Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases ...Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.展开更多
Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mech...Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mechanism of BZBS in the treatment of functional constipation(FC)has been little studied and remains unclear.In this study,a behavioral investigation,colon tissue morphology,enzyme-linked immunosorbent assay(Elisa)and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model.Methods:A FC rat model was constructed and BZBS was given as treatment.Observations and recordings were made of the fecal moisture content,the defecation time of the first black stool,and the rate of intestinal propulsion.Elisa was used to detect the expression levels of substance P(SP),vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT)in the colon.To ascertain the composition of the microbial community,a high throughput 16S ribosomal RNA(16S r RNA)gene sequencing technique was employed.Results:Oral administration of BZBS significantly ameliorated several key excretion parameters,including the time to first black stool defecation,stool water content,and the propulsion rate in the small intestine in FC rats.It increased the expression of SP,VIP and 5-HT in the colon.16S r RNA gene sequencing results showed that BZBS changed the microbial community structure,decreased the Bacteroidetes/Firmicutes ratio,increased the relative abundance of Blautia and Fusicatenibacter,and decreased the relative abundance of Ruminococcus and Roseburia.Conclusions:BZBS effectively alleviates FC and improves dysbacteriosis.展开更多
CuCe/Ti-A and CuCe/Ti-R catalysts were prepared using anatase TiO_(2)(TiO_(2)-A)and rutile TiO_(2)(TiO_(2)-R)as supports using the incipient wetness impregnation method for the carbon monoxide(CO)oxidation reaction an...CuCe/Ti-A and CuCe/Ti-R catalysts were prepared using anatase TiO_(2)(TiO_(2)-A)and rutile TiO_(2)(TiO_(2)-R)as supports using the incipient wetness impregnation method for the carbon monoxide(CO)oxidation reaction and were compared with a CuCe-C catalyst prepared using the co-precipitation method.The CuCe/Ti-A catalyst exhibited the highest activity,with complete CO conversion at 90℃,when the gas hourly space velocity was 24000 ml.g^(-1).h^(-1) and the CO concentration was approximately 1%(vol).A series of characterizations of the catalysts revealed that the CuCe/Ti-A catalyst has a larger specific surface area,more Cu+species and oxygen vacancies,and the Cu species of CuCe/Ti-A catalyst is more readily reduced.In situ FT-IR results indicate that the bicarbonate species generated on the CuCe/Ti-A catalyst have lower thermal stability than the carbonate species on CuCe/Ti-R,and will decompose more readily to form CO_(2).Therefore,CuCe/Ti-A has excellent catalytic activity for CO oxidation.展开更多
Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear.In this study,in vivo(60μg/day,42 days)and in...Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear.In this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,respectively.Our study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal flora.Desulfovibrionales-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in mice.Importantly,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn expression.In conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.展开更多
Ulcerative colitis(UC)is a chronic and recurrent inflammatory bowel disease(IBD)that has become a major gastroenterologic problem during recent decades.Numerous complicating factors are involved in UC development such...Ulcerative colitis(UC)is a chronic and recurrent inflammatory bowel disease(IBD)that has become a major gastroenterologic problem during recent decades.Numerous complicating factors are involved in UC development such as oxidative stress,inflammation,and microbiota disorder.These factors exacerbate damage to the intestinal mucosal barrier.Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products.However,there have been few studies on the treatment of UC using S.platensis aqueous extracts(SP),and the underlying mechanism of action of SP against UC has not yet been elucidated.Herein,we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier.Dextran sulfate sodium(DSS)was used to establish a normal human colonic epithelial cell(NCM460)injury model and UC animal model.The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and staining with Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model.Moreover,hematoxylin and eosin(H&E)staining,transmission electron microscopy(TEM),enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qPCR),western blot,and 16S ribosomal DNA(rDNA)sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice.In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury.SP also significantly reduced the excessive generation of intracellular reactive oxygen species(ROS)and prevented mitochondrial membrane potential reduction after DSS challenge.In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group.Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins(TJs)post-SP treatment.SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon.Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction,inhibition of DSS-induced ROS production,and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.展开更多
Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has bee...Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.展开更多
基金sponsored by the National Key R&D Program of China (2018YFD0901102)the Natural Science Foundation of Zhejiang Province (LQ22D060002)+2 种基金the Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products (ZS20190105)the Fundamental Research Funds for the Provincial Universities of Zhejiang (SJLY2021015)the K.C.Wong Magna Fund of Ningbo University。
文摘Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.
