BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linke...BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers.AIM To explore GMEB1’s biological functions in hepatocellular carcinoma(HCC)and figuring out the molecular mechanism.METHODS GMEB1 expression in HCC tissues was analyzed employing the StarBase database.Immunohistochemical staining,Western blotting and quantitative realtime PCR were conducted to examine GMEB1 and Yes-associate protein 1(YAP1)expression in HCC cells and tissues.Cell counting kit-8 assay,Transwell assay and flow cytometry were utilized to examine HCC cell proliferation,migration,invasion and apoptosis,respectively.The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region.RESULTS GMEB1 was up-regulated in HCC cells and tissues,and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients.GMEB1 overexpression facilitated HCC cell multiplication,migration,and invasion,and suppressed the apoptosis,whereas GMEB1 knockdown had the opposite effects.GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells.CONCLUSION GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.展开更多
Short-chain fatty acids are important nutrients that regulate milk fat synthesis.They regulate milk syn-thesis via the sterol regulatory element binding protein 1(SREBP1)pathway;however,the details are still unknown.H...Short-chain fatty acids are important nutrients that regulate milk fat synthesis.They regulate milk syn-thesis via the sterol regulatory element binding protein 1(SREBP1)pathway;however,the details are still unknown.Here,the regulation and mechanism of sodium acetate(SA)in milk fat synthesis in bovine mammary epithelial cells(BMECs)were assessed.BMECs were treated with SA supplementation(SAþ)or without SA supplementation(SA-),and milk fat synthesis and activation of the SREBP1 pathway were increased(P=0.0045;P=0.0042)by SAþand decreased(P=0.0068;P=0.0031)by SA-,respectively.Overexpression or inhibition of SREBP1 demonstrated that SA promoted milk fat synthesis(P=0.0045)via the SREBP1 pathway.Overexpression or inhibition of TATA element modulatory factor 1(TMF1)demon-strated that TMF1 suppressed activation of the SREBP1 pathway(P=0.0001)and milk fat synthesis(P=0.0022)activated by SAþ.Overexpression or inhibition of TMF1 and SREBP1 showed that TMF1 suppressed milk fat synthesis(P=0.0073)through the SREBP1 pathway.Coimmunoprecipitation analysis revealed that TMF1 interacted with SREBP1 in the cytoplasm and suppressed the nuclear localization of SREBP1(P=0.0066).The absence or presence of SA demonstrated that SA inhibited the expression of TMF1(P=0.0002)and the interaction between TMF1 and SREBP1(P=0.0001).Collectively,our research sug-gested that TMF1 was a new negative regulator of milk fat synthesis.In BMECs,SA promoted the SREBP1 pathway and milk fat synthesis by suppressing TMF1.This study enhances the current understanding of the regulation of milk fat synthesis and provides new scientific data for the regulation of milk fat synthesis.展开更多
Background:Mushrooms include a wide variety of bioactive compounds that have been linked to therapeutic and nutritional benefits,making them a potential source of new medications and functional foods.Objective:The goa...Background:Mushrooms include a wide variety of bioactive compounds that have been linked to therapeutic and nutritional benefits,making them a potential source of new medications and functional foods.Objective:The goal of this study is to offer a complete overview of the mushroom’s modulatory effects on inflam-matory signaling pathways,which leads to the inhibition of inflammation in various types of immune cells and animal models.Methods:This study reviewed the inhibitory effects of mushrooms on the inflammation process through the modulation of the pro-inflammatory mediators and associated signaling pathways.A literature search in PubMed and Google Scholar was conducted for the relevant original research and review articles on the anti-inflammatory effects of mushrooms.Related articles published in English were selected,studied and discussed.Results:As revealed by the selected articles,bioactive molecules which include peptides,polysaccharides,ter-penes,sterols,fatty acids,and phenols have been extracted from the powder,concentrate,and different solvent extracts of edible mushrooms.These bioactive molecules have shown significant efficacy in inhibiting the major pro-inflammatory biomarkers and associated pathways in in vivo and in vitro settings.Conclusion:This review demonstrated that mushrooms significantly inhibit the production of pro-inflammatory mediators and can be developed for clinical use as anti-inflammatory agents.Further research is required to establish the comparative efficacy between mushrooms and NSAID especially in the in vivo inhibitory activity against the production of cyclooxygenase and pro-inflammatory cytokines.展开更多
