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Dos Santos TG, Dos Santos KAG, de Oliveira EJF, Brenig B, Paulo EM, Marques PH, Cardoso VN, Aburjaile FF, Soares SC, da Silva WM, Azevedo V, Carvalho RDDO. Genomic Scale Analysis Foresees Enteroprotective and Butyrogenic Properties in Brazilian Isolates of Lactiplantibacillus plantarum. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10495-5. [PMID: 40009329 DOI: 10.1007/s12602-025-10495-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2025] [Indexed: 02/27/2025]
Abstract
Probiogenomics offers a rapid and comprehensive approach to characterizing the beneficial properties of microorganisms, allowing the identification and selection of specific strains for improving human health. The species Lactiplantibacillus plantarum is highly ubiquitous and presents great genetic diversity making it difficult to conduct massive screening of probiotic strains when using conventional methods. Hence, this work aimed to taxonomically and functionally characterize the complete genomes of six novel L. plantarum strains isolated in Brazil through high-standard NGS. The taxonomy of strains E6, E10, E14, E18, Lpl2, and Lpl4 was investigated through average nucleotide identity analysis using the genome of L. plantarum SK151 from the GENBANK database as a reference. Moreover, multilocus phylogenetic analyses were performed to investigate their genetic relatedness to probiotic L. plantarum strains using a total of 225 complete genomes from the same database. To investigate specific health-promoting and safety properties, the isolates from Brazil were analyzed using several bioinformatic tools to predict antimicrobials and anti-inflammatory biomolecules and potential risk factors including drug resistance, virulence genes, and genetic mobility elements. The results confirmed that all six isolates belong to the species L. plantarum and the phylogenetic analysis suggests high proximity to known probiotics and strains that have demonstrated protective effects against inflammation and pathogens. Several bacteriocin genes were identified in the Brazilian isolates, mostly plantaricins, suggesting antimicrobial properties, especially in the strain E14 that presented 9 bacteriocins genes. Furthermore, the study revealed the potential capacity of these strains to produce anti-inflammatory compounds including metabolites such as butyrate through the fermentation of fructan sugars, and IL-10 stimulation activity mediated by adhesin proteins from the bacterial cell wall. The lpl4 strain glutamate decarboxylase (GADB) gene showed a high degree of genetic and structural conservation prediction and increased stabilization of the predicted protein compared to a functional homologous GADB from L. plantarum Taj-Apis362, suggesting lpl4 potential for the modulation of the gut-brain axis functions by the production of GABA. Regarding the presence of virulence and resistance genes, only one resistance island was observed in strain E6 genome. In conclusion, it is possible to suggest that most of the evaluated strains are safe and we highlight the strains Lpl4 and E14 for presenting outstanding enteroprotective properties such as the potential production of GABA and several bacteriocins.
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Affiliation(s)
- Thayra Gomes Dos Santos
- Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil
| | | | | | - Bertram Brenig
- Institute of Veterinary Medicine, University of Göttingen, Göttingen, Germany
| | - Elinalva Maciel Paulo
- Laboratory of Applied Microbiology and Public Health, State University of Feira de Santana, Feira de Santana, Brazil
| | - Pedro Henrique Marques
- Department of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Valbert Nascimento Cardoso
- Laboratory of Radioisotopes, Department of Clinical Analysis and Toxicology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Flávia Figueira Aburjaile
- Preventive Veterinary Medicine Departament, Veterinary School, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Siomar Castro Soares
- Department of Microbiology, Immunology and Parasitology, Federal University of Triangulo Mineiro, Uberaba, Brazil
| | | | - Vasco Azevedo
- Department of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Rodrigo Dias de Oliveira Carvalho
- Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.
- Department of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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Srirangan P, Sabina EP. Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach. Drug Chem Toxicol 2025:1-43. [PMID: 39847469 DOI: 10.1080/01480545.2025.2455442] [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: 07/09/2024] [Revised: 12/24/2024] [Accepted: 01/14/2025] [Indexed: 01/25/2025]
Abstract
Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, and its resulting organ-specific toxicities. Despite its clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian cancer, and other diseases, CPM is associated with significant adverse effects on the kidneys, liver, heart, lungs, and intestines. The discussion delves into the molecular mechanisms underlying these toxicities, highlighting dysregulation in key signaling pathways, including Nrf2, NF-κB, MAPK/ERK, and AKT. In addressing these challenges, recent studies have identified various herbal drugs and phytochemicals capable of mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, and curcumin have demonstrated protective effects. Integrating these herbal formulations with CPM therapy is proposed to enhance patient safety and treatment efficacy. This review underscores the influence of CPM on apoptosis and inflammation pathways, which lead to alterations in organ-specific biomarkers. Phytochemicals may exert protective effects by restoring disrupted signaling pathways and normalizing altered biomarkers. The compilation of phytochemicals presented in this review serves as a valuable resource for researchers exploring other herbal products with potential protective effects against CPM toxicity. A significant gap in the current literature is the lack of clinical trials evaluating phytochemicals that mitigate CPM toxicity in vivo. Rigorous clinical studies are necessary to establish the efficacy and safety of herbal formulations in cancer treatment. Such research will clarify the role of natural remedies in complementing conventional therapies, ultimately improving patient outcomes.
