Chronic Bowel Research Articles

Overexpression of MCL1 attenuates irritable bowel syndrome by regulating cuproptosis: Screening and validation

Irritable bowel syndrome (IBS) is a type of chronic bowel disorder with a poorly understood pathophysiology. Recently, the imbalance of copper has been reported to influence the progression of IBS, suggesting cuproptosis, a new type of copper-induced cell death, may play a role in IBS. This study found 17 cuproptosis-related differentially expressed genes in IBS through bioinformatic analysis. Six hub genes were identified after the protein-protein interaction network analysis, namely myeloid cell leukemia 1 (MCL1), epidermal growth factor receptor 2, cadherin-associated protein beta 1, solute carrier family 25 members 37, solute carrier family 39 members 14, and six transmembrane epithelial antigens of the prostate 3. We selected MCL1 for further verification. Human normal colon epithelial cell line (NCM460) was used to construct models of IBS or cuproptosis in vitro by lipopolysaccharide (LPS) or LPS combined with copper (II) chloride (CuCl2). We observed that overexpression of MCL1 promoted cell viability and proliferation ability, and inhibited the secretion of inflammatory factors and expression of Bax and caspase-3 of NCM460 cells treated with LPS or LPS combined with CuCl2. In addition, up-regulated MCL1 significantly suppressed the protein levels of ferredoxin 1 and lipoyl synthase, two key regulators of cuproptosis. In conclusion, our study demonstrates that cuproptosis is involved in IBS and identifies a cuproptosis-related gene, MCL1, that helps alleviate IBS by promoting cell growth, reducing inflammation, and suppressing cuproptosis, making it a promising therapeutic target in IBS.

Lifestyle factors as predictors of incident functional somatic disorder. Five-year follow-up of The DanFunD study.

To assess whether lifestyle factors, including sleep pattern, are predictors for the development of functional somatic disorder (FSD). A population-based prospective cohort of 9656 men and women aged 18-76 years was established in 2011-2015 and invited for re-examination in 2017-2020, when 5738 participated. Median follow-up period was 65 months. Participants filled in validated questionnaires on lifestyle, sleep pattern and various delimitations of FSD, which were operationalized using two different approaches: bodily distress syndrome (BDS) and functional somatic syndromes (FSS) (i.e. chronic fatigue, chronic widespread pain (CWP), irritable bowel, and multiple chemical sensitivity (MCS)). Baseline lifestyle and sleep pattern in relation to incidence of BDS and FSS (chronic fatigue, CWP, irritable bowel, MCS) was analysed by logistic regressions, adjusted for age, sex and subjective social status. Inferior sleep quality at baseline predicted both incidence of BDS and all FSS delimitations except MCS. Smoking, alcohol intake, and low physical activity, but not diet, were predictors for the development of BDS. No uniform pattern was observed for the FSS. Smoking predicted development of chronic fatigue, CWP and irritable bowel, but not MCS. Alcohol and food quality only influenced the development of chronic fatigue whereas low physical activity only influenced the development of chronic fatigue and CWP. Lifestyle factors and sleep pattern seem to be predictors for some delimitations of FSD, but the importance of the various lifestyle factors is different for the different delimitations. The study shows the importance of analysing the various FSSs separately.

Long-Term Efficacy and Safety of Adhesion Prevention Agents in Abdominal and Pelvic Surgeries: A Systematic Review.

This systematic review evaluates the long-term efficacy and safety of adhesion prevention agents in abdominal and pelvic surgeries, synthesizing data from randomized controlled trials and meta-analyses. Adhesions, common postoperative complications, can lead to significant morbidity, including chronic pain, infertility, and bowel obstruction. Various agents, including hyaluronic acid-carboxymethylcellulose films and icodextrin solutions, have been developed to mitigate these risks. Our review highlights that agents like bioresorbable membranes (Seprafilm) and icodextrin significantly reduce the incidence and severity of adhesions, particularly in high-risk surgeries. However, certain complications such as anastomotic leaks and infections are associated with some agents, emphasizing the need for careful consideration in clinical decision-making. Additionally, while these agents reduce postoperative morbidity and enhance recovery, further research is needed to assess their long-term impact, particularly regarding fertility outcomes and chronic pain. This review underscores the importance of integrating adhesion prevention agents into surgical protocols, which has the potential to reduce healthcare costs, improve patient outcomes, and optimize postoperative care pathways. Standardization of adhesion prevention practices could further enhance surgical efficiency and patient recovery, particularly in high-risk patient populations and complex surgeries.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 μg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Transanal irrigation: a review of indications, key assessments, benefits, contraindications, complications, efficacy and safety

