Small Colon Research Articles

Joint analysis of genome-wide cross-trait and multi-omics reveals molecular mechanisms of inflammatory bowel disease and nominates its novel therapeutic genes.

Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions. Subsequently, we revealed tissue and cell-specific heritability enrichment, particularly in whole blood, small intestine terminal ileum, spleen, lung, and colon transverse. Leveraging multi-omics datasets, we adopted a two-pronged approach comprising summary data-based Mendelian randomization (SMR) and transcriptome-wide association study (TWAS) to pinpoint likely causal genes and variants. Further, RNA-seq analysis facilitated the evaluation of differential expression and co-expression in intestinal tissues. Through a multi-stage prioritization strategy, compelling evidence for putative targets was nominated; notably highlighting several potential susceptibility genes such as IL27 and SBNO2. Finally, we utilized Mendelian randomization (MR) analysis with diverse datasets to verify the convergence of these two endophenotype-driven genes. Our investigation yields valuable insights to inform genetic mechanisms in IBD and reveal potential causal gene targets.

Management of pediatric Peutz-Jeghers syndrome: Highlighting the efficacy and safety of endoscopic ischemic polypectomy.

Patients with Peutz-Jeghers syndrome (PJS) require continuous medical management throughout their lives. However, few case series regarding the clinical course, polyp surveillance, and treatment, including endoscopic ischemic polypectomy (EIP) for pediatric patients with PJS, were reported. We analyzed the current status and clinical course of pediatric patients with PJS under the management of our institute, including those treated with EIP. Medical information on double-balloon enteroscopy (DBE) performed between January 2006 and December 2023 and patient backgrounds were retrospectively collected. The location of polyps, breakdown of treatment methods, and differences in complication rates of each treatment method were analyzed. The median age at diagnosis of PJS was 9 years (0-18 years), and the prevalence of intussusception before the first DBE among the patients was 68.2%. In total, 115 procedures were performed in 22 pediatric patients with PJS. There were 100 therapeutic procedures, and the total number of treated polyps was 462 (362, 54, and 46 in the small bowel, colon, and stomach, respectively). Conventional polypectomy was performed for 106 polyps, and ischemic polypectomy was performed for 356 polyps. The incidence rates of post-polypectomy bleeding and perforation associated with conventional polypectomy and EIP were 2.83% and 0.28%, respectively (p = 0.042). Eight patients (36.4%) had polyps larger than 15 mm under the age of 8 years. Proper imaging evaluation and endoscopic treatment for gastrointestinal (GI) polyps are essential to prevent GI complications in pediatric patients with PJS, even those younger than 8 years old. Moreover, EIP may be the ideal procedure for managing polyps in this population.

Early changes in intestinal lymphoid and myeloid populations in experimental autoimmune encephalomyelitis.

Intestinal immunity is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes. Recent evidence also suggests its implication in the pathogenesis of autoimmune diseases affecting the central nervous system, such as multiple sclerosis (MS). However, there is ongoing debate regarding which part of the intestinal tract contributes to the development of MS. Therefore, our study aimed to explore the early changes in lymphoid and myeloid immune cells populations in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We also sought to determine the roles of the colon and/or small intestine in the pathogenesis of EAE. By using flow cytometry, we revealed a transient increase in T and B lymphocytes in the ileal lamina propria of EAE mice just before the onset of motor symptoms. Additionally, we highlighted an increase in dendritic cells and monocytes/macrophages in the colonic lamina propria of EAE animals during the presymptomatic phase. Altogether, our findings indicate that both small intestine and colon are involved in the pathogenesis of EAE, despite engaging distinct immunological processes. This study provides new insights for understanding the roles of intestinal lymphoid and myeloid immune cells on the pathogenesis of MS and other autoimmune diseases.

