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Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.
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RESUMEN Introducción: Se ha tratado de identificar los factores genéticos relacionados con susceptibilidad para enfermedad inflamatoria intestinal (EII), y los hallazgos actuales se inclinan por un modelo de patología complejo, sin un patrón hereditario claro. Objetivo: Realizar caracterización fenotípica y genotípica de pacientes con EII en población colombiana y describir su posible asociación con predisposición. Materiales y métodos: Serie de casos, 16 pacientes con EII por criterios clínicos y anatomopatológicos, inicio de síntomas gastrointestinales después de los 18 años. Todos tuvieron asesoramiento genético pre-test y se realizaron árboles genealógicos de mínimo tres generaciones. También, genotipificación, por medio de un panel de genes múltiples que incluía genes relacionados con EII y algunos trastornos autoinmunitarios. Finalmente, se realizó análisis genómico de variantes. Resultados: 9 mujeres y 7 hombres, con edad media de diagnóstico de EII 35 años, y 32 años para aparición de síntomas gastrointestinales. 11/16(68,75%) requirieron terapia biológica. 10/16 (62,5%) presentaron refractariedad a terapia estándar. 3/16 (18,75%) tenían antecedentes familiares positivos de EII. 100% casos presentaron al menos un single nucleotide polymorphism relacionado con riesgo de EII en más de un gen. Los genes más relacionados con colitis ulcerosa (CU), fueron CD48, CD6, y TYK2 para CU, y CD6 e ITGAM para la enfermedad de Crohn. El gen más frecuente fue CD6. Se observó en 3/16 (18,75%) presencia de hasta 5 genes, 4 en 3/16 (18,75%), y tres en 5/16 (31,25%). Conclusión: En EII hay presencia de variantes genéticas con predisposición asociada, pero sin patogenicidad confirmada, y cuya sumatoria parece contribuir en su fisiopatología.
ABSTRACT Introduction: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. Objective: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. Materials and methods: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multigene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. Results: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). Conclusion: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.
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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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ABSTRACT Tuberculosis stands as one of humanity's oldest afflictions, intrinsically intertwined with social disparities. This formidable disease spares no age group and remains the prevailing cause of infection-induced mortality worldwide, particularly in developing nations. We present a case of a 56-year-old woman with diabetes who was diagnosed with Pulmonary Tuberculosis. After receiving antituberculosis drugs as part of her treatment, she experienced a range of systemic manifestations and suffered from severe ulcerative esophagitis. This adverse reaction led to uncontrollable gastrointestinal intolerance, tragically resulting in her untimely demise. The incident underscores the potential seriousness of adverse reactions that can arise from tuberculosis treatment medications.
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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.
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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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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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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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Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.
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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.
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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.
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ABSTRACT Background: Latent tuberculosis (LTB) is a condition where the patient is infected with Mycobacterium tuberculosis but does not develop active TB. There's a possibility of tuberculosis (TB) activation following the introduction of anti-TNFs. Objective: To assess the risk of biological therapy inducing LTB during inflammatory bowel diseases (IBD) treatment over 15 years in a high-risk area in Brazil. Methods: A retrospective study of an IBD patients' database was carried out in a private reference clinic in Brazil. All patients underwent TST testing and chest X-ray prior to treatment, and once a year after starting it. Patients were classified according to the Montreal stratification and risk factors were considered for developing TB. Results: Among the analyzed factors, age and gender were risk factors for LTB. DC (B2 and P) and UC (E2) patients showed a higher number of LTB cases with statistical significance, what was also observed for adalimumab and infliximab users, compared to other medications, and time of exposure to them favored it significantly. Other factors such as enclosed working environment have been reported as risk. Conclusion: The risk of biological therapy causing LTB is real, so patients with IBD should be continually monitored. This study reveals that the longer the exposure to anti-TNFs, the greater the risk.
RESUMO Contexto: A tuberculose latente (TBL) é uma condição em que o paciente está infectado com Mycobacterium tuberculosis, mas não desenvolve tuberculose (TB) ativa. Existe a possibilidade de ativação da TB após a introdução de anti-TNFs. Objetivo: Avaliar o risco da terapia biológica induzindo TBL durante o tratamento de doenças inflamatórias intestinais (DII) ao longo de 15 anos em uma área de alto risco no Brasil. Métodos: Foi realizado um estudo retrospectivo de um banco de dados de pacientes com DII em uma clínica privada de referência no Brasil. Todos os pacientes foram submetidos a teste de TST e radiografia de tórax antes do tratamento e uma vez por ano após seu início. Os pacientes foram classificados de acordo com a estratificação de Montreal e foram considerados fatores de risco para o desenvolvimento de TB. Resultados: Entre os fatores analisados, a idade e o sexo foram fatores de risco para TBL. Os pacientes com doença de Crohn' (B2 e P) e colite ulcerativa (E2) apresentaram maior número de casos de TBL com significância estatística, o que também foi observado para usuários de adalimumab e infliximab, em comparação com outros medicamentos, e o tempo de exposição a eles favoreceu significativamente. Outros fatores, como ambiente de trabalho fechado, foram relatados como riscos. Conclusão: O risco da terapia biológica causar TBL é real, por isso os pacientes com DII devem ser monitorados continuamente. Este estudo revela que quanto maior a exposição aos anti-TNFs, maior o risco.