Transanal irrigation (TAI) is a therapeutic procedure designed to manage chronic bowel dysfunction, including constipation and faecal incontinence, particularly in individuals with neurogenic bowel dysfunction. TAI offers symptom relief and improves quality of life by providing autonomy in bowel management. This article explores the benefits, clinical indications and contraindications of TAI. The article also emphasises the importance of thorough patient assessments before initiating TAI, such as evaluating bowel function, manual dexterity and motivation. Furthermore, the review discusses the role of structured education programmes in ensuring long-term adherence and safety, particularly within the first 3 months. In addition, it covers the complications associated with TAI, such as bowel perforation and autonomic dysreflexia, and offers management strategies. Finally, the review outlines the conditions under which TAI should be discontinued and provides guidance on ensuring patient safety throughout the treatment.

S832 Impact of Weight on the Efficacy, Time to Response, and Safety of Linaclotide in Adults With Chronic Idiopathic Constipation or Irritable Bowel Syndrome With Constipation: Post Hoc Descriptive Analysis by Body Mass Index

S832 Impact of Weight on the Efficacy, Time to Response, and Safety of Linaclotide in Adults With Chronic Idiopathic Constipation or Irritable Bowel Syndrome With Constipation: Post Hoc Descriptive Analysis by Body Mass Index

Adverse outcomes and mortality in individuals with eating disorder-related electrolyte abnormalities in Ontario, Canada: a population-based cohort study

Individuals with eating disorders are at a higher risk of electrolyte abnormalities than the general population. We conducted the first representative cohort study assessing whether electrolyte abnormalities in people with eating disorders were associated with mortality and physical health outcomes. This was a retrospective population-based cohort study in Ontario including people aged 13 years or older with an eating disorder and an outpatient electrolyte measure within 1 year (between Jan 1, 2008 and June 30, 2019). An electrolyte abnormality was any of hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, hypomagnesaemia, hypophosphataemia, metabolic acidosis, or metabolic alkalosis. The primary outcome was all-cause mortality. Secondary outcomes were hospitalisation, a cardiac event, infection, acute or chronic kidney disease, fracture, and bowel obstruction. In additional analyses, we examined a younger cohort (<25 years old) and individuals with no previously diagnosed secondary outcome. We involved people with related lived or family experience in the study. 6163 patients with an eating disorder and an electrolyte measure within 1 year since diagnosis (mean age 26·8 years [SD 17·5]; 5456 [88·5%] female, 707 [11·5%] male; median follow-up 6·4 years [IQR 4-9]) were included. Ethnicity data were not available. The most common electrolyte abnormalities were hypokalaemia (994/1987 [50·0%]), hyponatraemia (752/1987 [37·8%]), and hypernatraemia (420/1987 [21·1%]). Overall, mortality occurred in 311/1987 (15·7%) of those with an electrolyte abnormality versus 234/4176 (5·6%) in those without (absolute risk difference 10·1%; adjusted hazard ratio 1·23 [95% CI 1·03-1·48]). Hospitalisation (1202/1987 [60·5%] vs 1979/4176 [47·4%]; 1·35 [1·25-1·46]), acute kidney injury (206/1987 [10·4%] vs 124/4176 [3%]; 1·91 [1·50-2·43]), chronic kidney disease (245/1987 [12·3%] vs 181/4176 [4·3%]; 1·44 [1·17-1·77]), bone fracture (140/1987 [7·0%] vs 167/4176 [4·0%]; 1·40 [1·10-1·78]), and bowel obstruction (72/1987 [3·6%] vs 57/4176 [1·4%]; 1·62 [1·12-2·35]) were associated with an electrolyte abnormality, but not infection or a cardiovascular event. Findings were consistent in young individuals (<25 years old) and those without secondary outcomes at baseline, by eating disorder type, and by sex. Electrolyte abnormalities are associated with death and poor physical health outcomes, supporting the importance of monitoring and possible interventions to prevent adverse outcomes. Findings also call for a refinement of the definition of severity of eating disorder and replication of these findings in other jurisdictions. None.