CCL3 as a novel biomarker in the diagnosis of necrotizing enterocolitis

ObjectivesNeonatal necrotizing enterocolitis (NEC) is a common intestinal disease that threatens the lives of newborns and is characterized by ischemic necrosis of the small intestine and colon. As early diagnosis of NEC improves prognosis, the identification of new or complementary biomarkers is of great importance. In this study, we evaluate the diagnostic value of CCL3 in NEC and compare its effectiveness with other commonly used biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP).Participants and designSerum samples were collected from 64 patients with NEC and 38 jaundice neonatal controls. Before initiating therapy, blood samples for the whole blood count, CRP, PCT and CCL3 were obtained from all neonates. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed.SettingDepartment of Clinical Laboratory, Children’s Hospital of Chongqing Medical University.ResultsThe serum CCL3 level of the NEC group was significantly higher than that of the Control group. The ROC area under the curve (AUC) was 0.8614 (95%confidence interval (CI) 0.7863–0.936; p < 0.0001) for CCL3, 0.8534 (95% CI 0.7682–0.9386; p < 0.0001) for PCT, 0.675 (95% CI 0.5625–0.788; p < 0.0001) for CRP, 0.579 (95% CI 0.4402–0.7188 p = 0.2460) for WBC, and 0.7384 (95% CI 0.6215–0.8554 p = 0.0005) for PLT. With a cut-off value of 83.33 ng/ml, the diagnostic sensitivity and negative predictive value of CCL3 were 83.33% and 80.55%, respectively. The combined use of CCL3 and PCT could significantly improve diagnostic performance for NEC (0.903; 95% CI 0.810–0.960; p < 0.0001).ConclusionsCCL3 may be used as a promising biomarker for the diagnosis of NEC, and the combined use of CCL3 and PCT could improve the diagnosis of NEC.

Effect of High-glucose Incubation on the Antioxidant System in Rat Gastrointestinal Tract Wall Tissue

Abstract Background: Hyperglycemic metabolic disorders such as diabetes can impair gastrointestinal (GI) physiological functions leading to multiple digestive manifestations. Oxidative stress which is an imbalance between reactive oxygen species production and antioxidants is contributed to GI complications that occur during hyperglycemia. Aim: To investigate the effect of high-glucose concentration on the antioxidant enzymes in the GI tract. Methods: Small intestine and colon tissues extracted from rats were incubated in a high-glucose medium for 3 hours. Following tissue homogenization, antioxidant enzyme activity and expression were evaluated. Results: Catalase (CAT) activity was increased in the small intestine (1742 ± 113.1–2265 ± 242.4 [mU/mL]) and decreased in the colon (3791 ± 516.2–1532 ± 292.9). Total antioxidant capacity was decreased in the small intestine (10.1 ± 1.83–9.048 ± 0.441 [nmole/μl]) and increased in the colon (8.114 ± 0.9–11.01 ± 0.99). Messenger RNA (mRNA) expression of antioxidant enzymes in the small intestine was increased (CAT: 0.03941 ± 0.0041–0.1917 ± 0.0165, glutathione peroxidase 1 [GPx1]: 1.156 ± 0.0855–16.24 ± 1.618, glutathione reductase [GR]: 0.0413 ± 0.0014-0.1549 ± 0.0145, superoxide dismutase 1 [SOD1]: 1.03 ± 0.1095–8.52 ± 0.471, SOD2: 0.00106 ± 3.559e-005–0.0028 ± 0.00052, SOD3: 0.0352 ± 0.0044–0.0493 ± 0.0223). mRNA expression of antioxidant enzymes in the colon was decreased (CAT: 0.02148 ± 0.0032–0.01057 ± 0.0014, GPx1: 0.48 ± 0.146–0.1090 ± 0.0209, GPx4: 0.2391 ± 0.063–0.01671 ± 0.0019, GR: 0.0393 ± 0.0031–0.0093 ± 0.0014, SOD1: 0.389 ± 0.1159–0.088 ± 0.0251, SOD2: 0.000934 ± 0.00020–0.000233 ± 2.39023e-05, SOD3: 0.0114 ± 0.00107–0.0017 ± 0.000176). Conclusion: Most of the results indicate a state of oxidative stress in the GI tract mediated by the exposure to high glucose level. Diabetic GI complications could be reversed using specific modalities that act to increase the antioxidant capacity.

Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation.

Bisacodyl is a widely used laxative that stimulates both motility and secretion. Our aim was to exploit the unique capabilities of MRI to define bisacodyl's mode of action. Two placebo-controlled cross-over trials were performed, one using a single dose of Bisacodyl 5 mg while the second dosed daily for 3 consecutive days. Serial MRI was performed every 75 minutes. Primary endpoint: ascending colon water content as assessed by T1AC AUC300-450 minutes. Secondary endpoints included: small bowel water content, whole gut transit time (WGTT), colonic volumes, stool frequency, and consistency using Bristol Stool Form Score (BSFS). Exploratory endpoints: changes in the serial segmental volumes were quantified from the number of "mass movements" defined as episodes when segmental volume change from the previous scan was > 20% of baseline volume. We also measure the time to defecate after dosing. After 3 days of bisacodyl, ascending colon water content (T1) was 62% greater than after placebo, mean difference T1 AUC300-450 minutes 50.2 (61.0) sec.min, 95% CI (9.2, 91.2), P = 0.02, while after a single dose difference was only 11% (P = 0.58). Both single and repeated doses shortened WGTT (P < 0.049) and time to defecate (P 0.01). Only repeated doses significantly increased small bowel water content (P < 0.03), the number of "mass movements" (P = 0.048), bowel frequency (P = 0.006), and BSFS (P = 0.03). Repeated, compared to single dosing of Bisacodyl, additionally increases small bowel and colon water content and increases the number of "mass movements" thereby increasing its laxative effect. MRI is a non-invasive, patient-acceptable technique for evaluating drugs which alter secretion and/or motility.

Percutaneous image-guided mesenteric biopsy: how we do it in a high-volume training center.

Lesions in the mesentery are unique from other potential biopsy targets in the abdomen or pelvis for several reasons. Mesenteric lesions are among the deepest in the abdomen and are often surrounded by or adjacent to small bowel or colon. Mesenteric vasculature is often crowded, and traversing the mesentery often involves crossing multiple vascular planes. Mesenteric lesions and the structures surrounding them within the peritoneal cavity are often highly mobile. All these features can be daunting to any radiologist asked to perform a mesenteric biopsy. We provide a comprehensive overview and guide to percutaneous mesenteric biopsy informed by available literature and experience at two high volume teaching centers. Topics covered include the pitfalls of using prior imaging to determine whether mesenteric biopsy is possible, techniques specific to US or CT-guidance and complications including hemorrhage and bowel injury.

Effects of 3,4-methylenedioxymethamphetamine on the gut microbiota and metabolites in the small intestine, cecum, and colon of male rats.

3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10mg/kg/day for 14days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.

Effect of encapsulated Tahongai (Kleinhovia hospita l.) leaf extract on growth performance, intestinal condition and antioxidative status of broilers raised in high stocking density pens

