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 In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with ...Background In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with the growth of intensive aquaculture,demand for fishmeal as a key protein source outstrips supply,driving up prices.This study investigated the therapeutic potential of reducing dietary protein levels by 3%and adding enzymatic cottonseed protein(ECP)in juvenile yellow catfish with dextran sulfate sodium(DSS)-induced enteritis.Methods A total of 1,260 healthy juvenile yellow catfish(Pelteobagrus fulvidraco),with an average body weight of 5.90±0.05 g,were randomly allocated into 7 experimental groups,each with 3 replicates.The fish were fed one of seven diets for 10 weeks:a normal-protein diet(42%;NP)and 6 low-protein diets(39%;LP)supplemented with graded levels of ECP at 0%(ECP0),1%(ECP1),2%(ECP2),3%(ECP3),4%(ECP4),and 5%(ECP5),respectively.Subsequently,48 fish from each group were selected to receive 1 mL of 6%DSS solution.Results Our findings demonstrated that:(1)The DSS+ECP0 group aggravated DSS-induced enteritis in juvenile yellow catfish compared to the DSS+NP group.(2)Dietary supplementation of ECP in LP diets significantly enhanced the enzymatic activity and levels of immunoreactive substances,including LZM,C3,C4,and ACP(P<0.05).Mechanistically,first,ECP supplementation modulated macrophage polarization by inhibiting the M1 phenotype while promoting the M2 phenotype,potentially through the JAK-STAT signaling pathway;second,dietary ECP suppressed the phosphorylation cascade of key necroptosis-related proteins,including RIP1,RIP3,and MLKL,potentially via the NF-κB and MAPK signaling pathways.(3)The DSS+ECP2 group demonstrated comparable or superior efficacy to the DSS+NP group in mitigating DSS-induced intestinal enteritis.Conclusions Our results demonstrated that ECP can alleviate DSS-induced enteritis by regulating macrophage polarization and reducing necroptosis.Furthermore,ECP supplementation effectively counteracted the exacerbation of enteritis caused by dietary protein reduction.These findings highlighted the effectiveness and feasibility of ECP in alleviating enteritis and saving protein.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic relapsing inflammatory bowel disease with rising global incidence.Current therapies for UC often provide incomplete relief and are associated with adverse side effects,hig...BACKGROUND Ulcerative colitis(UC)is a chronic relapsing inflammatory bowel disease with rising global incidence.Current therapies for UC often provide incomplete relief and are associated with adverse side effects,highlighting the need for alternatives with increased safety and effectiveness.Compound spleen-tonifying composition(CSTC)contains ingredients,such as Pulsatilla chinensis(Bunge)Regel and Glycyrrhiza uralensis Fisch,that have been shown to be efficacious in the treatment of UC.Its mechanism needs to be investigated further.AIM To study the therapeutic effect and mechanism of CSTC in dextran sulfate sodium(DSS)-induced UC in rats.METHODS Sprague-Dawley rats were freely given 4%DSS solution for seven days to establish the UC model.After intervention with CSTC and its different solvent extracts,body weight changes,the disease activity index(DAI),and colon histopathology were assessed to evaluate therapeutic outcomes.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),myeloperoxidase(MPO),glutathione peroxidase(GSH-px),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in colon tissue were determined to investigate changes in biochemical indicators.RESULTS DSS administration triggered severe UC symptoms,including weight loss,colon shortening,elevated DAI scores,and histological damage.These symptoms were accompanied with oxidative stress(reduced SOD and GSH-px levels and increased MDA and MPO levels),inflammation(elevated TNF-α,IL-1β,and IL-6 levels),and a reduction in the expression levels of tight junction proteins[zonula occludens-1(ZO-1)and occluding].High-and mediumdose CSTC treatment significantly alleviated clinical symptoms,restored colon morphology,normalized oxidative stress markers,suppressed proinflammatory cytokines,and enhanced ZO-1 and occludin levels,demonstrating dose-dependent efficacy.Notably,solvent extraction critically influenced bioactivity:Nonpolar extracts(chloroform and petroleum ether)showed minimal effects,whereas polar extracts(ethyl acetate and n-butanol)remarkably improved clinical symptoms.CONCLUSION The above findings highlight CSTC’s multifaceted anti-UC effects,which are mediated through oxidative stress mitigation and cytokine modulation,while emphasizing the polarity-dependent efficacy of its extracts.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
