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ABSTRACT Background: Microscopic colitis (MC) is a chronic inflammatory bowel disease causing non-bloody diarrhea, and several cases are undiagnosed as a hidden cause of chronic diarrhea. Objective: We aimed to report the symptoms, delay diagnosis and the treatment of MC in a case series. Methods: All patients were treated at a Gastroenterology reference office from May 2022 to June 2023. Personal history including preexisting disorders, use of medications and smoking habits were collected. The delay between the onset of symptoms and the correct diagnosis was informed. All patients consented to use budesonide MMX (Corament®) off label. Results: During the study period, six Caucasoid patients were diagnosed with MC, five females and one male, between the ages of 65 and 74. All patients had comorbities and were taking multiple prescription drugs. Laboratory findings showed negative serology for celiac disease for all patients, normal levels of albumin and vitamin B12. The delay between the symptoms and the MC diagnosis varied from 2 months to 6 years. All patients had a previous diagnosis of irritable bowel syndrome. All patients were in complete clinical remission during the treatment and referred no side effects of the drug. Conclusion: Older females using high-risk medications are suggestive of MC. Preventing delay in the diagnosis of MC is crucial to improvement in patients´ quality of life. Budesonide MMX appears to be effective, safe and well-tolerated.
RESUMO Contexto: A colite microscópica (CM) é uma doença inflamatória intestinal crônica que causa diarreia não sanguinolenta, e vários casos não são diagnosticados como uma causa oculta de diarreia crônica. Objetivo: Esse estudo visou relatar os sintomas, qual o atraso diagnóstico e o tratamento da CM em uma série de casos. Métodos: Todos os pacientes foram atendidos em um consultório de referência em Gastroenterologia no período de maio de 2022 a junho de 2023. Foram coletados antecedentes pessoais, incluindo distúrbios preexistentes, uso de medicamentos e tabagismo. Foi buscado o período entre o início dos sintomas e o diagnóstico correto. Todos os pacientes consentiram em usar budesonida MMX (Corament®) off label. Resultados: Durante o período do estudo, seis pacientes caucasóides foram diagnosticados com CM, cinco mulheres e um homem, com idades entre 65 e 74 anos. Todos os pacientes apresentavam comorbidades e faziam uso de vários medicamentos prescritos. Os achados laboratoriais mostraram sorologia negativa para doença celíaca em todos os pacientes, níveis normais de albumina e vitamina B12. O atraso entre os sintomas e o diagnóstico de CM variou de 2 meses a 6 anos. Todos os pacientes tinham diagnóstico prévio de síndrome do intestino irritável. Todos os pacientes apresentaram remissão clínica completa durante o tratamento e não referiram efeitos colaterais da droga. Conclusão: As mulheres mais velhas que usam medicamentos de alto risco são sugestivas de CM. Evitar o atraso no diagnóstico de CM é fundamental para melhorar a qualidade de vida dos pacientes. A budesonida MMX foi eficaz, segura e bem tolerada.
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ABSTRACT Background: Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce studies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Methods: Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. Results: A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). Conclusion: There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting.
RESUMO Contexto: As doenças inflamatórias intestinais (DII) têm taxas crescentes de incidência e prevalência em todo o mundo. Na DII, são escassos os estudos comparando as diferenças entre os pacientes de acordo com o nível socioeconômico. Objetivo: Nosso objetivo foi avaliar comparativamente as hospitalizações, o uso de biológicos e as taxas de cirurgia em pacientes com DII entre os sistemas público e privado de saúde. Métodos: Estudo de coorte retrospectivo unicêntrico em pacientes com DII de uma unidade terciária de referência da América Latina, entre 2015 e 2021. Os pacientes com DC (doença de Crohn) e retocolite ulcerativa foram classificados em dois subgrupos: sistema público e privado. Características demográficas, hospitalizações, necessidade de cirurgia e biológicos foram comparadas. Resultados: Foram inclusos 500 pacientes, sendo 322 com DC e 178 com retocolite ulcerativa. Internações por DC foram frequentes em ambos os sistemas de saúde (76,28% na rede privada e 67,46% na rede pública). Mais da metade dos pacientes havia sido submetida a uma ou mais cirurgias abdominais relacionadas à DC, sem diferença significativa entre os subgrupos. Embora não tenha havido diferença nas taxas de uso de terapia biológica nos subgrupos de DC, o infliximabe foi mais utilizado no ambiente público (57,69% vs 43,97%). Não houve diferença nas internações relacionadas a retocolite ulcerativa entre os subgrupos (público 30,69% e privado 37,66%) e nas taxas de colectomia (público: 16,83%, privado: 19,48%). Os biológicos foram prescritos quase duas vezes mais no privado do que no público (45,45 vs 22,77%). Conclusão: Não houve diferença nas taxas de internação hospitalar e de cirurgia abdominal entre os sistemas. Nos pacientes com retocolite ulcerativa, houve maior utilização da terapia biológica no setor privado de saúde.