Clinical features of gastrointestinal symptoms in women with recurrent course of deep infiltrative endometriosis

Background. Endometriosis is a chronic multifactorial disease that affects more than 170 million women of reproductive age worldwide, causing pelvic pain syndrome, dyspareunia, and symptoms of gastrointestinal dyspepsia, thereby having a negative impact on the psycho-emotional state of patients. Despite a wide range of medical and surgical treatments, the relapse rate reaches 50%, which is a global economic and social problem.The purpose of the study. To determine the spectrum of clinical features of the gastrointestinal tract in women with recurrent deep infiltrative endometriosis.Materials and methods. The study included 113 patients of reproductive age who underwent surgical treatment of common forms of external genital endometriosis. The main group consisted of 32 patients who underwent repeated surgical treatment due to relapse of deep infiltrative endometriosis, the comparison group — 51 patients without relapse of the disease one year after the primary operation, the control group — 30 patients of reproductive age who did not suffer from external genital endometriosis. An analysis of the somatic anamnesis was carried out, as well as questionnaire data on pelvic pain on a visual analogue scale (VAS) and functional bowel disorders in patients with deep infiltrating endometriosis, depending on the status of relapse of the disease.Results and discussion. Patients of the main group suffered significantly more often from functional diseases of the gastrointestinal tract (71.9% (23/32) versus 51.3% (26/51) in the comparison group; p = 0.006, the spectrum of which was represented by chronic gastritis and irritable bowel syndrome. In the main group, the clinical manifestations of gastrointestinal dyspepsia before surgical treatment correspond to a moderately severe degree of 17.706 (4.601) points. A significantly higher initial level of functional intestinal disorders was established during subjective assessment in the main observation group: 17.706 (4.601) points versus 10.66 (3.61) points in the comparison group; p=0.001. In women of the main observation group, one month after surgical treatment, there was a significant decrease in subjective assessment of the severity of functional intestinal disorders (from 17.71 (4.60) points to 9.86 (4.73) points; p = 0.001). The integral VAS pain score in the main group was 6.65 (1.53) points, which is significantly higher than in patients in the comparison group without relapse of the disease.Conclusions. The identified clinical and anamnestic predictors of the recurrent course of deep infiltrative endometriosis will allow us to formulate a personalized approach at the pre- and postoperative stage, aimed at preventing relapse of the disease, which will directly improve the psycho-emotional state and quality of life of women.

Sinisan Alleviates Stress-Induced Intestinal Dysfunction and Depressive-like Behaviors in Mice with Irritable Bowel Syndrome by Enhancing the Intestinal Barrier and Modulating Central 5-Hydroxytryptamine

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice.

Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study

Background and aimThe ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation.MethodsThe subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed.ResultsA total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group.Conclusions2LPEG + 2L is a feasible bowel preparation regimen.

Serial transverse enteroplasty in adults with parenteral nutrition dependence: A case series.

Serial transverse enteroplasty is used to treat patients with chronic intestinal failure owing to short bowel syndrome. Current literature lacks discussion of its role for other etiologies of intestinal failure and its impact on adult patients' nutrition support needs and quality of life. We performed a case series on adults with parenteral nutrition (PN) dependence who underwent serial transverse enteroplasty at Emory University Hospital, a quaternary referral center between 2011 and 2022. Data collected included demographics, operative technique, and preoperative and postoperative PN requirements. A phone survey was administered to evaluate the impact of PN and the operation on quality of life. Ten patients underwent the procedure of interest during the study period. Indications included short bowel syndrome following multiple abdominal operations or intra-abdominal catastrophe and chronic partial bowel obstruction with dysmotility. Bowel length increased by a median of 83%. All patients were discharged home after a median hospital stay of 21 days. At 1-year follow-up, survival was 100%, two (20%) patients fully weaned from PN, three others (30%) reduced PN frequency, and six (60%) decreased their daily parenteral energy requirement. Two additional patients fully weaned from PN by 18 months postoperatively. This represents one of the largest case series of serial transverse enteroplasty in adults. Small intestinal length nearly doubled, and PN dependence was reduced in most patients. Given the low morbidity and good quality of life observed in this series, this procedure should be more widely investigated for patients with chronic intestinal failure.