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Affiliation(s)
- Prathap Srirangan
- Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, India
| | - Evan Prince Sabina
- Department of Biotechnology, School of Biosciences and Technology, VIT University, Vellore, India
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Miao J, Cui L, Zeng H, Hou M, Wang J, Hang S. Lactiplantibacillus plantarum L47 and inulin affect colon and liver inflammation in piglets challenged by enterotoxigenic Escherichia coli through regulating gut microbiota. Front Vet Sci 2024; 11:1496893. [PMID: 39664894 PMCID: PMC11631943 DOI: 10.3389/fvets.2024.1496893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 11/07/2024] [Indexed: 12/13/2024] Open
Abstract
Introduction Infection by pathogenic bacteria during weaning is a common cause of diarrhea and intestinal inflammation in piglets. Supplementing the diet with synbiotics is beneficial for animal health. The strain of Lactiplantibacillus plantarum L47 (L47) isolated in our lab exhibited good probiotic properties when combined with inulin. Here, the effectiveness of combining L47 and inulin (CLN) in protecting against enterotoxigenic Escherichia coli (ETEC) induced colon and liver inflammation in weaned piglets was evaluated. Methods Twenty-eight piglets aged 21 days were randomly assigned into 4 groups: CON (control), LI47 (oral CLN culture fluid, 1010 CFU/d of L47 and 1 g/d of inulin), ECON (oral ETEC culture fluid, 1010 CFU/d), and ELI47 (oral CLN and ETEC culture fluid). After 24 days, the colon and liver samples were collected for further analysis. Results and discussion CLN alleviated colon damage caused by ETEC challenge, as evidenced by an increase of colonic crypt depth, mRNA expression of tight junction Claudin-1 and Occludin, GPX activity, the concentration of IL-10 and sIgA (p < 0.05). Moreover, there was a decrease in MDA activity, the load of E. coli, the concentration of LPS, gene expression of TLR4, and the concentration of TNF-α and IL-6 (p < 0.05) in colonic mucosa. Additionally, CLN counteracted liver damage caused by ETEC challenge by modulating pathways associated with immunity and disease occurrence (p < 0.05). Conclusion Supplementing with CLN alleviated colon inflammation induced by ETEC challenge by decreasing the E. coli/LPS/TLR4 pathway and regulating hepatic immune response and disease-related pathways, suggesting that CLN could protect intestinal and liver health in animals.
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Affiliation(s)
| | | | | | | | | | - Suqin Hang
- Laboratory of Gastrointestinal Microbiology, National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, China
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Rezaie N, Aghamohammad S, Haj Agha Gholizadeh Khiavi E, Khatami S, Sohrabi A, Rohani M. The preventive effects of native probiotic and postbiotic on inflammation and oxidative stress in DSS-induced colitis with normal diet: Which of these agents may offer greater advantages? Heliyon 2024; 10:e37279. [PMID: 39296101 PMCID: PMC11408073 DOI: 10.1016/j.heliyon.2024.e37279] [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: 06/07/2024] [Revised: 08/28/2024] [Accepted: 08/30/2024] [Indexed: 09/21/2024] Open
Abstract
Background Maintaining a well-rounded and healthy diet is essential to promote the well-being and optimal performance of the body, especially for those suffering from Inflammatory Bowel Disease (IBD). The objective of this study is to examine whether probiotics and postbiotics can modulate oxidative stress and inflammation, and to evaluate the properties of these compounds. Methods A total of eighty eight strains of Lactobacillus and Bifidobacterium were assessed for their antioxidant activities. C57BL/6 mice were allocated into four groups: normal diet (ND) + PBS, ND + DSS, ND + DSS + 10⁹ cfu/ml of probiotics, and ND + DSS + 10⁹ cfu/ml of postbiotics. Biochemical antioxidant assays, along with colitis indices, were evaluated. The ELISA assay was conducted to measure oxidant/antioxidant properties and cytokines. Additionally, the genes enrolled in NF-kB and Nrf2 signaling pathways was analyzed. Results In comparison to the groups exposed to DSS alone, mice that received our native agents in addition to DSS demonstrated an improvement in the negative effects induced by DSS on DAI and pathological scores, as well as on colon length and body weight. The levels of cytokines and antioxidant markers have also been normalized following the administration of our native agents, along with molecular markers. It should also be noted that our native postbiotic was able to develop more pronounced and significant anti-inflammatory and antioxidant effects in comparison to the probiotic strains. Conclusion In this study, our native postbiotic has demonstrated a more pronounced ability to exhibit antioxidant and anti-inflammatory effects. This finding is particularly important for individuals with impaired immune function, for whom the use of live bacteria could be risky. Therefore, the utilization of agents like probiotics and postbiotics, which come with minimal side effects in compared to chemical drugs, could be essential in managing symptoms in IBD patients.
