretical basis for anti-inflammatory research on and clinical medication using Inula cappa.
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Affiliation(s)
| | | | | | - Siming Wang
- School of Basic Medical Sciences, Hebei University, Baoding 071000, China; (N.W.); (S.W.); (Y.Z.)
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4
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Blessing E, Teichmann E, Hinz B. Anandamide Inhibits Vascular Smooth Muscle Migration, Endothelial Adhesion Protein Expression and Monocyte Adhesion of Human Coronary Artery Cells. Cells 2024; 13:2108. [PMID: 39768198 PMCID: PMC11727187 DOI: 10.3390/cells13242108] [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: 10/23/2024] [Revised: 11/29/2024] [Accepted: 12/03/2024] [Indexed: 01/16/2025] Open
Abstract
Endocannabinoids have been shown to play a complex role in the pathophysiology of a number of cardiovascular disorders. In the present study, the effects of the two major endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were investigated in human coronary artery smooth muscle cells (HCASMC) and human coronary artery endothelial cells (HCAEC) with regard to potential atheroprotective and anti-inflammatory effects. In HCASMC, AEA showed an inhibitory effect on platelet-derived growth factor-induced migration, but not proliferation, independent of major cannabinoid-activatable receptors (CB1, CB2, TRPV1), while 2-AG left both responses unaffected. In HCAEC, AEA at concentrations of 6 and 10 µM significantly inhibited the interleukin (IL)-1β- and lipopolysaccharide (LPS)-stimulated expression of vascular cell adhesion molecule-1 (VCAM-1) and LPS-induced intercellular adhesion molecule-1 (ICAM-1), again independently of the abovementioned receptors. Corresponding effects were observed to a lesser extent in the presence of 2-AG, in most cases not significantly. The detection of activated phosphoproteins as well as experiments with inhibitors of corresponding signaling pathways suggest that AEA interferes with IL-1β-induced VCAM-1 expression via inhibition of protein kinase B/Akt and Src kinase activation and attenuates LPS-induced VCAM-1 and ICAM-1 expression via inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation. As expected, AEA also led to a significant inhibition of monocyte adhesion to IL-1β- and LPS-stimulated HCAEC, with siRNA experiments confirming the functional role of VCAM-1 and ICAM-1 in this assay. 2-AG showed a comparatively weaker but, in the case of LPS stimulation, still significant inhibition of adhesion. In summary, the results emphasize the potential of AEA as a protective regulator of atherosclerotic and inflammation-related changes in HCASMC and HCAEC and encourage further corresponding preclinical studies with this endocannabinoid.
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Affiliation(s)
| | | | - Burkhard Hinz
- Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany; (E.B.)
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5
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Padoan F, Piccoli E, Pietrobelli A, Moreno LA, Piacentini G, Pecoraro L. The Role of Zinc in Developed Countries in Pediatric Patients: A 360-Degree View. Biomolecules 2024; 14:718. [PMID: 38927121 PMCID: PMC11201578 DOI: 10.3390/biom14060718] [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: 05/14/2024] [Revised: 06/09/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Zinc is an important trace element for growth and health at pediatric ages. Zinc is fundamental in inflammatory pathways, oxidative balance, and immune function. Zinc exhibits anti-inflammatory properties by modulating Nuclear Factor-kappa (NF-κB) activity and reducing histamine release from basophils, leukocytes, and mast cells. Furthermore, its antioxidant activity protects against oxidative damage and chronic diseases. Finally, zinc improves the ability to trigger effective immune responses against pathogens by contributing to the maturation of lymphocytes, the production of cytokines, and the regulation of apoptosis. Given these properties, zinc can be considered an adjunctive therapy in treating and preventing respiratory, nephrological, and gastrointestinal diseases, both acute and chronic. This review aims to deepen the role and metabolism of zinc, focusing on the role of supplementation in developed countries in pediatric diseases.
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Affiliation(s)
- Flavia Padoan
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics University of Verona, 37126 Verona, Italy
| | - Elena Piccoli
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics University of Verona, 37126 Verona, Italy
| | - Angelo Pietrobelli
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics University of Verona, 37126 Verona, Italy
| | - Luis A. Moreno
- Growth, Exercise, Nutrition and Development (GENUD), Research Group, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón (IIS Aragón), Universidad de Zaragoza, 50001 Zaragoza, Spain
| | - Giorgio Piacentini
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics University of Verona, 37126 Verona, Italy
| | - Luca Pecoraro
- Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics University of Verona, 37126 Verona, Italy
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6
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Shi Y, Zhang X, Pei S, Wang Y. Ethnopharmacological study on Adenosma buchneroides Bonati inhibiting inflammation via the regulation of TLR4/MyD88/NF-κB signaling pathway. NATURAL PRODUCTS AND BIOPROSPECTING 2024; 14:36. [PMID: 38833115 DOI: 10.1007/s13659-024-00458-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 05/27/2024] [Indexed: 06/06/2024]
Abstract
Adenosma buchneroides Bonati, also known as fleagrass, is an important medicinal plant used by the Akha (Hani) people of China for treating inflammation-related skin swelling, acne, and diarrhoea, among other conditions. In this study, we aimed to evaluate the anti-inflammatory activities and explore the molecular mechanisms of fleagrass on treating skin swelling and acne. The results demonstrated that fleagrass inhibited the enzymatic activities of 5-LOX and COX-2 in vitro, and decreased the release of NO, IL-6, TNF-α, and IL-10 in the LPS-induced RAW264.7 macrophages. The levels of proteins associated with the nuclear factor-kappa B (NF-κB) pathway were examined by western blotting and immunofluorescence, demonstrating that fleagrass downregulated the expression of TLR4, MyD88, NF-κB/p65, and iNOS and blocked the nuclear translocation of NF-κB/p65. Furthermore, fleagrass exhibited acute anti-inflammatory activity in paw oedema models. The results confirm that fleagrass exhibits remarkable anti-inflammatory activity and can be used in alleviating inflammation, suggesting that fleagrass has the potential to be a novel anti-inflammatory agent.
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Affiliation(s)
- Yuru Shi
- Department of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Lanhei Road 132, Heilongtan, Kunming, 650201, Yunnan, China
| | - Xiaoqian Zhang
- Department of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Lanhei Road 132, Heilongtan, Kunming, 650201, Yunnan, China
| | - Shengji Pei
- Department of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Lanhei Road 132, Heilongtan, Kunming, 650201, Yunnan, China
| | - Yuhua Wang
- Department of Economic Plants and Biotechnology, Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Lanhei Road 132, Heilongtan, Kunming, 650201, Yunnan, China.
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7
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Wang R, Su D, Liu Y, Huang H, Qiu J, Cao Z, Yang G, Chen H, Luo W, Tao J, Weng G, Zhang T. The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3. iScience 2024; 27:109406. [PMID: 38510132 PMCID: PMC10951638 DOI: 10.1016/j.isci.2024.109406] [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: 08/25/2023] [Revised: 01/13/2024] [Accepted: 02/29/2024] [Indexed: 03/22/2024] Open
Abstract
Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p-SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.
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Affiliation(s)
- Ruobing Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Dan Su
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yueze Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hua Huang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jiangdong Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zhe Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Gang Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hao Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wenhao Luo
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jinxin Tao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Guihu Weng
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
- Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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8
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Shi R, Wang F, Fu Q, Zeng P, Chen G, Chen Z. Molecular mechanism analysis of apoptosis induced by silk fibroin peptides. Int J Biol Macromol 2024; 264:130687. [PMID: 38462112 DOI: 10.1016/j.ijbiomac.2024.130687] [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: 01/09/2024] [Revised: 03/01/2024] [Accepted: 03/05/2024] [Indexed: 03/12/2024]
Abstract
Silk fibroin derived from silkworm cocoons exhibits excellent mechanical properties, good biocompatibility, and low immunogenicity. Previous studies showed that silk fibroin had an inhibitory effect on cells, suppressing proliferation and inducing apoptosis. However, the source of the toxicity and the mechanism of apoptosis induction are still unclear. In this study, we hypothesized that the toxicity of silk fibroin might originate from the crystalline region of the heavy chain of silk fibroin. We then verified the hypothesis and the specific induction mechanism. A target peptide segment was obtained from α-chymotrypsin. The potentially toxic mixture of silk fibroin peptides (SFPs) was separated by ion exchange, and the toxicity was tested by an MTT assay. The results showed that SFPs obtained after 4 h of enzymatic hydrolysis had significant cytotoxicity, and SFPs with isoelectric points of 4.0-6.8 (SFPα II) had a significant inhibitory effect on cell growth. LC-MS/MS analysis showed that SFPα II contained a large number of glycine-rich and alanine-rich repetitive sequence polypeptides from the heavy-chain crystallization region. A series of experiments showed that SFPα II mediated cell death through the apoptotic pathway by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein. SFPα II mainly affected the p53 pathway and the AMPK signaling pathway in HepG2 cells. SFPα II may indirectly increase the expression of Cers2 by inhibiting the phosphorylation of EGFR, which activated apoptotic signaling in the cellular mitochondrial pathway and inhibited the Akt/NF-κB pathway by increasing the expression of PPP2R2A.
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Affiliation(s)
- Ruyu Shi
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
| | - Fuping Wang
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
| | - Qiang Fu
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
| | - Peng Zeng
- The Seventh People's Hospital of Chongqing, Chongqing 400054, China
| | - Guobao Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
| | - Zhongmin Chen
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China.
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Jiang Z, Zhou W, Tian X, Zou P, Li N, Zhang C, Li Y, Liu G. A Protective Role of Canonical Wnt/ β-Catenin Pathway in Pathogenic Bacteria-Induced Inflammatory Responses. Mediators Inflamm 2024; 2024:8869510. [PMID: 38445290 PMCID: PMC10914433 DOI: 10.1155/2024/8869510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 10/04/2023] [Accepted: 02/09/2024] [Indexed: 03/07/2024] Open
Abstract
Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/β-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/β-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/β-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.
