BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of U...Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.展开更多
Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extr...Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.展开更多
Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Lite...Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.展开更多
Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is...Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.展开更多
OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was establi...OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was established and therapeutic effects of GQD were determined by detecting body weight,disease activity index(DAI),colon length and histopathological changes.Then,the expression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay,the expression levels of tight junction proteins were detected by immunohistochemistry and the expression levels of ferroptosis-associated proteins were detected by western blotting.RESULTS:GQD treatment attenuated weight loss and DAI score,increased colon length,ameliorated intestinal histopathological damage,inhibited colonic inflammatory cytokine release and enhanced epithelial barrier function in mice with ulcerative colitis(UC).Furthermore,GQD administration obviously improved the expression of ferroptosis-associated proteins(solute carrier family 7 member 11 and acyl-Co A synthetase long chain family member 4).CONCLUSION:GQD could exert a therapeutic effect on colitis by alleviating colon damage and promoting intestinal mucosal barrier repair in DSS-induced colitis mice through the inhibition of ferroptosis,which may provide an effective natural therapy for the treatment of UC.展开更多
OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with e...OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed t...Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.展开更多
Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-perfo...Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.展开更多
Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To e...BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To evaluate the outcomes of 5-ASA withdrawal due to non-adherence in UC patients while in remission on monotherapy.METHODS Adult patients with UC who were followed up between July 2019 and April 2025 were screened.Patients in remission receiving 5-ASA monotherapy who experienced treatment withdrawal due to non-adherence were included in this study.RESULTS Among 880 patients with UC,30(3.4%)had 5-ASA withdrawal due to nonadherence while in remission on monotherapy.Twelve patients(40%)had disease relapse after a median of 20 months.The rate of patients in remission was 89%in the first year,decreasing to 73%in the second year,and to 64%in the third year.There were no significant differences between patients with and without relapse in terms of demographics,disease extent,remission duration before 5-ASA withdrawal,previous medications,steroid dependence,5-ASA formulation,baseline inflammatory markers,or partial and endoscopic Mayo scores.Most patients(75%)who experienced relapse were successfully treated with 5-ASA monotherapy,while one-fourth of them required corticosteroids.No patients required biologic agents,hospitalization,or surgical intervention.CONCLUSION Intermittent therapy may be safe and feasible for UC patients,especially those in long-term remission,with treatment interruption up to one year considered acceptable.展开更多
BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these pati...BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these patients.CASE SUMMARY A patient with extensive UC presented with steroid dependence and contraindications(past medical history included breast cancer and previous myocardial infarction)to treatment with tumor necrosis factor and Janus kinase inhibitors.DBT ofα4β7 integrin antagonist(vedolizumab)and interleukin 23p19 inhibitor(mirikizumab)resulted in a sustained clinical and biochemical remission.No adverse events were recorded during the follow-up.CONCLUSION This case highlighted the challenge of managing refractory UC,especially in frail patients.展开更多
BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with t...BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of e...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of extraintestinal malignancies.However,no association has been established between these therapies and endometrial stromal sarcoma.This report presents a rare case of endometrial stromal sarcoma in a patient with UC undergoing immunosuppressive treatment and includes a literature review to explore any possible correlation between the disease,the therapies used,and the development of this rare tumor.CASE SUMMARY Female,49 years old,with UC pancolitis extension since 2017.She used aminosalicylates and AZA with non-response.She started infliximab and AZA combination therapy in 2020,with optimization in 2021 due to endoscopic activity.In the same year,the patient presented to the emergency room with ascitis and underwent diagnostic paracentesis,which showed serum-ascites albumin gradient<1.1 g/dL,absence of neoplastic cells,and abdominal and pelvic tomography reported a hypoechoic nodular lesion in the posterior wall of the uterus and elevated carbohydrate antigen 125.Given the suspicion of neoplasia,the suspension of immunosuppressive therapy was indicated.The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy,and the pathological result reported low-grade endometrial sarcoma.It was decided to introduce vedolizumab for the management of UC;however,even after induction therapy,intense clinical and endoscopic disease activity was maintained,with total proctocolectomy being indicated due to clinical refractoriness and a history of neoplasia.CONCLUSION Patients with inflammatory bowel disease have a higher risk of cancer due to inflammation or treatment.Proper screening with multidisciplinary care can improve outcomes.展开更多
The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of t...The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of the factors reducing tolerance to self-antigens.In addition,patients with UC often experience anxiety,depression and other negative emotional and psychological factors aggravating the course of the underlying disease.The study presented by Wang et al shows that the traditional Chinese medicine Wuling can exert its therapeutic effect by reversing the aberrant precursor of brain-derived neurotrophic factor(BDNF)/BDNF signaling in mice with UC and depression.The combination of Wuling powder with mesalazine can exhibit an antidepressant effect and reduce intestinal inflammation.Undoubtedly,the study by Chinese authors deserves attention,and changes in the balance of precursor of BDNF/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signaling may become a novel therapeutic target for clinical treatment and further development of research.展开更多
Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek t...Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.展开更多
Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmenta...Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金Supported by National Natural Science Foundation of China,No.82374200Construction of Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Projects in Pudong New Area-High-Level Research-Oriented Traditional Chinese Medicine Hospital Construction,No.YC-2023-0901.