The objective of the present study was to investigate the effect of Kleinhovia hospita L. extract (KE) on growth performance, intestinal condition and antioxidative status of broilers raised in high stocking density pens. A total of 370-day-old broiler chicks were randomly grouped into five groups with five replicates. The groups were T0 (chicks raised in normal density, 10 birds/m2; as a negative control), KE0 (chicks raised in high density, 16 birds/m2, without KE supplementation; as a positive control), KE0.25, KE0.5 and KE1 (chicks raised in high density with KE supplementation of 2.5, 5 and 10 g/kg, respectively). Based on the completely randomized design, the data were treated. Results showed that KE1 chicks had the highest (p&lt;0.05) body weight (BW) at day 21 and 28. The T0, KE0 and KE2.5 chicks consumed more (p&lt;0.05) feed than the other treatment groups. The KE0.25, KE0.5 and KE1 showed lower (p&lt;0.05) FCR than the KE0 group. The KE0 chicks showed lower (p&lt;0.05) carcass yield than the other groups. The KE0 had the highest (p&lt;0.05) heart relative weight of all groups. The KE1 had the highest (p&lt;0.05) small intestinal weight, cecum, colon and abdominal fat of any treatment group. Among the groups, crypt depth of the duodenum in KE0 was the lowest (p&lt;0.05). There was no substantial effect of the treatments on the counts of coliform and lactic acid bacteria in the ileum of broilers. The superoxide dismutase (SOD) levels in KE0.5 and KE1 were higher (p&lt;0.05) than those in T0, KE0 and KE0.25 groups. In conclusion, stocking in high density pens negatively af-fected the carcass yield of broiler chickens. Dietary KE supplementation was beneficial in improving FCR and antioxidant status of broiler chickens.

Glucagon-Like Peptide 1 Receptor Agonists Are Not Associated With an Increased Risk of Ileus or Intestinal Obstruction in Patients with Inflammatory Bowel Disease-A Danish Nationwide Cohort Study.

There is a global increase in the prevalence of obesity, including among individuals with inflammatory bowel disease (IBD). Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are potential anti-obesity medications due to their weight-lowering effects. However, concerns exist regarding ileus and intestinal obstruction as a severe side effect. This nationwide Danish cohort study evaluates the risk of ileus and intestinal obstruction in patients with IBD receiving GLP-1RAs. Patients with IBD and their exposure to GLP-1RAs were identified using Danish health registries. Cox regression analysis was used to estimate hazard ratios for the risk of ileus and intestinal obstruction adjusted for age at diagnosis of IBD, sex, type of IBD, prior ileus or intestinal obstruction, diabetes status, steroid use, and small bowel or colon surgery. This study found that GLP-1RA exposure was not associated with an increased risk of ileus or intestinal obstruction in patients with IBD. This study suggests that GLP-1RAs do not increase the risk of ileus or intestinal obstruction in patients with IBD.

Dietary Bovine Lactoferrin Reduces the Deleterious Effects of Lipopolysaccharide Injection on Mice Intestine.

Injection of lipopolysaccharides (LPS) in experimental models induces a systemic inflammatory response that is associated with deleterious effects on intestinal morphology and physiology. In this study, we have studied in female mice the effects of dietary supplementation with bovine lactoferrin (bLF) given before intraperitoneal injection of LPS on jejunum and colon. The first study evaluated the efficiency of different bLF and LPS concentrations to determine the optimal experimental conditions. For the second study mice were fed with 1% bLF before the LPS challenge (3 mg/kg body weight). Plasmatic markers of inflammation, intestinal morphology, permeability, and expression of genes related to epithelial differentiation, epithelial barrier function and intestinal inflammation in both small intestine and colon were evaluated. bLF ingestion before the LPS challenge reduced the TNF-α circulating concentration, compared to control animals. This decrease in plasma TNF-α was correlated with improved intestinal permeability. The morphology of jejunal epithelium, which was affected by LPS challenge, was partly maintained by bLF. Measurement of the expression of genes encoding proteins involved in epithelial differentiation, intestinal inflammation, and epithelial barrier function suggests an overall protective effect of bLF against the adverse effects of LPS in the jejunum. In the colon, the effects of bLF ingestion on the subsequent LPS challenge, although protective, remain different when compared with those observed on jejunum. Taken together, our data indicate that bLF dietary supplementation does have a protective effect on the deleterious intestinal alterations induced by LPS systemic inflammation.

A Phase II, multicentric, randomized, double-blind, placebo controlled, proof of concept study of efficacy and safety of Rifamycin SV-MMX® 600 mg tablets administered three or two times daily to patients with diarrhea-predominant irritable bowel syndrome (IBS-D).

