Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreati...Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.展开更多
OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabol...OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.展开更多
An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases.Fusobacterium nucleatum,a ubiquitous periodontitis-causing bacterium in the oral cavit...An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases.Fusobacterium nucleatum,a ubiquitous periodontitis-causing bacterium in the oral cavity,is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases,including cancers,cardiovascular diseases,and adverse pregnancy outcomes(APOs).F.nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a‘model species’for studying the impact of oral health on systemic health.The establishment and development of genetic manipulation tools for F.nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F.nucleatum.Here,we review the establishment and development of the genetic manipulation systems for F.nucleatum and summarize the characteristics of various genetic manipulation tools,such as suicide plasmid-based systems for gene inactivation,replicable plasmid-based systems controlling gene expression,and transposon-based random mutagenesis systems.Notably,we summarize and analyze their applications in the study of the pathogenic mechanisms of F.nucleatum.We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F.nucleatum and other Fusobacterium species.展开更多
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population.Given the increased incidence of cancer and the population ageing trend globally,it is very imp...Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population.Given the increased incidence of cancer and the population ageing trend globally,it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer.In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer(CAC),we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation,although ageing does not affect the incidence of AOM-induced,sporadic non-inflammatory CRC.Mechanistically,reduced fibroblasts were observed in the colitis microenvironment of ageing mice.Through conditional lineage tracing,an important source of fibroblasts potentially derived from intestinal smooth muscle cells(ISMCs)was identified orchestrating intestinal wound healing and CAC initiation in young mice.However,the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice,accompanied by decreased intestinal wound healing and decreased CAC initiation.ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments.We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts.Meanwhile,the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice.Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment,decreased intestinal wound healing and decreased CAC initiation,similar to the phenotype of ageing mice.In addition,the data from intestine samples derived from inflammatory bowel disease(IBD)patients show that activation of YAP/TAZ also occurs in ISMCs from these patients.Collectively,our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation.Furthermore,our work also identified a potential source of fibroblasts involved in colitis and CAC.展开更多
The prebiotic inulin has been vaunted for its potential to reduce the risk of colorectal cancer.Inulin fermentation resulting in the production of short-chain fatty acids,primarily butyrate,has been reported to be ass...The prebiotic inulin has been vaunted for its potential to reduce the risk of colorectal cancer.Inulin fermentation resulting in the production of short-chain fatty acids,primarily butyrate,has been reported to be associated with properties that are beneficial for gut health and has led to an increased consumption of inulin in the Western population through processed food and over-the-counter dietary supplements.However,in clinical trials,there is limited evidence of the efficacy of inulin in preventing colorectal cancer.Moreover,recent data suggest that improper inulin consumption may even be harmful for gastro-intestinal health under certain circumstances.The main objective of this review is to provide insight into the beneficial and potentially detrimental effects of inulin supplementation in the context of colorectal cancer prevention and enhancement of treatment efficacy.展开更多
Tumor-associated inflammation is an important component of the tumor microenvironment,and an important factor affecting tumor progression.In the tumor microenvironment,tumor-associated macrophages(TAMs)receive differe...Tumor-associated inflammation is an important component of the tumor microenvironment,and an important factor affecting tumor progression.In the tumor microenvironment,tumor-associated macrophages(TAMs)receive different stimuli and can be polarized into classically activated M1 macrophages and alternatively activated M2 macrophages.Many studies have indicated that the polarization of TAMs is closely related to tumor progression.展开更多
The burden of respiratory syncytial virus(RSV)disease is widely recognized.Main risk factors for severe disease,such as extreme ages,chronic cardiopulmonary conditions,and immunosuppression,typically coincide withpoor...The burden of respiratory syncytial virus(RSV)disease is widely recognized.Main risk factors for severe disease,such as extreme ages,chronic cardiopulmonary conditions,and immunosuppression,typically coincide withpoorer outcomes.While the majority of RSV hospitalizations involve healthy children,a higher proportion ofhospitalized adults with underlying conditions need intensive care.Presently,treatment primarily consists ofsupportive measures.RSV-induced wheezing should be distinguished from respiratory tract thickening,withoutresponse to bronchodilators.Obstructive RSV disease frequently overlaps with viral pneumonia.Non-invasivemechanical ventilation and high-flow oxygen therapy represented significant advancements in the managementof severe RSV disease in children and may also hold considerable importance in specific phenotypes of RSV diseasein adults.Most severe infections manifest with refractory hypoxemia necessitating more advanced ventilatorysupport and/or extracorporeal membrane oxygenation therapy.Although bacterial co-infection rates are low,they have been associated with worse outcomes.Antibiotic prescription rates are high.Accurately diagnosingbacterial co-infections remains a challenge.Current evidence and antibiotic stewardship policies advise againstindiscriminate antibiotic usage,even in severe cases.The role of currently developing antiviral therapies in severeRSV disease will be elucidated in the coming years,contingent upon the success of new vaccines and immunepassive strategies involving nirsevimab.展开更多
基金supported by the Russian Science Foundation(No.22-16-00128),“Investigation of the Toxic Effect of Glyphosates on the Functional State of the Bird Intestinal Microbial Community,Their Growth and Development,and the Development of a Biological Product Based on the Glyphosate Degrading Strain”.
文摘Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.
基金National Natural Science Foundation of China(81873059,82004016)。
文摘OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.
