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Bifidobacterium breve CCFM1078 regulates bone development in growing BALB/c mice via gut microbiota and metabolites to balance bone formation and resorption

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Food Science and Human Wellness 2024年

作者： Bowen Li Mengfan Ding Xiaoming Liu Haiqin Chen Jianxin Zhao r.paul ross Catherine Stanton Shilong Jiang Wei Chen Bo Yang State Key Laboratory of Food Science and Technology， Jiangnan University School of Food Science and Technology， Jiangnan University International Joint research Center for Probiotics & Gut Health， Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food research Centre Nutrition and Metabolism research Division， Innovation Center， Heilongjiang Feihe Dairy Co.， Ltd. PKUHSC-China Feihe Joint research Institute of Nutrition and Healthy Lifespan Development National Engineering research Center for Functional Food， Jiangnan University

This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice. Newborn BALB/c mice were assigned to the control group (administration saline) and the CCFM1078 group (administration B. breve CCFM1078， 3 × 109CFU/day) in 3-， 4-， and 5-week tests. All the groups have male and female distinctions. Our findings demonstrate that B. breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites (hexadecanamide， linoleoyl ethanolamide， and palmitoyl ethanolamide)， the genes and proteins expression related to the GH/IGF-1 axis and Gs/PKA/CrEB signaling pathways， as well as downstream osteogenic and osteoclastic differentiation factors. The effects of B. breve CCFM1078 were different with age and gender dependent. This finding suggests B. breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.

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Bifidobacterium longum subsp. infantis CCFM1269 promotes intestinal barrier and release of IFN-β through TLr4-TrIF dependent way in growing mice

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Food Science and Human Wellness 2024年

作者： Mengfan Ding Bo Yang Bowen Li Haiqin Chen renqiang Yu r.paul ross Catherine Stanton Shilong Jiang Jianxin Zhao Wei Chen State Key Laboratory of Food Science and resources， Jiangnan University School of Food Science and Technology， Jiangnan University International Joint research Center for Probiotics & Gut Health， Jiangnan University Department of Neonatology， Wuxi Maternity and Child Health Care Hospital， Affiliated Women's Hospital of Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food research Centre Nutrition and Metabolism research Division， Innovation Center， Heilongjiang Feihe Dairy Co.， Ltd. PKUHSC-China Feihe Joint research Institute of Nutrition and Healthy Lifespan Development National Engineering research Center for Functional Food， Jiangnan University

Bifidobacterium longum subsp. infantis is a commensal bacterium that predominates in the infant gut， playing a critical role in both preventing foreign infections and facilitating immune development. This study aimed to explore the effects of B. longum subsp. infantis supplementation on interferon-beta (IFN-β) secretion and intestinal barrier improvement in growing mice. Female and male mice were orally administered either saline or B. longum subsp. infantis CCFM1269 or I5TI (1 × 109CFU/mice per day， n = 8) from 1-week-age until 3-， 4-， and 5-week-age. rNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2’-5’ oligoadenylate synthetase (OAS). Additionally， CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLr4-TrIF-dependent signaling pathway. However， this effect was not observed in 4- and 5-week-old mice. Furthermore， both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-， 4-， and 5-week-old mice. In summary， the results of this study suggested that B. longum subsp. infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.

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Limosilactobacillus mucosae FZJTZ26M3 prevents NAFLD in mice through modulation of lipid metabolism and gut microbiota dysbiosis

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Food Science and Human Wellness 2024年第3期13卷 1589-1601页

作者： Danting Dang Bowen Li Mengfan Ding rpaul ross Catherine Stanton Jianxin Zhao Bo Yang Wei Chen State Key Laboratory of Food Science and resources Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China International Joint research Center for Probiotics&Gut Health Jiangnan UniversityWuxi 214122China APC Microbiome Ireland University College CorkCork T12 YT20Ireland Teagasc Food research Centre MooreparkFermoyCork T12 YT20Ireland National Engineering research Center for Functional Food Jiangnan UniversityWuxi 214122China

Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this ***-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).*** FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of *** to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after *** FZJTZ26M3 *** pathology showed that *** FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD ***,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that *** FZJTZ26M3 could alleviate NAFLD by regulating lipid ***,the results of 16S rrNA gene sequencing revealed a drop in the relative abundance of ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after *** FZJTZ26M3 ***,*** FZJTZ26M3 could be a candidate to prevent NAFLD.

关键词： Limosilactobacillus mucosae Nonalcoholic fatty liver disease(NAFLD) Probiotic Lipid metabolism Gut microbiota

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Protective effects of Bifi dobacterium breve on imiquimod-induced psoriasis in mice through secondary bile acid production and FXr-TLr4/NF-κB pathway

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Food Science and Human Wellness 2024年第6期13卷 3447-3460页

作者： Xinqi Chen Yang Chen Catherine Stanton rpaul ross Jianxin Zhao Bo Yang Wei Chen State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China International Joint research Center for Probiotics&Gut Health Jiangnan UniversityWuxi 214122China APC Microbiome Ireland University College CorkCork T12 YT20Ireland Teagasc Food research Centre Cork T12 YT20Ireland National Engineering research Center for Functional Food Jiangnan UniversityWuxi 214122China

This study aimed to evaluate the effects of Bifi dobacterium breve CCFM683 on psoriasis and to investigate the underlying *** CCFM683 significantly ameliorated psoriasis in mice as well as elevated the deoxycholic acid(DCA)and lithocholic acid(LCA)in the colon compared with those of the imiquimod(IMQ)-treated ***,*** CCFM683 increased the relative abundance of DCA-producing Lachnoclostridium and diminished the harmful Desulfovibrio and Prevotellaceae ***,the farnesoid X receptor(FXr)in the skin was activated and the expression of the Toll-like receptor 4(TLr4)/nuclear factor kappa-B(NF-κB)pathway was inhibited,and the downstream interleukin(IL)-17 and tumor necrosis factor(TNF)-αwere downregulated whereas IL-10 was ***,the subsequent hyperproliferation of keratinocytes and the dysfunction of the epidermal barrier were *** conclusion,CCFM683 administration ameliorated IMQ-induced psoriasis via modulating gut microbiota,promoting the DCA production,regulating the FXr-TLr4/NF-κB pathway,diminishing proinflammatory cytokines,and regulating keratinocytes and epidermal *** findings may be conducive to elucidating the mechanism for probiotics to ameliorate psoriasis and to promote its clinical trials in skin disease.