BACKGROUND Acute pancreatitis(AP)is a frequent gastrointestinal emergency characterized by inflammation.It has the potential to progress to organ failure.Fluid therapy plays a critical role in early AP management,miti...BACKGROUND Acute pancreatitis(AP)is a frequent gastrointestinal emergency characterized by inflammation.It has the potential to progress to organ failure.Fluid therapy plays a critical role in early AP management,mitigating hypovolemia-induced ischemia and systemic inflammatory response syndrome(SIRS).AIM To evaluate dextran 40+Ringer’s lactate solution(RLS)vs RLS alone for fluid therapy in mild to moderate AP.METHODS We conducted a single-center,single-blind,randomized controlled trial involving 108 patients with mild to moderate AP.Participants were randomized to receive either dextran 40+RLS(1:3 ratio)or RLS alone.All patients underwent standardized,goal-directed fluid therapy and were monitored for clinical response,inflammatory markers,and complications.The primary outcomes were reduction in C-reactive protein(CRP)and resolution of SIRS at 72 hours.Secondary outcomes included organ failure,intensive care unit admission,mortality,and length of hospital stay.RESULTS The dextran 40+RLS group demonstrated significantly lower CRP levels.No differences were observed in SIRS changes,fluid overload,refractory status mortality,local complications,or organ failure rates.Hospitalization tended to be shorter in the dextran 40+RLS group(5 days vs 6 days)although not to a statistically significant level(P=0.1).Adverse events were mild and comparable in both groups.CONCLUSION Dextran 40+RLS improved the early CRP response in patients with AP without added complications.Although medium-term outcomes were similar,early benefits support its use in initial management.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
2025年8月22日,北京大学药学院李中军教授/李忠堂副研究员团队与石河子大学药学院王恒教授团队合作,在Carbohydrate Polymers期刊发表了题为“Low-molecular-weight dextran sulfate sodium as novel heparanase inhibitor preventing b...2025年8月22日,北京大学药学院李中军教授/李忠堂副研究员团队与石河子大学药学院王恒教授团队合作,在Carbohydrate Polymers期刊发表了题为“Low-molecular-weight dextran sulfate sodium as novel heparanase inhibitor preventing breast cancer metastasis in mice by inhibiting migration and angiogenesis”的研究论文。该研究发现,低分子量硫酸化葡聚糖通过抑制乙酰肝素酶的活性,阻断乳腺癌细胞的侵袭和迁移,为攻克侵袭性乳腺恶性肿瘤提供了新的可靠治疗策略。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.
基金National Science Fund for Distinguished Young Scholars of China(32425056)National Natural Science Foundation of China(U23A20250)+2 种基金the earmarked fund for CARS(CARS-45)the National Key R&D Program of China(2023YFD2400600)Sichuan Innovation Team of National Modern Agricultural Industry Technology System(SCCXTD-2024-15).
文摘Background In intensive aquaculture systems,the frequent incidence of enteritis reduces production efficiency and results in significant economic losses.Protein feeds account for 40%–60%of aquafeed expenses,and with the growth of intensive aquaculture,demand for fishmeal as a key protein source outstrips supply,driving up prices.This study investigated the therapeutic potential of reducing dietary protein levels by 3%and adding enzymatic cottonseed protein(ECP)in juvenile yellow catfish with dextran sulfate sodium(DSS)-induced enteritis.Methods A total of 1,260 healthy juvenile yellow catfish(Pelteobagrus fulvidraco),with an average body weight of 5.90±0.05 g,were randomly allocated into 7 experimental groups,each with 3 replicates.The fish were fed one of seven diets for 10 weeks:a normal-protein diet(42%;NP)and 6 low-protein diets(39%;LP)supplemented with graded levels of ECP at 0%(ECP0),1%(ECP1),2%(ECP2),3%(ECP3),4%(ECP4),and 5%(ECP5),respectively.Subsequently,48 fish from each group were selected to receive 1 mL of 6%DSS solution.Results Our findings demonstrated that:(1)The DSS+ECP0 group aggravated DSS-induced enteritis in juvenile yellow catfish compared to the DSS+NP group.(2)Dietary supplementation of ECP in LP diets significantly enhanced the enzymatic activity and levels of immunoreactive substances,including LZM,C3,C4,and ACP(P<0.05).Mechanistically,first,ECP supplementation modulated macrophage polarization by inhibiting the M1 phenotype while promoting the M2 phenotype,potentially through the JAK-STAT signaling pathway;second,dietary ECP suppressed the phosphorylation cascade of key necroptosis-related proteins,including RIP1,RIP3,and MLKL,potentially via the NF-κB and MAPK signaling pathways.(3)The DSS+ECP2 group demonstrated comparable or superior efficacy to the DSS+NP group in mitigating DSS-induced intestinal enteritis.Conclusions Our results demonstrated that ECP can alleviate DSS-induced enteritis by regulating macrophage polarization and reducing necroptosis.Furthermore,ECP supplementation effectively counteracted the exacerbation of enteritis caused by dietary protein reduction.These findings highlighted the effectiveness and feasibility of ECP in alleviating enteritis and saving protein.