Isabel grape(IG)products have high contents of phenolic compounds and fiber recognized for their positive impacts on microorganisms associated with health benefits to host.This study evaluated the effects of goat yogu...Isabel grape(IG)products have high contents of phenolic compounds and fiber recognized for their positive impacts on microorganisms associated with health benefits to host.This study evaluated the effects of goat yogurts formulated with ingredients from IG integral valorization on the growth and metabolism of different probiotic strains,as well as on the population of selected bacterial groups and metabolic activity of human colonic microbiota in vitro.Goat yogurts with IG ingredients(IGI)stimulated the growth of tested Lactobacillus and Bifidobacterium probiotic strains during a 48-h cultivation,as well as decreased the pH values and enhanced the organic acid production.Goat yogurts with IGI increased the population of Lactobacillus spp.and Bifidobacterium spp.during a 24-h in vitro colonic fermentation.A stable Firmicutes:Bacteroidetes ratio close to 1 was found in media with goat yogurt formulations during the colonic fermentation,being similar to the effect caused by fructooligosaccharides.Goat yogurt formulations with IGI caused increased production of short-chain fatty acids and sugar consumption during colonic fermentation.Goat yogurts with IGI should be a valuable strategy for development of novel added-value foods with beneficial effects on gut microbiota and human health.展开更多
Pancreatic cancer(PC)is one of the most common causes of cancer-associated death worldwide,with a low rate of 5-year survival.Currently,the pathogenesis of PC is complicated,with no efficient therapy.Coronavirus disea...Pancreatic cancer(PC)is one of the most common causes of cancer-associated death worldwide,with a low rate of 5-year survival.Currently,the pathogenesis of PC is complicated,with no efficient therapy.Coronavirus disease 2019(COVID-19)disease caused by severe acute respiratory syndrome coronavirus 2 further exacerbates the challenge of patients with PC.The alteration of gut microbiota caused by COVID-19 infection may impact PC progression in patients via immune regulation.The expression of inflammatory immune mediators such as interleukin(IL)-6,IL-8,and IL-10 has been found to increase in both PC and COVID-19 patients,which is associated with the disease severity and prognostic outcome.Gut microbiome serves as a critical connector between viral infection and PC.It can regulate host systemic immune response and impact the efficacy of immunotherapy.Here,we first demonstrated the features of inflammatory cytokines in both diseases and their impact on disease outcomes.Then,we demonstrated the importance of immunotherapeutic strategies.This includes the immune modulation that targets a single or dual receptors using a single agent or their combinations for the treatment of PC in patients who get infected with COVID-19.Additionally,we explored the possibility of managing the disease by regulating gut microbiome.Overall,modulation of the lung-gut-pancreases axis can boost anti-cancer immunotherapy and reduce adverse prognostic outcomes.展开更多
The emergence and rapid spread of antimicrobial resistance is of global public health concern.The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and ve...The emergence and rapid spread of antimicrobial resistance is of global public health concern.The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes(ARGs).In this review,we describe the reservoirs of gut ARGs and their dynamics in both animals and humans,use the One Health perspective to track the transmission of ARG-containing bacteria between humans,animals,and the environment,and assess the impact of antimicrobial resistance on human health and socioeconomic development.The gut resistome can evolve in an environment subject to various selective pressures,including antibiotic administration and environmental and lifestyle factors(e.g.,diet,age,gender,and living conditions),and interventions through probiotics.Strategies to reduce the abundance of clinically relevant antibiotic-resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance.With the help of effective measures taken at the national,local,personal,and intestinal management,it will also result in preventing or minimizing the spread of infectious diseases.This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.展开更多