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Affiliation(s)
- Zhongjia Jiang
- Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang 110034, China
- Key Laboratory of Environment Pollution and Microecology of Liaoning Province, Shenyang 110034, China
| | - Weiping Zhou
- Department of Pathogen Biology, Shenyang Medical College, Shenyang 110034, China
| | - Xing Tian
- Department of Physiology, Shenyang Medical College, Shenyang 110034, China
| | - Peng Zou
- Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang 110034, China
| | - Ning Li
- Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang 110034, China
| | - Chunmeng Zhang
- Department of Pathogen Biology, Shenyang Medical College, Shenyang 110034, China
| | - Yanting Li
- Department of Pathogen Biology, Shenyang Medical College, Shenyang 110034, China
| | - Guangyan Liu
- Key Laboratory of Environment Pollution and Microecology of Liaoning Province, Shenyang 110034, China
- Department of Pathogen Biology, Shenyang Medical College, Shenyang 110034, China
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10
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Chen C, Chen Y, Lu M, Xu L, Yan R, Li X, Song X. IFN-γ inhibitory molecules derived from Eimeria maxima inhibit IL-12 secretion by modulating MAPK pathways in chicken macrophages. Poult Sci 2024; 103:103359. [PMID: 38128458 PMCID: PMC10776662 DOI: 10.1016/j.psj.2023.103359] [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: 11/03/2023] [Revised: 11/30/2023] [Accepted: 12/02/2023] [Indexed: 12/23/2023] Open
Abstract
IFN-γ plays a crucial role in resisting intracellular parasitic protozoa, such as Eimeria species. In our previous study, we identified 4 molecules derived from Eimeria maxima (E. maxima) that significantly inhibited IFN-γ production. However, the mechanism underlying this inhibitory effect remains unknown. In this study, we first investigated the effects of these 4 IFN-γ inhibitory molecules on the expression levels of chicken Toll-like receptors (chTLRs), IL-12, IL-10, TGF-β, and TNF-α in chicken macrophage HD11 and bone marrow-derived dendritic cells (BMDCs). The results demonstrated that these 4 inhibitory molecules significantly downregulated the mRNA levels of chTLR-2, chTLR-4, chTLR-21, and both mRNA and protein levels of IL-12. Subsequently, to clarify the effects of these 4 inhibitory molecules on the IL-12 secretion-related signaling pathways in chicken macrophages, qRT-PCR and Western blot were used to detect the changes of key molecules involved in the signaling pathways of IL-12 secretion (NF-κB, ERK1/2, p38, JNK, STAT3) following coincubation with these inhibitory molecules. Finally, RNAi was employed to verify the function of key molecules in the signaling pathway. The results revealed a significant upregulation in the expression of ERK1/2 phosphorylated protein induced by the 4 inhibitory molecules. Knockdown of the ERK1/2 gene significantly reduced the inhibitory effect of the 4 E. maxima inhibitory molecules on IL-12. These findings indicate that the 4 inhibitory molecules can inhibit the secretion of IL-12 by upregulating the expression of ERK1/2 phosphorylated protein, which is a key molecule in the ERK-MAPK pathway. Our study may contribute to elucidating the mechanisms underlying immune evasion during E. maxima infections, thereby providing new insights for the control of chicken coccidiosis.
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Affiliation(s)
- Chen Chen
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Yufeng Chen
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Mingmin Lu
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Lixin Xu
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Ruofeng Yan
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Xiangrui Li
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China
| | - Xiaokai Song
- Ministry of Education (MOE) Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
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11
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Benedeto-Stojanov D, Ničković VP, Petrović G, Rancić A, Grgov I, Nikolić GR, Marčetić ZP, Popović MR, Lazarević M, Mitić KV, Sokolović D. Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage. Int J Mol Sci 2023; 25:455. [PMID: 38203627 PMCID: PMC10779228 DOI: 10.3390/ijms25010455] [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: 11/06/2023] [Revised: 12/11/2023] [Accepted: 12/16/2023] [Indexed: 01/12/2024] Open
Abstract
Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.
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Affiliation(s)
| | - Vanja P. Ničković
- COVID Hospital Kruševac, University Clinical Centre of Niš, 37000 Kruševac, Serbia;
| | | | - Andrija Rancić
- Clinic of Gastroenterohepatology, University Clinical Centre of Niš, 18000 Niš, Serbia;
| | - Ivan Grgov
- General Hospital Leskovac, Department of General Surgery with Traumatology, 16000 Leskovac, Serbia;
| | - Gordana R. Nikolić
- Faculty of Medicine, University of Priština, 38220 Kosovska Mitrovica, Serbia; (G.R.N.); (Z.P.M.)
| | - Zoran P. Marčetić
- Faculty of Medicine, University of Priština, 38220 Kosovska Mitrovica, Serbia; (G.R.N.); (Z.P.M.)
| | - Milica R. Popović
- Pediatrics Clinic, Clinical Centre Priština, 38205 Gracanica, Serbia;
| | - Milan Lazarević
- Clinic for Cardiovascular and Transplant Surgery, Faculty of Medicine, University Clinical Centre of Niš, 18000 Niš, Serbia;
| | - Katarina V. Mitić
- Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia;
| | - Dušan Sokolović
- Institute for Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia;
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12
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Teichmann E, Blessing E, Hinz B. Non-Psychoactive Phytocannabinoids Inhibit Inflammation-Related Changes of Human Coronary Artery Smooth Muscle and Endothelial Cells. Cells 2023; 12:2389. [PMID: 37830604 PMCID: PMC10571842 DOI: 10.3390/cells12192389] [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: 08/18/2023] [Revised: 09/08/2023] [Accepted: 09/12/2023] [Indexed: 10/14/2023] Open
Abstract
Atherosclerosis is associated with vascular smooth muscle cell proliferation, chronic vascular inflammation, and leukocyte adhesion. In view of the cardioprotective effects of cannabinoids described in recent years, the present study investigated the impact of the non-psychoactive phytocannabinoids cannabidiol (CBD) and tetrahydrocannabivarin (THCV) on proliferation and migration of human coronary artery smooth muscle cells (HCASMC) and on inflammatory markers in human coronary artery endothelial cells (HCAEC). In HCASMC, CBD and THCV at nontoxic concentrations exhibited inhibitory effects on platelet-derived growth factor-triggered proliferation (CBD) and migration (CBD, THCV). When interleukin (IL)-1β- and lipopolysaccharide (LPS)-stimulated HCAEC were examined, both cannabinoids showed a concentration-dependent decrease in the expression of vascular cell adhesion molecule-1 (VCAM-1), which was mediated independently of classical cannabinoid receptors and was not accompanied by a comparable inhibition of intercellular adhesion molecule-1. Further inhibitor experiments demonstrated that reactive oxygen species, p38 mitogen-activated protein kinase activation, histone deacetylase, and nuclear factor κB (NF-κB) underlie IL-1β- and LPS-induced expression of VCAM-1. In this context, CBD and THCV were shown to inhibit phosphorylation of NF-κB regulators in LPS- but not IL-1β-stimulated HCAEC. Stimulation of HCAEC with IL-1β and LPS was associated with increased adhesion of monocytes, which, however, could not be significantly abolished by CBD and THCV. In summary, the results highlight the potential of the non-psychoactive cannabinoids CBD and THCV to regulate inflammation-related changes in HCASMC and HCAEC. Considering their effect on both cell types studied, further preclinical studies could address the use of CBD and THCV in drug-eluting stents for coronary interventions.
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Affiliation(s)
| | | | - Burkhard Hinz
- Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany; (E.T.); (E.B.)
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13
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Al-Rashidi RR, Noraldeen SAM, Kareem AK, Mahmoud AK, Kadhum WR, Ramírez-Coronel AA, Iswanto AH, Obaid RF, Jalil AT, Mustafa YF, Nabavi N, Wang Y, Wang L. Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs. Pharmacol Res 2023; 194:106775. [PMID: 37075872 DOI: 10.1016/j.phrs.2023.106775] [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: 01/20/2023] [Revised: 04/09/2023] [Accepted: 04/16/2023] [Indexed: 04/21/2023]
Abstract
Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.
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Affiliation(s)
| | | | - Ali Kamil Kareem
- Biomedical Engineering Department, Al-Mustaqbal University College, 51001, Hillah, Iraq
| | | | - Wesam R Kadhum
- Department of Pharmacy, Kut University College, Kut 52001, Wasit, Iraq
| | - Andrés Alexis Ramírez-Coronel
- Azogues Campus Nursing Career, Health and Behavior Research Group (HBR), Psychometry and Ethology Laboratory, Catholic University of Cuenca, Ecuador; University of Palermo, Buenos Aires, Argentina; Epidemiology and Biostatistics Research Group, CES University, Colombia
| | - Acim Heri Iswanto
- Department of Public Health, Faculty of Health Science, University of Pembangunan Nasional Veteran Jakarta, Jakarta, Indonesia
| | - Rasha Fadhel Obaid
- Department of Biomedical Engineering, Al-Mustaqbal University College, Babylon, Iraq
| | - Abduladheem Turki Jalil
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6 Vancouver, BC, Canada.
| | - Yuzhuo Wang
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6 Vancouver, BC, Canada; Department of Experimental Therapeutics, BC Cancer Research Institute, V5Z1L3 Vancouver, BC, Canada.
| | - Lin Wang
- Department of Geriatrics, Xijing Hospital, The Air Force Military Medical University, Xi'an 710032, China.
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14
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Mondal S, Das M, Ghosh R, Singh M, Adhikari A, Darbar S, Kumar Das A, Bhattacharya SS, Pal D, Bhattacharyya D, Ahmed ASA, Mallick AK, Al-Rooqi MM, Moussa Z, Ahmed SA, Pal SK. Chitosan functionalized Mn 3O 4 nanoparticles counteracts ulcerative colitis in mice through modulation of cellular redox state. Commun Biol 2023; 6:647. [PMID: 37328528 PMCID: PMC10275949 DOI: 10.1038/s42003-023-05023-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 06/07/2023] [Indexed: 06/18/2023] Open
Abstract
Recent findings suggest a key role for reactive oxygen species (ROS) in the pathogenesis and progression of ulcerative colitis (UC). Several studies have also highlighted the efficacy of citrate functionalized Mn3O4 nanoparticles as redox medicine against a number of ROS-mediated disorders. Here we show that synthesized nanoparticles consisting of chitosan functionalized tri-manganese tetroxide (Mn3O4) can restore redox balance in a mouse model of UC induced by dextran sulfate sodium (DSS). Our in-vitro characterization of the developed nanoparticle confirms critical electronic transitions in the nanoparticle to be important for the redox buffering activity in the animal model. A careful administration of the developed nanoparticle not only reduces inflammatory markers in the animals, but also reduces the mortality rate from the induced disease. This study provides a proof of concept for the use of nanomaterial with synergistic anti-inflammatory and redox buffering capacity to prevent and treat ulcerative colitis.
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Affiliation(s)
- Susmita Mondal
- Department of Chemical, Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata, 700106, India
| | - Monojit Das
- Department of Zoology, Uluberia College, University of Calcutta, Uluberia, Howrah, 711315, India
- Department of Zoology, Vidyasagar University, Rangamati, Midnapore, 721102, India
| | - Ria Ghosh
- Department of Chemical, Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata, 700106, India
| | - Manali Singh
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Bhadson Road, Patiala, Punjab, 147004, India
| | - Aniruddha Adhikari
- Department of Chemical, Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata, 700106, India
| | - Soumendra Darbar
- Research & Development Division, Dey's Medical Stores (Mfg.) Ltd, 62, Bondel Road, Ballygunge, Kolkata, 700019, India
| | - Anjan Kumar Das
- Department of Pathology, Cooch Behar Government Medical College & Hospital, Vivekananda Rd, Khagrabari, Cooch Behar, West Bengal, 736101, India
| | | | - Debasish Pal
- Department of Zoology, Uluberia College, University of Calcutta, Uluberia, Howrah, 711315, India
| | - Debasish Bhattacharyya
- Department of Gynecology & Obstetrics, Nil Ratan Sircar Medical College & Hospital, 138, AJC Bose Road, Sealdah, Raja Bazar, Kolkata, 700014, India
| | - Ahmed S A Ahmed
- Faculty of Medicine, Assiut University, 71516, Assiut, Egypt
| | - Asim Kumar Mallick
- Department of Pediatric Medicine, Nil Ratan Sirkar Medical College and Hospital, 38, Acharya Jagadish Chandra Bose Rd, Sealdah, Raja Bazar, Kolkata, West Bengal, 700014, India
| | - Munirah M Al-Rooqi
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, 21955, Makkah, Saudi Arabia
| | - Ziad Moussa
- Department of Chemistry, College of Science, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates
| | - Saleh A Ahmed
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
- Department of Chemistry, Faculty of Science, Assiut University, 71516, Assiut, Egypt.
| | - Samir Kumar Pal
- Department of Chemical, Biological Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata, 700106, India.