Prevalence and correlates of oral antibiotic use in Canada.

Antimicrobial use (AMU) is a known driver of antimicrobial resistance. Insight into prevalence and correlates of AMU can help identify health inequities and areas for targeted action. To better understand sociodemographic and medical dimensions of AMU in Canada, the Public Health Agency of Canada, in partnership with Statistics Canada, developed a Rapid Response Module questionnaire on self-reported oral antibiotic use, to be administered as part of the 2018 Canadian Community Health Survey (CCHS). To provide data on the proportion of people in Canada that self-report the use of antibiotics and sociodemographic and health factors associated with use. This cross-sectional study used data from the CCHS, a national survey of 24,176 people with a clustered multi-stage stratified random sampling design. In 2018, an antibiotic use module was administered to CCHS participants. Among respondents 18 years and older, 26% reported receipt of at least one oral antibiotic over the past year. Several sociodemographic and health factors had higher adjusted odds of receiving an antibiotic prescription, including those aged 18 years compared to aged 48 years (mean), women compared to men, immigrants compared to non-immigrants (excluding Indigenous), current and former smokers compared to those who have never smoked, and those with comorbidities (asthma, chronic obstructive pulmonary disease, arthritis, heart disease, cancer, bowel disorder and urinary incontinence). Variations in AMU across different key populations and sociodemographic groups highlight the need to improve our understanding of different drivers of AMU and for tailored interventions to reduce inequitable risks of antimicrobial resistance.

Association of chronic constipation and chronic diarrhea with renal stones: a cross-sectional study of the National Health and Nutrition Examination Survey 2007-2010.

Renal stone is a highly prevalent life-long disease with a high recurrence rate. Chronic bowel diseases, including chronic gastrointestinal symptoms (chronic constipation or chronic diarrhea), are common gastrointestinal problems. We aimed to evaluate the associations of chronic constipation and chronic diarrhea with renal stones. This large-scale, cross-sectional study was performed within participants (≥20 years old) from the National Health and Nutrition Examination Survey from 2007 to 2010. Logistic regression and sensitivity analyses were conducted to clarify the association between chronic bowel diseases and renal stones. A total of 8,067 participants aged ≥20 years were included. The prevalence of renal stones is 9.14%. Chronic diarrhea was positively related to the risk of renal stones [odds ratio (OR) =1.681, 95% confidence interval (CI): 1.212 to 2.330, P=0.004] after adjusting for all covariates. In participants with body mass index (BMI) over 30 kg/m2, chronic constipation was correlated with kidney stones in fully adjusted model 2 (OR =2.142, 95% CI: 1.389 to 3.303, P=0.004). Our findings provide evidence that chronic diarrhea is associated with an increased risk of renal stones. Chronic constipation is positively related to the risk of renal stones in participants with BMI over 30 kg/m2. Health care should focus more on bowel health status for the prevention of related diseases. More prospective cohort studies are needed.

Assessment of Metformin Intolerance: A Retrospective Chart Review.

Objective: The aim of the present study is to determine similarities between patients with type 2 diabetes not on metformin therapy compared to patients on metformin therapy at a resident-led primary care clinic. Methods: An exploratory, single-center retrospective chart review was performed on patients 18 years and older with a documented diagnosis of type 2 diabetes seen at the University of Arkansas for Medical Sciences Family Medicine Clinic in Little Rock, Arkansas. Of the 2452 patients who met criteria for the study, 1085 patients did not have a documented metformin allergy. A subset of 216 patients who were not currently prescribed metformin and had no documented metformin allergy were further examined and compared to the 869 patients who were prescribed metformin. We sought to determine reasons for nonuse by evaluating their EPIC electronic health record. Information on these patients such as race, gender, hemoglobin A1c (A1c), kidney function, stated metformin intolerance, and comorbid disease states such as neuropathy, chronic kidney disease (CKD), ulcerative colitis, and irritable bowel syndrome were collected. Further examination was performed to determine why patients were not on metformin therapy and potential similarities between metformin intolerant patients. Results: The results of the study indicated a significant difference between metformin users and non-users in relation to body mass index (BMI) and diagnosis of CKD. Metformin non-users were found to have significantly lower mean BMI (30.87 vs. 35.43; p-value <0.0001), and significantly higher rates of CKD (25.93% vs 14.73%; p-value <0.0001) as compared to metformin users. BMI value of patients (coefficient: 0.2033, p value: <0.0001) was found to be significantly and positively correlated with metformin use, and CKD (coefficient: - 0.1191, p-value: <0.0001) was found to be significantly and negatively correlated with metformin use. A1c levels for patients not on metformin therapy were evaluated. Most non-metformin patients fell in prediabetic A1c levels ranging from 5-6.4% (84 patients; 38.89%), and 31 patients (14.35%) should be on insulin therapy according to guidelines. Conclusion: The results demonstrated that patients with lower BMI, CKD, or A1c in the prediabetic range were less likely to be prescribed metformin.