Treatment with non-resorbable antibiotics is effective in diarrhea predominant irritable bowel syndrome (IBS-D). Multimatrix® (MMX®) formulations ensure targeted drug delivery to the mid-distal small bowel and colon - traditionally considered the origin of IBS symptoms. To assess the efficacy of Rifamycin SV-MMX for the treatment of IBS-D. Randomized controlled trial in IBS-D patients (Rome IV). Patients received Rifamycin SV-MMX® 600 mg (b.i.d = 1200mg/day or t.i.d =1800mg/day) or placebo for 2 weeks. Primary endpoint was responder rate in the first treatment week on the full analysis set (FAS). Response was defined as decrease in average abdominal pain ≥ 30% AND ≥50% reduction of days with stool type 6 or 7 based on daily reporting. 279 patients were randomized (= ITT), 264 of were included in the FAS. More patients with Rifamycin SV-MMX® b.i.d (22/88, 25.00%) met the primary endpoint than t.i.d (10/81, 12.35%) or placebo (9/95, 9.47%) in both FAS and ITT. Adjusted Odds ratio (AOR) for b.i.d. vs placebo was 3.26 (95% CI: 1.39-7.67; p=0.007) and for t.i.d. vs b.i.d. 0.40 (95% CI: 0.17-0.92; p=0.031). Following treatment, the percentage of monthly global responders was higher in the b.i.d. group vs placebo in the first month (64.2% vs 46.6 %, AOR= 2.14 95% CI: 1.15; 4.00; p=0.0173) and first 2 months. Rifamycin SV-MMX® 600mg b.i.d. was more effective than placebo and t.i.d. dosing in the first week of treatment. Two months following treatment, Rifamycin SV-MMX® 600mg b.i.d. provided more global symptom relief than placebo.

Distribution Characteristics and Impacting Factors of Drug CYP Enzymes and Transporters in the Gastrointestinal Tract of Chinese Healthy Subjects.

The abundance of drug metabolic enzymes (DMEs) and transporters (DTs) in the human gastrointestinal tract significantly affects xenobiotic exposure in the circulating system, the basis of these compounds acting on humans. However, accurately predicting individual exposure in healthy subjects remains challenging due tolimited data on protein levels throughout the gastrointestinal tract within the same individuals and inadequate assessment of factors influencing these levels. Therefore, we conducted a clinical study to obtain biopsy samples from 8 different gastrointestinal segments in 24 healthy Chinese volunteers. Concurrently, blood and fecal samples were collected for genotypic analysis and fecal microbiota metagenomic sequencing. Using an optimized LC-MS/MS method, we quantified the absolute protein abundance of CYP2C9, CYP2C19, CYP2D6, CYP3A4, P-gp, and BCRP from the stomach to the colon. Our results revealed significant regional differences in protein expression: CYP3A4 was the most abundant in the small intestine, whereas CYP2C9 was predominantly found in the colon. CYP2D6 was primarily located in the ileum, while other DMEs/DTs showed higher concentrations in the jejunum. Meanwhile, the enzyme abundance in the small intestine and colon and the relative ratio of transporters in different regions to the jejunum were accurately calculated, providingvaluable data for refining the physiological parameters in the virtual gastrointestinal tract of Chinese healthy population in PBBMs. Additionally, BMI, IBW, sex, age, genotype, and fecal microbiota were identified as critical factors influencing the protein levels of these DMEs/DTs throughout the gastrointestinal tract, with notable regional differences. Consequently, this study provides a unique foundation for understanding xenobiotic absorption in humans.

Effect of Coptidis Rhizoma on gastrointestinal system before and after processing with wine based on gut microbiota and short chain fatty acids.