- Department of Zoology, Uluberia College, University of Calcutta, Uluberia, Howrah, 711315, India.
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15
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Deka K, Li Y. Transcriptional Regulation during Aberrant Activation of NF-κB Signalling in Cancer. Cells 2023; 12:788. [PMID: 36899924 PMCID: PMC10001244 DOI: 10.3390/cells12050788] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/16/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
The NF-κB signalling pathway is a major signalling cascade involved in the regulation of inflammation and innate immunity. It is also increasingly recognised as a crucial player in many steps of cancer initiation and progression. The five members of the NF-κB family of transcription factors are activated through two major signalling pathways, the canonical and non-canonical pathways. The canonical NF-κB pathway is prevalently activated in various human malignancies as well as inflammation-related disease conditions. Meanwhile, the significance of non-canonical NF-κB pathway in disease pathogenesis is also increasingly recognized in recent studies. In this review, we discuss the double-edged role of the NF-κB pathway in inflammation and cancer, which depends on the severity and extent of the inflammatory response. We also discuss the intrinsic factors, including selected driver mutations, and extrinsic factors, such as tumour microenvironment and epigenetic modifiers, driving aberrant activation of NF-κB in multiple cancer types. We further provide insights into the importance of the interaction of NF-κB pathway components with various macromolecules to its role in transcriptional regulation in cancer. Finally, we provide a perspective on the potential role of aberrant NF-κB activation in altering the chromatin landscape to support oncogenic development.
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Affiliation(s)
- Kamalakshi Deka
- School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore 637551, Singapore
| | - Yinghui Li
- School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore 637551, Singapore
- Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore 138673, Singapore
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16
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Li Y, Zhang Y, Li L, Zhang M, Song N, Zhao Q, Liu Z, Diao A. TMEPAI promotes degradation of the NF-κB signaling pathway inhibitory protein IκBα and contributes to tumorigenesis. Int J Biol Macromol 2023; 235:123859. [PMID: 36868334 DOI: 10.1016/j.ijbiomac.2023.123859] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/20/2023] [Accepted: 02/24/2023] [Indexed: 03/05/2023]
Abstract
The transmembrane prostate androgen-induced protein (TMEPAI) is known to be highly expressed in various types of cancer and promoted oncogenic abilities. However, the mechanisms whereby TMEPAI facilitates tumorigenesis are not fully understood. Here we reported that expression of TMEPAI activated the NF-κB signaling. TMEPAI showed direct interaction with NF-κB pathway inhibitory protein IκBα. Though ubiquitin ligase Nedd4 (neural precursor cell expressed, developmentally down-regulated 4) did not interact with IκBα directly, TMEPAI recruited Nedd4 for ubiquitination of IκBα, leading to IκBα degradation through the proteasomal and lysosomal pathway, and promoted activation of NF-κB signaling. Further study indicated NF-κB signaling is involved in TMEPAI-induced cell proliferation and tumor growth in immune deficient mice. This finding helps to further understand the mechanism of TMEPAI on tumorigenesis and suggests TMEPAI is potential target for cancer treatment.
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Affiliation(s)
- Yuyin Li
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China.
| | - Yaxin Zhang
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Lu Li
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Mei Zhang
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Ning Song
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Qing Zhao
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Zhenxing Liu
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China
| | - Aipo Diao
- School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China.
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17
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The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review. Int J Mol Sci 2023; 24:ijms24032901. [PMID: 36769226 PMCID: PMC9917883 DOI: 10.3390/ijms24032901] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of the NF-κB pathway in the development and progression of most vital endometrial diseases in human and animal species. Immune modulation by NF-κB in endometritis, endometrosis, endometriosis, and carcinoma results in changes in cell migration, proliferation, and inflammation intensity in both the stroma and epithelium. In endometrial cells, the NF-κB signaling pathway may be activated by multiple stimuli, such as bacterial parts, cytokines, or hormones binding to specific receptors. The dysregulation of the immune system in response to NF-κB involves aberrant production of chemokines and cytokines, which plays a role in endometritis, endometriosis, endometrosis, and endometrial carcinoma. However, estrogen and progesterone influence on the reproductive tract always plays a major role in its regulation. Thus, sex hormones cannot be overlooked in endometrial disease physiopathology. While immune system dysregulation seems to be NF-κB-dependent, the hormone-independent and hormone-dependent regulation of NF-κB signaling in the endometrium should be considered in future studies. Future goals in this research should be a step up into clinical trials with compounds affecting NF-κB as treatment for endometrial diseases.
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18
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ElKhatib MAW, Isse FA, El-Kadi AOS. Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy. Drug Metab Rev 2022; 55:50-74. [PMID: 36573379 DOI: 10.1080/03602532.2022.2162075] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the metabolism of arachidonic acid (AA), which is present in the cell membrane phospholipids, is modulated. Metabolism of AA gives rise to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) via cytochrome P450 (CYP) ω-hydroxylases and CYP epoxygenases, respectively. A plethora of studies demonstrated the involvement of CYP-mediated AA metabolites in the pathogenesis of CH. Also, inflammation is known to be a characteristic hallmark of CH. In this review, our aim is to highlight the impact of inflammation on CYP-derived AA metabolites and CH. Inflammation is shown to modulate the expression of various CYP ω-hydroxylases and CYP epoxygenases and their respective metabolites in the heart. In general, HETEs such as 20-HETE and mid-chain HETEs are pro-inflammatory, while EETs are characterized by their anti-inflammatory and cardioprotective properties. Several mechanisms are implicated in inflammation-induced CH, including the modulation of NF-κB and MAPK. This review demonstrated the inflammatory modulation of cardiac CYPs and their metabolites in the context of CH and the anti-inflammatory strategies that can be employed in the treatment of CH and HF.
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Affiliation(s)
| | - Fadumo Ahmed Isse
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada
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19
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Illig D, Kotlarz D. Dysregulated inflammasome activity in intestinal inflammation - Insights from patients with very early onset IBD. Front Immunol 2022; 13:1027289. [PMID: 36524121 PMCID: PMC9744759 DOI: 10.3389/fimmu.2022.1027289] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 11/11/2022] [Indexed: 11/30/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disorder triggered by imbalances of the microbiome and immune dysregulations in genetically susceptible individuals. Several mouse and human studies have demonstrated that multimeric inflammasomes are critical regulators of host defense and gut homeostasis by modulating immune responses to pathogen- or damage-associated molecular patterns. In the context of IBD, excessive production of pro-inflammatory Interleukin-1β has been detected in patient-derived intestinal tissues and correlated with the disease severity or failure to respond to anti-tumor necrosis factor therapy. Correspondingly, genome-wide association studies have suggested that single nucleotide polymorphisms in inflammasome components might be associated with risk of IBD development. The relevance of inflammasomes in controlling human intestinal homeostasis has been further exemplified by the discovery of very early onset IBD (VEO-IBD) patients with monogenic defects affecting different molecules in the complex regulatory network of inflammasome activity. This review provides an overview of known causative monogenic entities of VEO-IBD associated with altered inflammasome activity. A better understanding of the molecular mechanisms controlling inflammasomes in monogenic VEO-IBD may open novel therapeutic avenues for rare and common inflammatory diseases.
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Affiliation(s)
- David Illig
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Daniel Kotlarz
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-University (LMU), Munich, Germany,Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany,*Correspondence: Daniel Kotlarz,
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20
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Santonocito S, Ferlito S, Polizzi A, Ronsivalle V, Sclafani R, Valletta A, Lo Giudice A, Cavalcanti R, Spagnuolo G, Isola G. Therapeutic and Metagenomic Potential of the Biomolecular Therapies against Periodontitis and the Oral Microbiome: Current Evidence and Future Perspectives. Int J Mol Sci 2022; 23:13708. [PMID: 36430182 PMCID: PMC9693164 DOI: 10.3390/ijms232213708] [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: 10/25/2022] [Revised: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 11/09/2022] Open
Abstract
The principles of periodontal therapy are based on the control of microbial pathogens and host factors that contribute to biofilm dysbiosis, with the aim of modulating the progression of periodontitis and periodontal tissue destruction. It is currently known how differently each individual responds to periodontal treatment, depending on both the bacterial subtypes that make up the dysbiotic biofilm and interindividual variations in the host inflammatory response. This has allowed the current variety of approaches for the management of periodontitis to be updated by defining the goals of target strategies, which consist of reducing the periodontopathogenic microbial flora and/or modulating the host-mediated response. Therefore, this review aims to update the current variety of approaches for the management of periodontitis based on recent target therapies. Recently, encouraging results have been obtained from several studies exploring the effects of some targeted therapies in the medium- and long-term. Among the most promising target therapies analyzed and explored in this review include: cell-based periodontal regeneration, mediators against bone resorption, emdogain (EMD), platelet-rich plasma, and growth factors. The reviewed evidence supports the hypothesis that the therapeutic combination of epigenetic modifications of periodontal tissues, interacting with the dysbiotic biofilm, is a key step in significantly reducing the development and progression of disease in periodontal patients and improving the therapeutic response of periodontal patients. However, although studies indicate promising results, these need to be further expanded and studied to truly realize the benefits that targeted therapies could bring in the treatment of periodontitis.
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Affiliation(s)
- Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Salvatore Ferlito
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, 95123 Catania, Italy
| | - Alessandro Polizzi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Vincenzo Ronsivalle
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Rossana Sclafani
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Alessandra Valletta
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, 80138 Napoli, Italy
| | - Antonino Lo Giudice
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Raffaele Cavalcanti
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
| | - Gianrico Spagnuolo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples “Federico II”, 80138 Napoli, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via Sofia 78, 95125 Catania, Italy
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21
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Wang S, Chen Y, Ling Z, Li J, Hu J, He F, Chen Q. The role of dendritic cells in the immunomodulation to implanted biomaterials. Int J Oral Sci 2022; 14:52. [PMCID: PMC9636170 DOI: 10.1038/s41368-022-00203-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/06/2022] Open
Abstract
Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming “biomaterial-associated molecular patterns (BAMPs)”. Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
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Affiliation(s)
- Siyuan Wang
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Yanqi Chen
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Zhaoting Ling
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Jia Li
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Jun Hu
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Fuming He
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
| | - Qianming Chen
- grid.13402.340000 0004 1759 700XStomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Disease of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310006 China
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Zhou J, Mao Y, Shi X, Zhang Y, Yu X, Liu X, Diao L, Yang X, Liu C, Liu D, Tan X, Liu M. Peimine suppresses collagen-induced arthritis, activated fibroblast-like synoviocytes and TNFα-induced MAPK pathways. Int Immunopharmacol 2022; 111:109181. [PMID: 36027853 DOI: 10.1016/j.intimp.2022.109181] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/05/2022] [Accepted: 08/15/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND PURPOSE Peimine (PM), a main isosterol alkaloid component isolated from the bulbs of traditional Chinese herb Fritillaria cirrhosa D. Don, has been demonstrated to exhibit multiple pharmacological properties, including anti-inflammation, anti-cancer and pain suppression. However, its effect on rheumatoid arthritis (RA) remains unknown. In the present study, we investigated the effect of PM on collagen-induced arthritis (CIA) rats in vivo and its inhibition on destructive behaviors of arthritic fibroblast-like synoviocytes (FLSs) in vitro. METHODS Arthritis was induced in rats by chicken type II collagen. Arthritis score, radiological evaluation, and histopathological assessment were used to evaluate the therapeutic effects of PM on CIA rats. EdU assay, wound healing assay and real-time PCR were used to examine the inhibitory effect of PM on proliferation, migration, and over-expression of pro-inflammatory cytokines in TNFα-induced arthritic FLSs. TRAP staining and scanning electron microscopy were used to analyze the effect of PM on osteoclastogensis and bone resorption. Western blot was used to reveal PM's molecular mechanism of action on RA. RESULTS PM significantly suppressed synovitis and bone destruction in CIA rats. In vitro experiments showed that PM treatment significantly inhibited TNFα-induced destructive behaviors of arthritic FLSs, including over-proliferation, migration and over-expression of pro-inflammatory cytokines. Additionally, RANKL-induced osteoclast formation and bone-resorpting function were also inhibited by PM. Further molecular mechanism studies revealed that PM treatment significantly suppressed TNFα-induced activations of MAPKs (ERK, JNK and p38) in arthritic FLSs. CONCLUSION Our findings provide strong evidence that PM has the potential to be developed as a therapeutic agent for patients with RA.
