Incidence Of Ulcerative Colitis Research Articles

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.

Chimonanthus nitens Oliv. Leaf Granule Ameliorates DSS-Induced Acute Colitis Through Treg Cell Improvement, Oxidative Stress Reduction, and Gut Microflora Modulation.

The rising incidence of ulcerative colitis has become a new challenge for public health. Chimonanthus nitens Oliv. leaf granule (COG) is a natural medicine used for the treatment of respiratory diseases, which has excellent anti-inflammatory and antioxidant effects. However, the therapeutic effect of COG in ulcerative colitis (UC) has not been reported. Here, the experimental colitis was treated with dextran sodium sulfate (DSS) and COG. After treatment with high (30 g/kg), medium (15 g/kg), and low (7.5 g/kg) doses of COG for 11 consecutive days, the body weight, disease activity index (DAI) score, colon length, colon weight index, and the pathological score of mice were effectively improved. COG significantly reduced the levels of inflammatory cytokines in UC mice in vitro and in vivo and restored the secretion levels of IL-6 and IL-10 in the colon. Meanwhile, compared to mice with colitis, COG-treated mice showed lower levels of MDA, MPO, NO, and eNOS and higher levels of GSH-Px and MAO, which indicated that oxidative stress damage in colitic mice was alleviated by COG. Moreover, less Th17 and more Tregs were observed in the COG-treated groups. In addition, COG improved the diversity and relative abundance of gut microflora in the colon of colitic mice, and Lachnospiraceae_NK4A136_group and Lachnospiraceae_UCG-006 were obviously regulated at the genus level. In summary, COG has a protective effect on DSS-induced experimental colitis, mainly through inhibition of immune-inflammatory responses and oxidative stress and regulation of mTreg cell responses and intestinal flora composition.

Carbocisteine as a Modulator of Nrf2/HO-1 and NFκB Interplay in Rats: New Inspiration for the Revival of an Old Drug for Treating Ulcerative Colitis.

Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.

Analysis of the Clinical Efficacy of Infliximab in the Treatment of Steroid-Refractory Ulcerative Colitis in Children

Background: Incidence of ulcerative colitis (UC) in children has increased worldwide. Objectives: In the current study, we summarized our clinical experience using infliximab (IFX) in the treatment of children with steroid-refractory UC. Methods: The clinical data of 9 steroid-refractory UC patients with average age of 8 years who were treated with IFX in our hospital were analyzed. Results: At the end of the induction period, 6 achieved a clinically significant response. Of the 6 children, 4 had mucosal healing and 2 had endoscopic remission. At week 30, among the 6 children who achieved a clinically significant response, 3 had persistent clinical remission and mucosal healing, 1 achieved mucosal healing from endoscopic remission, 1 had mild disease, and the other child had not reached 30 weeks of treatment as of this writing. At week 54, 6 of 9 children achieved clinical remission and 5 had mucosal healing. The hemoglobin concentration in the children who achieved a clinically significant response was higher than pre-treatment and the inflammation markers were lower than pre-treatment. During IFX treatment, five children had a loss of response, three had a primary non-response, and two had a secondary non-response. The latter children achieved clinical remission with optimized treatment. Conclusions: IFX is a salvage treatment option for children with moderate-to-severe steroid-refractory UC. The course of treatment and the timing of drug withdrawal warrants further study.

Clinical results following colonic resection for ulcerative colitis in elderly individuals (elderly-onset vs. nonelderly onset)

