Objective:To investigate the effect of synbiotic mulberry on kidney injury in a dextran sodium sulfate(DSS)-induced colitis model.Methods:Male Wistar rats were given drinking water containing 4%DSS for 7 days.Subseque...Objective:To investigate the effect of synbiotic mulberry on kidney injury in a dextran sodium sulfate(DSS)-induced colitis model.Methods:Male Wistar rats were given drinking water containing 4%DSS for 7 days.Subsequently,the rats were treated by oral gavage with synbiotic mulberry at 250,500,and 1000 mg/kg,sulfasalazine at 100 mg/kg,or synbiotic at 1000 mg/kg for an additional 7 days while receiving 0.4%DSS in drinking water.The severity of colitis was evaluated based on the disease activity index score.On day 14,plasma was collected,and the kidneys were harvested to evaluate kidney injury parameters and histological changes.In addition,the expression of genes associated with kidney injury was determined by quantitative RT-PCR.Results:Treatment with all doses of synbiotic mulberry significantly lowered the disease activity index score,accompanied by reductions in kidney histopathological changes,malondialdehyde concentration,and plasma cystatin C levels.Kidney fibrosis was also ameliorated by 500 and 1000 mg/kg of synbiotic mulberry.Treatment with 250 and 500 mg/kg of synbiotic mulberry downregulated IL-18 mRNA expression,while KIM-1 mRNA expression was reduced and plasma lipopolysaccharide-binding protein level was restored by 1000 mg/kg of synbiotic mulberry.Conclusions:Synbiotic mulberry ameliorates kidney injury in rats with DSS-induced colitis.It may be further explored as a treatment of kidney injury under colitis conditions.展开更多
Background Intestinal inflammation is an energy-consuming process that may alter energy supply and demand in poultry.During inflammation,the intestinal energy metabolic profile and the patterns of energy partitioning ...Background Intestinal inflammation is an energy-consuming process that may alter energy supply and demand in poultry.During inflammation,the intestinal energy metabolic profile and the patterns of energy partitioning remain unclear.This study investigated the effects of intestinal inflammation on energy intake,heat production(HP),retained energy(RE)and intestinal energy metabolites in layer pullets.Methods After 7 d dietary adaption,32“Jing Tint 6”layer pullets with average body weight(1,123.50±8.55 g)were selected from 96 birds,and randomly assigned to two groups(CON:Control group,INFL:Inflammation group)with 8 replicates per group.Indirect calorimetry analysis was conducted over 7 d to determine HP and fasting HP(FHP).During this period,pullets in INFL group received 4 mL/d of 0.6 g/mL dextran sulfate sodium(DSS)via oral gavage to induce intestinal inflammation.After the calorimetry,intestinal tissues were collected post-euthanasia from one bird per replicate for morphological and mucosal metabolomic analysis.Results Birds exhibited significantly lower apparent metabolizable energy(AME)intake(P<0.001)during intestinal inflammation,accompanied by compromised RE and RE as fat(P<0.001),suggesting that birds consumed body energy to sustain energy demands.Targeted metabolomic studies identified 11 energy metabolites differentially expressed in ileal mucosa between CON and INFL groups.Specifically,DSS induction significantly increased(P<0.05)adenosine triphosphate(ATP)level and reduced(P<0.001)nicotinamide adenine dinucleotide(NAD^(+))level in ileal mucosa of pullets.In parallel,metabolic adaptations such as enhanced glycolytic intermediates,reduced amino acids,α-ketoglutarate(α-KG)accumulation and suppressed expression of genes encoding enzymes involved in tricarboxylic acid(TCA)cycle were observed in the inflamed ileum of pullets.Conclusion Immune stimulation by DSS induced a negative energy balance in layer pullets,characterized by reduced AME intake(-190.47 kJ/kg BW^(0.75))and compromised RE(-18.81%of AME intake).Disruption of intestinal energy profiling was observed in inflammation-challenged pullets,such as accumulation ofα-KG and ATP,reduced NAD^(+)and amino acids,which could provide valuable insights for developing effective intervention strategies.展开更多
BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a r...BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.展开更多
Chondroitin sulfate(CS)is one of the main bioactive compounds in animal cartilage.In this study,the antiinflammatory activity of sturgeon-derived chondroitin sulfate(SCS)was evaluated in the dextran sulfate sodium(DSS...Chondroitin sulfate(CS)is one of the main bioactive compounds in animal cartilage.In this study,the antiinflammatory activity of sturgeon-derived chondroitin sulfate(SCS)was evaluated in the dextran sulfate sodium(DSS)-induced BALB/c mice model.Orally administration of SCS significantly alleviated the DSSinduced colitis symptoms,including the reduction of crypt depth,inhibition of the abnormal crypt foci formation,down-regulation of the proinflammatory biomarkers(NO,interleukin(IL)-6,IL-1βand tumor necrosis factor-α)and up-regulation of the anti-inflammatory biomarkers(IL-10 and IL-4).The gut microbiota analysis revealed that SCS alters the intestinal microbiota composition in colitis mice,especially the increase of the relative abundance of Ruminococcaceae and Lachnospiraceae.This alternation further induced primary bile acids convert into secondary bile acids.With SCS administration,the levels of deoxycholic acid(DCA)and litho cholic acid(LCA)were increased by 1.5-and 2.5-fold,respectively.The stimulated secretion of DCA and LCA showed further activation of the NF-κB signaling pathway,thereby suppressing the inflammatory response and attenuating inflammatory bowel disease(IBD)in mice.This study provided a valuable strategy for colitis prevention and treatment with sturgeon cartilage by-products.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogeni...Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.展开更多
Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improv...Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improves DSS-induced impaired liver cholesterol metabolism.Here,we established the DSS-induced model and clarified that DSS exacerbated gut inflammation accompanied by disorders of liver cholesterol metabolism.Pu-erh tea reshaped gut microbes,limited gut oxidative stress and inflammation(nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species/myeloid differentiation primary response protein 88/nuclear factor kappa-B,24.97%-52.89%),reduced gut bile acid reabsorption(up-regulation of farnesoid X receptor(FXR)/fibroblast growth factor 15,24.53%-55.91%),and promoted liver bile acid synthesis(up-regulation of peroxisome proliferator-activated receptor-α/cholesterol 7-alpha hydroxylase,34.65%-79.14%),thereby partly restoring liver cholesterol metabolism(regulated FXR/small heterodimer partner/sterol-regulatory element binding proteins,53.19%-95.40%).Altered bile acid metabolic profiles(increased chenodeoxycholic acid,ursodeoxycholic acid,lithocholic acid,etc.)may also improve liver cholesterol metabolism by altering gut and liver inflammation.Thus,gut microbial reshaping and altered bile acid metabolism may be key targets of Pu-erh tea for improving DSS-induced liver cholesterol metabolism disorders via the gut-gut microbe-bile acid-liver axis.展开更多
The spatiotemporal distributions of microbes in soil by different methods could affect the efficacy of the microbes to reduce the soil hydraulic conductivity.In this study,the specimens of bio-mediated sands were prep...The spatiotemporal distributions of microbes in soil by different methods could affect the efficacy of the microbes to reduce the soil hydraulic conductivity.In this study,the specimens of bio-mediated sands were prepared using three different methods,i.e.injecting,mixing,and pouring a given microbial so-lution onto compacted sand specimens.The hydraulic conductivity was measured by constant-head tests,while any soil microstructural changes due to addition of the microbes were observed by scan-ning electron microscope(SEM)and mercury intrusion porosimetry(MIP)tests.The amount of dextran concentration produced by microbes in each type of specimen was quantified by a refractometer.Results show that dextran production increased exponentially after 5-7 d of microbial settling with the supply of culture medium.The injection and mixing methods resulted in a similar amount and uniform dis-tribution of dextran in the specimens.The pouring method,however,produced a nonuniform distri-bution,with a higher concentration near the specimen surface.As the supply of culture medium discontinued,the dextran content near the surface produced by the pouring method decreased dramatically due to high competition for nutrients with foreign colonies.Average dextran concentration was negatively and correlated with hydraulic conductivity of bio-mediated soils exponentially,due to the clogging of large soil pores by dextran.The hydraulic conductivity of the injection and mixing cases did not change significantly when the supply of culture medium was absent.展开更多
Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and t...Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.展开更多
BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported ...BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.展开更多
Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distil...Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.展开更多
Dextran in sugarcane production process is formed by Leuconostoc rnesenteroides. The content levels of dextran is related to sugarcane varieties, field condition （planting pattern, temperature, humidity, sunlight, so...Dextran in sugarcane production process is formed by Leuconostoc rnesenteroides. The content levels of dextran is related to sugarcane varieties, field condition （planting pattern, temperature, humidity, sunlight, soil, foreign material）, de- gree of injury （refractory cane, harvesting methods）, and can be rapidly and accu- rately measured by Dextran Immunonephelometric Test Kit. The presence of dextran indicates that sucrose has been lost, so sugarcane dextran is a direct and reliable indicator to measure sugarcane freshness and quality.展开更多
基金supported by the Mae Fah Luang University Research Development Grant 2023,Mae Fah Luang University,Chiang Rai Thailand(Grant no.661B07007 to KW)the Technology and Innovation-Based Enterprise Development Fund:Fund(Grant no.YP043/2565 to AO and PW).