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Affiliation(s)
- Junnan Zhou
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Yuhang Mao
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Xiaotian Shi
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Yudie Zhang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Xiaolu Yu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Xuan Liu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Li Diao
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Xue Yang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Changze Liu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Dan Liu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Xin Tan
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China
| | - Mei Liu
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life sciences, Nanjing Normal University, Nanjing 210023, China.
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Yue Q, Zhang W, Lin S, Zheng T, Hou Y, Zhang Y, Li Z, Wang K, Yue L, Abay B, Li M, Fan L. Ejiao ameliorates lipopolysaccharide-induced pulmonary inflammation via inhibition of NFκB regulating NLRP3 inflammasome and mitochondrial ROS. Biomed Pharmacother 2022; 152:113275. [PMID: 35714510 DOI: 10.1016/j.biopha.2022.113275] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 11/19/2022] Open
Abstract
There is no effective treatment for acute lung injury (ALI) at present. Some studies have reported the anti-inflammatory effect of Ejiao, but no study has addressed the underlying action mechanism. In this study, the CCK8 assay displayed Ejiao had a protective effect against LPS-elicited inflammatory lung epithelial Beas 2B cells (LILEB 2B cells). Beas 2B cells treated with LPS and Ejiao were challenged with NFκB inhibitor Bay11-7082 and ROS scavenger N-acetyl cysteine (NAC) alone and in combination. The results of qRT-PCR, Western blotting and fluorescence labeling experiments using Bay11-7082 and NAC demonstrated Ejiao could significantly decrease the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β related to pyroptosis of LILEB 2B cells. Moreover, Ejiao reduced the production of mitochondrial ROS and reversed the change of mitochondrial membrane potential of LILEB 2B cells. Then, HE staining demonstrated Ejiao had a protective effect against the LPS-elicited ALI mouse model (LAMM). Ejiao also dramatically decreased the cell amount and the overall protein concentration of bronchoalveolar lavage fluid in LAMM. Immunohistochemical staining showed Ejiao remarkably reduced the expression of p-p65 and p-IκBα in NFκB signaling pathway and its downstream NLRP3, ASC, Caspase-1 and IL-1β. The ELISA of IL-1β revealed Ejiao could dose-dependably decrease the concentration of IL-1β in lung tissues, serum and BALF of LAMM. Finally, fluorescence labeling demonstrated Ejiao significantly reduced the mitochondrial ROS generation in the lung tissue of LAMM. This finding may afford a novel strategy for the precaution and therapy of ALI.
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Affiliation(s)
- Qingxi Yue
- Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Wen Zhang
- Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shumeng Lin
- Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tiansheng Zheng
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yaqin Hou
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yanfei Zhang
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ziye Li
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Kai Wang
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liduo Yue
- Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Baigenzhin Abay
- National Scientific Medical Research Center, Astana, Kazakhstan
| | - Ming Li
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Lihong Fan
- Institute of Energy Metabolism and Health, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China.
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24
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Ferrer JLM, Garcia RL. Antioxidant Systems, lncRNAs, and Tunneling Nanotubes in Cell Death Rescue from Cigarette Smoke Exposure. Cells 2022; 11:2277. [PMID: 35892574 PMCID: PMC9330437 DOI: 10.3390/cells11152277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 12/10/2022] Open
Abstract
Cigarette smoke is a rich source of carcinogens and reactive oxygen species (ROS) that can damage macromolecules including DNA. Repair systems can restore DNA integrity. Depending on the duration or intensity of stress signals, cells may utilize various survival and adaptive mechanisms. ROS levels are kept in check through redundant detoxification processes controlled largely by antioxidant systems. This review covers and expands on the mechanisms available to cigarette smoke-exposed cancer cells for restoring the redox balance. These include multiple layers of transcriptional control, each of which is posited to be activated upon reaching a particular stress threshold, among them the NRF2 pathway, the AP-1 and NF-kB pathways, and, finally, TP53, which triggers apoptosis if extreme toxicity is reached. The review also discusses long noncoding RNAs, which have been implicated recently in regulating oxidative stress-with roles in ROS detoxification, the inflammatory response, oxidative stress-induced apoptosis, and mitochondrial oxidative phosphorylation. Lastly, the emerging roles of tunneling nanotubes in providing additional mechanisms for metabolic rescue and the regulation of redox imbalance are considered, further highlighting the expanded redox reset arsenal available to cells.
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Affiliation(s)
| | - Reynaldo L. Garcia
- Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Quezon City 1101, Philippines;
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25
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Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction. Int J Mol Sci 2022; 23:ijms23137360. [PMID: 35806363 PMCID: PMC9266418 DOI: 10.3390/ijms23137360] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/24/2022] [Accepted: 06/28/2022] [Indexed: 12/10/2022] Open
Abstract
Endometrosis is a frequently occurring disease decreasing mares’ fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the follicular (FLP) and mid-luteal (MLP) phases of the estrous cycle, as well as with fibrosis progression. This study aimed to investigate the transcription of genes of estrogen (ESR1, ESR2) and progesterone receptors (PGR) in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples (n = 100), collected in FLP or MLP, were classified histologically, and examined using quantitative PCR. The phase of the cycle was determined through the evaluation of ovarian structures and hormone levels (estradiol, progesterone) in serum. The transcription of ESR1, ESR2, and PGR decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of ESR1, ESR2, and PGR were noted between FLP and MLP in the specific categories and histopathological type of equine endometrosis. In FLP and MLP, specific moderate and strong correlations between ESR1, ESR2, PGR and genes of the NF-κB pathway were evidenced. The transcription of endometrial steroid receptors can be subjected to dysregulation with the degree of equine endometrosis, especially in both destructive types of endometrosis, and mediated by the canonical NF-κB pathway depending on the estrous cycle phase.
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26
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Kociszewska D, Vlajkovic SM. The Association of Inflammatory Gut Diseases with Neuroinflammatory and Auditory Disorders. Front Biosci (Elite Ed) 2022; 14:8. [PMID: 35730449 DOI: 10.31083/j.fbe1402008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 02/11/2022] [Accepted: 02/24/2022] [Indexed: 11/06/2022]
Abstract
Disorders such as inflammatory bowel disease (IBD) and celiac disease (CeD) result in intestinal hyperpermeability or 'leaky' gut. The increased permeability of the intestinal barrier allows microbial metabolites, toxins, and pathogens to infiltrate the bloodstream and extraintestinal tissues, causing systemic inflammation. Despite differences in aetiology and pathophysiology, IBD and CeD share several extraintestinal manifestations such as neuroinflammation, neurological and psychiatric manifestations, and sensorineural hearing loss (SNHL). This narrative review focuses on the association between intestinal hyperpermeability with the brain and inner ear diseases. We postulate that the microbial metabolites and pathogens released from the gut increase the permeability of natural barriers, such as the blood-brain barrier (BBB) and blood-labyrinth barrier (BLB). The barrier breakdown allows the spreading of inflammatory processes to the brain and inner ear, leading to disease.
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Affiliation(s)
- Dagmara Kociszewska
- Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 1142 Auckland, New Zealand
| | - Srdjan M Vlajkovic
- Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 1142 Auckland, New Zealand
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27
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Usategui-Martín R, Rigual R, Ruiz-Mambrilla M, Fernández-Gómez JM, Dueñas A, Pérez-Castrillón JL. Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling. Int J Mol Sci 2022; 23:ijms23063233. [PMID: 35328654 PMCID: PMC8953213 DOI: 10.3390/ijms23063233] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 12/31/2022] Open
Abstract
Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.
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Affiliation(s)
- Ricardo Usategui-Martín
- Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
- IOBA, University of Valladolid, 47011 Valladolid, Spain
- Correspondence: (R.U.-M.); (J.L.P.-C.)
| | - Ricardo Rigual
- Department of Biochemistry, Molecular Biology and Physiology, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
- IBGM, University of Valladolid, 47003 Valladolid, Spain
| | - Marta Ruiz-Mambrilla
- Department of Surgery, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
| | - José-María Fernández-Gómez
- Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
| | - Antonio Dueñas
- Department of Medicine, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
- Department of Toxicology, Río Hortega University Hospital, 47012 Valladolid, Spain
| | - José Luis Pérez-Castrillón
- Department of Medicine, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain;
- Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain
- Correspondence: (R.U.-M.); (J.L.P.-C.)
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28
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Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. The NF-κB signaling pathway in mare's endometrium infiltrated with the inflammatory cells. Reprod Domest Anim 2022; 57:598-610. [PMID: 35182075 PMCID: PMC9305511 DOI: 10.1111/rda.14099] [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: 12/22/2021] [Accepted: 02/17/2022] [Indexed: 11/30/2022]
Abstract
Endometritis is an important issue decreasing mares' fertility. In the case of endometritis both, inflammatory cells infiltration and proinflammatory molecules production are regulated by various cellular and gene-regulatory mechanisms, including the nuclear factor-κB (NF-κB) dependent pathway. NF-κB signaling pathway has been recently studied in the equine endometrium in the context of endometrosis. Thus, this study aimed to determine gene transcription of NF-κB subunits (RelA; NF-κB1; NF-κB2), proinflammatory molecules (MCP-1; IL-6), and hyaluronan synthases (HAS 1; HAS 2; HAS 3) in endometritis and compare them with the intensity and type of inflammatory cell infiltration. Endometrial samples, collected post-mortem from cyclic mares in estrus or diestrus, were classified histologically and examined using quantitative PCR. Transcription NF-κB subunits genes did not differ with either inflammatory intensity or type of inflammatory cell infiltration. Transcription of MCP-1 and IL-6 genes increased with the severity of inflammation, with the involvement of HAS 3 and HAS 2 genes, as opposed to HAS 1 genes. These proinflammatory molecules and hyaluronan synthases in the equine inflamed endometrium do not seem to be regulated by the NF-κB pathway. Hence, separate signaling pathways for the development and progression of equine endometritis and endometrosis may be suggested.