Chunk decomposition is defined as a cognitive process which breaks up familiar items into several parts to reorganize them in an alternative approach.The present study investigated the effective connectivity of visual...Chunk decomposition is defined as a cognitive process which breaks up familiar items into several parts to reorganize them in an alternative approach.The present study investigated the effective connectivity of visual streams in chunk decomposition through dynamic causal modeling(DCM).The results revealed that chunk familiarity and perceptual tightness made a combined contribution to highlight not only the "what" and the "where" streams,but also the effective connectivity from the left inferior temporal gyrus to the left superior parietal lobule.展开更多
Objectives:The goal of this study was to evaluate the modulatory effect of chitosan oligosaccharide-nisin conjugate(CON-C)on intestinal microbiota of human flora-associated(HFA)mice and also reveal its effect towards ...Objectives:The goal of this study was to evaluate the modulatory effect of chitosan oligosaccharide-nisin conjugate(CON-C)on intestinal microbiota of human flora-associated(HFA)mice and also reveal its effect towards the high-fat diet(HFD)-induced obesity.Both Chitosan oligosaccharides and nisin showed great potential in modulating the intestinal microbiota,so it is worth to explore whether the modulation effect of chitosan oligosaccharide could be improved by covalently binding with nisin.Materials and Methods:CON-C was prepared by heating the mixed solution of chitosan oligosaccharide and nisin at 80℃ and pH 2.0 for 24h.The structure of CON-C were analyzed by Fourier transform-infrared spectroscopy(FT-IR)and X-ray diffraction(XRD).The CON-C’s anti-obesity effect and modulatory effect toward intestinal microbiota were analyzed using human flora-associated(HFA)mice model.Results:CON-C could alleviated HFD-induced gut dysbiosis,by significantly decreasing the numbers of Bifidobacterium and Lactobacillus/Enterococcus spp.,and increasing the numbers of Bacteroides-Prevotella and Clostridium groups.CON-C could also enriched the most differentially expressed genes through KEGG pathways of biosynthesis of amino acids,two-component system,and ATP binding cassette(ABC)transporters.Conclusions:The improved therapeutic effect of CON-C against HFD-induced obesity has been approved,and hence,CON-C has a great potential to be utilized as a functional food ingredient in reducing body weight.展开更多
文摘BACKGROUND Glucocorticoid modulatory element-binding protein 1(GMEB1),which has been identified as a transcription factor,is a protein widely expressed in various tissues.Reportedly,the dysregulation of GMEB1 is linked to the genesis and development of multiple cancers.AIM To explore GMEB1’s biological functions in hepatocellular carcinoma(HCC)and figuring out the molecular mechanism.METHODS GMEB1 expression in HCC tissues was analyzed employing the StarBase database.Immunohistochemical staining,Western blotting and quantitative realtime PCR were conducted to examine GMEB1 and Yes-associate protein 1(YAP1)expression in HCC cells and tissues.Cell counting kit-8 assay,Transwell assay and flow cytometry were utilized to examine HCC cell proliferation,migration,invasion and apoptosis,respectively.The JASPAR database was employed for predicting the binding site of GMEB1 with YAP1 promoter.Dual-luciferase reporter gene assay and chromatin immunoprecipitation-qPCR were conducted to verify the binding relationship of GMEB1 with YAP1 promoter region.RESULTS GMEB1 was up-regulated in HCC cells and tissues,and GMEB1 expression was correlated to the tumor size and TNM stage of HCC patients.GMEB1 overexpression facilitated HCC cell multiplication,migration,and invasion,and suppressed the apoptosis,whereas GMEB1 knockdown had the opposite effects.GMEB1 bound to YAP1 promoter region and positively regulated YAP1 expression in HCC cells.CONCLUSION GMEB1 facilitates HCC malignant proliferation and metastasis by promoting the transcription of the YAP1 promoter region.
基金supported by China Postdoctoral Science Foundation funded project(2019M662971)The Basic Scientific Research Operating Expenses of Higher Education Institutions of Heilongjiang Province(No.2020-KYYWF-0283).