文摘Objective:To investigate the effect of synbiotic mulberry on kidney injury in a dextran sodium sulfate(DSS)-induced colitis model.Methods:Male Wistar rats were given drinking water containing 4%DSS for 7 days.Subsequently,the rats were treated by oral gavage with synbiotic mulberry at 250,500,and 1000 mg/kg,sulfasalazine at 100 mg/kg,or synbiotic at 1000 mg/kg for an additional 7 days while receiving 0.4%DSS in drinking water.The severity of colitis was evaluated based on the disease activity index score.On day 14,plasma was collected,and the kidneys were harvested to evaluate kidney injury parameters and histological changes.In addition,the expression of genes associated with kidney injury was determined by quantitative RT-PCR.Results:Treatment with all doses of synbiotic mulberry significantly lowered the disease activity index score,accompanied by reductions in kidney histopathological changes,malondialdehyde concentration,and plasma cystatin C levels.Kidney fibrosis was also ameliorated by 500 and 1000 mg/kg of synbiotic mulberry.Treatment with 250 and 500 mg/kg of synbiotic mulberry downregulated IL-18 mRNA expression,while KIM-1 mRNA expression was reduced and plasma lipopolysaccharide-binding protein level was restored by 1000 mg/kg of synbiotic mulberry.Conclusions:Synbiotic mulberry ameliorates kidney injury in rats with DSS-induced colitis.It may be further explored as a treatment of kidney injury under colitis conditions.
基金supported by the National Key R&D Program of China(2024YFE0111600)the 2115 Talent Development Program of China Agricultural University。
文摘Background Intestinal inflammation is an energy-consuming process that may alter energy supply and demand in poultry.During inflammation,the intestinal energy metabolic profile and the patterns of energy partitioning remain unclear.This study investigated the effects of intestinal inflammation on energy intake,heat production(HP),retained energy(RE)and intestinal energy metabolites in layer pullets.Methods After 7 d dietary adaption,32“Jing Tint 6”layer pullets with average body weight(1,123.50±8.55 g)were selected from 96 birds,and randomly assigned to two groups(CON:Control group,INFL:Inflammation group)with 8 replicates per group.Indirect calorimetry analysis was conducted over 7 d to determine HP and fasting HP(FHP).During this period,pullets in INFL group received 4 mL/d of 0.6 g/mL dextran sulfate sodium(DSS)via oral gavage to induce intestinal inflammation.After the calorimetry,intestinal tissues were collected post-euthanasia from one bird per replicate for morphological and mucosal metabolomic analysis.Results Birds exhibited significantly lower apparent metabolizable energy(AME)intake(P<0.001)during intestinal inflammation,accompanied by compromised RE and RE as fat(P<0.001),suggesting that birds consumed body energy to sustain energy demands.Targeted metabolomic studies identified 11 energy metabolites differentially expressed in ileal mucosa between CON and INFL groups.Specifically,DSS induction significantly increased(P<0.05)adenosine triphosphate(ATP)level and reduced(P<0.001)nicotinamide adenine dinucleotide(NAD^(+))level in ileal mucosa of pullets.In parallel,metabolic adaptations such as enhanced glycolytic intermediates,reduced amino acids,α-ketoglutarate(α-KG)accumulation and suppressed expression of genes encoding enzymes involved in tricarboxylic acid(TCA)cycle were observed in the inflamed ileum of pullets.Conclusion Immune stimulation by DSS induced a negative energy balance in layer pullets,characterized by reduced AME intake(-190.47 kJ/kg BW^(0.75))and compromised RE(-18.81%of AME intake).Disruption of intestinal energy profiling was observed in inflammation-challenged pullets,such as accumulation ofα-KG and ATP,reduced NAD^(+)and amino acids,which could provide valuable insights for developing effective intervention strategies.
文摘BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.
基金funded by grants from Beijing Fishery Innovation Team Project(BAIC07-2023-13)National Natural Science Foundation of China(32201994)。
文摘Chondroitin sulfate(CS)is one of the main bioactive compounds in animal cartilage.In this study,the antiinflammatory activity of sturgeon-derived chondroitin sulfate(SCS)was evaluated in the dextran sulfate sodium(DSS)-induced BALB/c mice model.Orally administration of SCS significantly alleviated the DSSinduced colitis symptoms,including the reduction of crypt depth,inhibition of the abnormal crypt foci formation,down-regulation of the proinflammatory biomarkers(NO,interleukin(IL)-6,IL-1βand tumor necrosis factor-α)and up-regulation of the anti-inflammatory biomarkers(IL-10 and IL-4).The gut microbiota analysis revealed that SCS alters the intestinal microbiota composition in colitis mice,especially the increase of the relative abundance of Ruminococcaceae and Lachnospiraceae.This alternation further induced primary bile acids convert into secondary bile acids.With SCS administration,the levels of deoxycholic acid(DCA)and litho cholic acid(LCA)were increased by 1.5-and 2.5-fold,respectively.The stimulated secretion of DCA and LCA showed further activation of the NF-κB signaling pathway,thereby suppressing the inflammatory response and attenuating inflammatory bowel disease(IBD)in mice.This study provided a valuable strategy for colitis prevention and treatment with sturgeon cartilage by-products.