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Affiliation(s)
- Niloofar Rezaie
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | | | | | - Shohreh Khatami
- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
| | - Aria Sohrabi
- Department of Epidemiology and Biostatistics, Research Centre for Emerging and Re-emerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran
| | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
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Saghir SAM, Al Hroob AM, Al-Tarawni AH, Abdulghani MAM, Tabana Y, Aldhalmi AK, Mothana RA, Al-Yousef HM. Effect of Lactiplantibacillus plantarum on the growth, hemato-biochemical, inflammation, apoptosis, oxidative stress markers, involved gens and histopathological alterations in growing rabbits challenged with aflatoxin B1. Poult Sci 2024; 103:104002. [PMID: 39053371 PMCID: PMC11320459 DOI: 10.1016/j.psj.2024.104002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 06/03/2024] [Accepted: 06/19/2024] [Indexed: 07/27/2024] Open
Abstract
Aflatoxin B1 (AFB1) is a significant pollutant found in food and feed, posing a threat to public health. The objective of this study was to assess the effect of Lactiplantibacillus plantarum (LACP) against AFB1 in growing rabbits by investigating growth, serum metabolites, immunity, antioxidant capacity, and inflammatory response. A total of 60 growing male rabbits (721.5 ± 2.68g) were allocated to 4 experimental groups. The control group receiving only a basal diet, the AFB1 group (0.3 mg AFB1/kg diet), the LACP group (1 × 109 cfu/g /kg diet), and the combination group (1 × 109 cfu/g + 0.3 mg AFB1/kg diet; AFB1+ LACP) for 8 wk. The administration of AFB1 alone significantly decreased the final body weight, body gain, and feed intake, while significantly increasing the feed conversion ratio (P < 0.05). A significant decline in total proteins and globulins, along with elevated levels of hepatic enzymes (AST, ALP, ALT, and GGT) and renal function markers (creatinine and uric acid), were observed in the AFB1-contaminated group (P < 0.05). Immunoglobulins (IgG and IgM) were significantly decreased, alongside a significant elevation of triglycerides, direct bilirubin, and indirect bilirubin in growing rabbits fed diets with AFB1 (P < 0.05). Supplementing the AFB1 diet with LACP restored the growth reduction, improved liver (AST, ALP, ALT, and GGT) and kidney (creatinine and uric acid) functions, and enhanced immune markers in rabbit serum (P < 0.05). Antioxidant indices (SOD, GSH, and CAT) were significantly decreased in the AFB1 group (P < 0.05). However, the addition of LACP to the AFB1-contaminated diets improved antioxidant capacity and malondialdehyde (MDA) and protein carbonylation (PC) in hepatic tissues of rabbits (P < 0.05). Serum interlukin-4 (IL-4) and interferon gamma (IFN-γ) levels were significantly increased in the AFB1 group (P < 0.05), but the addition of LACP significantly reversed this elevation. AFB1 downregulated the expression of immune-inflammatory genes such Nrf2, IL-10, and BCL-2 genes, while up-regulating the caspase-3 (CASP3) gene (P < 0.05). Supplementing AFB1 diet with LACP significantly decreased the expression of immune-inflammatory genes (Nrf2, IL-10, and BCL-2) and reduced the expression of the apoptotic-related gene CASP3. This study highlights the potential of L. plantarum (1 × 109 cfu/g /kg diet) as a protective agent against AFB1 in growing rabbits by enhancing antioxidant and immune function and reducing apoptosis and inflammation pathways.
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Affiliation(s)
- Sultan A M Saghir
- Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Medical Sciences, Al-Hussein Bin Talal University, Ma'an 71111, Jordan.
| | - Amir M Al Hroob
- Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Medical Sciences, Al-Hussein Bin Talal University, Ma'an 71111, Jordan
| | - Ayat H Al-Tarawni
- Department of Biological Sciences, Mutah University, Mutah, Al-Karak 61710, Jordan
| | - Mahfoudh A M Abdulghani
- Pharmacology Department, International Medical School Management and Science University, Shah Alam, Selangor 40100, Malaysia
| | - Yasser Tabana
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton AB T6G 2E1, Canada; Department of Biochemistry, University of Alberta, Edmonton, AB, Canada
| | - Ahmed K Aldhalmi
- College of Pharmacy, Al- Mustaqbal University, 51001 Babylon, Iraq
| | - Ramzi A Mothana
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Hanan M Al-Yousef
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
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Guo Z, He K, Pang K, Yang D, Lyu C, Xu H, Wu D. Exploring Advanced Therapies for Primary Biliary Cholangitis: Insights from the Gut Microbiota-Bile Acid-Immunity Network. Int J Mol Sci 2024; 25:4321. [PMID: 38673905 PMCID: PMC11050225 DOI: 10.3390/ijms25084321] [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: 03/13/2024] [Revised: 04/05/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the effectiveness of conventional immunosuppressive therapy is disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and evidence is increasing that gut microbiota and bile acids play an important role in the pathogenesis of cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Autoimmune cholangitis has the potential to be improved through immune system modulation. Considering the failure of conventional immunotherapies and the involvement of gut microbiota and bile acids in the pathogenesis, targeting immune factors associated with them, such as bile acid receptors, microbial-derived molecules, and related specific immune cells, may offer breakthroughs. Understanding the gut microbiota-bile acid network and related immune dysfunctions in PBC provides a new perspective on therapeutic strategies. Therefore, we summarize the latest advances in research of gut microbiota and bile acids in PBC and, for the first time, explore the possibility of related immune factors as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.