文摘Short-chain fatty acids are important nutrients that regulate milk fat synthesis.They regulate milk syn-thesis via the sterol regulatory element binding protein 1(SREBP1)pathway;however,the details are still unknown.Here,the regulation and mechanism of sodium acetate(SA)in milk fat synthesis in bovine mammary epithelial cells(BMECs)were assessed.BMECs were treated with SA supplementation(SAþ)or without SA supplementation(SA-),and milk fat synthesis and activation of the SREBP1 pathway were increased(P=0.0045;P=0.0042)by SAþand decreased(P=0.0068;P=0.0031)by SA-,respectively.Overexpression or inhibition of SREBP1 demonstrated that SA promoted milk fat synthesis(P=0.0045)via the SREBP1 pathway.Overexpression or inhibition of TATA element modulatory factor 1(TMF1)demon-strated that TMF1 suppressed activation of the SREBP1 pathway(P=0.0001)and milk fat synthesis(P=0.0022)activated by SAþ.Overexpression or inhibition of TMF1 and SREBP1 showed that TMF1 suppressed milk fat synthesis(P=0.0073)through the SREBP1 pathway.Coimmunoprecipitation analysis revealed that TMF1 interacted with SREBP1 in the cytoplasm and suppressed the nuclear localization of SREBP1(P=0.0066).The absence or presence of SA demonstrated that SA inhibited the expression of TMF1(P=0.0002)and the interaction between TMF1 and SREBP1(P=0.0001).Collectively,our research sug-gested that TMF1 was a new negative regulator of milk fat synthesis.In BMECs,SA promoted the SREBP1 pathway and milk fat synthesis by suppressing TMF1.This study enhances the current understanding of the regulation of milk fat synthesis and provides new scientific data for the regulation of milk fat synthesis.
文摘Background:Mushrooms include a wide variety of bioactive compounds that have been linked to therapeutic and nutritional benefits,making them a potential source of new medications and functional foods.Objective:The goal of this study is to offer a complete overview of the mushroom’s modulatory effects on inflam-matory signaling pathways,which leads to the inhibition of inflammation in various types of immune cells and animal models.Methods:This study reviewed the inhibitory effects of mushrooms on the inflammation process through the modulation of the pro-inflammatory mediators and associated signaling pathways.A literature search in PubMed and Google Scholar was conducted for the relevant original research and review articles on the anti-inflammatory effects of mushrooms.Related articles published in English were selected,studied and discussed.Results:As revealed by the selected articles,bioactive molecules which include peptides,polysaccharides,ter-penes,sterols,fatty acids,and phenols have been extracted from the powder,concentrate,and different solvent extracts of edible mushrooms.These bioactive molecules have shown significant efficacy in inhibiting the major pro-inflammatory biomarkers and associated pathways in in vivo and in vitro settings.Conclusion:This review demonstrated that mushrooms significantly inhibit the production of pro-inflammatory mediators and can be developed for clinical use as anti-inflammatory agents.Further research is required to establish the comparative efficacy between mushrooms and NSAID especially in the in vivo inhibitory activity against the production of cyclooxygenase and pro-inflammatory cytokines.
文摘Isabel grape(IG)products have high contents of phenolic compounds and fiber recognized for their positive impacts on microorganisms associated with health benefits to host.This study evaluated the effects of goat yogurts formulated with ingredients from IG integral valorization on the growth and metabolism of different probiotic strains,as well as on the population of selected bacterial groups and metabolic activity of human colonic microbiota in vitro.Goat yogurts with IG ingredients(IGI)stimulated the growth of tested Lactobacillus and Bifidobacterium probiotic strains during a 48-h cultivation,as well as decreased the pH values and enhanced the organic acid production.Goat yogurts with IGI increased the population of Lactobacillus spp.and Bifidobacterium spp.during a 24-h in vitro colonic fermentation.A stable Firmicutes:Bacteroidetes ratio close to 1 was found in media with goat yogurt formulations during the colonic fermentation,being similar to the effect caused by fructooligosaccharides.Goat yogurt formulations with IGI caused increased production of short-chain fatty acids and sugar consumption during colonic fermentation.Goat yogurts with IGI should be a valuable strategy for development of novel added-value foods with beneficial effects on gut microbiota and human health.
文摘Pancreatic cancer(PC)is one of the most common causes of cancer-associated death worldwide,with a low rate of 5-year survival.Currently,the pathogenesis of PC is complicated,with no efficient therapy.Coronavirus disease 2019(COVID-19)disease caused by severe acute respiratory syndrome coronavirus 2 further exacerbates the challenge of patients with PC.The alteration of gut microbiota caused by COVID-19 infection may impact PC progression in patients via immune regulation.The expression of inflammatory immune mediators such as interleukin(IL)-6,IL-8,and IL-10 has been found to increase in both PC and COVID-19 patients,which is associated with the disease severity and prognostic outcome.Gut microbiome serves as a critical connector between viral infection and PC.It can regulate host systemic immune response and impact the efficacy of immunotherapy.Here,we first demonstrated the features of inflammatory cytokines in both diseases and their impact on disease outcomes.Then,we demonstrated the importance of immunotherapeutic strategies.This includes the immune modulation that targets a single or dual receptors using a single agent or their combinations for the treatment of PC in patients who get infected with COVID-19.Additionally,we explored the possibility of managing the disease by regulating gut microbiome.Overall,modulation of the lung-gut-pancreases axis can boost anti-cancer immunotherapy and reduce adverse prognostic outcomes.