文摘Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.
基金financially supported by the Natural Science Foundation of Zhejiang Province(LY22C010002)China Postdoctoral Science Foundation(2022M721732)+1 种基金the project of sending sci-tech experts to rural areas in Ningbo city(2022S205)the K.C.Wong Magna Fund of Ningbo University.
文摘Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.
基金financial support from the Postdoctoral Fund of Hebei Medical University(30705010038)the Chunyu Project Initial Funding of Hebei Medical University(CYQD2023012)+3 种基金the Science Research Project of Hebei Education Department(QN2025145)the Hebei Yanzhao Golden Platform Talent Gathering Plan Backbone Talent Project(B2024003013)the Natural Science Foundation of Hebei Province(H2024206375,C2022206018,H2023206068)the Traditional Chinese Medicine Administration Project of Hebei Province(2025427).
文摘Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.
基金financially supported by the Science and Technology Project of Nantong City(Grant No.JC2021097)the Key Project Fund for Clinical Medicine Special Program of Nantong University(Grant No.2024JZ043)Jiangsu Provincial Administration for Market Regulation Science and Technology Program Project(Grant No.KJ2026104).
文摘Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.
基金National Natural Science Foundation Project:Study on the Mechanism of Gegen Qinlian Decoction in Reshaping Macrophage Polarization via Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2-Mediated Neutrophil Extracellular Traps Formation for the Treatment of Ulcerative Colitis with Dampness-Heat Syndrome(No.82505455)。
文摘OBJECTIVE:To explore whether Gegen Qinlian decoction(葛根芩连汤,GQD)targets ferroptosis pathway to ameliorate experimental colitis in mice.METHODS:A mice model of dextran sulfate sodium(DSS)induced colitis was established and therapeutic effects of GQD were determined by detecting body weight,disease activity index(DAI),colon length and histopathological changes.Then,the expression levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay,the expression levels of tight junction proteins were detected by immunohistochemistry and the expression levels of ferroptosis-associated proteins were detected by western blotting.RESULTS:GQD treatment attenuated weight loss and DAI score,increased colon length,ameliorated intestinal histopathological damage,inhibited colonic inflammatory cytokine release and enhanced epithelial barrier function in mice with ulcerative colitis(UC).Furthermore,GQD administration obviously improved the expression of ferroptosis-associated proteins(solute carrier family 7 member 11 and acyl-Co A synthetase long chain family member 4).CONCLUSION:GQD could exert a therapeutic effect on colitis by alleviating colon damage and promoting intestinal mucosal barrier repair in DSS-induced colitis mice through the inhibition of ferroptosis,which may provide an effective natural therapy for the treatment of UC.
基金Supported by Shandong Provincial Natural Science,Study on the Structure-Activity Relationship and Mechanism of Licorice Chalcone Components in Synergizing with Immune Checkpoint Inhibitors for Anticancer Therapy(No.ZR2020MH380)Mechanisms of the Novel Flavone C-Glycoside 6'-ORhamnosyllutonarin from Dianthus superbus Improves Non-alcoholic Fatty Liver Disease via Modulating the Juxtaposed with Another Zinc Finger gene 1/Adenosine Monophosphate-activated Protein Kinase/Sterol Regulatory Element-Binding Protein Pathway(No.ZR2024MC209)。
文摘OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金financially supported by the Major Science and Technology Special Projects in Henan Province(231100310200)the Key R&D Projects in Henan Province(241111314200)+1 种基金the National Natural Science Foundation of China(32302172)the Natural Science Foundation of Henan Province(252300423038).
文摘Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.
基金supported by the Key Research and Development Project of Hainan Province(ZDYF2022SHFZ099)the Academic Enhancement Support Program of Hainan Medical University(XSTS2025040 and XSTS2025063).
文摘Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
文摘BACKGROUND 5-aminosalicylates(5-ASA)are the primary treatment for mild to moderate ulcerative colitis(UC).Maintenance therapy with 5-ASA has been shown to reduce both the risk of relapse and colorectal cancer.AIM To evaluate the outcomes of 5-ASA withdrawal due to non-adherence in UC patients while in remission on monotherapy.METHODS Adult patients with UC who were followed up between July 2019 and April 2025 were screened.Patients in remission receiving 5-ASA monotherapy who experienced treatment withdrawal due to non-adherence were included in this study.RESULTS Among 880 patients with UC,30(3.4%)had 5-ASA withdrawal due to nonadherence while in remission on monotherapy.Twelve patients(40%)had disease relapse after a median of 20 months.The rate of patients in remission was 89%in the first year,decreasing to 73%in the second year,and to 64%in the third year.There were no significant differences between patients with and without relapse in terms of demographics,disease extent,remission duration before 5-ASA withdrawal,previous medications,steroid dependence,5-ASA formulation,baseline inflammatory markers,or partial and endoscopic Mayo scores.Most patients(75%)who experienced relapse were successfully treated with 5-ASA monotherapy,while one-fourth of them required corticosteroids.No patients required biologic agents,hospitalization,or surgical intervention.CONCLUSION Intermittent therapy may be safe and feasible for UC patients,especially those in long-term remission,with treatment interruption up to one year considered acceptable.