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Objective @#To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients.@*Methods@#Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. @*Results@#MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one.@*Conclusions@#Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.
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AIM:To explore the anti-ulcerative colitis mechanism of Buzhongyiqi pills based on the network pharmacology and experimental verification. METHODS: UPLC-QE-MS was used for qualitative analysis of Buzhongyiqi pills. Targets of the chemistry constituents and the disease were retrieved from GeneCards. Then the protein-protein interaction (PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Ulcerative colitis mouse model was established to verify the key targets. RESULTS: A total of 41 constituents migrating of Buzhongyiqi pills were identified. A total of 123 common targets of the constituents and the disease and 24 core targets were screened out.KEGG enrichment and PPI network analysis showed that Buzhongyiqi pills may play a role in the treatment of ulcerative colitis through Akt, PI3K and other pathways. Furthermore, the results of animal experiments showed that Buzhongyiqi pills could significantly improve the depression behaviors of ulcerative colitis, reduce the levels of IL-6 and TNF-α in serum, inhibition Akt/PI3K signaling, and reduce the protein expression of PI3K. CONCLUSION: Buzhongyiqi pills may play a role in the treatment of ulcerative colitis by inhibition Akt / PI3K signaling pathway, and inhibiting PI3K and reduce the levels of IL-6 and TNF-α in the mice.
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Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.
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@#Introduction: Understand the progression of colorectal cancer from the beginning until the advance stages is difficult and challenging. However, this could be overcome with a good animal model. Methods: In this study, a modified approach had been used to develop colorectal cancer model. The model was developed and monitored from colitis formation until the late stage of colorectal cancer. The changes of neutrophil lymphocyte ratio (NLR), serum microRNAs and infiltrate neutrophil in different stages of colorectal cancer were assessed in this study. Results: Results showed that the progression of the disease is correlated with NLR as early as the formation of colitis (r=0.121, p<0.026). Meanwhile, the size of the tumor at each stage is also associated with the NLR value (r=0.185, p<0.0012). In the serum microRNAs study, it was found microRNAs expression in blood serum change in different stages of colorectal cancer. In the early stage of colitis formation, miR223 (> 3 fold expression, p < 0.0025) were abundantly found in the blood serum. Meanwhile in others stage mild (miRNA345 > 2.5 fold, p<0.0011), moderate (miRNA347 & miR512 > 3 fold, p<0.002) and severe (miR31 & miR145 > 2 fold, p<0.0001) microRNAs were also found expressed differently. The quantities of infiltrate neutrophil were varied in different stages of the disease. Conclusion: This study provides an insight into the immunity and molecular level of colorectal cancer and it allows a progressive monitoring on the changes in the molecular, cellular and histological level.
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Ulcerative colitis （UC） is a chronic inflammatory bowel disease primarily affecting the colon and rectum， with the typical symptoms such as abdominal pain， bloody diarrhea， and tenesmus. The pathogenesis of UC remains to be fully elucidated. The disease is prone to recurrence， seriously affecting the patients' quality of life. Conventional therapies for UC have limitations， including unsatisfactory clinical efficacy， lengthy courses， and adverse reactions. Therefore， there is an urgent need to explore new therapeutic agents. Peroxisome proliferator-activated receptor gamma （PPARγ）， a ligand-dependent nuclear receptor protein that plays a crucial role in maintaining intestinal homeostasis， is closely associated with the onset and development of UC. Traditional Chinese medicine （TCM） has advantages such as multi-targeting and mild side effects in the treatment of UC. Recent studies have shown that TCM can exert the therapeutic effects on UC by modulating PPARγ. The TCM methods for regulating PPARγ include clearing heat， drying dampness， moving Qi， activating blood， resolving stasis， invigorating the spleen， warming the kidney， and treating with both tonification and elimination. On one hand， TCM directly activates PPARγ or mediates signaling pathways such as nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， Toll-like receptor 4 （TLR4）， and regulates helper T cell 17 （Th17）/regulatory T cell （Treg） balance to promote macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype， thereby inhibiting intestinal inflammation. On the other hand， TCM regulates the intestinal metabolism to activate PPARγ， lower the nitrate level， and maintain local hypoxia. In this way， it can restore the balance between specialized anaerobes and facultative anaerobes， thereby improving the gut microbiota and treating UC. This article summarizes the role of PPARγ in UC and reviews the research progress of TCM in treating UC by intervening in PPARγ in the last five years， aiming to give insights into the treatment and new drug development for UC.
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ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg-1）， and QHJ high-dose （QHJ-H， 40 g·kg-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5th week to the 14th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.