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Affiliation(s)
- Ziqi Guo
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; (Z.G.); (K.P.); (D.Y.)
| | - Kun He
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; (K.H.); (C.L.)
| | - Ke Pang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; (Z.G.); (K.P.); (D.Y.)
| | - Daiyu Yang
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; (Z.G.); (K.P.); (D.Y.)
| | - Chengzhen Lyu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; (K.H.); (C.L.)
| | - Haifeng Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Dong Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; (K.H.); (C.L.)
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Mukherjee A, Breselge S, Dimidi E, Marco ML, Cotter PD. Fermented foods and gastrointestinal health: underlying mechanisms. Nat Rev Gastroenterol Hepatol 2024; 21:248-266. [PMID: 38081933 DOI: 10.1038/s41575-023-00869-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/01/2023] [Indexed: 12/20/2023]
Abstract
Although fermentation probably originally developed as a means of preserving food substrates, many fermented foods (FFs), and components therein, are thought to have a beneficial effect on various aspects of human health, and gastrointestinal health in particular. It is important that any such perceived benefits are underpinned by rigorous scientific research to understand the associated mechanisms of action. Here, we review in vitro, ex vivo and in vivo studies that have provided insights into the ways in which the specific food components, including FF microorganisms and a variety of bioactives, can contribute to health-promoting activities. More specifically, we draw on representative examples of FFs to discuss the mechanisms through which functional components are produced or enriched during fermentation (such as bioactive peptides and exopolysaccharides), potentially toxic or harmful compounds (such as phytic acid, mycotoxins and lactose) are removed from the food substrate, and how the introduction of fermentation-associated live or dead microorganisms, or components thereof, to the gut can convey health benefits. These studies, combined with a deeper understanding of the microbial composition of a wider variety of modern and traditional FFs, can facilitate the future optimization of FFs, and associated microorganisms, to retain and maximize beneficial effects in the gut.
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Affiliation(s)
| | - Samuel Breselge
- Teagasc Food Research Centre, Moorepark, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Eirini Dimidi
- Department of Nutritional Sciences, King's College London, London, UK
| | - Maria L Marco
- Department of Food Science & Technology, University of California, Davis, CA, USA
| | - Paul D Cotter
- Teagasc Food Research Centre, Moorepark, Cork, Ireland.
- APC Microbiome Ireland, Cork, Ireland.
- VistaMilk, Cork, Ireland.
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Hajian H, Motallebi M, Akhavan Taheri M, Kheiripour N, Aghadavod E, Shahaboddin ME. The preventive effect of heat-killed Lactobacillus plantarum on male reproductive toxicity induced by cholestasis in rats. Food Chem Toxicol 2024:114571. [PMID: 38452966 DOI: 10.1016/j.fct.2024.114571] [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: 11/07/2023] [Revised: 02/23/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024]
Abstract
This study investigated the preventive effect of heat-killed Lactobacillus plantarum (L. plantarum) on cholestasis-induced male reproductive toxicity in rats. Rats were divided into control normal, sham control, bile duct ligation (BDL) control, and BDL with heat-killed L. plantarum supplementation groups. The effects on sexual hormones, testicular and epididymal histology, sperm parameters, oxidative stress markers, and inflammatory gene expression were evaluated. Compared to the BDL control group, the BDL + heat-killed L. plantarum group showed higher levels of normal sperm, luteinizing hormone, testosterone, total antioxidant capacity, and catalase activity, indicating improved reproductive function. Conversely, markers of oxidative stress, such as total oxidative status, oxidative stress index, and carbonyl protein, were lower in the BDL + heat-killed L. plantarum group. The expression levels of inflammatory genes tumor necrosis factor-alpha and interleukin-6 were reduced, while interleukin-10 gene expression was increased in the BDL + heat-killed L. plantarum group. Histological evaluation confirmed the positive effects of heat-killed L. plantarum intervention on testicular parameters. In conclusion, heat-killed L. plantarum supplementation protects against cholestasis-induced male reproductive dysfunction in rats, as evidenced by improvements in hormonal balance, sperm quality, oxidative stress, and inflammation.