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Affiliation(s)
- Tomasz Jasiński
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland
| | - Łukasz Zdrojkowski
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland
| | - Ewa Kautz
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Jastrzębiec, Poland
| | - Edyta Juszczuk-Kubiak
- Laboratory of Biotechnology and Molecular Engineering, Department of Microbiology, Prof. Wacław, Dąbrowski Institute of Agricultural and Food Biotechnology-State Research Institute, Warsaw, Poland
| | - Graça Ferreira-Dias
- Departmento de Morfologia e Função, CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisbon, Portugal
| | - Małgorzata Domino
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS - SGGW), Warsaw, Poland
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29
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Donaldson DS, Shih BB, Mabbott NA. Aging-Related Impairments to M Cells in Peyer's Patches Coincide With Disturbances to Paneth Cells. Front Immunol 2021; 12:761949. [PMID: 34938288 PMCID: PMC8687451 DOI: 10.3389/fimmu.2021.761949] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 11/17/2021] [Indexed: 11/26/2022] Open
Abstract
The decline in mucosal immunity during aging increases susceptibility, morbidity and mortality to infections acquired via the gastrointestinal and respiratory tracts in the elderly. We previously showed that this immunosenescence includes a reduction in the functional maturation of M cells in the follicle-associated epithelia (FAE) covering the Peyer’s patches, diminishing the ability to sample of antigens and pathogens from the gut lumen. Here, co-expression analysis of mRNA-seq data sets revealed a general down-regulation of most FAE- and M cell-related genes in Peyer’s patches from aged mice, including key transcription factors known to be essential for M cell differentiation. Conversely, expression of ACE2, the cellular receptor for SARS-Cov-2 virus, was increased in the aged FAE. This raises the possibility that the susceptibility of aged Peyer’s patches to infection with the SARS-Cov-2 virus is increased. Expression of key Paneth cell-related genes was also reduced in the ileum of aged mice, consistent with the adverse effects of aging on their function. However, the increased expression of these genes in the villous epithelium of aged mice suggested a disturbed distribution of Paneth cells in the aged intestine. Aging effects on Paneth cells negatively impact on the regenerative ability of the gut epithelium and could indirectly impede M cell differentiation. Thus, restoring Paneth cell function may represent a novel means to improve M cell differentiation in the aging intestine and increase mucosal vaccination efficacy in the elderly.
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Affiliation(s)
- David S Donaldson
- The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom
| | - Barbara B Shih
- The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom
| | - Neil A Mabbott
- The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom
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30
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Zhou Z, Xu J, Li Z, Lv Y, Wu S, Zhang H, Song Y, Ai Y. Viral deubiquitinases and innate antiviral immune response in livestock and poultry. J Vet Med Sci 2021; 84:102-113. [PMID: 34803084 PMCID: PMC8810313 DOI: 10.1292/jvms.21-0199] [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] [Indexed: 11/22/2022] Open
Abstract
Among many of the pathogens, virus is the main cause of diseases in livestock and poultry. A host infected with the virus triggers a series of innate and adaptive immunity. The realization of innate immune responses involves the participation of a series of protein molecules in host cells, including receptors, signal molecules and antiviral molecules. Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular or viral deubiquitinases (DUBs). DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. In this review, we briefly introduce the mechanisms of ubiquitination and deubiquitination, present antiviral innate immune response and its regulation by ubiquitin, and summarize the prevalence of DUBs encoded by viruses (Arteriviridae, Asfarviridae, Nairoviridae, Coronaviridae, Herpesviridae, and Picornaviridae) infecting domestic animals and poultry. It is found that these DUBs suppress the innate immune responses mainly by affecting the production of type I interferon (IFN), which causes immune evasion of the viruses and promotes their replication. These findings have important reference significance for understanding the virulence and immune evasion mechanisms of the relevant viruses, and thus for the development of more effective prevention and treatment measures.
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Affiliation(s)
- Zhengxuan Zhou
- College of Animal Science, Jilin University.,Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University
| | - Jiacui Xu
- College of Animal Science, Jilin University.,Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University
| | - Zhanjun Li
- College of Animal Science, Jilin University.,Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University
| | - Yan Lv
- College of Animal Science, Jilin University
| | - Shanli Wu
- College of Basic Medical Sciences, Jilin University
| | - Huanmin Zhang
- Avian Disease and Oncology Laboratory, Agriculture Research Service, United States Department of Agriculture
| | - Yu Song
- Key laboratory of Utilization and Conservation for Tropical Marine Bioresources (Hainan Tropical Ocean University), Ministry of Education of the People's Republic of China.,Hainan Key Laboratory for Conservation and Utilization of Tropical Marine Fishery Resources
| | - Yongxing Ai
- College of Animal Science, Jilin University.,Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Institute of Zoonosis, Jilin University
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Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M. Equine Endometrosis Pathological Features: Are They Dependent on NF-κB Signaling Pathway? Animals (Basel) 2021; 11:ani11113151. [PMID: 34827882 PMCID: PMC8614257 DOI: 10.3390/ani11113151] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/02/2021] [Accepted: 11/03/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Endometrosis is a serious problem mainly affecting older mares’ fertility. Despite the importance of this disease, its etiology and pathogenesis are not fully known. Thus, no effective treatment exists to cease or restore degenerative processes and fibrogenesis in the mares’ endometria. The nuclear factor kappaB (NF-κB) is an important factor regulating cell metabolism. Nevertheless, it is also known to promote inflammation and fibrosis in various tissues and species, as well as in the mares’ endometria. The main goal was to bring new knowledge regarding endometrosis pathogenesis, which could allow for therapy development. Endometrial samples, collected postmortem from cyclic mares in estrus or diestrus, were classified histologically and used for gene expression assessment. Gene transcription of NF-κB subunits (subunit RelA—RelA; subunit 1—NF-κB1; subunit 2—NF-κB2), pro-inflammatory molecules (monocyte chemoattractant protein-1—MCP-1; interleukin-6—IL-6), and hyaluronan synthases (hyaluronan synthase 1—HAS 1; hyaluronan synthase 2—HAS 2; hyaluronan synthase 3—HAS 3) were compared among endometrosis types (active, non-active, destructive, non-destructive), according to the classification of Hoffmann and co-authors. These results suggest that activation of the NF-κB canonical pathway is involved especially in destructive endometrosis, the type when endometrial glands are damaged. These data give substantial information for further evaluations and treatment development. Abstract Endometrosis is an important mares’ disease which considerably decreases their fertility. As classic endometrial classification methods might be insufficient for tissue pathological evaluation, further categorization into active/inactive and destructive/non-destructive types was developed by Hoffmann and others. This study aimed to compare NF-κB pathway genes transcription among histopathological types of endometrosis, following Hoffmann and co-authors’ classification. Endometrial samples, collected postmortem from cyclic mares (n = 100) in estrus or diestrus, were classified histologically and used for gene transcription assessment. Gene transcription of NF-κB subunits (RelA, NF-κB1, NF-κB2), pro-inflammatory molecules (MCP-1, IL-6), and hyaluronan synthases (HAS 1, HAS 2, HAS 3) was compared among endometrosis types (active, non-active, destructive, non-destructive). Most individual mRNA samples showed high expression of RelA, NF-κB1, and MCP-1 gene transcripts and the destructive type of endometrosis, simultaneously. The expression of RelA and NF-κB1 genes was higher in active destructive group than in the other groups only in the follicular phase, as well as being higher in the inactive destructive group than in the others, only in the mid-luteal phase. The increase in gene transcription of the NF-κB canonical activation pathway in destructive endometrosis may suggest the highest changes in extracellular matrix deposition. Moreover, the estrous cycle phase might influence fibrosis pathogenesis.
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Affiliation(s)
- Tomasz Jasiński
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland;
| | - Łukasz Zdrojkowski
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland;
- Correspondence: (Ł.Z.); (M.D.)
| | - Ewa Kautz
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, 05-552 Jastrzębiec, Poland;
| | - Edyta Juszczuk-Kubiak
- Laboratory of Biotechnology and Molecular Engineering, Department of Microbiology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology—State Research Institute, 02-532 Warsaw, Poland;
| | - Graça Ferreira-Dias
- Departmento de Morfologia e Função, CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-47 Lisbon, Portugal;
| | - Małgorzata Domino
- Department of Large Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland;
- Correspondence: (Ł.Z.); (M.D.)
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Pacurari M, Mitra A, Turner T. Idiopathic Pulmonary Comorbidities and Mechanisms. Int J Inflam 2021; 2021:3963659. [PMID: 34691383 PMCID: PMC8528608 DOI: 10.1155/2021/3963659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 09/24/2021] [Accepted: 10/05/2021] [Indexed: 11/20/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a disease with an unknown etiology mainly characterized by a progressive decline of lung function due to the scarring of the tissue deep in the lungs. The overall survival after diagnosis remains low between 3 and 5 years. IPF is a heterogeneous disease and much progress has been made in the past decade in understanding the disease mechanisms that contributed to the development of two new drugs, pirfenidone and nintedanib, which improved the therapeutic management of the disease. The understanding of the cofactors and comorbidities of IPF also contributed to improved management of the disease outcome. In the present review, we evaluate scientific evidence which indicates IPF as a risk factor for other diseases based on the complexity of molecular and cellular mechanisms involved in the disease development and of comorbidities. We conclude from the existing literature that while much progress has been made in understating the mechanisms involved in IPF development, further studies are still necessary to fully understand IPF pathogenesis which will contribute to the identification of novel therapeutic targets for IPF management as well as other diseases for which IPF is a major risk factor.
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Affiliation(s)
- Maricica Pacurari
- Department of Biology, College of Science, Engineering, and Technology, Jackson State University, Jackson, MS 39217, USA
| | - Amal Mitra
- Department of Epidemiology and Biostatistics, School of Public Health, Jackson State University, Jackson, MS 39217, USA
| | - Timothy Turner
- Department of Biology, College of Science, Engineering, and Technology, Jackson State University, Jackson, MS 39217, USA
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Baranwal A, Aggarwal P, Rai A, Kumar N. Pharmacological actions and underlying mechanisms of Catechin: A review. Mini Rev Med Chem 2021; 22:821-833. [PMID: 34477517 DOI: 10.2174/1389557521666210902162120] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 04/28/2021] [Accepted: 07/26/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Catechin is a phytochemical and is a major component of our daily use beverages, which has shown great potential in improving general health and fighting against several medical conditions. Clinical studies have confirmed its effectiveness in conditions ranging from acute upper respiratory tract infection, neuroprotection, to cardio-protection effects. Though most studies relate their potential to anti-oxidative action and radical scavenging action, still the mechanism of action is not clearly understood. OBJECTIVE The present review article is focused on addressing various pharmacological actions and underlying mechanisms of catechin. Additionally, we will try to figure out the major adverse effect and success in trials with catechin and lead to a conclusion for its effectiveness. METHODS This review article is based on the recent/ most cited papers of PubMed and Scopus databases. DESCRIPTION Catechin can regulate Nrf2 and NFkB pathways in ways that impact oxidative stress and inflammation by influencing gene expression. Other pathways like MAPKs and COMT and receptor tyrosine kinase are also affected by catechin and EGCG that alter their action and barge the cellular activity. This review article explored the structural aspect of catechin and its different isomers and analogs. It also evaluated its various therapeutic and pharmacological arrays . CONCLUSION Catechin and its stereo-isomers have shown their effectiveness as anti-inflammatory, anti-diabetic, anti-cancer, anti-neuroprotective, bactericidal, memory enhancer, anti-arthritis, and hepato-protective mainly through its activity to alter the pathway by NF-κB, Nrf-2, TLR4/NF-κB, COMT, and MAPKs.