BackgroundThe incidence of ulcerative colitis (UC) is increasing, but there are few reports comparing elderly UC patients undergoing colectomy for elderly-onset UC (EO) and nonelderly-onset UC (NEO). The aim of this study was to analyze the differences between EO and NEO patients who underwent UC-related surgery.MethodsWe identified 1973 patients with UC who underwent colectomy at Hyogo College of Medicine between January 1, 1984, and December 31, 2018. Only patients aged 65 years old and older who underwent colectomy were enrolled in this study (n = 221, 11.2%), and their clinical records were retrospectively reviewed. Patients were divided into two groups according to their age at disease onset: those with onset at younger than 60 years old (NEO) and at 60 years old or older (EO).ResultsIn the 221 UC patients who underwent colectomy at 65 years old or older, there were 155 cases of EO and 66 cases of NEO. The main surgical indication in NEO patients was colitis-associated cancer/dysplasia (32/66, 47%). In contrast, refractory to medical treatment was the leading cause of surgery in EO patients (80/155, 52%). The distributions of surgical indications were different between the two groups (p < 0.01). The preoperative daily dose of steroids was significantly higher in the EO group than in the NEOgroup (0 mg vs. 10 mg, p < 0.01). The rates of immunosuppressant, infliximab (IFX) and adalimumab use did not differ significantly between the groups. Significantly more patients underwent emergency surgery in the EO group than in the NEO group (14% vs. 35%, p < 0.01). The proportions of patients with postoperative morbidity (Clavien-Dindo grade III or higher) were 17.4% (27/155) in the EO group and 13.6% (9/66) in the NEO group. There was no significant difference between the two groups (p = 0.48). The prognosis of the EO patients who underwent UC-related emergency surgery was worse than that of the NEO patients (p < 0.01). In the EO group, 8 (14.8%) of 54 patients died within 30 postoperative days, while there were no deaths in the NEO group.ConclusionAmong elderly UC patients undergoing UC-related surgery, EO patients undergoing emergency surgery had very poor outcomes, and the mortality rate was 14.8%. In such cases, it is important for physicians and surgeons to begin communication at an early stage so that the optimal surgical timeframe is not missed.

What Are the Different Phenotypes of Inflammatory Bowel Disease in Asia?

The burden of inflammatory bowel disease (IBD) in Asia has been increasing over the past decades. Although patients with IBD show heterogenous phenotypes depending on the individual characteristics, no significant differences have been established in the IBD phenotypes of Western and Asian populations. However, despite the much lower incidence of IBD in Asia than in Western countries, the incidence has been rapidly increasing in Asia while remaining stable in Western countries. The incidence of ulcerative colitis (UC) showed an earlier and a more marked increase than the incidence of Crohn disease (CD), but the UC-to-CD ratio has recently decreased because of a relative increase in the incidence of CD in Asia. While CD shows a significant male predominance, UC only shows a slight male predominance. A recent study reported that the incidence of IBD in Asia showed a bimodal age distribution with increasing IBD prevalence, similar to the findings of Western studies. CD in Asian patients, especially those in East Asia, is characterized by ileocolonic involvement and perianal fistula. The frequency of extraintestinal manifestations, including primary sclerosing cholangitis, appears to be lower in Asia, but this finding should be interpreted with caution due to the transient and nonspecific nature of these manifestations. Although familial aggregation is lower in East Asia, it may also be explained by the low prevalence of IBD in Asia. Thus, more studies should focus on the differences in phenotypes in Asian IBD patients versus Western patients.

Regional features of the course of ulcerative colitis: clinical observations (on the example of Rostov-on-Don)

The aim of the study was to identify the clinical, epidemiological and therapeutic features of ulcerative colitis in children in Rostov-on-Don. Under the observation were 34 children aged 1 to 14 years with a diagnosis of ulcerative colitis, which was based on anamnesis, clinical picture, laboratory results, and colonoscopy. The activity of ulcerative colitis was assessed taking into account the PUCAI index. To determine the reliability of the compared indicators (%), the χ2 criterion was used. Clinical and epidemiological studies have shown an increase in the incidence of ulcerative colitis in children in Rostov-on-Don over the past 10 years. In the clinic of ulcerative colitis, mild, erased forms of the course of the disease dominated, which determined the later diagnosis at the prehospital stage. There was a «rejuvenation» of the disease: ulcerative colitis was more often detected in the preschool group of children. The incidence of ulcerative colitis in boys was higher than in girls. In the treatment of mild and moderate forms of ulcerative colitis, the use of basic drugs is very effective, taking into account the principle of «step up».