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Affiliation(s)
- Hajar Hajian
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mitra Motallebi
- Department of Immunology and Microbiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Maryam Akhavan Taheri
- Institute for Basic Sciences, Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Nejat Kheiripour
- Institute for Basic Sciences, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Esmat Aghadavod
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Esmaeil Shahaboddin
- Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran; Institute for Basic Sciences, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
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Lee DY, Shin JW, Shin YJ, Han SW, Kim DH. Lactobacillus plantarum and Bifidobacterium longum Alleviate Liver Injury and Fibrosis in Mice by Regulating NF-κB and AMPK Signaling. J Microbiol Biotechnol 2024; 34:149-156. [PMID: 38105432 PMCID: PMC10840473 DOI: 10.4014/jmb.2310.10006] [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: 10/06/2023] [Revised: 11/14/2023] [Accepted: 11/22/2023] [Indexed: 12/19/2023]
Abstract
In a preliminary study, live biotherapeutic products (LBPs) Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 inhibited the secretion of alanine transaminase (ALT) and aspartate transaminase (AST) in LPS-stimulated HepG2 cells, while Escherichia coli K1 (Ec) increased ALT and ALT secretion. Therefore, we examined the effects of LC27 and LC67 on LPS-induced liver injury and fibrosis in mice and the correlation between their biomarkers in cell and animal experiments. Orally administered LC27 or LC67 significantly decreased blood ALT, AST, γ-glutamyl transferase (γGTP), TNF-α, triglyceride (TG), total cholesterol (TCh), total bile acid, and LPS levels, liver TNF-α, toll-like receptor-4 gene (Tlr4), α-smooth muscle actin (αSMA), and collagen-1 expression and αSMA+GFAP+ and NF-κB+F4/80+ cell populations, and colonic Tlr4, TNF-α, and IL-6 expression and NF-κB-positive cell population in LPS-treated mice. Furthermore, they increased AMPKa phosphorylation in the liver and colon. However, Ec increased the expression of TNF-α and IL-6 in blood, liver, and colon. The suppression of LPS-stimulated ALT and AST secretion in HepG2 cells by LBPs was positively correlated with their ameliorating effects on LPS-induced blood γGTP, ALT, and AST levels and liver αSMA and collagen-1 expression in mice. Based on these findings, LC27 and LC67 may improve liver injury and fibrosis by regulating NF-κB and AMPK signaling pathway and a protocol that can assay the inhibitory activity of LBPs on LPS-induced ALT and AST secretion in HepG2 may be useful for guessing their antihepatitic effects in the in vivo experiments.
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Affiliation(s)
- Dong-Yun Lee
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Jung-Woo Shin
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Yoon-Jung Shin
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Seung-Won Han
- PB Department, NVP Healthcare, Inc., Suwon 16209, Republic of Korea
| | - Dong-Hyun Kim
- Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea
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Gao C, Wei J, Lu C, Wang L, Dong D, Sun M. A new perspective in intestinal microecology: lifting the veil of exercise regulation of cardiometabolic diseases. Gut Microbes 2024; 16:2404141. [PMID: 39305272 PMCID: PMC11418258 DOI: 10.1080/19490976.2024.2404141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 09/02/2024] [Accepted: 09/09/2024] [Indexed: 09/25/2024] Open
Abstract
Cardiometabolic diseases (CMDs), encompassing cardiovascular and metabolic dysfunctions, characterized by insulin resistance, dyslipidemia, hepatic steatosis, and inflammation, have been identified with boosting morbidity and mortality due to the dearth of efficacious therapeutic interventions. In recent years, studies have shown that variations in gut microbiota and its own metabolites can influence the occurrence of CMDs. Intriguingly, the composition and function of the gut microbiota are susceptible to exercise patterns, thus affecting inflammatory, immune, and metabolic responses within the host. In this review, we introduce the key mechanisms of intestinal microecology involved in the onset and development of CMDs, discuss the relationship between exercise and intestinal microecology, and then analyze the role of intestinal microecology in the beneficial effects of exercise on CMDs, aiming at elucidating the gut-heart axis mechanisms of exercise mediated protective effect on CMDs, building avenues for the application of exercise in the management of CMDs.
