Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

The role of a novel antibacterial substance,cyclic opine-producing Lacticaseibacillus rhamnosus LS8 in ameliorating ulcerative colitis:a fecal microbiota transplantation study

Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.

Construction of the underlying circRNA-miRNA-mRNA regulatory network and a new diagnostic model in ulcerative colitis by bioinformatics analysis

BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.

Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome

Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

Enhancing Ulcerative Colitis Diagnosis:A Multi-Level Classification Approach with Deep Learning

The evaluation of disease severity through endoscopy is pivotal in managing patients with ulcerative colitis,a condition with significant clinical implications.However,endoscopic assessment is susceptible to inherent variations,both within and between observers,compromising the reliability of individual evaluations.This study addresses this challenge by harnessing deep learning to develop a robust model capable of discerning discrete levels of endoscopic disease severity.To initiate this endeavor,a multi-faceted approach is embarked upon.The dataset is meticulously preprocessed,enhancing the quality and discriminative features of the images through contrast limited adaptive histogram equalization(CLAHE).A diverse array of data augmentation techniques,encompassing various geometric transformations,is leveraged to fortify the dataset’s diversity and facilitate effective feature extraction.A fundamental aspect of the approach involves the strategic incorporation of transfer learning principles,harnessing a modified ResNet-50 architecture.This augmentation,informed by domain expertise,contributed significantly to enhancing the model’s classification performance.The outcome of this research endeavor yielded a highly promising model,demonstrating an accuracy rate of 86.85%,coupled with a recall rate of 82.11%and a precision rate of 89.23%.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

Exploring the autophagy-related pathogenesis of active ulcerative colitis

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Unraveling the mechanism of malancao in treating ulcerative colitis:A multi-omics approach

BACKGROUND Malancao(MLC)is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis(UC).Nevertheless,the precise molecular mechanisms underlying its efficacy remain elusive.This study leveraged ultrahigh-performance liquid chromatography coupled with exactive mass spectrometry(UHPLC-QE-MS),network pharmacology,molecular docking(MD),and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management.AIM To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing.METHODS This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples.Furthermore,the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets.Additionally,the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC.Finally,MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential.RESULTS Firstly,through a comprehensive analysis of UHPLC-QE-MS data and public database resources,we identified 146 drug-disease cross targets related to 11 bioactive components.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management,lipid metabolism,atherosclerosis,and other processes.They also affect AGE-RAGE and apoptosis signaling pathways.Secondly,by analyzing the differences in diseases,we identified key research targets.These core targets are related to 11 active substances,including active ingredients such as quercetin and luteolin.Finally,MD analysis revealed the stability of compound-protein binding,particularly between JUNLuteolin,JUN-Quercetin,HSP90AA1-Wogonin,and HSP90AA1-Rhein.Therefore,this suggests that MLC may help alleviate intestinal inflammation in UC,restore abnormal lipid accumulation,and regulate the expression levels of core proteins in the intestine.CONCLUSION The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway.The amalgamation of botanical resources,metabolomics,natural products,MD,and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis

BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.

Refractory autoimmune hemolytic anemia in a patient with systemic lupus erythematosus and ulcerative colitis:A case report

BACKGROUND Ulcerative colitis(UC)and systemic lupus erythematosus(SLE)are both systemic immunoreactive diseases,and their pathogenesis depends on the interaction between genes and environmental factors.There are no reports of UC with SLE in China,but six cases of SLE with UC have been reported in China.The combination of these two diseases has distinct effects on the pathogenesis of both diseases.CASE SUMMARY A female patient(30 years old)came to our hospital due to dull umbilical pain,diarrhea and mucous bloody stool in August 2018 and was diagnosed with UC.The symptoms were relieved after oral administration of mesalazine(1 g po tid)or folic acid(5 mg po qd),and the patient were fed a control diet.On June 24,2019,the patient was admitted for treatment due to anemia and tinnitus.During hospitalization,the patient had repeated low-grade fever and a progressively decreased Hb level.Blood tests revealed positive antinuclear antibody test,positive anti-dsDNA antibody,0.24 g/L C3(0.9-1.8 g/L),0.04 g/L C4(0.1-0.4 g/L),32.37 g/L immunoglobulin(8-17 g/L),and 31568.1 mg/24 h total 24-h urine protein(0-150 mg/24 h).The patient was diagnosed with SLE involving the joints,kidneys and blood system.Previously reported cases of SLE were retrieved from PubMed to characterize clinicopathological features and identify prognostic factors for SLE.CONCLUSION The patient was discharged in remission after a series of treatments,such as intravenous methylprednisolone sodium succinate,intravenous human immunoglobulin,cyclophosphamide injection,and plasma exchange.After discharge,the patient took oral prednisone acetate tablets,cyclosporine capsules,hydroxychloroquine sulfate tablets and other treatments for symptoms and was followed up regularly for 1 month,after which the patient's condition continued to improve and stabilize.

Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway

BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging.Moreover,no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.AIM To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.METHODS This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021.The patients with UC were divided into two groups(control and experimental).The peripheral blood of the experimental and control groups were collected under aseptic conditions.The expression of TLR4 protein,NF-κB,IL-6,and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug.Linear co rrelation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17,and P<0.05 was considered statistically significant.RESULTS There were no significant differences in the patient characteristics between the control and experimental groups.The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group(P<0.05).The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group(P<0.05).The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17(r=0.823,P<0.05).CONCLUSION Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

A systematic review of the efficacy of traditional Chinese medicine retention enema in the treatment of ulcerative colitis

The objective of this study is to summarize the efficacy and safety of traditional Chinese medicine(TCM)enema in the treatment of ulcerative colitis(UC).The randomized controlled trials on TCM enema intervention in the treatment of UC were searched in seven databases:PubMed,Embase,Web of Science,CBM,CNKI,Wanfang Database,and VIP Database from January 1,2013 to June 6,2022,and the data were analyzed using RevMan 5.3 software.A total of 18 studies involving 1514 UC patients were included.Meta analysis results showed that compared with conventional Western medicine,Chinese medicine enema had a significant effect on UC,and the clinical effective rate of the experimental group using Chinese medicine enema was 4.45 times that of the control group using conventional Western medicine(odds ratio=4.45,95%confidence interval[3.27,6.06]).Therefore,Chinese medicine enema is effective in the treatment of UC,and can significantly reduce related symptoms.

Treatment endpoints in ulcerative colitis:Does one size fit all?

A treat-to-target strategy in inflammatory bowel disease(IBD)involves treatment intensification in order to achieve a pre-determined endpoint.Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician’s subjective assessment of symptoms.However,choice of treatment endpoints remains a challenge in management of IBD via a treat-to-target strategy.The treatment endpoints for ulcerative colitis(UC),recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)consensus have changed somewhat over time.The latest STRIDE-II consensus advises immediate(clinical response),intermediate(clinical remission and biochemical normalisation)and long-term treatment(endoscopic healing,absence of disability and normalisation of health-related quality of life,as well as normal growth in children)endpoints in UC.However,achieving deeper levels of remission,such as histologic normalisation or healing of the gut barrier function,may further improve outcomes among UC patients.Generally,all medical therapy should seek to improve short-and long-term mortality and morbidity.Hence treatment endpoints should be chosen based on their ability to predict for improvement in short-and long-term mortality and morbidity.Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient.In addition,changing therapy that has achieved partial response may lead to worse outcomes,with failure to recapture response on treatment reversion.Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians,or may have strong opinions re certain therapies.Potential benefits and harms of therapies,incremental benefits of achieving deeper levels of remission,as well as uncertainties of the same,need to be discussed with individual patients,and a treatment endpoint agreed upon with the clinician.Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.focus on quantifying the incremental benefits and risks of achieving deeper levels of remission,such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.

Gut microbiota predicts the diagnosis of ulcerative colitis in Saudi children

BACKGROUND Ulcerative colitis(UC)is an immune-mediated chronic inflammatory condition with a worldwide distribution.Although the etiology of this disease is still unknown,the understanding of the role of the microbiota is becoming increasingly strong.AIM To investigate the predictive power of the gut microbiota for the diagnosis of UC in a cohort of newly diagnosed treatment-naïve Saudi children with UC.METHODS The study population included 20 children with a confirmed diagnosis of UC and 20 healthy controls.Microbial DNA was extracted and sequenced,and shotgun metagenomic analysis was performed for bacteria and bacteriophages.Biostatistics and bioinformatics demonstrated significant dysbiosis in the form of reduced alpha diversity,beta diversity,and significant difference of abundance of taxa between children with UC and control groups.The receiver operating characteristic curve,a probability curve,was used to determine the difference between the UC and control groups.The area under the curve(AUC)represents the degree of separability between the UC group and the control group.The AUC was calculated for all identified bacterial species and for bacterial species identified by the random forest classification algorithm as important potential biomarkers of UC.A similar method of AUC calculation for all bacteriophages and important species was used.RESULTS The median age and range were 14(0.5-21)and 12.9(6.8-16.3)years for children with UC and controls,respectively,and 40%and 35%were male for children with UC and controls,respectively.The AUC for all identified bacterial species was 89.5%.However,when using the bacterial species identified as important by random forest classification algorithm analysis, the accuracy increased to 97.6%. Similarly, the AUC for all theidentified bacteriophages was 87.4%, but this value increased to 94.5% when the important bacteriophagebiomarkers were used.CONCLUSIONThe very high to excellent AUCs of fecal bacterial and viral species suggest the potential use of noninvasivemicrobiota-based tests for the diagnosis of unusual cases of UC in children. In addition, the identification ofimportant bacteria and bacteriophages whose abundance is reduced in children with UC suggests the potential ofpreventive and adjuvant microbial therapy for UC.

Shao Yao Decoction exerts a protective effect on ulcerative colitis by inhibiting inflammation mediated by hypercoagulability

Background:Shaoyao decoction(SYD)has been found widespread clinical use in treating ulcerative colitis(UC).However,the mechanism underlying SYD impact on UC remains elusive.Materials and methods:We preliminarily evaluated the therapeutic effect of SYD intervention in a dextran sulfate sodium-induced UC mouse model by analyzing the body weight change,disease activity index score,colon length,and HE staining results of colon tissue in each group of mice.Subsequently,we determined pro-inflammatory cytokines level and blood coagulation markers in the colon tissues of mice in each group to evaluate the effect of SYD intervention on colonic inflammatory response and coagulation function in UC mice.Results:Our findings emphasize the significant therapeutic effect of SYD on UC,including slowed down body weight loss,reduced disease activity index score,increased colon length,and reduced inflammatory infiltration in colon tissue.Moreover,SYD intervention significantly downregulated the levels of pro-inflammatory cytokines IL-1β,IL-6,and IL-17A in the colon.Furthermore,SYD intervention reversed the coagulation-related indicators such as prothrombin time,fibrinogen,P-selectin,D-dimer,and platelet glycomembrane protein IIb/IIIa.Conclusion:Our results elucidate the substantial therapeutic impact of SYD on UC mice.Importantly,the therapeutic mechanism of SYD in addressing UC potentially involves the inhibiting of inflammatory response mediated by hypercoagulability.