基金the National Natural Science Foundation of China(Grant Nos.92478133,81930097,and 82151223)by the State Key Laboratory of Natural and Biomimetic Drugs(Grant No.K202430).
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.
基金supported by the National Natural Science Foundation of China funded project(32172627)Chongqing Modern Tea Technology System for Efficient Agriculture in Mountainous Areas 2022[8]the Germplasm Creation Research Program of Southwest University。
文摘Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improves DSS-induced impaired liver cholesterol metabolism.Here,we established the DSS-induced model and clarified that DSS exacerbated gut inflammation accompanied by disorders of liver cholesterol metabolism.Pu-erh tea reshaped gut microbes,limited gut oxidative stress and inflammation(nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species/myeloid differentiation primary response protein 88/nuclear factor kappa-B,24.97%-52.89%),reduced gut bile acid reabsorption(up-regulation of farnesoid X receptor(FXR)/fibroblast growth factor 15,24.53%-55.91%),and promoted liver bile acid synthesis(up-regulation of peroxisome proliferator-activated receptor-α/cholesterol 7-alpha hydroxylase,34.65%-79.14%),thereby partly restoring liver cholesterol metabolism(regulated FXR/small heterodimer partner/sterol-regulatory element binding proteins,53.19%-95.40%).Altered bile acid metabolic profiles(increased chenodeoxycholic acid,ursodeoxycholic acid,lithocholic acid,etc.)may also improve liver cholesterol metabolism by altering gut and liver inflammation.Thus,gut microbial reshaping and altered bile acid metabolism may be key targets of Pu-erh tea for improving DSS-induced liver cholesterol metabolism disorders via the gut-gut microbe-bile acid-liver axis.
基金The first author(V.Kamchoom)acknowledges the grant(Grant No.FRB66065/0258-RE-KRIS/FF66/53)from King Mongkut’s Insti-tute of Technology Ladkrabang(KMITL)and National Science,Research and Innovation Fund(NSRF)the grant under Climate Change and Climate Variability Research in Monsoon Asia(CMON3)from the National Research Council of Thailand(NRCT)(Grant No.N10A650844)the National Natural Science Foundation of China(NSFC).
文摘The spatiotemporal distributions of microbes in soil by different methods could affect the efficacy of the microbes to reduce the soil hydraulic conductivity.In this study,the specimens of bio-mediated sands were prepared using three different methods,i.e.injecting,mixing,and pouring a given microbial so-lution onto compacted sand specimens.The hydraulic conductivity was measured by constant-head tests,while any soil microstructural changes due to addition of the microbes were observed by scan-ning electron microscope(SEM)and mercury intrusion porosimetry(MIP)tests.The amount of dextran concentration produced by microbes in each type of specimen was quantified by a refractometer.Results show that dextran production increased exponentially after 5-7 d of microbial settling with the supply of culture medium.The injection and mixing methods resulted in a similar amount and uniform dis-tribution of dextran in the specimens.The pouring method,however,produced a nonuniform distri-bution,with a higher concentration near the specimen surface.As the supply of culture medium discontinued,the dextran content near the surface produced by the pouring method decreased dramatically due to high competition for nutrients with foreign colonies.Average dextran concentration was negatively and correlated with hydraulic conductivity of bio-mediated soils exponentially,due to the clogging of large soil pores by dextran.The hydraulic conductivity of the injection and mixing cases did not change significantly when the supply of culture medium was absent.
基金supported by the Natural Science Foundation of Jiangsu Province (BK20200084)The National Natural Science Foundation of China (U1903205 and 31972971)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.
基金the Natural Science Foundation of Hainan Province,No.823MS046the Talent Program of Hainan Medical University,No.XRC2022007.
文摘BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.
基金AProject of the Health Bureau of Chongqing (No.2004-B-31)
文摘Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.
基金Supported by Special Fund for Construction Project of Bagui ScholarsSpecial Fund for Modern Agricultural Industry Technology System Construction(CARS-20-4-5)
文摘Dextran in sugarcane production process is formed by Leuconostoc rnesenteroides. The content levels of dextran is related to sugarcane varieties, field condition （planting pattern, temperature, humidity, sunlight, soil, foreign material）, de- gree of injury （refractory cane, harvesting methods）, and can be rapidly and accu- rately measured by Dextran Immunonephelometric Test Kit. The presence of dextran indicates that sucrose has been lost, so sugarcane dextran is a direct and reliable indicator to measure sugarcane freshness and quality.