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Affiliation(s)
- Aadrika Baranwal
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnakata, India
| | - Punita Aggarwal
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, EPIP, Industrial Area, Vaishali 844102, Bihar, India
| | - Amita Rai
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnakata, India
| | - Nitesh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, EPIP, Industrial Area, Vaishali 844102, Bihar, India
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Bao J, Ma Y, Ding M, Wang C, Du G, Zhou Y, Guo L, Kang H, Wang C, Gu B. Preliminary exploration on the serum biomarkers of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae based on mass spectrometry. J Clin Lab Anal 2021; 35:e23915. [PMID: 34331328 PMCID: PMC8418493 DOI: 10.1002/jcla.23915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 07/06/2021] [Accepted: 07/11/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI) must be rapidly identified to improve patient survival rates. This study investigated a new mass spectrometry-based method for improving the identification of CRKP BSI and explored potential biomarkers that could differentiate CRKP BSI from sensitive. METHODS Mouse models of BSI were first established. MALDI-TOF MS was then used to profile serum peptides in CRKP BSI versus normal samples before applying BioExplorer software to establish a diagnostic model to distinguish CRKP from normal. The diagnostic value of the model was then tested against 32 clinical CRKP BSI and 27 healthy serum samples. Finally, the identities of the polypeptides used to establish the diagnostic model were determined by secondary mass spectrometry. RESULTS 107 peptide peaks were shared between the CRKP and normal groups, with 18 peaks found to be differentially expressed. Five highly expressed peptides in the CRKP group (m/z 1349.8, 2091.3, 2908.2, 4102.1, and 8129.5) were chosen to establish a diagnostic model. The accuracy, specificity and sensitivity of the model were determined as 79.66%, 81.48%, and 78.12%, respectively. Secondary mass spectrometry identified the Fibrinogen alpha chain (FGA), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and Serum amyloid A-2 protein (SAA2) as the source of the 5 serum peptides. CONCLUSIONS We successfully established a serum peptide-based diagnostic model that distinguished clinical CRKP BSI samples from normal healthy controls. The application of MALDI-TOF MS to measure serum peptides, therefore, represents a promising approach for early BSI diagnosis of BSI, especially for multidrug-resistant bacteria where identification is urgent.
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Affiliation(s)
- Jinfeng Bao
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Yating Ma
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Mengshan Ding
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Chi Wang
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Gaofei Du
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
| | - Yuan Zhou
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
| | - Ling Guo
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Haiquan Kang
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
| | - Chengbin Wang
- Department of Clinical LaboratoryThe First Medical CentreThe PLA General HospitalBeijingChina
| | - Bing Gu
- College of Medical TechnologyXuzhou Medical UniversityXuzhouChina
- Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouChina
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Koshman YE, Lai-Zhang J, Wilsey AS, Bird BM, Sadilek S, Weisbecker DA, Ebert PA, Polakowski JS, Mittelstadt SW, Foley CM, LeRoy BE. Automated blood sampling in canine telemetry model: Enhanced assessment of immune liabilities. J Pharmacol Toxicol Methods 2021; 112:107115. [PMID: 34403748 DOI: 10.1016/j.vascn.2021.107115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/08/2021] [Accepted: 08/11/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION This manuscript presents a successful integration of multi-timepoint biomarker blood sampling (e.g., cytokines) in a conscious dog cardiovascular study using automated blood sampling via vascular access ports in telemetry instrumented dogs. In addition to determining plasma exposure of the test compound, the assessment of biomarkers of interest allows for more comprehensive preclinical evaluation on a traditional conscious dog cardiovascular (CV) telemetry study especially for immunology and immune-oncology molecules. This model system provides a rapid and efficient means to quickly gain understanding of potential effects on key cardiovascular parameters in large species that are commonly used for preclinical safety evaluations while collecting multiple blood samples for drug and cytokine analysis. METHODS Male beagle dogs were chronically implanted with telemetry devices (PhysioTel™ model D70-PCTP) and vascular access ports (SPMID-GRIDAC-5NC). BASi Culex-L automated blood sampling (ABS) (Bioanalytical Systems, Inc) system was used to collect blood samples at multiple time points for cytokine analysis. Four beagles received low-dose lipopolysaccharide solution (LPS) (0.1 and 0.5 μg/mL). The following cytokines were measured by Milliplex® map Canine Cytokine Magnetic Bead Panel: Interleukin (IL) 2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, TNF-α, MCP-1, KC-like, GM-CSF, IFN gamma, and IP10. RESULTS Low dose LPS administration induced a pronounced dose-dependent, transient release of key inflammatory cytokines (IL-2, IL-6, IL-10, TNF-α, MCP-1, and KC-like). Cytokine responses were similar to other canine and human endotoxin models. LPS administration led to an increase in body temperature, heart rate, and mean arterial pressure, as well as a decrease in QTcV interval. CONCLUSION Successful incorporation of cytokine analysis in telemetry instrumented dogs with vascular access ports allows for translational PK/PD modeling of both efficacy and safety of compounds in the immunology as well as the immune-oncology therapeutic areas designed to modulate the immune system. Remote collection of blood samples simultaneously with CV endpoints is a significant enhancement for assessment of biomarkers that are sensitive to animal handling and excitement associated with room disturbances which are obligatory with manual blood collection. Furthermore, implementing this approach has also refined our animal welfare procedure by reducing the handling during a study and thereby reducing stress (positive refinement 3R impact).
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Affiliation(s)
- Yevgeniya E Koshman
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America.
| | - Jie Lai-Zhang
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Amanda S Wilsey
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Brandan M Bird
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Sabine Sadilek
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Debra A Weisbecker
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Paige A Ebert
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - James S Polakowski
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Scott W Mittelstadt
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - C Michael Foley
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
| | - Bruce E LeRoy
- AbbVie Inc., 1 North Waukegan Rd., North Chicago, IL 60064, United States of America
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Ng MG, Ng KY, Koh RY, Chye SM. Potential role of melatonin in prevention and treatment of leukaemia. Horm Mol Biol Clin Investig 2021; 42:445-461. [PMID: 34355548 DOI: 10.1515/hmbci-2021-0009] [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: 01/31/2021] [Accepted: 07/06/2021] [Indexed: 11/15/2022]
Abstract
Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.
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Affiliation(s)
- Ming Guan Ng
- School of Health Science, International Medical University, Kuala Lumpur, Malaysia
| | - Khuen Yen Ng
- School of Pharmacy, Monash University Malaysia, Selangor, Malaysia
| | - Rhun Yian Koh
- Division of Biomedical Science and Biotechnology, School of Health Science, International Medical University, Kuala Lumpur, Malaysia
| | - Soi Moi Chye
- Division of Biomedical Science and Biotechnology, School of Health Science, International Medical University, Kuala Lumpur, Malaysia
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Conte C. Possible Link between SARS-CoV-2 Infection and Parkinson's Disease: The Role of Toll-Like Receptor 4. Int J Mol Sci 2021; 22:7135. [PMID: 34281186 PMCID: PMC8269350 DOI: 10.3390/ijms22137135] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/19/2021] [Accepted: 06/29/2021] [Indexed: 12/13/2022] Open
Abstract
Parkinson's disease (PD) is the most common neurodegenerative motor disorder characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain, depletion of dopamine (DA), and impaired nigrostriatal pathway. The pathological hallmark of PD includes the aggregation and accumulation α-synuclein (α-SYN). Although the precise mechanisms underlying the pathogenesis of PD are still unknown, the activation of toll-like receptors (TLRs), mainly TLR4 and subsequent neuroinflammatory immune response, seem to play a significant role. Mounting evidence suggests that viral infection can concur with the precipitation of PD or parkinsonism. The recently identified coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of ongoing pandemic coronavirus disease 2019 (COVID-19), responsible for 160 million cases that led to the death of more than three million individuals worldwide. Studies have reported that many patients with COVID-19 display several neurological manifestations, including acute cerebrovascular diseases, conscious disturbance, and typical motor and non-motor symptoms accompanying PD. In this review, the neurotropic potential of SARS-CoV-2 and its possible involvement in the pathogenesis of PD are discussed. Specifically, the involvement of the TLR4 signaling pathway in mediating the virus entry, as well as the massive immune and inflammatory response in COVID-19 patients is explored. The binding of SARS-CoV-2 spike (S) protein to TLR4 and the possible interaction between SARS-CoV-2 and α-SYN as contributing factors to neuronal death are also considered.
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Affiliation(s)
- Carmela Conte
- Department of Pharmaceutical Sciences, University of Perugia, via Fabretti, 06123 Perugia, Italy
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Tavakoli P, Vollmer-Conna U, Hadzi-Pavlovic D, Grimm MC. A Review of Inflammatory Bowel Disease: A Model of Microbial, Immune and Neuropsychological Integration. Public Health Rev 2021; 42:1603990. [PMID: 34692176 PMCID: PMC8386758 DOI: 10.3389/phrs.2021.1603990] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 04/01/2021] [Indexed: 12/11/2022] Open
Abstract
Objective: Inflammatory bowel diseases (IBDs) are complex chronic inflammatory disorders of the gastro-intestinal (GI) tract with uncertain etiology. IBDs comprise two idiopathic disorders: Crohn's disease (CD) and ulcerative colitis (UC). The aetiology, severity and progression of such disorders are still poorly understood but thought to be influenced by multiple factors (including genetic, environmental, immunological, physiological, psychological factors and gut microbiome) and their interactions. The overarching aim of this review is to evaluate the extent and nature of the interrelationship between these factors with the disease course. A broader conceptual and longitudinal framework of possible neuro-visceral integration, core microbiome analysis and immune modulation assessment may be useful in accurately documenting and characterizing the nature and temporal continuity of crosstalk between these factors and the role of their interaction (s) in IBD disease activity. Characterization of these interactions holds the promise of identifying novel diagnostic, interventions, and therapeutic strategies. Material and Methods: A search of published literature was conducted by exploring PubMed, EMBASE, MEDLINE, Medline Plus, CDSR library databases. Following search terms relating to key question were set for the search included: "Inflammatory bowel diseases," "gut microbiota," "psychological distress and IBD," "autonomic reactivity and IBD," "immune modulation," "chronic inflammation," "gut inflammation," "enteric nervous system," "gut nervous system," "Crohn's disease," "Ulcerative colitis", "depression and IBD", "anxiety and IBD", "quality of life in IBD patients," "relapse in IBDs," "remission in IBDs," "IBD disease activity," "brain-gut-axis," "microbial signature in IBD," "validated questionnaires in IBD," "IBD activity indices," "IBD aetiology," "IBDs and stress," "epidemiology of IBDs", "autonomic nervous system and gut inflammation", "IBD and environment," "genetics of IBDs," "pathways of immune response in IBDs," "sleep disturbances in IBD," "hypothalamic-pituitary-adrenal axis (HPA)," "sympatho-adrenal axis," "CNS and its control of gut function" "mucosal immune response," "commensal and pathogenic bacteria in the gut," "innate and adaptive immunity." Studies evaluating any possible associations between gut microbiome, psychological state, immune modulation, and autonomic function with IBDs were identified. Commonly cited published literatures with high quality research methodology/results and additional articles from bibliographies of recovered papers were examined and included where relevant. Results: Although there is a substantial literature identifying major contributing factors with IBD, there has been little attempt to integrate some factors over time and assess their interplay and relationship with IBD disease activity. Such contributing factors include genetic and environmental factors, gut microbiota composition and function, physiological factors, psychological state and gut immune response. Interdependences are evident across psychological and biological factors and IBD disease activity. Although from the available evidence, it is implausible that a single explanatory model could elucidate the interplay between such factors and the disease course as well as the sequence of the effect during the pathophysiology of IBD. Conclusion: Longitudinal monitoring of IBD patients and integrating data related to the contributing/risk factors including psychological state, physiological conditions, inflammatory/immune modulations, and microbiome composition/function, could help to explain how major factors associate and interrelate leading to exacerbation of symptoms and disease activity. Identifying the temporal trajectory of biological and psychosocial disturbances may also help to assess their effects and interdependence on individuals' disease status. Moreover, this allows greater insight into understanding the temporal progressions of subclinical events as potential ground for disease severity in IBD. Furthermore, understanding the interaction between these risk factors may help better interventions in controlling the disease, reducing the costs related to disease management, further implications for clinical practice and research approaches in addition to improving patients' mental health and quality of life.
