Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty aci...Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty acid produced by gut microbiota,exhibits significant anti-inflammatory effects in AD.Yet,its delivery via butyrylated starch for prolonged release in the colon has not been adequately investigated.In this study,butyrylated Smilax glabra starch(BSGS)was synthesized and its therapeutic potential against AD via modulation of the gut–skin axis was examined.BSGS exhibited a C-type crystalline structure and highly resistance to gastrointestinal digestion.In vitro anaerobic fermentation showed that BSGS effectively promoted the generation of short-chain fatty acids,especially butyrate,and positively influenced the gut microbial composition.In AD mice,BSGS administration considerably mitigated cutaneous inflammation,lowered serum proinflammatory cytokines,restored intestinal barrier integrity,and modulated gut microbiota by increasing Bacteroides and norank_f__Prevotellaceae while decreasing Alistipes and norank_o__RF39.This therapeutic effect was associated with butyrate release and NF-κB pathway suppression,as evidenced by the reduced phosphorylation of p65 and IκBα.These findings establish that BSGS,a novel colon-targeted butyrate donor,holds promising potential in AD treatment by modulating the immune system via the gut–skin axis.展开更多
With the highest utilization rates of all short-chain fatty acids(SCFAs),butyric acid(BA)is essential for human health.In this study,we investigated butyrylated lotus seed starch(LSB)effects on small intestinal bacter...With the highest utilization rates of all short-chain fatty acids(SCFAs),butyric acid(BA)is essential for human health.In this study,we investigated butyrylated lotus seed starch(LSB)effects on small intestinal bacteria and SCFA levels in mice.Mouse body weights,after lotus seed resistant starch(RS)and LSB of different degrees of substitution(DS)treatment for 4 weeks,showed no significant difference.LSB of low DS improved small intestine morphology.Relative Lactobacillaceae and Lachnospiraceae abundance was promoted,and several harmful genera e.g.,Desulfovibrio were suppressed in LSB groups.From correlation analyses,BA production was negatively related to Bacteroides and Corynebacterium.In this study,we identified butyrylated starch effects on small intestinal bacteria and provided a foundation for designing functional dietary fibers,which induced high BA levels.展开更多
The title compound S-(+)-N'-tertbutylaminocarbonyl-N-[3-methyl-2-(4-chlorophenyl)butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There...The title compound S-(+)-N'-tertbutylaminocarbonyl-N-[3-methyl-2-(4-chlorophenyl)butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There exist intramolecular N(2)-H(2A)…O(1), C(17)-H(17A)… O(2) and N(3)-H(3A)…S(1) hydrogen bonds as well as intermolecular N-H…O interaction between the carbonyl and amidogen groups. Crystallographic data: CITH24ClN3O2S, Mr = 369.90, monoclinic, space group C2/c with a = 22.9922(19), b = 14.4844(12), c = 12.4618(11) A, β = 92.608(2)°, V = 4145.8(6) ]k3, Z = 8, Dc = 1.185 g/cm^3, F(000) = 1568, g(MoKa) = 0.298 mm^-1, R = 0.0578 and wR = 0.1308.展开更多
Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life.Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation,...Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life.Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation,but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension(Or HTN)remain unclear.In this study,we observed a significant proliferation of Desulfobacterota and Proteobacteria,while a decrease in the abundance of several butyrate-producing bacterial genera,accompanied by decreased fecal and plasma butyrate levels in high-fat diet(HFD)-induced Or HTN rats.Histone 3 lysine 9 butyrylation(H3K9bu)modification in the kidney of Or HTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1.Subsequent transplantation of cecal contents from Or HTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity.Furthermore,in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentrationdependent manner.In conclusion,our findings suggest that gut microbiota may contribute to the development of Or HTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation.This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.展开更多
Post-translational modifications(PTM)are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids.PTMs play essential roles in biological f...Post-translational modifications(PTM)are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids.PTMs play essential roles in biological function and regulation and have been linked with several diseases.Modifications of protein acylation(Kac),a type of PTM,are known to induce epigenetic regulatory processes that promote various diseases.Thus,an increasing number of studies focusing on acylation modifications are being undertaken.Butyrylation(Kbu)is a new acylation process found in animals and plants.Kbu has been recently linked to the onset and progression of several diseases,such as cancer,cardiovascular diseases,diabetes,and vascular dementia.Moreover,the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels,suggesting that butyrylation may play a therapeutic role in these diseases.In addition,butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth,development,and metabolism of rice.The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated.This study reviews the potential role of histone Kbu,as well as the mechanisms underlying this process.It also summarizes various enzymes and analytical methods associated with Kbu,with the goal of providing new insights into the role of Kbu in gene regulation and diseases.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82174074).