COMPARING THE GUT METABOLOMIC PROFILES IN HISPANIC AND NON-HISPANIC PEDIATRIC ULCERATIVE COLITIS PATIENTS

Abstract BACKGROUND Diagnosis of ulcerative colitis (UC), a subgroup of inflammatory bowel disease (IBD), is frequently overlooked among the Hispanic population. Although previously thought to impact predominantly white populations, epidemiological studies have shown an increased incidence of UC among Hispanics. Other studies have also noted variations in disease phenotype when comparing Hispanic UC patients to non-Hispanic patients. These variations could be linked to differences in the gut microbiome and shifts in the metabolomic profile. This study aims to compare the profiles of Hispanic UC patients to those of non-Hispanic whites. METHODS Participants aged 7-21 with mild to moderate UC were enrolled at Children’s Hospital of Los Angeles. Eighteen Hispanic and forty non-Hispanic patients were included in this analysis. Metabolite profiling yielded 230 known metabolites. Independent sample T-tests were used to identify significant differences (p&amp;lt;0.05) in metabolites between Hispanic and non-Hispanic UC samples. The average for each metabolite was calculated in Hispanic, non-Hispanic, and healthy patients. Averages were then compared and used to define metabolites as enhanced or diminished. RESULTS 66 metabolites were found to be significantly different between Hispanic and non-Hispanic UC patients. When comparing the profiles of Hispanic to that of non-Hispanic patients, 2 metabolites were enhanced and 64 were diminished. The two enhanced metabolites included 1-monostearin and 1-monopalmitin. Figure 1 depicts the top 10 most diminished metabolites in Hispanic patients compared to non-Hispanic patients. These 10 metabolites were amino acids, amino acid degradation products, and one polyol compound. DISCUSSION This study found a significant difference in the metabolomic profiles of Hispanic UC patients compared to non-Hispanics. This difference could suggest a relationship between ethnicity and the gut’s metabolomic profile. Most notably, Hispanic patients were found to have diminished levels of nearly all significantly different metabolites when compared to non-Hispanic patients. This includes protective fatty acids, amino acids, and amino acid degradation byproducts. Increased deficits of protective anti-inflammatory mediators can be linked to increased risk of severe disease among Hispanic UC patients. These findings support the need for therapeutics targeting specific metabolite deficiencies within Hispanic UC patients.

DOP02 Increasing incidence of Inflammatory Bowel Disease in a high prevalence country: A nationwide study in Finland

Abstract Background The burden of inflammatory bowel disease (IBD) in health care is high and the incidence and prevalence rates of IBD in Finland are among the highest in the world. Our aim was to assess the actual incidence and the trends of IBD in Finland during 2000–2020 using nationwide registry-based data. We also estimated the nationwide prevalence of IBD in 2000 and 2020. Methods This study included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2021. Data were retrieved from the Social Insurance Institution of Finland. Incidence and prevalence rates were calculated by dividing the number of annual new IBD cases by the size of the population at risk during each calendar year. Results A total of 42,498 new IBD cases were identified during years 2000–2020; 31,372 with ulcerative colitis (UC) and 11,126 with Crohn’s disease (CD).The crude annual incidence per 100,000 increases in CD from 7.5 to 13.4 (IRR 1.02, CI 1.019 - 1.025) and in UC from 20.4 to 34.7 (IRR 1.03, CI 1.023 - 1.027) (Fig. 1). The crude prevalence of IBD increases from 376 to 972 per 100,000 (PRR 1.05, CI 1.046–1.047).Men have significantly higher incidence than women in UC (IRR 1.26, CI 1.228–1.284). In contrast, there is no difference between genders among CD patients (IRR 0.98, CI 0.95–1.02). In UC, the peak incidence occurs in the age group 25–29 (Fig. 2), whereas in CD, the incidence is highest in slightly younger patients (Fig. 3). Figure 1. Incidence of ulcerative colitis and Crohn`s disease in Finland during 2000–2020 Figure 2. Annual incidence of UC by age groups during 2000–2020 Figure 3. Annual incidence of CD by age groups during 2000–2020 Conclusion During the first two decades of the 21st century, the incidence of UC and CD continues to increase in Finland, and almost one percent of the population has IBD.

