Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.

The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.

BACKGROUND & AIMS: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms. METHODS: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quantitative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms. RESULTS: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory responses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3. CONCLUSIONS: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.

Effect of Dietary Patterns on Inflammatory Bowel Disease: A Machine Learning Bibliometric and Visualization Analysis.

AIMS: This study aimed to analyze the related research on the influence of dietary patterns on IBD carried out over the past 30 years to obtain the context of the research field and to provide a scientific basis and guidance for the prevention and treatment of IBD. METHODS: The literature on the effects of dietary patterns on inflammatory bowel disease published over the past three decades was retrieved from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer, the R software (version 4.3.0) bibliometrix package, the OALM platform, and other tools were used for the analyses. RESULTS: The growth of scientific papers related to this topic can be divided into two stages: before and after 2006. Overall, the growth of the relevant literature was in line with Price's literature growth curve. Subrata Ghosh and Antonio Gasbarrini are the authors with the highest academic influence in the field, and Lee D.'s research results are widely recognized by researchers in this field. Among the 72 countries involved in the study, the United States contributed the most, while China developed rapidly with regard to research being carried out in this area. From a regional perspective, countries and institutions in North America, Europe, and East Asia have made the most significant contributions to this field and have the closest cooperation. Among the 1074 articles included in the study, the most influential ones tended to consider the mechanism of the effect of dietary patterns on IBD from the perspective of the microbiome. Multiple tools were used for keyword analysis and mutual verification. The results showed that NF-κB, the Mediterranean diet, fatty acids, fecal microbiota, etc., are the focus and trends of current research. CONCLUSIONS: A Mediterranean-like dietary pattern may be a good dietary habit for IBD patients. Carbohydrates, fatty acids, and inulin-type fructans are closely related to IBD. Fatty acid, gut microbiota, NF-κB, oxidative stress, and endoplasmic reticulum stress are the hot topics in the study of the effects of dietary patterns on IBD and will be emerging research trends.

Research progress of N-nitrosamine detection methods: a review.

N-nitrosamines (nitrosamines) are attracting increased attention because of their high toxicity and wide distribution. They have been strictly restricted by regulations in many fields. Researchers around the world have conducted substantial work on nitrosamine detection. This paper reviews the progress of research on nitrosamine detection methods with emphasis on biological-matrix samples. After introducing the category, toxicity, regulatory limit and source of nitrosamines, the paper discusses the most commonly used sample-preparation techniques and instrumental-detection techniques for nitrosamine detection, including some typical application cases.

Preexisting diabetes, serum calcium and D-dimer levels as predictable risk factors for pancreatic necrosis of patients with acute pancreatitis: a retrospective study.

BACKGROUND: Some individuals with acute pancreatitis (AP) suffer from pancreatic necrosis. Diabetes affects the severity of AP, but whether diabetes influences pancreatic necrosis is unclear. This study aims to investigate the clinical characteristics of AP patients with and without diabetes as well as analyze the risk factors of pancreatic necrosis. RESEARCH DESIGN AND METHODS: A total of 625 AP patients participated in the study. Clinical and laboratory data were retrieved. Multivariate logistic regression analysis was used to identify the risk factors for pancreatic necrosis. ROC curves assess the accuracy of indicators for predicting pancreatic necrosis in AP. RESULTS: AP patients with diabetes had high BMI, CTSI scores, pancreatitis severity, WBC, neutrophil, CRP, triacylglycerols and glucose levels. Diabetes, serum calcium and D-dimer were independent risk factors for pancreatic necrosis. Pancreatic necrosis in diabetes patients is also associated with sex and age. D-dimer is a better predictor of pancreatic necrosis in AP patients than serum calcium. CONCLUSIONS: Diabetic patients are more likely to suffer severe AP. Serum calcium and D-dimer are independent predictors for pancreatic necrosis. Furthermore, low serum calcium, high D-dimer levels, younger age and female sex are independent risk factors for pancreatic necrosis in AP patients with diabetes.

Highly Sensitive W18O49 Mesocrystal Raman Scattering Substrate with Large-Area Signal Uniformity.

Although mesocrystals with ordered building units have great potential in many fields because of the large amount of organic molecules used as structure-directing agents during their synthesis process, severe matrix interference makes their surface-enhanced Raman scattering (SERS) properties rarely understood. Herein, a rapid (20 s) and green microwave synthetic route is developed for the 100 g scale preparation of plasmonic W18O49 mesocrystals with no additives. The ultrathin (1.5 nm) and oxygen vacancy-rich W18O49 nanowires as a building unit greatly improve the interface charge transfer, while the periodic mesocrystal structure significantly enhances the localized surface plasmon resonance effect and creates high-density electromagnetic hot spots among the nanowires. An outstanding enhancement factor of 1.2 × 107 and an ultralow detectable limit of 10-11 M are achieved, and the single-molecule imaging is also realized on this mesocrystal-based SERS substrate. Moreover, the relative standard deviation of the fabricated large-area (2.2 cm2) SERS substrate is only 6.8%.

Synthesis and biological activities of novel nonpeptide angiotensin II receptor antagonists based on benzimidazole derivatives bearing a heterocyclic ring.

A series of benzimidazole derivatives bearing a heterocyclic ring imidazole (1), 5-chloroimidazole (2), 1,2,4-triazol (3), and imidazoline (4) were synthesized and evaluated for angiotensin II antagonistic activities. The synthetic compounds 1-4 were biologically evaluated in vitro using an AT(1) receptor binding assay, where compounds 1 and 3 provided weak binding affinity, compound 2 showed moderate binding affinity, and compound 4 showed good binding affinity. Moreover, compound 4 was found to be almost equipotent with telmisartan in vivo biological evaluation study.