基金foundation support of the National Natural Science Foundation of China(82270980,82071122)the National Young Scientist Support Foundation(2019),the Major Innovation Projects in Shandong Province(2021SFGC0502)+2 种基金the Oral Microbiome Innovation Team of Shandong Province(2020KJK001)Shandong Province Key Research and Development Program(2021ZDSYS18)Intramural Joint Program Fund of State Key Laboratory of Microbial Technology(SKLMTIJP-2024-08)。
文摘An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases.Fusobacterium nucleatum,a ubiquitous periodontitis-causing bacterium in the oral cavity,is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases,including cancers,cardiovascular diseases,and adverse pregnancy outcomes(APOs).F.nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a‘model species’for studying the impact of oral health on systemic health.The establishment and development of genetic manipulation tools for F.nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F.nucleatum.Here,we review the establishment and development of the genetic manipulation systems for F.nucleatum and summarize the characteristics of various genetic manipulation tools,such as suicide plasmid-based systems for gene inactivation,replicable plasmid-based systems controlling gene expression,and transposon-based random mutagenesis systems.Notably,we summarize and analyze their applications in the study of the pathogenic mechanisms of F.nucleatum.We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F.nucleatum and other Fusobacterium species.
基金National Natural Science Foundation of China (No.81673662) The Program for Professor of Special Appointment (Eastern Scholar)+1 种基金Shuguang Scholar (No. 16SG36)Shanghai Institutions of Higher Learning from Shanghai Municipal Education Commission.
基金This study was supported by the National Natural Science Foundation of China Program grant(no.81972607,81772939)the National Key R&D Program of China grant(no.2022YFA1105602)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD20003).We thank Xinyue Hu for his contribution to the illustration in Fig.8.
文摘Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population.Given the increased incidence of cancer and the population ageing trend globally,it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer.In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer(CAC),we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation,although ageing does not affect the incidence of AOM-induced,sporadic non-inflammatory CRC.Mechanistically,reduced fibroblasts were observed in the colitis microenvironment of ageing mice.Through conditional lineage tracing,an important source of fibroblasts potentially derived from intestinal smooth muscle cells(ISMCs)was identified orchestrating intestinal wound healing and CAC initiation in young mice.However,the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice,accompanied by decreased intestinal wound healing and decreased CAC initiation.ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments.We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts.Meanwhile,the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice.Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment,decreased intestinal wound healing and decreased CAC initiation,similar to the phenotype of ageing mice.In addition,the data from intestine samples derived from inflammatory bowel disease(IBD)patients show that activation of YAP/TAZ also occurs in ISMCs from these patients.Collectively,our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation.Furthermore,our work also identified a potential source of fibroblasts involved in colitis and CAC.
基金supported by grants from the Canadian Institutes of Health Research[CIHR,grant PJT-159775]the Natural Sciences and Engineering Research Council of Canada[NSERC,grant RGPIN-2018-06442]to M.M.S.
文摘The prebiotic inulin has been vaunted for its potential to reduce the risk of colorectal cancer.Inulin fermentation resulting in the production of short-chain fatty acids,primarily butyrate,has been reported to be associated with properties that are beneficial for gut health and has led to an increased consumption of inulin in the Western population through processed food and over-the-counter dietary supplements.However,in clinical trials,there is limited evidence of the efficacy of inulin in preventing colorectal cancer.Moreover,recent data suggest that improper inulin consumption may even be harmful for gastro-intestinal health under certain circumstances.The main objective of this review is to provide insight into the beneficial and potentially detrimental effects of inulin supplementation in the context of colorectal cancer prevention and enhancement of treatment efficacy.
基金supported by the National Natural Science Foundation of China(No.81902435)Natural Science Foundation of Fujian Province of China(No.2021J011371)+4 种基金Sichuan Science and Technology Program of China(No.2021YFS0375,2023NSFSC1899)Science and technology project of Henan Province,China(No.222102310037)Henan Province Medical Science and Technology Project of China(No.LHGJ20220018)Medjaden Academy&Research Foundation for Young Scientists(China)(No.MJR20221014)Project of Sichuan Provincial People's Hospital(China)(No.2022QN03,2021LY14).
文摘Tumor-associated inflammation is an important component of the tumor microenvironment,and an important factor affecting tumor progression.In the tumor microenvironment,tumor-associated macrophages(TAMs)receive different stimuli and can be polarized into classically activated M1 macrophages and alternatively activated M2 macrophages.Many studies have indicated that the polarization of TAMs is closely related to tumor progression.
文摘The burden of respiratory syncytial virus(RSV)disease is widely recognized.Main risk factors for severe disease,such as extreme ages,chronic cardiopulmonary conditions,and immunosuppression,typically coincide withpoorer outcomes.While the majority of RSV hospitalizations involve healthy children,a higher proportion ofhospitalized adults with underlying conditions need intensive care.Presently,treatment primarily consists ofsupportive measures.RSV-induced wheezing should be distinguished from respiratory tract thickening,withoutresponse to bronchodilators.Obstructive RSV disease frequently overlaps with viral pneumonia.Non-invasivemechanical ventilation and high-flow oxygen therapy represented significant advancements in the managementof severe RSV disease in children and may also hold considerable importance in specific phenotypes of RSV diseasein adults.Most severe infections manifest with refractory hypoxemia necessitating more advanced ventilatorysupport and/or extracorporeal membrane oxygenation therapy.Although bacterial co-infection rates are low,they have been associated with worse outcomes.Antibiotic prescription rates are high.Accurately diagnosingbacterial co-infections remains a challenge.Current evidence and antibiotic stewardship policies advise againstindiscriminate antibiotic usage,even in severe cases.The role of currently developing antiviral therapies in severeRSV disease will be elucidated in the coming years,contingent upon the success of new vaccines and immunepassive strategies involving nirsevimab.