P653 The changing epidemiology of IBD in the western world: a population-based study from Denmark

Abstract Background Mitigating the burden of inflammatory bowel disease (IBD) in Western countries requires understanding how its epidemiology is evolving. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2018 in the Danish nationwide cohort. Methods We used the Danish Civil Registration System (CRS) to obtain demographic information on all residents in Denmark between January 1, 1995 and December 31, 2018. We obtained information on Crohn’s disease (CD) and ulcerative colitis (UC) diagnosis from the National Patient Registry (NPR) using International Classification of Disease 8/10 codes. IBD diagnosis was defined as having at least two CD- or UC-related registrations within a two-year period and the date of the first IBD-related registration was considered as the date of diagnosis. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex. Results 52,407 individuals met the criteria for IBD diagnosis in the period 1995–2018, of which 17,355 (33%) were diagnosed with CD and 35,052 (67%) were diagnosed with UC. The median age at diagnosis (IQR) for CD and UC was 34 (22, 53) and 43 (29, 60) years, respectively. 9,745 (56.2%) and 18,332 (52.3%) individuals with CD and UC, respectively, were of female sex. During the study period, 1995–2018, the overall incidence rate (95% CI) rose from 9.2 (8.4, 10) per 100,000 person years (PY) to 18 (16.8, 19) per 100,000 PY for CD, corresponding to a 94.9% increase, and from 21.1 (19.9, 22.4) per 100,000 PY to 28.4 (27, 29.8) per 100,000 PY for UC, corresponding to a 34.1% increase. The incidence rates of CD and UC increased for all age groups, at different rates, highest for CD in age group 15–39 years (Figure). While CD incidence was consistently higher in women, increase in CD and UC incidence was comparable between both sexes. The prevalence of IBD also increased from 1995–2018 (225.6% and 218.4% for CD and UC, respectively) with the greatest increase in UC prevalence among individuals older than 40 years of age (248.4%). Conclusion The epidemiology of IBD has shifted in the last 20 years with a still increasing incidence of CD and UC in young adults, and a sharply increased prevalence in older age groups, especially for UC. These findings have implications towards understanding environmental shifts associated with this evolution as well as preparing for management of an aging IBD population.

P635 Incidence, prevalence, disease phenotype and maximal therapeutic step in Ulcerative Colitis patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem County cohort

Abstract Background Recent trends indicate a change in the epidemiology of inflammatory bowel disease (IBD) with previously low incidence areas now reporting progressive rise. The number of epidemiological population-based studies are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to analyze the incidence and disease phenotype at diagnosis, and the maximal therapeutic step distributions during follow-up in a prospective population-based database from Veszprem Province, including incident ulcerative colitis (UC) patients diagnosed between January 1, 2007 and December 31, 2018. Methods Data of 467 incident UC patients were analyzed (male/female:236/231; median age at diagnosis:36 years(y)[IQR: 25–54]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The source of age- and gender-specific demographic data for statistical analysis was derived from the results of a national population census in 2011. Results Adjusted mean incidence rate was 11.02(CI95%:10.1–12.1)/105 person-years in this 12 year period[males:11.53(CI95%:10.2–13.1)/105; females:10.54(CI95%:9.3–12.0)/105]. Prevalence rate was 283.51(CI95%:265.7–300.7)/105 persons in 2011 and 317.79(CI95%:298.8–335.8) in 2015. For detailed annual incidence rates and age-specific mean incidence rates see Figure 1 and 2. Peak onset age in UC was 20–29 years of age. Diagnostic delay from symptom onset was ≥1year in 19.1%, and ≥3 years in 4.1% of the patients. Disease extension was proctitis(E1) in 22.3%, left sided colitis(E2) in 43.9%, and extensive colitis(E3) in 33.8% of the patients at diagnosis. Patients with extensive colitis were younger(32.9y,SD:16.6) at diagnosis compared to patients with proctitis(40.1y,SD:15.9;p&amp;lt;0.001) or left sided colitis(44.0y;SD:19.1;p&amp;lt;0.001). Extraintestinal manifestations were as follows: hepatic5.4%(PSC 2.1%), arthritis10.7%, ocular0.9%, skin3.6%. Active smokers at diagnosis were 12.6%. Distribution of maximal therapeutic steps during the course of follow-up (8.34y,SD: 3.5) were 5-ASA in 46.9%, systemic corticosteroids in 16.3%, immunosuppressive therapy in 19.3%; anti-TNF biologic therapy in 12.2% and other biologic therapy in 4.3%. Conclusion The incidence of UC in this 12 year period was high, comparable to high-incidence areas in Western European countries, and comparable to previous data from the Veszprem cohort, while prevalence rates continue to rise compared to our previous data.(Lakatos 2011, IBD). Disease extension at diagnosis and distribution of highest treatment step was comparable to European population-based data.(Burisch 2019, JCC).