The primary nutritional approach in pediatric celiac disease: a mini-review

Background: Celiac disease (CD) is chronic small bowel inflammation with villous atrophy, consequently, an immune-mediated disorder triggered by ingesting Gluten in wheat, barley, and rye in genetically susceptible individuals. Aims: Summarize the fundamental principles for managing the diet of patients with CD. This Mini-Review using relevant articles in PubMed's online databases followed the medical keywords Celiac Disease, Gluten, gluten-free diet, nutritional approach, and diet adherence. The institution's Ethics Committee has waived the need to review the ethical aspects of this text. The cornerstone of the treatment is the lifelong adherence to a Gluten-Free Diet (GFD). This dietary regimen, which forms the basis of the patient's treatment, requires eliminating all food components containing Gluten and its derivatives from the diet. However, the treatment approach has changed from focusing on food avoidance to a wide-ranging evaluation of the various factors influencing the dietary choices in the patient's life. The Global Approach to the Follow-up of Celiac Disease is based on 1) control of symptomatology and dietary adherence; 2) improving emotional and social wellness in treating CD patients, with the active involvement of a psychologist; and 3) ensuring successful education of both the child and the family about its management. Indeed, the impact of CD extends beyond the patient and affects the well-being of caregivers and 4) evaluate socioeconomic burden, considering that Gluten-free food products remain significantly more expensive than gluten-containing equivalents with variable availability. So, the GFD is the primary treatment for CD, and difficulties in managing the Disease can lead to impaired Quality of Life. In conclusion, strict adherence to the GFD is imperative, requiring a multidisciplinary team involving physicians, dietitians, and psychologists on a regular visit schedule to assess dietary adherence and avoid long-term complications.

Aggravated Ulcerative Colitis via circNlgn-Mediated Suppression of Nuclear Actin Polymerization.

Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine, with its precise underlying causes remaining incompletely understood. In this study, we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis. Colitis patients produce significant higher levels of circNlgn. Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression, primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNlgn. Nlgn173 undergoes translocation into cell nuclei, where it interacts with actin, impeding the binding of actin-related protein 2 and 3 (Arp2/3) complex to actin molecules. Consequently, this leads to a reduction in actin polymerization. Mechanistically, Nlgn173 enhances tyrosine-53 phosphorylation of nuclear actin, diminishing its capacity to interact with the Arp2/3 complex and causing a decrease in filamentous actin levels. These alterations in actin dynamics result in inhibited cell cycle progression, increased apoptosis, and decreased proliferation of colonic epithelial cells, thereby exacerbating colitis development and progression. In contrast, the silencing of circNlgn or the targeted inhibition of Nlgn173 translation and nuclear translocation leads to the promotion of nuclear actin polymerization, enhanced cell survival, and reduced apoptosis and ultimately improves the outcome of colitis invivo. Interestingly, nuclear actin polymerization is highly related with expression of PIAS3, which modulates signal transducer and activator of transcription 3 and NF-κB activity in colitis. Strategies such as circNlgn knockdown and targeting nuclear actin polymerization of the colonic epithelium may explore a novel avenue for acute ulcerative colitis clinical intervention.