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Affiliation(s)
- P. Tavakoli
- St George and Sutherland Clinical School, Sydney, NSW, Australia
| | - U. Vollmer-Conna
- School of Psychiatry, University of New South Wales, Sydney, Australia
| | - D. Hadzi-Pavlovic
- School of Psychiatry, University of New South Wales, Sydney, Australia
| | - M. C. Grimm
- St George and Sutherland Clinical School, Sydney, NSW, Australia
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Sidibé H, Dubinski A, Vande Velde C. The multi-functional RNA-binding protein G3BP1 and its potential implication in neurodegenerative disease. J Neurochem 2021; 157:944-962. [PMID: 33349931 PMCID: PMC8248322 DOI: 10.1111/jnc.15280] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/09/2020] [Accepted: 12/11/2020] [Indexed: 12/12/2022]
Abstract
Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) is a multi-functional protein that is best known for its role in the assembly and dynamics of stress granules. Recent studies have highlighted that G3BP1 also has other functions related to RNA metabolism. In the context of disease, G3BP1 has been therapeutically targeted in cancers because its over-expression is correlated with proliferation of cancerous cells and metastasis. However, evidence suggests that G3BP1 is essential for neuronal development and possibly neuronal maintenance. In this review, we will examine the many functions that are carried out by G3BP1 in the context of neurons and speculate how these functions are critical to the progression of neurodegenerative diseases. Additionally, we will highlight the similarities and differences between G3BP1 and the closely related protein G3BP2, which is frequently overlooked. Although G3BP1 and G3BP2 have both been deemed important for stress granule assembly, their roles may differ in other cellular pathways, some of which are specific to the CNS, and presents an opportunity for further exploration.
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Affiliation(s)
- Hadjara Sidibé
- Department of NeurosciencesUniversité de Montréal, and CHUM Research CenterMontréalQCCanada
| | - Alicia Dubinski
- Department of NeurosciencesUniversité de Montréal, and CHUM Research CenterMontréalQCCanada
| | - Christine Vande Velde
- Department of NeurosciencesUniversité de Montréal, and CHUM Research CenterMontréalQCCanada
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Point Mutation Specific Antibodies in B-Cell and T-Cell Lymphomas and Leukemias: Targeting IDH2, KRAS, BRAF and Other Biomarkers RHOA, IRF8, MYD88, ID3, NRAS, SF3B1 and EZH2. Diagnostics (Basel) 2021; 11:diagnostics11040600. [PMID: 33801781 PMCID: PMC8065453 DOI: 10.3390/diagnostics11040600] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/16/2021] [Accepted: 03/24/2021] [Indexed: 12/17/2022] Open
Abstract
B-cell and T-cell lymphomas and leukemias often have distinct genetic mutations that are diagnostically defining or prognostically significant. A subset of these mutations consists of specific point mutations, which can be evaluated using genetic sequencing approaches or point mutation specific antibodies. Here, we describe genes harboring point mutations relevant to B-cell and T-cell malignancies and discuss the current availability of these targeted point mutation specific antibodies. We also evaluate the possibility of generating novel antibodies against known point mutations by computationally assessing for chemical and structural features as well as epitope antigenicity of these targets. Our results not only summarize several genetic mutations and identify existing point mutation specific antibodies relevant to hematologic malignancies, but also reveal potential underdeveloped targets which merit further study.
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41
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Fordjour FA, Asiedu E, Larbi A, Kwarteng A. The role of nuclear factor kappa B (NF-κB) in filarial pathology. J Cell Commun Signal 2021; 15:185-193. [PMID: 33630268 DOI: 10.1007/s12079-021-00607-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 01/24/2021] [Indexed: 12/11/2022] Open
Abstract
The transcription factor NF-κB promotes immunity by controlling the expression of genes involved in inflammation. Cytokines and pathogen-associated molecular patterns stimulate cell surface receptors, including toll-like receptors, to initiate a signalling cascade resulting in the activation of NF-κB. NF-κB drives the expression of target genes that mediate cell proliferation and release antimicrobial molecules and cytokines to activate an immune response. Filariasis is one of the most complex infections of humans. The actual causes of the heterogeneity in infection are not well understood. However, they have been attributed to differences in inflammatory processes that are immune-mediated, secondary bacterial infections, and host immune-genetics. Elevated production of angiogenic molecules (VEGFs, CEACAM and MMPs) in filarial pathology has been shown to be dependent on phosphorylation and intracellular activation of NF-κB. This review examines the role of NF-κB in filarial pathology and its potential therapeutic options for individuals with the disease.
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Affiliation(s)
- Fatima Amponsah Fordjour
- Department of Microbiology, University for Development Studies, UDS, Tamale, Ghana. .,Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana.
| | - Ebenezer Asiedu
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana
| | - Amma Larbi
- Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana
| | - Alexander Kwarteng
- Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana.,Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana
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Ma T, Kong M. Interleukin-18 and -10 may be associated with lymph node metastasis in breast cancer. Oncol Lett 2021; 21:253. [PMID: 33664817 PMCID: PMC7882877 DOI: 10.3892/ol.2021.12515] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/06/2021] [Indexed: 12/09/2022] Open
Abstract
Reports on the expression of interleukin (IL)-10 in breast cancer are rare. The present study investigated the correlation between IL-18 and −10 in breast cancer, and assessed their clinical significance. Breast cancer (n=104) and breast fibroadenoma (n=31) tissues that were surgically removed and pathologically confirmed at Jinan Central Hospital Affiliated to Shandong University (Jinan, China) between November 2016 and January 2019 were collected. The expression of IL-18 and −10 was observed via immunohistochemistry. Breast cancer tissues were positive for IL-18 expression, which was primarily located in the cell membrane and cytoplasm. A significant difference in IL-18 expression was observed between breast cancer and fibroadenoma tissues (75.0 vs. 19.4%; P<0.001). IL-10 was expressed in breast cancer tissues and primarily located in the cytoplasm. Breast cancer tissues showed a significantly higher level of IL-10 expression compared with breast fibroadenoma tissues (78.8 vs. 22.6%; P<0.001). The regions of positive IL-18 and −10 expression were consistent. Tissues with positive expression of IL-18 and/or −10 had a significantly higher rate of lymph node metastasis than those with negative expression (IL-18: 67.9 vs. 42.3%; P=0.035; and IL-10: 67.1 vs. 40.9%; P=0.047). In conclusion, IL-18 is highly expressed in breast cancer and correlates positively with IL-10. Both IL-18 and −10 may correlate positively with lymph node metastasis in breast cancer.
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Affiliation(s)
- Teng Ma
- Department of Internal Medicine, The Fifth People's Hospital of Jinan, Jinan, Shandong 250000, P.R. China
| | - Meng Kong
- Department of General Surgery, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, P.R. China
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Knockdown of TRAF6 inhibits chondrocytes apoptosis and inflammation by suppressing the NF-κB pathway in lumbar facet joint osteoarthritis. Mol Cell Biochem 2021; 476:1929-1938. [PMID: 33502650 DOI: 10.1007/s11010-021-04048-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 01/08/2021] [Indexed: 12/24/2022]
Abstract
Tumor necrosis factor receptor-associated factor 6 (TRAF6), a regulator of NF-κB signaling, has been discovered recently to be probably related to osteoarthritis, while the function of TRAF6 in lumbar facet joint osteoarthritis(FJOA)still remains unknown. The aim of this study was to probe the specific function of TRAF6 in chondrocytes and its connection with the pathophysiology of FJOA. We found upregulation of TRAF6 in FJOA cartilage by western blot analysis. In vitro, we stimulated immortalized human chondrocytes by LPS to establish the cells apoptosis model. Western blot analysis demonstrated that levels of TRAF6 and cleaved caspase-3/8 in the chondrocyte injury model increased significantly. Knockdown of TRAF6 suppressed the expression of matrix metallopeptidase-13 (MMP-13) and interleukin-6 (IL-6) induced by LPS, and alleviated cell apoptosis. Meanwhile, western blot and immunofluorescent staining demonstrated that IκBα degradation and p65 nuclear transportation were also inhibited, revealing that knockdown of TRAF6 suppressed activation of the NF-κB pathway in LPS-induced chondrocytes apoptosis model. Collectively, our findings suggest that TRAF6 plays a crucial role in FJOA development by regulating NF-κB signaling pathway. Knockdown of TRAF6 may supply a potential therapeutic strategy for FJOA.
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Michaelis L, Treß M, Löw HC, Klees J, Klameth C, Lange A, Grießhammer A, Schäfer A, Menz S, Steimle A, Schulze-Osthoff K, Frick JS. Gut Commensal-Induced IκBζ Expression in Dendritic Cells Influences the Th17 Response. Front Immunol 2021; 11:612336. [PMID: 33542719 PMCID: PMC7851057 DOI: 10.3389/fimmu.2020.612336] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 11/30/2020] [Indexed: 12/26/2022] Open
Abstract
Intestinal commensal bacteria can have a large impact on the state of health and disease of the host. Regulation of Th17 cell development by gut commensals is known to contribute to their dichotomous role in promoting gut homeostasis and host defense, or development of autoimmune diseases. Yet, the underlying mechanisms remain to be fully elucidated. One candidate factor contributing to Th17 differentiation, and the expression of which could be influenced by commensals is the atypical nuclear IκB protein IκBζ. IκBζ acts as a transcriptional regulator of the expression of Th17-related secondary response genes in many cell types including dendritic cells (DCs). Insights into the regulation of IκBζ in DCs could shed light on how these immune sentinel cells at the interface between commensals, innate and adaptive immune system drive an immune-tolerogenic or inflammatory Th17 cell response. In this study, the influence of two gut commensals of low (Bacteroides vulgatus) or high (Escherichia coli) immunogenicity on IκBζ expression in DCs and its downstream effects was analyzed. We observed that the amount of IκBζ expression and secretion of Th17-inducing cytokines correlated with the immunogenicity of these commensals. However, under immune-balanced conditions, E. coli also strongly induced an IκBζ-dependent secretion of anti-inflammatory IL-10, facilitating a counter-regulative Treg response as assessed in in vitro CD4+ T cell polarization assays. Yet, in an in vivo mouse model of T cell-induced colitis, prone to inflammatory and autoimmune conditions, administration of E. coli promoted an expansion of rather pro-inflammatory T helper cell subsets whereas administration of B. vulgatus resulted in the induction of protective T helper cell subsets. These findings might contribute to the development of new therapeutic strategies for the treatment of autoimmune diseases using commensals or commensal-derived components.