基金supported by the National Natural Science Foundation of China (41977137 and 42307048)the International Atomic Energy Agency Research Project (D15022)+5 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent (2022ZB460)the China Postdoctoral Science Foundation (2023M733593)Chinese Academy of Sciences President's International Fellowship Initiative (2020DC0005)Academy of Finland,Innovation Fund Denmark and the European Commission Horizon 2020 financed under the ERA-NET Aquatic Pollutants Joint Transnational Call (REWA,GA No 869178)the Center for Health Impacts of Agriculture (CHIA)of Michigan State Universitysupported by the fellowship of Alexander von Humboldt for experienced researchers,and Shennong Young Talents of the Ministry of Agriculture and Rural Affairs,China (SNYCQN006-2022).
文摘The emergence and rapid spread of antimicrobial resistance is of global public health concern.The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes(ARGs).In this review,we describe the reservoirs of gut ARGs and their dynamics in both animals and humans,use the One Health perspective to track the transmission of ARG-containing bacteria between humans,animals,and the environment,and assess the impact of antimicrobial resistance on human health and socioeconomic development.The gut resistome can evolve in an environment subject to various selective pressures,including antibiotic administration and environmental and lifestyle factors(e.g.,diet,age,gender,and living conditions),and interventions through probiotics.Strategies to reduce the abundance of clinically relevant antibiotic-resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance.With the help of effective measures taken at the national,local,personal,and intestinal management,it will also result in preventing or minimizing the spread of infectious diseases.This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.
基金supported by the Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. KSCX2-YW-R-28)the National Natural Science Foundation of China (Grant No. 30770708) the National Hi-Tech Research and Development Program of China (Grant No. 2008AA022604)
文摘Chunk decomposition is defined as a cognitive process which breaks up familiar items into several parts to reorganize them in an alternative approach.The present study investigated the effective connectivity of visual streams in chunk decomposition through dynamic causal modeling(DCM).The results revealed that chunk familiarity and perceptual tightness made a combined contribution to highlight not only the "what" and the "where" streams,but also the effective connectivity from the left inferior temporal gyrus to the left superior parietal lobule.
基金This work was sponsored by Key Research and Development Project of Zhejiang Province(2017C02039).
文摘Objectives:The goal of this study was to evaluate the modulatory effect of chitosan oligosaccharide-nisin conjugate(CON-C)on intestinal microbiota of human flora-associated(HFA)mice and also reveal its effect towards the high-fat diet(HFD)-induced obesity.Both Chitosan oligosaccharides and nisin showed great potential in modulating the intestinal microbiota,so it is worth to explore whether the modulation effect of chitosan oligosaccharide could be improved by covalently binding with nisin.Materials and Methods:CON-C was prepared by heating the mixed solution of chitosan oligosaccharide and nisin at 80℃ and pH 2.0 for 24h.The structure of CON-C were analyzed by Fourier transform-infrared spectroscopy(FT-IR)and X-ray diffraction(XRD).The CON-C’s anti-obesity effect and modulatory effect toward intestinal microbiota were analyzed using human flora-associated(HFA)mice model.Results:CON-C could alleviated HFD-induced gut dysbiosis,by significantly decreasing the numbers of Bifidobacterium and Lactobacillus/Enterococcus spp.,and increasing the numbers of Bacteroides-Prevotella and Clostridium groups.CON-C could also enriched the most differentially expressed genes through KEGG pathways of biosynthesis of amino acids,two-component system,and ATP binding cassette(ABC)transporters.Conclusions:The improved therapeutic effect of CON-C against HFD-induced obesity has been approved,and hence,CON-C has a great potential to be utilized as a functional food ingredient in reducing body weight.