AHR EXPRESSION ON VIL1-EXPRESSING COLONIC EPITHELIAL CELLS IS ESSENTIAL FOR I3C-MEDIATED PROTECTION AGAINST COLITIS

Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease that affects the colon and is characterized by localized tissue injury and disruption of the intestinal epithelial barrier. Pathophysiology of UC includes genetic predisposition, epithelial barrier defects, dysregulated immune responses, microbial dysbiosis, and environmental factors. Several therapeutic interventions for colitis have been identified, but many current treatments have various negative side effects, which is alarming given the incidence of UC is increasing around the world. Thus a search for safe therapeutic strategies to control the pathogenesis of colitis is still greatly needed. Previous studies from our laboratory reported that indole-3-carbinol (I3C), a natural plant product and ligand for the aryl hydrocarbon receptor (AhR), exhibited protective effects against colitis through innate lymphoid type 3 (ILC3) cells in an interleukin-22 (IL-22) dependent manner. The aim of this study was to ascertain the possible role of AhR in vil1-expressing colonic epithelial cells (CECs) during I3C-mediated protection against colitis. Using in vivo mouse studies and in vitro primary CEC organoid cultures, we investigated how key intestinal regulatory mediators (e.g. mucins and anti-microbial peptides, or AMPs) were altered in the absence or presence of AhR in CECs during I3C treatment under colitis or colitis-like conditions. We generated conditional AhR knockout mice in vil1-expressing CECs using the cre-flox system and induced colitis using the dextran sodium sulfate (DSS) model. Our results showed that the mice with AhR deficiency in CECs (AV mice) lost the protective effects of I3C treatment during colitis. Results showed that AV mice had a higher disease score and increased inflammation in the colon when compared to wild type (WT) or littermate (LM) controls. In addition, after treatment with I3C during DSS-induced colitis, AV mice were not able to prevent colitis-associated gut microbial dysbiosis even though flow cytometry analysis revealed AV mice were still capable of increasing IL-22 production by ILC3s in the colon. This suggested that the IL-22-ILC3 immune cell response was not the only major mechanism involved in I3C-mediated protection against colitis and regulation of the gut microbiome. Whole transcriptome analysis of RNA isolated from enriched CECs of experimental mice was performed and results showed significant altered expression of several microRNAs, mucins (muc3 and muc13), and tight junction proteins in AV mice when compared to wild type (WT) or littermate (LM) controls. PCR gene expression data and direct effects of I3C on CECs using colonic organoids from WT and AV mice validated these results. Collectively, these data showed that AhR expression in CECs play a critical role in I3C-mediated prevention of colitis.

COMPARING THE GUT METABOLOMIC PROFILES IN HISPANIC AND NON-HISPANIC PEDIATRIC ULCERATIVE COLITIS PATIENTS

Diagnosis of ulcerative colitis (UC), a subgroup of inflammatory bowel disease (IBD), is frequently overlooked among the Hispanic population. Although previously thought to impact predominantly white populations, epidemiological studies have shown an increased incidence of UC among Hispanics. Other studies have also noted variations in disease phenotype when comparing Hispanic UC patients to non-Hispanic patients. These variations could be linked to differences in the gut microbiome and shifts in the metabolomic profile.