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Affiliation(s)
- Lena Michaelis
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Marcel Treß
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Hanna-Christine Löw
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Johanna Klees
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Christian Klameth
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Anna Lange
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Anne Grießhammer
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Andrea Schäfer
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Sarah Menz
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
| | - Alex Steimle
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.,Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | | | - Julia-Stefanie Frick
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany
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Richard SA. Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids. Mediators Inflamm 2021; 2021:6699560. [PMID: 33505216 PMCID: PMC7808814 DOI: 10.1155/2021/6699560] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 12/09/2020] [Accepted: 12/19/2020] [Indexed: 12/11/2022] Open
Abstract
Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.
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Affiliation(s)
- Seidu A. Richard
- Department of Medicine, Princefield University, P. O. Box MA 128, Ho, Ghana
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Wang QQ, Han S, Li XX, Yuan R, Zhuo Y, Chen X, Zhang C, Chen Y, Gao H, Zhao LC, Yang S. Nuezhenide Exerts Anti-Inflammatory Activity through the NF-κB Pathway. Curr Mol Pharmacol 2021; 14:101-111. [PMID: 32525787 PMCID: PMC8778660 DOI: 10.2174/1874467213666200611141337] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 04/04/2020] [Accepted: 04/15/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Nuezhenide (NZD), an iridoid glycoside isolated from Ilex pubescens Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing away heat and toxic materials, displays a variety of biological activities such as anti-tumor, antioxidant, and other life-protecting activities. However, a few studies involving anti-inflammatory activity and the mechanism of NZD have also been reported. In the present study, the anti-inflammatory and antioxidative effects of NZD are illustrated. OBJECTIVE This study aims to test the hypothesis that NZD suppresses LPS-induced inflammation by targeting the NF-κB pathway in RAW264.7 cells. METHODS LPS-stimulated RAW264.7 cells were employed to detect the effect of NZD on the release of cytokines by ELISA. Protein expression levels of related molecular markers were quantitated by western blot analysis. The levels of ROS, NO, and Ca2+ were detected by flow cytometry. The changes in mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed and verified by fluorescence microscopy. Using immunofluorescence assay, the translocation of NF-κB/p65 from the cytoplasm into the nucleus was determined by confocal microscopy. RESULTS NZD exhibited anti-inflammatory activity and reduced the release of inflammatory cytokines such as nitrite, TNF-α, and IL-6. NZD suppressed the expression of the phosphorylated proteins like IKKα/β, IκBα, and p65. Besides, the flow cytometry results indicated that NZD inhibited the levels of ROS, NO, and Ca2+ in LPS-stimulated RAW264.7 cells. JC-1 assay data showed that NZD reversed LPS-induced MMP loss. Furthermore, NZD suppressed LPS-induced NF-B/p65 translocation from the cytoplasm into the nucleus. CONCLUSION NZD exhibits anti-inflammatory effects through the NF-κB pathway on RAW264.7 cells.
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Affiliation(s)
- Qin-Qin Wang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Shan Han
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Xin-Xing Li
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Renyikun Yuan
- State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Youqiong Zhuo
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Xinxin Chen
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Chenwei Zhang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Yangling Chen
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Hongwei Gao
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Li-Chun Zhao
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
| | - Shilin Yang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China
- Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530200
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Heidari Z, Mohammadi M, Sahebkar A. Possible Mechanisms and Special Clinical Considerations of Curcumin Supplementation in Patients with COVID-19. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1308:127-136. [PMID: 33861442 DOI: 10.1007/978-3-030-64872-5_11] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The novel coronavirus outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized in late 2019 in Wuhan, China. Subsequently, the World Health Organization declared coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. The proportion of potentially fatal coronavirus infections may vary by location, age, and underlying risk factors. However, acute respiratory distress syndrome (ARDS) is the most frequent complication and leading cause of death in critically ill patients. Immunomodulatory and anti-inflammatory agents have received great attention as therapeutic strategies against COVID-19. Here, we review potential mechanisms and special clinical considerations of supplementation with curcumin as an anti-inflammatory and antioxidant compound in the setting of COVID-19 clinical research.
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Affiliation(s)
- Zinat Heidari
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Marzieh Mohammadi
- Department of Pharmaceutics, Faculty of pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
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Della Schiava N, Bordet M, Lermusiaux P. Letter by Della Schiava et al Regarding Article "Matrix Metalloproteinase-9 and Monocyte Chemoattractant Protein-1 Are Associated With Collateral Status in Acute Ischemic Stroke With Large Vessel Occlusion". Stroke 2020; 52:e15. [PMID: 33370195 DOI: 10.1161/strokeaha.120.031846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Nellie Della Schiava
- Department of vascular and endovascular surgery, Louis Pradel Hospital, Hospices civils de Lyon, France (N.D.S., M.B., P.L.)
| | - Marine Bordet
- Department of vascular and endovascular surgery, Louis Pradel Hospital, Hospices civils de Lyon, France (N.D.S., M.B., P.L.).,Claude Bernard University Lyon 1, France (M.B., P.L.)
| | - Patrick Lermusiaux
- Department of vascular and endovascular surgery, Louis Pradel Hospital, Hospices civils de Lyon, France (N.D.S., M.B., P.L.).,Claude Bernard University Lyon 1, France (M.B., P.L.)
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Hu L, Chen Y, Chen T, Huang D, Li S, Cui S. A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach. Front Pharmacol 2020; 11:582520. [PMID: 33424592 PMCID: PMC7789873 DOI: 10.3389/fphar.2020.582520] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 10/16/2020] [Indexed: 01/21/2023] Open
Abstract
Objective: To investigate the mechanism of Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson (SC) and Patrinia scabiosifolia (PS) against Pelvic Inflammatory Disease with Dampness-Heat Stasis Syndrome via network pharmacological approach and experimental validation. Methods: The active compounds with OB ≥ 30% and DL ≥ 0.18 were obtained from TCMSP database and further confirmed by literature research. The targets of the compounds and disease were acquired from multiple databases, such as GeneCards, CTD and TCMSP database. The intersection targets were identified by Venny software. Cytoscape 3.7.0 was employed to construct the protein-protein interaction (PPI) network and compound-target network. Moreover, GO enrichment and KEGG pathway analysis were analyzed by DAVID database. Finally, CCK-8, Griess assay and a cytometric bead array (CBA) immunoassay were used for experimental validation by detecting the influence of the active compounds on proliferation of macrophage, release of NO and TNF-α after LPS treatment. Results: 9 bioactive compounds were identified from SC and PS. Those compounds corresponded to 134 targets of pelvic inflammatory disease with dampness-heat stasis syndrome. The targets include vascular endothelial growth factor A (VEGFA), von willebrand factor (VWF), interleukin 6 (IL6), tumor necrosis factor (TNF) and nuclear transcription factor 1 (NFκB1). They act on the signaling pathways like advanced glycation end products-receptor of advanced glycation end products (AGE-RAGE), focal adhesion (FA), Toll-like receptor (TLR) and nuclear transcription factor κB (NF-κB). In addition, by in vitro validation, the selected active components of SC and PS such as acacetin, kaempferol, linarin, isovitexin, sinoacutine could significantly inhibit the release of NO induced by LPS, respectively. Moreover, different dose of acacetin, kaempferol, isovitexin and sinoacutine significantly inhibits the TNF-α production. Conclusion: This study provides solid evidence for the anti-inflammatory mechanism of SC and PS against pelvic inflammatory disease with dampness-heat stasis syndrome, which will provide a preliminary evidence and novelty ideas for future research on the two herbs.
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Affiliation(s)
- Luanqian Hu
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, China
| | - Yuqi Chen
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, China
| | - Tingting Chen
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, China
| | - Dan Huang
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, China
| | - Shihua Li
- Department of Gynecology and Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Shuna Cui
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College of Yangzhou University, Yangzhou, China.,Department of Gynecology and Obstetrics, Affiliated Hospital of Yangzhou University, Yangzhou, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou, China
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Wu D, Li S, Liu X, Xu J, Jiang A, Zhang Y, Liu Z, Wang J, Zhou E, Wei Z, Yang Z, Guo C. Alpinetin prevents inflammatory responses in OVA-induced allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways in mice. Int Immunopharmacol 2020; 89:107073. [PMID: 33039967 DOI: 10.1016/j.intimp.2020.107073] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 12/11/2022]
Abstract
Allergic asthma is the most common type of asthma which characterized by inflammatory responses of the airways. Alpinetin, a flavonoid compound derived from the ginger family of medicinal herbs, possesses various biological properties including anti-inflammatory, anti-oxidant and other medical effects. In this study, we aimed to evaluate the effects of alpinetin on OVA-induced allergic asthma, and further to examine its molecular mechanisms underlying these processes in vivo and in vitro. Mice were sensitized and challenged with OVA to build allergic asthma model in vivo. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells analysis and lung tissues were examined for histopathological examination. The levels of IL-5, IL-13, IL-4, IgE, TNF-α, IL-6 and IL-1β were determined by the respective ELISA kits. The PI3K/AKT/NF-κB and HO-1 signaling pathways were examined by western blot analysis. The results showed that alpinetin significantly ameliorated OVA-induced pathologic changes of lungs, such as decreasing massive inflammatory cell infiltration and mucus hypersecretion, and reduced the number of inflammatory cells in BALF. Alpinetin also decreased the OVA-induced levels of IL-4, IL-5, IL-13 and IgE. Furthermore, alpinetin inhibited OVA-induced phosphorylation of p65, IκB, PI3K and AKT, and the activity of HO-1 in vivo. More importantly, these anti-inflammatory effects and molecular mechanisms of alpinetin has also been confirmed in LPS-stimulated RAW 264.7 macrophages in vitro. In conclusion, above results indicate that alpinetin exhibites a potent anti-inflammatory activity in allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways, which would be used as a promising therapy agent for allergic asthma.
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Affiliation(s)
- Di Wu
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Shuangqiu Li
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Xiao Liu
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Jingnan Xu
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Aimin Jiang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Yong Zhang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Ziyi Liu
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Jingjing Wang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China
| | - Ershun Zhou
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Zhengkai Wei
- College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China
| | - Zhengtao Yang
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China; College of Life Sciences and Engineering, Foshan University, Foshan 528225, Guangdong Province, PR China.
| | - Changmin Guo
- Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, PR China.
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