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Affiliation(s)
- Can Gao
- College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, P. R. China
| | - Jinwen Wei
- College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, P. R. China
| | - Changxu Lu
- College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, P. R. China
| | - Lijie Wang
- Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, P. R. China
| | - Dan Dong
- College of Basic Medical Science, China Medical University, Shenyang, Liaoning, P. R. China
| | - Mingli Sun
- College of Exercise and Health, Shenyang Sport University, Shenyang, Liaoning, P. R. China
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Zhang Y, Gao C, Zhu M, Chen F, Sun Y, Jiang Y, Zhou Q, Gao X. Astaxanthin, Haematococcus pluvialis and Haematococcus pluvialis Residue Alleviate Liver Injury in D-Galactose-induced Aging Mice through Gut-liver Axis. J Oleo Sci 2024; 73:729-742. [PMID: 38692895 DOI: 10.5650/jos.ess24003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024] Open
Abstract
Astaxanthin is a keto-based carotenoid mainly obtained from marine organisms, like Haematococcus pluvialis (H. pluvialis). Previous studies indicated the protective effects of Astaxanthin and H. pluvialis on aging related oxidative injury in liver, while the potential mechanisms are largely unknown. In addition, H. pluvialis residue is a by-product after astaxanthin extraction, which is rarely studied and utilized. The present study aimed to compare the effects of astaxanthin, H. pluvialis and H. pluvialis residue on the oxidant injury of liver in D-galactose-induced aging mice and explore the potential mechanisms through gut-liver axis. The results showed that all the three supplements prevented D-galactose-induced tissue injury, oxidative stress and chronic inflammation in liver and improved liver function. Gut microbiota analysis indicated that astaxanthin notably increased fecal levels of Bacteroidetes, unclassified_f__ Lachnospiraceae, norank_f__Lachnospiraceae, norank_f__norank_o__Clostridia_UCG-014, Prevotellaceae_ UCG-001, unclassified_f__Prevotellaceae in D-galactose-fed mice (p < 0.05). Compared to aging mice, H. pluvialis group had higher fecal levels of norank_f__Lachnospiraceae and Lachnospiraceae_UCG-006 (p < 0.05). H. pluvialis residue group displayed higher relative levels of Bacteroidetes, Streptococcus, and Rikenellaceae_RC9_gut_group (p < 0.05). Moreover, the production of fecal microbial metabolites, like SCFAs and LPS was also differently restored by the three supplements. Overall, our results suggest astaxanthin, H. pluvialis and H. pluvialis residue could prevent aging related hepatic injury through gutliver axis and provide evidence for exploiting of H. pluvialis residue as a functional ingredient for the treatment of liver diseases. Future studies are needed to further clarify the effect and mechanism of dominant components of H. pluvialis residue on liver injury, which is expected to provide a reference for the high-value utilization of H. pluvialis resources.
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Affiliation(s)
| | - Chunhao Gao
- College of Life Sciences, Qingdao University
| | - Mengjia Zhu
- College of Life Sciences, Qingdao University
| | - Fangtian Chen
- Department of Marine Technology, Rizhao Polytechnic; Shandong Engineering and Technology Research Center for Marine Crustacean Resources Comprehensive Utilization; Shandong Engineering Laboratory of Efficient Utilization Technology of Marine Food Resources; Rizhao Key Laboratory of Efficient Utilization of Marine Food Resources
| | - Yongye Sun
- Institute of Nutrition and Health, College of Public Health, Qingdao University
| | - Yu Jiang
- Experimental Animal Platform, Biomedical Center of Qingdao University, Qingdao University
| | - Qingxin Zhou
- Department of Marine Technology, Rizhao Polytechnic; Shandong Engineering and Technology Research Center for Marine Crustacean Resources Comprehensive Utilization; Shandong Engineering Laboratory of Efficient Utilization Technology of Marine Food Resources; Rizhao Key Laboratory of Efficient Utilization of Marine Food Resources
| | - Xiang Gao
- College of Life Sciences, Qingdao University
- Shandong Hongzai Biotechnology Co., LTD
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Lai X, Wu A, Bing Y, Liu Y, Luo J, Yan H, Zheng P, Yu J, Chen D. Retinoic acid protects against lipopolysaccharide-induced ferroptotic liver injury and iron disorders by regulating Nrf2/HO-1 and RARβ signaling. Free Radic Biol Med 2023; 205:202-213. [PMID: 37302616 DOI: 10.1016/j.freeradbiomed.2023.06.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/02/2023] [Accepted: 06/07/2023] [Indexed: 06/13/2023]
Abstract
Acute liver injury (ALI) can progress to severe liver diseases, making its prevention and treatment a focus of research. Retinoic acid (RA) has been shown to have anti-oxidative and iron-regulatory effects on organs. In this study, we investigated the effect of RA on lipopolysaccharide (LPS)-induced ALI in both in vivo and in vitro experiments. We found that RA significantly reduced LPS-induced serum iron and red blood cell-associated disorders, as well as decreased serum ALT and AST levels. RA also reversed the accumulation of non-heme iron and labile iron in LPS-induced mice and hepatocytes by increasing the expression of FTL/H and Fpn. Furthermore, RA inhibited tissue reactive oxygen species (ROS) and malondialdehyde (MDA) production and improved the expression of Nrf2/HO-1/GPX4 in mice and Nrf2 signaling in hepatocytes. In vitro experiments employing RAR agonists and antagonists have revealed that retinoic acid (RA) can effectively inhibit cell ferroptosis induced by lipopolysaccharide (LPS), erastin, and RSL3. The mechanism underlying this inhibition may involve the activation of retinoic acid receptors beta (RARβ) and gamma (RARγ). Knocking down the RARβ gene in Hepatocytes cells significantly diminished the RA's protective effect, indicating that the anti-ferroptotic role of RA was partially mediated by RARβ signaling. Overall, our study demonstrated that RA inhibited ferroptosis-induced liver damage by regulating Nrf2/HO-1/GPX4 and RARβ signaling.
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Affiliation(s)
- Xin Lai
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China
| | - Aimin Wu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Yu Bing
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Yao Liu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China
| | - Junqiu Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China
| | - Daiwen Chen
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China; Key Laboratory for Animal Disease-resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, China.