文摘BACKGROUND Despite advances in the treatment of ulcerative colitis(UC),some patients remain refractory to the currently available treatments.Dual biologic therapy(DBT)has emerged as a promising strategy for these patients.CASE SUMMARY A patient with extensive UC presented with steroid dependence and contraindications(past medical history included breast cancer and previous myocardial infarction)to treatment with tumor necrosis factor and Janus kinase inhibitors.DBT ofα4β7 integrin antagonist(vedolizumab)and interleukin 23p19 inhibitor(mirikizumab)resulted in a sustained clinical and biochemical remission.No adverse events were recorded during the follow-up.CONCLUSION This case highlighted the challenge of managing refractory UC,especially in frail patients.
文摘BACKGROUND Tofacitinib is an oral,selective Janus kinase inhibitor that is approved for the treatment of ulcerative colitis(UC).The 8-week induction protocol involves the administration of 10 mg twice daily(bid)with the possibility of extending the induction period to 16 weeks.The maintenance dose of tofacitinib is either 5 mg or 10 mg bid.AIM To assess predictors for clinical remission and drug persistence in patients with UC receiving the extended induction tofacitinib protocol.METHODS This was a real-world multicenter retrospective study in patients with moderateto-severe UC.Patients received physician-directed extended induction tofacitinib treatment.We collected clinical and demographic data at baseline and data regarding clinical,laboratory,and endoscopic evaluations,therapeutic modifications,and adverse events at the 52-week follow-up.Possible predictors for clinical remission at week 52 was the primary endpoint.Differences between patients receiving 5 mg bid vs 10 mg bid at week 52 and identification of predictors for treatment persistence were secondary endpoints.RESULTS Thirty-seven consecutive patients from 11 medical centers were included[51.4%males with median age 39(17-64)years].Twenty-eight patients continued treatment until week 52(75.7%)with 67.9%receiving 10 mg tofacitinib;all had prior history of biologic use.We observed that 57.1%of patients achieved clinical remission(66.7%in the 5 mg tofacitinib group and 52.6%in the 10 mg tofacitinib group,P=0.483).De-escalation to 5 mg tofacitinib was attempted in 17 patients with a success rate of 52.9%.Prior biologic use was significantly more frequent in patients treated with 10 mg tofacitinib.Active smoking was significantly associated with treatment discontinuation at week 52.We identified eight adverse events,and only one led to treatment discontinuation.CONCLUSION Our results supported the extended induction strategy with tofacitinib in selected patients with UC.Patients with prior failure of advanced therapies particularly benefitted,highlighting the importance of personalized maintenance regimens.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory bowel disease treated with immunosuppressants to control inflammation.Drugs like azathioprine(AZA)and anti-tumor necrosis factor agents increase the risk of extraintestinal malignancies.However,no association has been established between these therapies and endometrial stromal sarcoma.This report presents a rare case of endometrial stromal sarcoma in a patient with UC undergoing immunosuppressive treatment and includes a literature review to explore any possible correlation between the disease,the therapies used,and the development of this rare tumor.CASE SUMMARY Female,49 years old,with UC pancolitis extension since 2017.She used aminosalicylates and AZA with non-response.She started infliximab and AZA combination therapy in 2020,with optimization in 2021 due to endoscopic activity.In the same year,the patient presented to the emergency room with ascitis and underwent diagnostic paracentesis,which showed serum-ascites albumin gradient<1.1 g/dL,absence of neoplastic cells,and abdominal and pelvic tomography reported a hypoechoic nodular lesion in the posterior wall of the uterus and elevated carbohydrate antigen 125.Given the suspicion of neoplasia,the suspension of immunosuppressive therapy was indicated.The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy,and the pathological result reported low-grade endometrial sarcoma.It was decided to introduce vedolizumab for the management of UC;however,even after induction therapy,intense clinical and endoscopic disease activity was maintained,with total proctocolectomy being indicated due to clinical refractoriness and a history of neoplasia.CONCLUSION Patients with inflammatory bowel disease have a higher risk of cancer due to inflammation or treatment.Proper screening with multidisciplinary care can improve outcomes.
文摘The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of the factors reducing tolerance to self-antigens.In addition,patients with UC often experience anxiety,depression and other negative emotional and psychological factors aggravating the course of the underlying disease.The study presented by Wang et al shows that the traditional Chinese medicine Wuling can exert its therapeutic effect by reversing the aberrant precursor of brain-derived neurotrophic factor(BDNF)/BDNF signaling in mice with UC and depression.The combination of Wuling powder with mesalazine can exhibit an antidepressant effect and reduce intestinal inflammation.Undoubtedly,the study by Chinese authors deserves attention,and changes in the balance of precursor of BDNF/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signaling may become a novel therapeutic target for clinical treatment and further development of research.
文摘Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.
文摘Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.