关键词： Psoriasis Bifi dobacterium breve Gut microbiota Secondary bile acids FXr-TLr4/NF-κB pathway

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Molecularly targeted therapy for advanced hepatocellular carcinoma-a drug development crisis?

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World Journal of Gastrointestinal Oncology 2016年第2期8卷 173-185页

作者： Kiruthikah Thillai paul ross Debashis Sarker department of medical oncology guy’s and st thomas nhs trustLondon SE1 9RTUnited Kingdom division of cancer studies king’s college londonguy’s hospitalLondon SE1 9RTUnited Kingdom institute of liver studies king’s college hospital nhs trustLondon SE5 9RSUnited Kingdom

Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib,a multitargeted kinase inhibitor,is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer(HCC),this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase Ⅲ clinical trials of novel molecularly targeted therapies,warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity,trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC.

关键词： Hepatocellular carcinoma Molecular targets Genomics Sorafenib Tyrosine kinase inhibitors

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

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World Journal of Hepatology 2022年第4期14卷 754-765页

作者： ross Apostolov Emily Gianatti Darren Wong Numan Kutaiba paul Gow Mathis Grossmann Marie Sinclair Department of Gastroenterology and Liver Transplant Unit Austin HealthHeidelberg 3084VICAustralia Department of Medicine University of MelbourneParkville 3010VICAustralia Department of Endocrinology Fiona Stanley HospitalMurdoch 6150WAAustralia Department of radiology Austin HealthHeidelberg 3084VICAustralia Department of Endocrinology Austin HealthHeidelberg 3084VICAustralia

BACKGrOUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available *** To explore the effect of testosterone treatment on *** therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly *** This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MrI).rESULTS Of 88 patients enrolled in the index study,39 had liver MrIs of whom 20 received testosterone therapy and 19 received *** patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for *** liver fat at baseline was 15.0%(IQr 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo *** ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo *** week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQr 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%Pr controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,Prone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum *** randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

关键词： Hepatic steatosis Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Testosterone therapy Testosterone undecanoate Type 2 diabetes

Progress in pancreatic cancer therapeutics: The potential to exploit molecular targets

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World Journal of Pharmacology 2015年第2期4卷 180-192页

作者： Kiruthikah Thillai Debashis Sarker.paul ross Department of Medical Oncology Guy's and St Thomas NHS Trust

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be *** many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a signifcant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.

关键词： Pancreatic cancer Adenocarcinoma Targeted therapy Genomics Stroma KrAS Chemotherapy

reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients

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World Journal of Transplantation 2022年第6期12卷 120-130页

作者： Penelope Hey rudolf Hoermann paul Gow Timothy P Hanrahan Adam G Testro ross Apostolov Marie Sinclair Liver Transplant Unit Austin HealthHeidelberg 3084Australia Department of Medicine University of MelbourneMelbourne 3052Australia

BACKGrOUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation *** limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for *** To investigate the use of DEXA LM in predicting gender-stratified early posttransplant *** Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were *** included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACr)and intensive care and total hospital length of *** Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score *** time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males *** was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in *** women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of *** composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either *** were no significant predictors of early *** Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with *** upper limb LM provides a novel measure of muscle wasting that has prognostic value in this *** lack of association in women req

关键词： Dual-energy X-ray absorptiometry Sarcopenia Body composition Liver transplantation Survival

Infant feces-derived Bifidobacterium breve CCFM1078 inhibits the occurrence of rheumatoid cachexia by IrS1/PI3K/Akt signaling pathway

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Food Science and Human Wellness 2024年

作者： Bowen Li Mengfan Ding Chen Chi Guoxun Shi Xiaoming Liu Jianxin Zhao paul ross Catherine Stanton Wei Chen Bo Yang State Key Laboratory of Food Science and resources， Jiangnan University School of Food Science and Technology， Jiangnan University Department of rheumatology， Jiangnan University Medical Center International Joint research Center for Probiotics & Gut Health， Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food research Centre National Engineering research Center for Functional Food， Jiangnan University

This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia （rC）. Twenty-four female Wistar rats were assigned to three groups: CON group （normal saline by gavage）， CIA group （collagen-induced arthritis， normal saline by gavage）， and CCFM1078 group (collagen-induced arthritis， 3×109CFU/rat/day B breve CCFM1078 gavage). The results demonstrated that B. breve CCFM1078 not only improved skeletal muscle function in CIA rats， but also modulated the gut microbiota， skeletal muscle metabolism and hormone levels， reduced inflammation in the knee joint and skeletal muscles， decreased activity of the NF-κB inflammatory signaling pathway， enhanced the IrS1/PI3K/Akt signaling pathway， promoted skeletal muscle differentiation， and maintained skeletal muscle fiber diameter， consequently slowing down the progression of rC. These findings suggested that B. breve CCFM1078 may have a beneficial role as part of a dietary intervention for rC， enhancing overall therapeutic effects.

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