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Rizq AT, Sirwi A, El-Agamy DS, Abdallah HM, Ibrahim SRM, Mohamed GA. Cepabiflas B and C as Novel Anti-Inflammatory and Anti-Apoptotic Agents against Endotoxin-Induced Acute Kidney and Hepatic Injury in Mice: Impact on Bax/Bcl2 and Nrf2/NF-κB Signalling Pathways. BIOLOGY 2023; 12:938. [PMID: 37508369 PMCID: PMC10376508 DOI: 10.3390/biology12070938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/25/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023]
Abstract
Cepabiflas B and C (CBs) are flavonoid dimers separated from Allium cepa. They demonstrated antioxidant and α-glucosidase and protein tyrosine phosphatase 1B inhibition capacities. However, their anti-inflammatory activities and their effects on endotoxemia are unknown. The current study aimed at exploring the protective activities of CBs on lipopolysaccharide (LPS)-induced kidney and liver damage in mice and investigating the possible molecular mechanisms. Mice were orally treated with a low (40 mg/kg) or high (60 mg/kg) dose of CBs for five days prior to a single intraperitoneal injection of LPS (10 mg/kg). Samples of serum and hepatic and kidney tissues were collected 24 h after the LPS challenge. Changes in serum indices of hepatic and renal injury, pathological changes, molecular biological parameters, and proteins/genes related to inflammation and apoptosis of these organs were estimated. LPS injection resulted in deleterious injury to both organs as indicated by elevation of serum ALT, AST, creatinine, and BUN. The deteriorated histopathology of hepatic and renal tissues confirmed the biochemical indices. CBs treated groups showed a reduction in these parameters and improved histopathological injurious effects of LPS. LPS-induced hepatorenal injury was linked to elevated oxidative stress as indicated by high levels of MDA, 4-HNE, as well as repressed antioxidants (TAC, SOD, and GSH) in hepatic and kidney tissues. This was accompanied with suppressed Nrf2/HO-1 activity. Additionally, there was a remarkable inflammatory response in both organs as NF-κB signalling was activated and high levels of downstream cytokines were produced following the LPS challenge. Apoptotic changes were observed as the level and gene expression of Bax and caspase-3 were elevated along with declined level and gene expression of Bcl2. Interestingly, CBs reversed all these molecular and genetic changes and restricted oxidative inflammatory and apoptotic parameters after LPS-injection. Collectedly, our findings suggested the marked anti-inflammatory and anti-apoptotic activity of CBs which encouraged its use as a new candidate for septic patients.
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Affiliation(s)
- Akaber T Rizq
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Alaa Sirwi
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Dina S El-Agamy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Hossam M Abdallah
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Sabrin R M Ibrahim
- Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
| | - Gamal A Mohamed
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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Chen W, Du L, Cai C, Huang L, Zheng Q, Chen J, Wang L, Zhang X, Fang X, Wang L, Zhong Q, Zhong W, Wang J, Liao Z. Take chicks as an example: Rummeliibacillus stabekisii CY2 enhances immunity and regulates intestinal microbiota by degrading LPS to promote organism growth and development. J Funct Foods 2023; 105:105583. [DOI: 10.1016/j.jff.2023.105583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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15
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Bibi Z, Ashraf K, Shehzadi A, Rehman A, Abbas Bukhari D. Evaluation of isolated probiotics on the efficacy of immune system in male and female Wistar rats. Saudi Pharm J 2023; 31:1036-1046. [PMID: 37250360 PMCID: PMC10209143 DOI: 10.1016/j.jsps.2023.04.023] [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: 12/28/2022] [Accepted: 04/23/2023] [Indexed: 05/31/2023] Open
Abstract
Probiotics were isolated from fruits and vegetables. Microscopic, biochemical, and molecular tests were carried out for the characterization of strains of probiotics. To assess the effects of isolated probiotics on immunity, male and female (15 + 15) Wistar rats (n = 3) were randomly distributed into 5 groups: 0-day, negative control, positive control (commercially available Lactobacillus acidophilus-14), laboratory isolated probiotics with accession numbers; Lactobacillus plantarum (MZ707748) and Lactobacillus plantarum (MZ729681), respectively. After hematological investigations, the amounts of IgA and IgG in male and female groups were significantly different (p < 0.05). At the same time, the values of Alanine-transaminase (ALT) and Aspartate-aminotransferase (AST) in both genders were average, and there were no differences (p > 0.05). Male probiotic-treated groups had decreased levels of interleukin-6, bilirubin, and creatinine, but female probiotic-treated groups had a slight rise in bilirubin and creatinine values (p = 0.05). Cellular blood count levels of Hematocrit (HCT) and white blood cells (WBC) in male groups showed considerable differences (p < 0.05), while there were no differences (p > 0.05) in female groups. Levels of Red blood cells (RBC) and mean corpuscular hemoglobin concentration (MCHC) showed distinct changes (p < 0.05) in female groups, while these values were insignificant changes (p > 0.05) among male groups. There were considerable differences between the control and groups that were given probiotics. Histopathological results showed no damage to the liver and thymus. A fecal examination of rats was used to examine the viability and survival of Lactobacilli. Based on blood tests, it was observed that the immune system was boosted and improved in probiotic-treated groups compared to control groups.