基金Supported by Jilin Province Science and Technology Development Plan Project,No.20210204012YY.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic relapsing inflammatory bowel disease with rising global incidence.Current therapies for UC often provide incomplete relief and are associated with adverse side effects,highlighting the need for alternatives with increased safety and effectiveness.Compound spleen-tonifying composition(CSTC)contains ingredients,such as Pulsatilla chinensis(Bunge)Regel and Glycyrrhiza uralensis Fisch,that have been shown to be efficacious in the treatment of UC.Its mechanism needs to be investigated further.AIM To study the therapeutic effect and mechanism of CSTC in dextran sulfate sodium(DSS)-induced UC in rats.METHODS Sprague-Dawley rats were freely given 4%DSS solution for seven days to establish the UC model.After intervention with CSTC and its different solvent extracts,body weight changes,the disease activity index(DAI),and colon histopathology were assessed to evaluate therapeutic outcomes.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),myeloperoxidase(MPO),glutathione peroxidase(GSH-px),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)in colon tissue were determined to investigate changes in biochemical indicators.RESULTS DSS administration triggered severe UC symptoms,including weight loss,colon shortening,elevated DAI scores,and histological damage.These symptoms were accompanied with oxidative stress(reduced SOD and GSH-px levels and increased MDA and MPO levels),inflammation(elevated TNF-α,IL-1β,and IL-6 levels),and a reduction in the expression levels of tight junction proteins[zonula occludens-1(ZO-1)and occluding].High-and mediumdose CSTC treatment significantly alleviated clinical symptoms,restored colon morphology,normalized oxidative stress markers,suppressed proinflammatory cytokines,and enhanced ZO-1 and occludin levels,demonstrating dose-dependent efficacy.Notably,solvent extraction critically influenced bioactivity:Nonpolar extracts(chloroform and petroleum ether)showed minimal effects,whereas polar extracts(ethyl acetate and n-butanol)remarkably improved clinical symptoms.CONCLUSION The above findings highlight CSTC’s multifaceted anti-UC effects,which are mediated through oxidative stress mitigation and cytokine modulation,while emphasizing the polarity-dependent efficacy of its extracts.
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.
文摘BACKGROUND Acute pancreatitis(AP)is a frequent gastrointestinal emergency characterized by inflammation.It has the potential to progress to organ failure.Fluid therapy plays a critical role in early AP management,mitigating hypovolemia-induced ischemia and systemic inflammatory response syndrome(SIRS).AIM To evaluate dextran 40+Ringer’s lactate solution(RLS)vs RLS alone for fluid therapy in mild to moderate AP.METHODS We conducted a single-center,single-blind,randomized controlled trial involving 108 patients with mild to moderate AP.Participants were randomized to receive either dextran 40+RLS(1:3 ratio)or RLS alone.All patients underwent standardized,goal-directed fluid therapy and were monitored for clinical response,inflammatory markers,and complications.The primary outcomes were reduction in C-reactive protein(CRP)and resolution of SIRS at 72 hours.Secondary outcomes included organ failure,intensive care unit admission,mortality,and length of hospital stay.RESULTS The dextran 40+RLS group demonstrated significantly lower CRP levels.No differences were observed in SIRS changes,fluid overload,refractory status mortality,local complications,or organ failure rates.Hospitalization tended to be shorter in the dextran 40+RLS group(5 days vs 6 days)although not to a statistically significant level(P=0.1).Adverse events were mild and comparable in both groups.CONCLUSION Dextran 40+RLS improved the early CRP response in patients with AP without added complications.Although medium-term outcomes were similar,early benefits support its use in initial management.
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.
文摘2025年8月22日,北京大学药学院李中军教授/李忠堂副研究员团队与石河子大学药学院王恒教授团队合作,在Carbohydrate Polymers期刊发表了题为“Low-molecular-weight dextran sulfate sodium as novel heparanase inhibitor preventing breast cancer metastasis in mice by inhibiting migration and angiogenesis”的研究论文。该研究发现,低分子量硫酸化葡聚糖通过抑制乙酰肝素酶的活性,阻断乳腺癌细胞的侵袭和迁移,为攻克侵袭性乳腺恶性肿瘤提供了新的可靠治疗策略。
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.