Five-Flavor Sophora flavescens Enteric-Coated Capsules for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Background Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by abdominal pain, diarrhea, and mucopurulent bloody stool. In recent years, the incidence and prevalence of UC have been increasing consistently. Five-flavor Sophora falvescens enteric-coated capsule (FSEC), a licensed Chinese patent medicine, was specifically used to treat UC. This review was aimed to assess the effectiveness and safety of FSEC for the treatment of UC. Methods Six electronic databases were searched from inception to March 2021. Randomized clinical trials (RCTs) comparing FSEC or FSEC plus conventional Western medicine with conventional Western medicine in participants with UC were included. Two authors screened all references, assessed the risk of bias, and extracted data independently. Binary data were presented as risk ratios (RRs) with 95% confidence intervals (CIs) and metric data as mean difference (MD) with 95% CI. The overall certainty of the evidence was assessed by GRADE. Results We included 15 RCTs (1194 participants, 763 in the FSEC group and 431 in the control group). The treatment duration ranged from 42 to 64 days. Twelve trials compared FSEC with conventional Western medicine, and two trials compared FSEC plus conventional medicine with conventional medicine. Another trial compared FSEC plus mesalazine with compound glutamine enteric capsules plus mesalazine. FSEC showed a higher clinical effective rate (improved clinical symptoms, colonoscopy results, and stools) (RR 1.12, 95% CI 1.05 to 1.20; 729 participants; 8 trials; low-quality evidence) as well as the effective rate of traditional Chinese medicine (TCM) syndromes (RR 1.10, 95% CI 1.01 to 1.20; 452 participants; 5 trials; low-quality evidence) compared to mesalazine. There was no significant difference in the adverse events between FSEC and control groups. Conclusions FSEC may show effectiveness in UC treatment compared to conventional medicine, and the use of FSEC may not increase the risk of adverse events. Due to the limited number of clinical trials and low methodological quality of the included trials, our findings must be interpreted with discretion.

Risk Factors for the Diagnosis of Colorectal Cancer.

BackgroundColorectal cancer defined as cancer of the colon or rectum, is the third most frequently diagnosed cancer in men and the second in women, and, according to the World Health Organization database GLOBOCAN, it accounts for nearly 1.4 million new cases annually worldwide. The occurrence of colorectal cancer is associated with nonmodifiable risk factors, including age and hereditary factors, as well as with modifiable environmental and lifestyle factors.MethodsThe study included 800 patients, 400 diagnosed with colorectal cancer and 400 within the control group, who gave their written informed consent to participate in the study. Patients with cancer other than colorectal cancer were randomly selected for control group I, and patients with no cancer diagnosis were selected for control group II. The method used was a case-control study – an observational and analytical study with a control group, conducted among patients of the Clinical Oncology Centre and the Provincial Hospital in the years 2019–2020. The study comparing the exposure was carried out in a group of people who developed the endpoint, that is colorectal cancer, with the exposure in a well-matched group of controls who did not reach the endpoint. Assessment of activity and BMI was used according to WHO recommendations, as well as the expert system. The data were tested for the distribution and the homogeneity of variance was validated before applying the parameter tests. Comparison of quantitative variables between groups was performed using ANOVA.ResultsThe mean age of the patients was 64.53 ± 8.86 years, of the control group I – 59.64 ± 9.33 and the control group II – 57.5 (7.83). There was a strong positive association between the incidence of ulcerative colitis and the risk of colorectal cancer (P < .01). Among obese subjects, the risk of developing colorectal cancer was 1.27 (95% CI, 1.06–1.53) compared with nonobese subjects. A strong positive relationship was found between low physical activity converted to metabolic equivalent of MET effort per week and the risk of colorectal cancer (P < .001). The relative risk for current smokers was 2.17 (95% CI 1.79–2.66). There was an association between higher fat consumption and higher red meat consumption and the risk of developing colorectal cancer (P < .01).ConclusionsObesity, low physical activity, active and passive smoking and high salt and red meat consumption have been associated with an increased risk of colorectal cancer. These findings provide further evidence of the importance of maintaining a healthy lifestyle.