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Affiliation(s)
- Zuhra Bibi
- Department of Zoology, Government College University, Lahore, Pakistan
| | - Khadija Ashraf
- Department of Zoology, Government College University, Lahore, Pakistan
| | - Areeba Shehzadi
- Department of Zoology, Government College University, Lahore, Pakistan
| | - Abdul Rehman
- Institute of Microbiology and Molecular Genetics, University of the Punjab, Quaid-e-Azam Campus, 54590 Lahore, Pakistan
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16
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Xu GX, Wei S, Yu C, Zhao SQ, Yang WJ, Feng YH, Pan C, Yang KX, Ma Y. Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions. Front Cell Dev Biol 2023; 11:1199519. [PMID: 37261074 PMCID: PMC10228659 DOI: 10.3389/fcell.2023.1199519] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 05/05/2023] [Indexed: 06/02/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yong Ma
- *Correspondence: Kun-Xing Yang, ; Yong Ma,
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17
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Zhang CY, Liu S, Yang M. Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy. World J Hepatol 2023; 15:180-200. [PMID: 36926234 PMCID: PMC10011909 DOI: 10.4254/wjh.v15.i2.180] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 11/30/2022] [Accepted: 02/09/2023] [Indexed: 02/24/2023] Open
Abstract
Chronic liver disease (CLD) is a continuous process that causes a reduction of liver function lasting more than six months. CLD includes alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), chronic viral infection, and autoimmune hepatitis, which can lead to liver fibrosis, cirrhosis, and cancer. Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD. Molecular signaling pathways such as AMP-activated protein kinase (AMPK), C-Jun N-terminal kinase, and peroxisome proliferator-activated receptors (PPARs) are implicated in the pathogenesis of CLD. Therefore, antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD, NAFLD, and hepatocellular carcinoma (HCC). In this review, we summarize some powerful products that can be potential applied in all the stages of CLD, from ALD/NAFLD to HCC. The selected agents such as β-sitosterol, curcumin, genistein, and silymarin can regulate the activation of several important molecules, including AMPK, Farnesoid X receptor, nuclear factor erythroid 2-related factor-2, PPARs, phosphatidylinositol-3-kinase, and lysyl oxidase-like proteins. In addition, clinical trials are undergoing to evaluate their efficacy and safety.
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Affiliation(s)
- Chun-Ye Zhang
- Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States
| | - Shuai Liu
- The First Affiliated Hospital, Zhejiang University, Hangzhou 310006, Zhejiang Province, China
| | - Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65211, United States
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Kasztelan-Szczerbinska B, Rycyk-Bojarzynska A, Szczerbinska A, Cichoz-Lach H. Selected Aspects of the Intricate Background of Immune-Related Cholangiopathies-A Critical Overview. Nutrients 2023; 15:760. [PMID: 36771465 PMCID: PMC9921714 DOI: 10.3390/nu15030760] [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: 01/10/2023] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are rare immune-related cholangiopathies with still poorly explained pathogenesis. Although triggers of chronic inflammation with subsequent fibrosis that affect cholangiocytes leading to obliteration of bile ducts and conversion to liver cirrhosis are unclear, both disorders are regarded to be multifactorial. Different factors can contribute to the development of hepatocellular injury in the course of progressive cholestasis, including (1) body accumulation of bile acids and their toxicity, (2) decreased food intake and nutrient absorption, (3) gut microbiota transformation, and (4) reorganized host metabolism. Growing evidence suggests that intestinal microbiome composition not only can be altered by liver dysfunction, but in turn, it actively impacts hepatic conditions. In this review, we highlight the role of key factors such as the gut-liver axis, intestinal barrier integrity, bile acid synthesis and circulation, and microbiome composition, which seem to be strongly related to PBC and PSC outcome. Emerging treatments and future therapeutic strategies are also presented.
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Affiliation(s)
- Beata Kasztelan-Szczerbinska
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 8 Jaczewski Street, 20-954 Lublin, Poland
| | - Anna Rycyk-Bojarzynska
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 8 Jaczewski Street, 20-954 Lublin, Poland
| | | | - Halina Cichoz-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, 8 Jaczewski Street, 20-954 Lublin, Poland
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19
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Influence on the aroma substances and functional ingredients of apple juice by lactic acid bacteria fermentation. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.102337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Li ZJ, Gou HZ, Zhang YL, Song XJ, Zhang L. Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value. World J Gastroenterol 2022; 28:6213-6229. [PMID: 36504550 PMCID: PMC9730442 DOI: 10.3748/wjg.v28.i44.6213] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 10/31/2022] [Accepted: 11/10/2022] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.
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Affiliation(s)
- Zhen-Jiao Li
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hong-Zhong Gou
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yu-Lin Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Xiao-Jing Song
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Lei Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
- Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
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