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OBJECTIVE To analyze the current research status and hotspots of traditional Chinese medicine （TCM） in the treatment of ulcerative colitis （UC） via bibliometrics method. METHODS The clinical， basic， and pharmacological research of TCM in the treatment of UC in the CNKI core journals database and Web of Science core collection database were searched from January 2013 to April 2023. The CiteSpace 6.1. R6 software was adopted to analyze the number of authors， institutions and keywords. What’s more， a visual map was plotted. RESULTS Overall， 1 060 Chinese articles and 555 English articles were included. In 2013-2023， the number of relevant research documents issued by TCM in the treatment of UC has shown a significant upward trend. Among the included literature， there are 59 core authors in Chinese and 33 core authors in English. A stable group centered on multiple key scholars has been formed. Chinese research hotspots focus on the experience of famous doctors， classical famous prescriptions， etc.； English research hotspots center on cells， expression， activation，signaling pathway， etc. The study of intestinal flora， inflammatory factors， and other mechanisms has attracted much attention in both Chinese and English literature. CONCLUSIONS In recent years， some progress has been made in the study of treating UC with TCM. In the future， the top-level design of clinical research protocols based on maintaining the characteristics of TCM should be strengthened. Moreover， the long- term efficacy evaluation of TCM in the treatment of UC should be emphasized， and new technologies such as metabolomics and protein sequencing should be actively adopted to explore the scientific connotation of TCM compatibility in treating diseases.
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ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.
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OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.
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Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.
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Ulcerative colitis （UC） is a chronic inflammatory bowel disease with complex etiology. The pathogenesis of this disease， due to a combination of factors， is complex and has not yet been elucidated. Among them， intestinal mucosal barrier damage is the basic pathological change of UC. As a non-destructive response of cells， autophagy regulates intestinal mucosal immunity， inflammation， oxidative stress， and bacterial homeostasis through degradation and reabsorption to actively repair damaged intestinal mucosal barrier， exerting a key role in the occurrence and development of UC. The disease is mainly treated clinically with aminosalicylic acid preparations， glucocorticoids， and immunosuppressants. Western medicine treatment of the disease has a fast onset of effect， and the short-term efficacy is definite， but the long-term application is easy to be accompanied by more adverse reactions. Moreover， some drugs are expensive， bringing great physical and mental pain and economic burden to patients. Therefore， it is urgent to explore new therapies with stable efficacy and mild adverse effects. In recent years， a large number of studies have shown that Chinese medicine can regulate autophagy of the intestinal mucosa with multiple targets and effects and repair the intestinal mucosal barrier function， thereby inhibiting the development of UC. Many experiments have shown that the active ingredient or monomers and compound formulas of Chinese medicine can improve the immunity of the intestinal mucosa， inflammation， oxidative stress， and flora by regulating the level of autophagy to maintain the normal function of the intestinal mucosal barrier to effectively intervene in UC， providing a new measure for the prevention and treatment of UC. However， there is a lack of systematic review of Chinese medicine in regulating the level of autophagy in the intestinal mucosa for the prevention and treatment of UC. Therefore， based on the current research on UC， autophagy process， and Chinese medicine treatment， this article reviewed the relationship of autophagy and its key target proteins with UC to clarify the key role of autophagy in UC production and systematically summarized Chinese medicines targeting the regulation of autophagy to treat UC in recent years to provide new ideas for the treatment and drug development of UC.
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OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.
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ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg-1）， paeoniflorin （50 mg·kg-1） + inhibitor （20 mg·kg-1） group， and high dose （50 mg·kg-1）， medium dose （25 mg·kg-1）， and low dose （12.5 mg·kg-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.
ABSTRACT
Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.
ABSTRACT
The clinical changes of ulcerative colitis （UC） with the main syndrome of large intestine dampness-heat and the alterations of intestinal flora in UC were summarized to reveal the underlying mechanism. After review of the treatment methods for UC with the syndrome of large intestine dampness-heat， we identified the representative traditional Chinese medicines and compound prescriptions and explored the treatment mechanisms. Furthermore， we probed into the associations of UC and the treatment methods with the intestinal flora. The related articles were retrieved from China National Knowledge Infrastructure （CNKI）. The available studies have shown that Akkermansia muciniphila， Escherichia coli， Enterococcus， and probiotics such as Bifidobacterium and Lactobacillus are closely associated with Chinese medicines in UC patients with the syndrome of large intestine dampness-heat. However， due to the shortcomings in clinical research and the susceptibility of intestinal flora to diverse factors， it is still challenging to accurately characterize the intestinal flora changes associated with diseases. Additionally， the research on the mechanisms of Chinese medicines in regulating intestinal flora in UC patients with the syndrome of large intestine dampness-heat remains to be improved. The feasibility of using Chinese medicines and compound prescriptions for precise regulation of intestinal flora in these patients is still debatable. In this regard， scientific issues such as the biological connotation of UC with the syndrome of large intestine dampness-heat and the correlation between syndrome and intestinal flora have become primary research tasks. Additionally， attention should also be paid to the interactions between the intestinal lumen exposure profile of Chinese medicines and intestinal flora. Finally， the thinking of traditional Chinese medicine （TCM） and the concepts of modern medicine should be combined for the research on the formulation of TCM regimens for regulating intestinal flora in treating UC.