Coptis deltoidea C.Y. Cheng et Hsiao (CD), commonly used in the treatment of heat-toxin congestion and excessiveness. However, CD needs to be processed with wine for alleviating the bitter and cold of CD, meanwhile, reducing the gastrointestinal damage. The research assessed the discrepant effects of CD on gastrointestinal system before and after processing with wine, and explore the potential mechanisms. The ingredients in CD and CD processed with wine (PCD) were performed on Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC-MS). The mice were treated with CD and PCD once a day for 6weeks (0.65 and 2.6g/kg, i.g.). The pathological changes of gastrointestinal tract were evaluated, and the serum inflammatory factors and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) RelA (p65) protein of tissues were determined. The short chain fatty acids (SCFAs) of feces were analyzed by UPLC-MS, the gut microbiota (GM) changes were performed on 16S rRNA sequencing. Ingredients analysis declared that the alkaloids, flavonoids, phenylpropanoid compounds were the main metabolites in CD and PCD. CD reduced body weight and food intake, and the effect of CD on fecal water content increased first and then decreased with the prolongation of administration time, while its effect on intestinal transport time was exactly the opposite, reduced the SCFAs contents of feces. CD caused different degree of damage to the gastrointestinal tract, and the effect on the small intestine and colon was more obvious, which increased the expression of NF-κB p65 and elevated the inflammatory factors levels. PCD were weaker than that of CD. In addition, CD and PCD can change the composition of GM, and reduced the levels of Lactobacillus, Allobaculum, Ruminococcus, and norank_f_S24-7, increased the levels of Akkermansia, Dorea, Bacteroides, and Blautia at the genus level. However, PCD induced a milder effect of GM dysregulation than that of CD. CD can cause damage to the gastrointestinal tract, which may be related to the GM disorders, SCFAs changes-mediated by GM, abnormal NF-κB p65 expression and increased inflammatory factors levels, interestingly, PCD had a lower effect than CD, which may be related to the differences in the types and contents of ingredients in CD after processing. And this study provided data support for the mechanism of processing with wine to alleviate "bitter-cold injury the stomach" of CD.

Kallikrein-Related Peptidase 6 Contributes to Murine Intestinal Tumorigenesis Driven by a Mutant Adenomatous polyposis coli Gene.

The objective of this study was to assess the role of a secreted serine protease, kallikrein-related peptidase 6 (KLK6), during colorectal tumorigenesis driven by a mutant Adenomatous polyposis coli (APC) tumor suppressor gene. A first analysis of KLK6 expression in the intestinal tract of Apc-mutant multiple intestinal neoplasia (ApcMin/+) mice revealed up to four-fold induction of Klk6 mRNA levels in adenomas relative to its level in the adjacent mucosa. The presence of KLK6 protein in the adenomatous areas was confirmed by immunohistochemistry and optical coherence tomography/laser-induced fluorescence (OCT/LIF) imaging. To assess the contribution of the KLK6 expression on the Apc-mutant intestinal and colon tumorigenesis, we engineered a mouse with floxed alleles of the Klk6 gene (Klk6lox/lox) and crossed it with a mouse expressing the truncated APC protein under control of the intestinal tract-specific human CDX2P9.5-NLS Cre transgene (CPC;Apcfl/fl;Klk6+/+). We found that CPC;Apcfl/fl mice with disrupted Klk6 gene expression (CPC;Apcfl/fl;Klk6fl/fl) had a significantly smaller average size of the small intestinal and colon crypts (p < 0.001 and p = 0.04, respectively) and developed a significantly fewer adenomas (p = 0.01). Moreover, a decrease in high-grade adenomas (p = 0.03) and adenomas with a diameter above 2 mm (p < 0.0001) was noted in CPC;Apcfl/fl;Klk6fl/fl mice. Further molecular analysis showed that Klk6 gene inactivation in the small intestine and colon tissues of CPC;Apcfl/fl;Klk6fl/fl mice resulted in a significant suppression of transforming growth factor β2 (TGF-β2) protein (p ≤ 0.02) and mitogen-activated protein kinase (MAPK) phosphorylation (p ≤ 0.01). These findings demonstrate the oncogenic role of KLK6 in the mutant Apc-mediated intestinal tumorigenesis and suggest the utility of KLK6 for early diagnosis of colorectal tumors.