基金Natural Science Foundation of Zhejiang Province,Grant/Award Number:Y19H280022。
文摘Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mechanism of BZBS in the treatment of functional constipation(FC)has been little studied and remains unclear.In this study,a behavioral investigation,colon tissue morphology,enzyme-linked immunosorbent assay(Elisa)and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model.Methods:A FC rat model was constructed and BZBS was given as treatment.Observations and recordings were made of the fecal moisture content,the defecation time of the first black stool,and the rate of intestinal propulsion.Elisa was used to detect the expression levels of substance P(SP),vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT)in the colon.To ascertain the composition of the microbial community,a high throughput 16S ribosomal RNA(16S r RNA)gene sequencing technique was employed.Results:Oral administration of BZBS significantly ameliorated several key excretion parameters,including the time to first black stool defecation,stool water content,and the propulsion rate in the small intestine in FC rats.It increased the expression of SP,VIP and 5-HT in the colon.16S r RNA gene sequencing results showed that BZBS changed the microbial community structure,decreased the Bacteroidetes/Firmicutes ratio,increased the relative abundance of Blautia and Fusicatenibacter,and decreased the relative abundance of Ruminococcus and Roseburia.Conclusions:BZBS effectively alleviates FC and improves dysbacteriosis.
基金supported by the National Natural Science Foundation of China(U21A20306,U20A20152)Natural Science Foundation of Hebei Province(B2022202077).
文摘CuCe/Ti-A and CuCe/Ti-R catalysts were prepared using anatase TiO_(2)(TiO_(2)-A)and rutile TiO_(2)(TiO_(2)-R)as supports using the incipient wetness impregnation method for the carbon monoxide(CO)oxidation reaction and were compared with a CuCe-C catalyst prepared using the co-precipitation method.The CuCe/Ti-A catalyst exhibited the highest activity,with complete CO conversion at 90℃,when the gas hourly space velocity was 24000 ml.g^(-1).h^(-1) and the CO concentration was approximately 1%(vol).A series of characterizations of the catalysts revealed that the CuCe/Ti-A catalyst has a larger specific surface area,more Cu+species and oxygen vacancies,and the Cu species of CuCe/Ti-A catalyst is more readily reduced.In situ FT-IR results indicate that the bicarbonate species generated on the CuCe/Ti-A catalyst have lower thermal stability than the carbonate species on CuCe/Ti-R,and will decompose more readily to form CO_(2).Therefore,CuCe/Ti-A has excellent catalytic activity for CO oxidation.
基金the National Natural Science Foundation of China(No.82073520)the Beijing Natural Science Program and Scientific Research Key Program of Beijing Municipal Commission of Education(No.KZ201810025032)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(No.CIT&TCD 20170323).
文摘Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still unclear.In this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,respectively.Our study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal flora.Desulfovibrionales-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in mice.Importantly,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn expression.In conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.
基金the National Key R&D Program of China(No.2018YFC1603900)the National Natural Science Foundation of China(Nos.32070509 and 31501894)the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515220119),China。
文摘Ulcerative colitis(UC)is a chronic and recurrent inflammatory bowel disease(IBD)that has become a major gastroenterologic problem during recent decades.Numerous complicating factors are involved in UC development such as oxidative stress,inflammation,and microbiota disorder.These factors exacerbate damage to the intestinal mucosal barrier.Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products.However,there have been few studies on the treatment of UC using S.platensis aqueous extracts(SP),and the underlying mechanism of action of SP against UC has not yet been elucidated.Herein,we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier.Dextran sulfate sodium(DSS)was used to establish a normal human colonic epithelial cell(NCM460)injury model and UC animal model.The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and staining with Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide(PI)and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model.Moreover,hematoxylin and eosin(H&E)staining,transmission electron microscopy(TEM),enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qPCR),western blot,and 16S ribosomal DNA(rDNA)sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice.In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury.SP also significantly reduced the excessive generation of intracellular reactive oxygen species(ROS)and prevented mitochondrial membrane potential reduction after DSS challenge.In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group.Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins(TJs)post-SP treatment.SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon.Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction,inhibition of DSS-induced ROS production,and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.
基金supported by the National Natural Science Foundation of China (Nos. 21773169, 21973069, 21805144)Natural Science Foundation of Zhejiang Province (No. LY18B020016)the PEIYANG Young Scholars Program of Tianjin University (No. 2018XRX-0007)。
文摘Series tunneling across peptides composed of various amino acids is one of the main charge transport mechanisms for realizing the function of protein. Histidine, more frequently found in redox active proteins, has been proved to be efficient tunneling mediator. While how it exactly modulates charge transport in a long peptide sequence remains poorly explored. In this work, we studied charge transport of a model peptide junction, where oligo-alanine peptide was doped by histidine at different position,and the series of peptides were self-assembled into a monolayer on gold electrode with soft EGa In as top electrode to form molecular junction. It was found that histidine increased the overall conductance of the peptide, meanwhile, its position modulated the conductance as well. Quantitative analysis by transport model and ultraviolet photoelectron spectroscopy(UPS) indicated a sequence dependent energy landscape of the tunneling barrier of the junction. Density-functional theory(DFT) calculation on the electronic structure of histidine doped oligo-alanine peptides revealed localized highest occupied molecular orbital(HOMO) on imidazole group of the histidine, which decreased charge transport barrier.