Anemone chinensis Bunge aqueous enema alleviates dextran sulfate sodium-induced colitis via inhibition of inflammation and regulation of the colonic mucosal microbiota

Ethnopharmacological relevanceAlthough the incidence of ulcerative colitis (UC) increases every year, there is still a lack of satisfactory treatment options. Anemone chinensis Bunge (AB), a traditional Chinese herb, is a potent compound that can be prepared as a decoction, and then administered as an enema to relieve UC symptoms. However, the therapeutic effect and mechanisms of aqueous AB on UC are still unknown.Aim of the study: This study investigates the potential therapeutic value and mechanism of AB aqueous enema for UC. Materials and methodsFirst, the practical components in aqueous AB were extracted and identified by UPLC-MS/MS. Second, the potential active targets and target genes related to UC were predicted, mapped, and analyzed by network pharmacology. Then, the effects of AB aqueous enema on UC were assessed using the dextran sulfate sodium (DSS)-induced colitis model with mice. Finally, the level of inflammation, the expression level of proteins associated with the colonic mucosal barrier, and the microbiota associated with the intestinal mucosal were investigated. ResultsFourteen active ingredients in AB were identified. The network pharmacology-based analysis demonstrated that the active ingredients possibly affected ten key targets, such as IL-6, TNF, and PTGS2. They are also related to the tight junction proteins ZO-1, occludin, and claudin-1.Furthermore, mice treated with DSS developed severe mucosal colitis. AB aqueous enema decreased the disease activity index (DAI), significantly inhibited colonic damage, and greatly decreased colon length shortening (p < 0.05).AB also significantly restored tight junction proteins and the associated mucin proteins mucin-2 (MUC2) and mucin-3A (MUC3A). In addition, the diversity of the gut microbiota after administration of DSS was significantly decreased. However, the diversity was entirely restored after AB treatment. Recovery of the abundance of colonic mucosal bacteria, especially Lactobacillus reuteri and Lactobacillus gasseri, occurred at the species level after AB treatment. In vitro, AB can be utilized by the two bacteria, especially under glucose deficiency. ConclusionsOur study demonstrated that the AB aqueous enema alleviated colitis by restoring intestinal barrier proteins and regulating the gut microbiota.

Reactive Oxygen Species-Responsive Polyether Micelle Nanomaterials for Targeted Treatment of Ulcerative Colitis.

As one of the most challenging inflammatory diseases, the incidence of ulcerative colitis (UC) is increasing year by year, but the existing therapeutic drugs are not effective and lack of targeting. Nanomaterials are expected to become promising delivery system due to their good targeting effects. Here, we designed a nanomaterial sensitive to reactive oxygen species, which can be used to treat IBD, especially UC. It is a self-assembled polyether micelle that can be oxidized at the inflammation site where the concentration of reactive oxygen increases, and effectively release the encapsulated budesonide (Bud). Experiments have proved that for DSS-induced colitis, the synthetic drug-loaded nanoparticles have excellent therapeutic effects, can effectively repair intestinal barrier, and significantly improve the damaged colon tissue. At the same time, it has a beneficial regulatory effect on inflammatory factors. Molecular mechanism studies have shown that it achieves its therapeutic effects by activating the peroxisome proliferators-activated receptors-γ (PPAR-γ) pathway and inhibiting the nuclear factor (NF)-κB pathway. This study proves that oral nano-micelles have an important impact on improving the efficacy of UC treatment drugs and have far-reaching significance for the targeted treatment of gastrointestinal diseases.

Cerebrovascular Events in Pediatric Inflammatory Bowel Disease: A Review of Published Cases.