A rare atypical Idiopathic Mesenteric Phlebosclerosis( original text: IMP) characterized by widespread submucosal bulges of small bowel and colon: first report

A rare atypical Idiopathic Mesenteric Phlebosclerosis( original text: IMP) characterized by widespread submucosal bulges of small bowel and colon: first report

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn's Disease.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn's disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.

Innovative modified pectins enriched with galactose: Preparation, characterization, and gel-based properties of curcumin-delivered hydrogel beads

Gelling and thickening are the most important properties of pectin, and these properties are dependent on the molecule's structure. In this study, new types of pectin with varying degrees of modification were prepared by reducing the methyl ester groups on the galacturonic acid residues in pectin to hydroxyl groups using NaBH4, thereby converting methylated galacturonic acid to galactose. The physicochemical properties, rheological behavior, and gelling properties of the modified pectins were investigated. Galacturonic acid levels gradually decreased from 68.98% ± 0.40%–7.49% ± 0.09%, whereas galactose levels increased from 10.29% ± 0.48%–72.26% ± 0.62% with increasing degree of modification. The molecular weight exceeded 500 kDa, and solubility was high. The novel modified pectins underwent gelation without requiring sucrose addition and were calcium and pH sensitive. A higher degree of modification promoted gelation at higher temperatures. Addition of Ca2+ at 60 mg/g caused R-55 to gel at 37 °C and pH 2 but disintegrate at pH 6. Three types of R-55 hydrogel beads encapsulating curcumin were prepared. These beads effectively protected curcumin in the stomach; two allowed for its rapid and slow release in the small intestine, whereas one allowed for its release in the colon. Thus, R-55 can be used as a carrier for the targeted delivery of drugs to the small intestine and colon. The modified pectins are suitable for innovative applications in the food and pharmaceutical fields.

Indole-3-Acetic Acid Esterified with Waxy, Normal, and High-Amylose Maize Starches: Comparative Study on Colon-Targeted Delivery and Intestinal Health Impact.

Background: Accumulating research suggests that metabolites produced by gut microbiota are essential for maintaining a balanced gut and immune system. Indole-3-acetic acid (IAA), one of tryptophan metabolites from gut microbiota, is critical for gut health through mechanisms such as activating aryl hydrocarbon receptor. Delivery of IAA to colon is beneficial for treatment of gastrointestinal diseases, and one promising strategy is IAA esterified starch, which is digested by gut microbes in colon and releases loaded IAA. Amylose content is a key structural characteristic that controls the physicochemical properties and digestibility of starch. In the current study, IAA was esterified with three typical starches with distinct amylose content to obtain indolyl acetylated waxy maize starch (WMSIAA), indolyl acetylated normal maize starch (NMSIAA), and indolyl acetylated high-amylose maize starch (HAMSIAA). The study comparatively analyzed their respective physicochemical properties, how they behave under in vitro digestion conditions, their ability to deliver IAA directly to the colon, and their effects on the properties of the gut microbiota. The new characteristic peak of 1H NMR at 10.83 ppm, as well as the new characteristic peak of FTIR spectra at 1729 cm-1, represented the successful esterification of IAA on starch backbone. The following in vitro digestion study further revealed that treatment with indolyl acetylation significantly elevated the resistant starch content in the starch samples. In vivo experimental results demonstrated that WMSIAA exhibited the most significant increase in IAA levels in the stomach, whereas HAMSIAA and NMSIAA demonstrated the most remarkable increases in IAA levels in the small intestine and colon, respectively. The elevated IAA levels in the colon are conducive to promoting the growth of beneficial intestinal bacteria and significantly alleviating DSS-induced colitis. This research presents innovative insights and options for the advancement of colon-specific drug delivery systems aimed at preventing and curing gastrointestinal disorders.