ABSTRACT
Background and Aims: Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods: This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results: None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion: No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion. (AU)
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Immunoglobulin A , Inflammatory Bowel Diseases , Celiac Disease , Cohort Studies , AntibodiesABSTRACT
Objective: To evaluate the application of proactive pro-drug therapy (TDM) at week six in users of infliximab therapy in ulcerative colitis patients and to analyze the need for further disease optimization. Method: This is a retrospective analysis that will be carried out simultaneously at the Hospital de Clínicas de Passo Fundo and at the Endoclin Diagnostic Center in the city of Passo Fundo, with secondary data collection between January 2020 and May 2022. The sample included patients from both sexes, regardless of age, who are being followed up in the services mentioned above, by signing the informed Free and Clarified Consent Term. Results: 63.2% of patients required optimization of their treatment based on the serum level assessment at week six. Conclusion: Proactive TDM performed at week six benefits patients in order to complete indications for treatment to avoid lack of drug response and complications from the disease. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Colitis, Ulcerative/therapy , Drug Monitoring , Health Profile , Retrospective Studies , Infliximab/therapeutic useABSTRACT
ABSTRACT Background: Clostridioides difficile infection (CDI) is a potentially severe disease that can present with refractoriness, recurrence, and evolution to death. In Brazil, the epidemiology of CDI seems to differ from that of the United States and most European countries, with only one ribotype (RT) 027-related case and a high prevalence of RT106. Objective: The aim of this study was to evaluate the outcomes of CDI and its possible association with ribotypes at a university hospital in Brazil. Methods: A total of 65 patients with CDI were included and stool samples were submitted to A/B toxin detection and toxigenic culture, and toxigenic isolates (n=44) were also PCR ribotyped. Results: Patients' median age was 59 (20-87) years and there were 16 (24.6%) deaths. The median Charlson comorbidity index (CCI) was 4 (0-15) and 16.9% of the patients had CCI ≥8. The ATLAS score and non-improvement of diarrhea were related to higher mortality. A longer length of hospitalization was related to the enteral nutrition and use of multiple antibiotics. The period between CDI diagnosis and hospital discharge was longer in those who received new antibiotics after diagnosis, multiple antibiotics, and required intensive care treatment. Recurrence was associated with CCI >7. Twenty ribotypes were identified and RT106 was the most frequently detected strain (43.2%). No relationship was observed between the ribotypes and outcomes. CDI was present in patients with more comorbidities. Conclusion: Risk factors for higher mortality, longer hospital stay and recurrence were identified. A diversity of ribotypes was observed and C. difficile strains were not related to the outcomes.
RESUMO Contexto: A infecção pelo Clostridioides difficile (ICD) é uma doença potencialmente grave que pode se apresentar com refratariedade, recidiva e evoluir para óbito. No Brasil, a epidemiologia da ICD parece diferir da dos Estados Unidos e da maioria dos países europeus, com apenas um caso relacionado ao ribotipo (RT) 027 e alta prevalência do RT106. Objetivo: Avaliar os desfechos da ICD e sua possível associação com ribotipos em um hospital universitário do Brasil. Métodos: Um total de 65 pacientes com ICD foram incluídos e amostras de fezes foram submetidas à detecção de toxina A/B e cultura toxigênica e as cepas toxigênicas isoladas (n=44) também foram ribotipadas por PCR. Resultados: A idade mediana dos pacientes foi de 59 (20-87) anos e houve 16 (24,6%) óbitos. A mediana do índice de comorbidade de Charlson (ICC) foi de 4 (0-15) e 16,9% dos pacientes apresentaram ICC ≥8. O escore ATLAS e a não melhora da diarreia foram relacionados a maior mortalidade. Maior tempo de internação esteve relacionado à nutrição enteral e ao uso de múltiplos antibióticos. O período entre o diagnóstico de ICD e a alta hospitalar foi maior naqueles que receberam novos antibióticos após o diagnóstico, múltiplos antibióticos e necessitaram de tratamento intensivo. A recorrência foi associada com ICC >7. Vinte ribotipos foram identificados e o RT106 foi a cepa mais frequentemente detectada (43,2%). Não foi observada relação entre os ribotipos e os desfechos. ICD esteve presente em pacientes com mais comorbidades. Conclusão: Foram identificados fatores de risco para maior mortalidade, maior tempo de internação e recorrência. Uma diversidade de ribotipos foi observada e cepas de C. difficile não foram relacionadas aos desfechos.