Pediatric inflammatory bowel disease (PIBD) is a multisystem disorder characterized by intestinal and extraintestinal manifestations and complications. Cerebrovascular events (CVE) are rare extraintestinal complications in patients with PIBD. Statistics show that 3.3% patients with PIBD and 1.3–6.4% adult patients with inflammatory bowel disease (IBD) experience CVE during the course of the disease. Therefore, this study aimed to review the records of children with IBD who developed CVE during the course of the disease. We retrospectively reviewed 62 cases of PIBD complicated by CVE. The mean patient age at the time of thrombotic events was 12.48±4.13 years. The incidence of ulcerative colitis was significantly higher than that of Crohn’s disease (43 [70.5%] vs. 13 [21.3%] patients). Most patients (87.93%) were in the active phase of IBD at the time of CVE. The mean time interval between the onset of IBD and CVE was 20.84 weeks. Overall, 11 (26.83%) patients showed neurological symptoms of CVE at disease onset. The most frequent symptom on admission was persistent and severe headaches (67.85%). The most common site of cerebral venous thrombosis was the transverse sinuses (n=23, 53.48%). The right middle cerebral artery (n=3, 33.34%) was the predominant site of cerebral arterial infarction. Overall, 41 (69.49%) patients who were mostly administered unfractionated heparin or low-molecular-weight heparin (56.09%) recovered completely. Patients with IBD are at a risk of thromboembolism. CVE may be the most common type of thromboembolism. Based on these findings, the most common risk factor for CVE is IBD flares. In patients with CVE, anticoagulant therapy with heparin, followed by warfarin, is necessary.

Ulcerative colitis in Kingdom of Saudi Arabia

Ulcerative colitis (UC) is an inflammatory disease of the large intestine affecting mucosal lining of rectum (proctitis), rectum to splenic flexure (left-sided colitis), or entire colon (pancolitis). Common symptoms include diarrhea, blood in the stool, mucus in the stool, fecal urgency, tenesmus, abdominal pain, and constipation. Biochemical findings may include iron deficiency anemia, increased serum platelets, deficiency of serum albumin, presence of auto-immunoglobulins, and anti-neutrophil cytoplasmic antibodies. Currently, its complete pathophysiology is unclear, however, primary pathological features comprise disturbance in gastrointestinal mucosal barrier, abnormal gut immune responses, and imbalance in gut microbiota. In Saudi Arabia, a rise in incidence and prevalence of UC is observed, however, evidence is limited. Common risk factors include age, gender, race, ethnicity, family history, microbiome profile, medical history, and lifestyle elements. Antibiotics exposure at an early age, long-term use of non-steroidal anti-inflammatory drugs, and using oral contraceptives is associated with increased risk of UC. Management guidelines for the treatment of UC have been provided by the American Gastroenterological Association and the American College of Gastroenterology providing guidelines for therapeutic options and surgery. Development of personalized therapeutics and targeted treatment strategies based on genetic as well as cellular data are recommended as future potentials in the management of UC patients.

Is the Presence of Helicobacter Pylori in the Colonic Mucosa, Provocative of Activity in Ulcerative Colitis?

Background:Epidemiologic studies have shown world-wide increasing incidence of ulcerative colitis (UC) as an autoimmune disease of intestine. In the meantime, gastrointestinal H. Pylori infection is being decreased.Objectives:There are very few studies about comparing the presence of H. Pylori in the colon and the disease activity of UC. There is no study form Iran. In this study, we tried to investigate the presence of H. Pylori in the mucosa of colon by molecular and microbiological as well as pathological methods to find any association between the presence of this organism in the colon and the presence and activity of UC.Patients and Methods:In 100 patients who referred to colonoscopy clinic, colonoscopy was performed. Fifty-seven patients with the new diagnosis of UC were considered as cases and 43 patients with normal screening colonoscopy for polyps were considered as controls. Colon biopsies were evaluated according to histopathology, clinical findings, and laboratory results to confirm the diagnosis and the degree of activity in the cases of UC. Molecular studies were also performed to evaluate the presence of H. Pylori genome in the colon biopsies. A sample of colon was also cultured for H. Pylori. ELISA test was performed in a sample of blood to evaluate the level of IL-10 and IL-17 as regulatory cytokines of inflammation.Results:Cases with the diagnosis of UC showed significantly higher number of positive colonic H. Pylori comparing to normal colonic mucosa. Also, the presence of H. Pylori genome in the colon was associated with higher activity in the cases with UC and higher levels of inflammatory mediators especially IL17 and lower levels of inhibitory mediators such as IL-10.Conclusion:Colonic colonization of H. Pylori was higher in the patients with UC and higher activity of this disease comparing with normal control colonic mucosa.