文摘Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty acid produced by gut microbiota,exhibits significant anti-inflammatory effects in AD.Yet,its delivery via butyrylated starch for prolonged release in the colon has not been adequately investigated.In this study,butyrylated Smilax glabra starch(BSGS)was synthesized and its therapeutic potential against AD via modulation of the gut–skin axis was examined.BSGS exhibited a C-type crystalline structure and highly resistance to gastrointestinal digestion.In vitro anaerobic fermentation showed that BSGS effectively promoted the generation of short-chain fatty acids,especially butyrate,and positively influenced the gut microbial composition.In AD mice,BSGS administration considerably mitigated cutaneous inflammation,lowered serum proinflammatory cytokines,restored intestinal barrier integrity,and modulated gut microbiota by increasing Bacteroides and norank_f__Prevotellaceae while decreasing Alistipes and norank_o__RF39.This therapeutic effect was associated with butyrate release and NF-κB pathway suppression,as evidenced by the reduced phosphorylation of p65 and IκBα.These findings establish that BSGS,a novel colon-targeted butyrate donor,holds promising potential in AD treatment by modulating the immune system via the gut–skin axis.
基金supported by the Program for Leading Talent at Fujian Provincial University(Grant Number:660160190).
文摘With the highest utilization rates of all short-chain fatty acids(SCFAs),butyric acid(BA)is essential for human health.In this study,we investigated butyrylated lotus seed starch(LSB)effects on small intestinal bacteria and SCFA levels in mice.Mouse body weights,after lotus seed resistant starch(RS)and LSB of different degrees of substitution(DS)treatment for 4 weeks,showed no significant difference.LSB of low DS improved small intestine morphology.Relative Lactobacillaceae and Lachnospiraceae abundance was promoted,and several harmful genera e.g.,Desulfovibrio were suppressed in LSB groups.From correlation analyses,BA production was negatively related to Bacteroides and Corynebacterium.In this study,we identified butyrylated starch effects on small intestinal bacteria and provided a foundation for designing functional dietary fibers,which induced high BA levels.
基金This work was supported by the National Key Technologies R & D Programs of China (No. 2004BA-308A22-8)
文摘The title compound S-(+)-N'-tertbutylaminocarbonyl-N-[3-methyl-2-(4-chlorophenyl)butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There exist intramolecular N(2)-H(2A)…O(1), C(17)-H(17A)… O(2) and N(3)-H(3A)…S(1) hydrogen bonds as well as intermolecular N-H…O interaction between the carbonyl and amidogen groups. Crystallographic data: CITH24ClN3O2S, Mr = 369.90, monoclinic, space group C2/c with a = 22.9922(19), b = 14.4844(12), c = 12.4618(11) A, β = 92.608(2)°, V = 4145.8(6) ]k3, Z = 8, Dc = 1.185 g/cm^3, F(000) = 1568, g(MoKa) = 0.298 mm^-1, R = 0.0578 and wR = 0.1308.
基金supported by the Special Fund of Beijing Municipal Science&Technology Commission(Z211100002921035)Capital's Funds for Health Improvement and Research(CFH2022-3-2105)+4 种基金Beijing Hospitals Authority Clinical Medicine Development of special funding support(YGLX202532)Beijing Natural Science Foundation(7232008 and 7222017)the National Natural Science Foundation of China(81971397 and 82171652)the Public Service Development and Reform Pilot Project of Beijing Medical Research Institute(BMR201911)the Research Foundation of the Capital Institute of Pediatrics(CXYJ-2021-02)。
文摘Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life.Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation,but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension(Or HTN)remain unclear.In this study,we observed a significant proliferation of Desulfobacterota and Proteobacteria,while a decrease in the abundance of several butyrate-producing bacterial genera,accompanied by decreased fecal and plasma butyrate levels in high-fat diet(HFD)-induced Or HTN rats.Histone 3 lysine 9 butyrylation(H3K9bu)modification in the kidney of Or HTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1.Subsequent transplantation of cecal contents from Or HTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity.Furthermore,in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentrationdependent manner.In conclusion,our findings suggest that gut microbiota may contribute to the development of Or HTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation.This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.
基金supported by the National Natural Science Foundation of China(No.82270442 and 81870331)the Qingdao Municipal Science and Technology Bureau Project(China)(No.21-1-4-rkjk-12-nsh).
文摘Post-translational modifications(PTM)are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids.PTMs play essential roles in biological function and regulation and have been linked with several diseases.Modifications of protein acylation(Kac),a type of PTM,are known to induce epigenetic regulatory processes that promote various diseases.Thus,an increasing number of studies focusing on acylation modifications are being undertaken.Butyrylation(Kbu)is a new acylation process found in animals and plants.Kbu has been recently linked to the onset and progression of several diseases,such as cancer,cardiovascular diseases,diabetes,and vascular dementia.Moreover,the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels,suggesting that butyrylation may play a therapeutic role in these diseases.In addition,butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth,development,and metabolism of rice.The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated.This study reviews the potential role of histone Kbu,as well as the mechanisms underlying this process.It also summarizes various enzymes and analytical methods associated with Kbu,with the goal of providing new insights into the role of Kbu in gene regulation and diseases.