Impact of moderate wine consumption on immune-mediated diseases

This review critically assesses scientific literature in order to determine whether alcoholic beverages can positively or negatively affect the incidence and severity of immune-mediated disorders, including autoimmune diseases. Few scientific studies explore the association between alcoholic beverages and the immune system, in contrast to the extensive literature dedicated to the cardiovascular system. Because wine is the most investigated product in this review, it does not take into account studies that evaluate the role of alcohol itself without specifying the beverages included (e.g., wine, spirits and beer).The analysis of the data regarding the diseases reviewed here (allergies, celiac disease, the common cold and COVID-19, chronic inflammation bowel diseases, type 1 diabetes, dermatitis herpetiformis, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and thyroid disorders) revealed that, in principle (although with differences between the various pathologies), moderate consumption of wine does not negatively affect the risk of development or the progression of immune-mediated diseases. In some cases, the effect is mainly attributable to the alcohol itself, in others the wine is responsible for a more favourable trend compared to other alcoholic beverages.This review was limited by the scarcity of available papers, so that new prospective studies on the association between wine consumption and immune-mediated diseases should also be specifically designed to draw more solid conclusions.

Multipronged Electronic Health Record Analysis of Antidepressant Effectiveness on Depression Remission in Patients With Concurrent Depression and Irritable Bowel Syndrome.

Background Patients with irritable bowel syndrome (IBS) often experience chronic abdominal pain and bowel habit changes, with a heightened risk of depression and anxiety compared to the general population. Methods Using TriNetX data from 61 U.S. healthcare organizations, we conducted a retrospective study of three electronic health record (EHR) analyses. We usedInternational Classification of Diseases, Tenth Revision (ICD-10) and Anatomical Therapeutic Chemical Classification (ATC) codes to analyze depression remission among IBS patients, comparing those using antidepressants to those who were not and comparing outcomes among different types of medication. Statistical methods included risk difference, risk ratio, hazard ratio, Kaplan-Meier survival analysis, log-rank tests, and Cox hazard ratios Results Among 78,673 patients with both depression and IBS, those using antidepressants showed significantly higher rates of depressive remission compared to non-users: risk difference (RD), -0.056; risk ratio (RR), 0.380; and hazard ratio (HR), 0.413. Both atypical antidepressants bupropion and trazodone exhibited greater efficacy in achieving remission compared to selective serotonin reuptake inhibitors (SSRIs), sertraline and escitalopram. For SSRI vs bupropion, RD is -0.041, RR is 0.664, and HR is 0.655. For SSRIs vstrazodone, RD is -0.018 , RR is 0.822, and HR is 0.806. The comparative impact of bupropion versus trazodone on remission remains inconclusive. Conclusion Depression presents a significant comorbidity in IBS patients, with atypical antidepressants potentially offering superior efficacy in achieving remission compared to SSRIs. Further research should explore these medications' psychiatric outcomes in this population to better understand their therapeutic benefits beyond gastrointestinal (GI) symptoms.

Cross-sectional imaging of mimics of inflammatory bowel disease: not everything is Crohn's disease or ulcerative colitis.

Acute and chronic bowel pathologies can often be mistaken for manifestations of inflammatory bowel disease (IBD), and there are many entities with imaging and clinical features that overlap with IBD, making diagnosis difficult. We describe multiple inflammatory, infectious, neoplastic, and vascular entities with imaging and clinical features that may mimic IBD, and highlight differentiating features to assist in diagnosis.

Oral alginate microspheres for the efficient site-specific delivery of epidermal growth factor attenuated murine ulcerative colitis via repairing the mucosal barrier

Ulcerative colitis (UC) is a chronic bowel inflammatory disease affecting the colorectum. Epidermal growth factor (EGF) has been demonstrated to be effective to counteract UC. However, there exists the gastrointestinal challenges such as stomach acid, enzyme and bile salts for oral delivery of EGF. Herein, calcium alginate microsphere was prepared by the microfluidic technique to encapsulate EGF. The morphology of EGF-loaded microsphere (MS-EGF) was spherical and its average particle size was 80 ± 23 μm. The encapsulation efficiency of EGF was reaching to 93.8 % ± 1.6 %. In vitro release experiments showed that MS-EGF presented the good pH-sensitive properties, that was, it could effectively resist the gastric acid and small intestinal fluids, and undergone the rapid dissolution in the artificial colon fluid. In vitro cellular experiments demonstrated that the bioactivity of EGF was well preserved by microsphere. Moreover, in vivo murine colitis model showed that MS-EGF presented the obvious colitis alleviation. Furthermore, the colonic morphology of colitis mice was effectively recovered and the tight junction between the gut epithelium was obviously repaired. In conclusion, calcium alginate microsphere might be a promising vehicle of EGF for UC treatment.