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ABSTRACT Background: The most efficient way to prevent complications from inflammatory bowel disease (IBD) is to provide patients with optimized care. Nonetheless, in Brazil, there is no validated methodology for evaluating health services recognized as comprehensive care units (CCU), making it difficult to assess the quality of care provided. Objective: To understand the current scenario, map the distribution of centers and identify strengths and weaknesses, considering local and regional characteristics. Methods: The study was carried out in three phases. Initially, the Brazilian Organization for Crohn's disease and colitis (GEDIIB) developed 22 questions to characterize CCU in Brazil. In the second phase, all GEDIIB members were invited to respond to the survey with the 11 questions considered most relevant. In the last phase, an interim analysis of the results was performed, using the IBM SPSS Statistics v 29.0.1.0 software. Descriptive statistics were used to characterize the center's profile. The chi-square test was used to compare categorical variables. Results: There were 53 responses from public centers (11 excluded). Most centers were concentrated in the Southeastern (n=22/52.4%) and only 1 (2.4%) in the Northern region of Brazil. Thirty-nine centers (92.9%) perform endoscopic procedures, but only 9 (21.4%) have access to enteroscopy and/or small bowel capsule endoscopy. Thirty-three centers (78.6%) offer infusion therapy locally, 26 (61.9%) maintain IBD patient records, 13 (31.0%) reported having an IBD nurse, 34 (81.0%) have specific evidence-based protocols and only 7 (16.7%) have a patient satisfaction methodology. In the private scenario there were 56 responses (10 excluded). There is also a concentration in the Southeastern and Southern regions. Thirty-nine centers (84.8%) have access to endoscopic procedures and 19 perform enteroscopy and/or small bowel capsule endoscopy, more than what is observed in the public environment. Infusion therapy is available in 24 centers (52.2%). Thirty-nine centers (84.8%) maintain a specific IBD patient database, 17 (37%) have an IBD nurse, 36 (78.3%) have specific evidence-based protocols, and 22 (47. 8%) apply a patient satisfaction methodology. Conclusion: IBD CCU in Brazil were mainly located in the Southeastern and Southern regions of the country. Most centers have dedicated multidisciplinary teams and IBD specialists. There is still a current need to improve the proportion of IBD nurses in IBD care in Brazil.
RESUMO Contexto: A forma mais eficiente de prevenir complicações da doença inflamatória intestinal (DII) é proporcionar aos pacientes cuidados otimizados. Contudo, no Brasil não existe uma metodologia validada para avaliação de serviços de saúde reconhecidos como unidades de atenção integral (UAI), dificultando a avaliação da qualidade da assistência prestada. Objetivo: Compreender o cenário atual, mapear a distribuição dos polos e identificar pontos fortes e fracos, considerando as características locais e regionais. Métodos: O estudo foi realizado em três fases. Inicialmente, a Organização Brasileira para Doença de Crohn e Colite (GEDIIB) desenvolveu 22 questões para caracterizar as UAI no Brasil. Na segunda fase, todos os membros do GEDIIB foram convidados a responder ao inquérito com as 11 questões consideradas mais relevantes. Na última fase foi realizada uma análise dos resultados, utilizando o software IBM SPSS Statistics v 29.0.1.0. Estatísticas descritivas foram utilizadas para caracterizar o perfil do centro. O teste qui-quadrado foi utilizado para comparar variáveis categóricas. Resultados: Houve 53 respostas de centros públicos (11 excluídas). A maioria das UAI concentrou-se na região sudeste (n=22/52,4%) e apenas 1 (2,4%) na região norte do Brasil. Trinta e nove centros (92,9%) realizam procedimentos endoscópicos, mas apenas 9 (21,4%) têm acesso à enteroscopia e/ou cápsula endoscópica. Trinta e três centros (78,6%) oferecem terapia de infusão localmente, 26 (61,9%) mantêm registros de pacientes com DII, 13 (31,0%) relataram ter uma enfermeira para DII, 34 (81,0%) têm protocolos específicos baseados em evidências e apenas 7 (16,7%) %) possuem uma metodologia de satisfação do paciente. No cenário privado houve 56 respostas (10 excluídas). Há também concentração nas regiões sudeste e sul. Trinta e nove centros (84,8%) têm acesso a procedimentos endoscópicos e 19 realizam enteroscopia e/ou cápsula endoscópica, mais do que o observado no ambiente público. A terapia infusional está disponível em 24 centros (52,2%). Trinta e nove centros (84,8%) mantêm um banco de dados específico de pacientes com DII, 17 (37%) têm uma enfermeira para DII, 36 (78,3%) têm protocolos específicos baseados em evidências e 22 (47,8%) aplicam uma metodologia de satisfação do paciente. Conclusão: As UAI do DII no Brasil estavam localizadas principalmente nas regiões sudeste e sul do país. A maioria dos centros possui equipes multidisciplinares dedicadas e médicos com experiencia em DII. Ainda há uma necessidade atual de melhorar a proporção de enfermeiros no tratamento de DII no Brasil.
Résumé
Abstract Objective To describe the pro file of surgeons who treat patients with inflammatory bowel disease as well as the characteristics of inflammatory bowel disease care, unmet demands, and difficulties. Methods The research participants answered a Google Forms questionnaire. Results Of the 99 surgeons who participated in the survey, 84.5% were coloproctologists, 40% were from the southeastern region of Brazil, and 77.7% were male and had been working for more than 19 years. Regarding the healthcare sector, 63.6% of surgeons worked in both public and private clinics, and most clinically cared for up to 50 patients with inflammatory bowel disease and operated on up to 5 cases per year. Conclusion This is the first national study that aimed to identify the profile of surgeons working with inflammatory bowel disease in Brazil. The vast majority are experienced male coloproctologists, located in the southern and southeastern regions, who perform clinical and surgical treatment of these pathologies, with major surgeries being performed in large centers by a small number of surgeons.