Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Gastric submucosal lesion caused by an embedded fish bone: A case report.

BACKGROUND: Submucosal tumors (SMTs) refer to elevated lesions that originate from the layers below the mucosa of the digestive tract, including the muscularis, submucosa and muscularis propria. With the development and application of endoscopy and endoscopic ultrasonography (EUS), the detection rate of SMTs has increased significantly in recent years. Various diseases can lead to SMTs. However, a foreign body embedded in the gastric antrum showing clinical manifestations of a SMT is rare. CASE SUMMARY: We report the case of a 47-year-old woman, who presented with upper abdominal discomfort for one year, and was subsequently diagnosed with a gastric submucosal lesion caused by an embedded foreign body by EUS and computed tomography. Considering the size and potential complications of this lesion, endoscopic full-thickness resection was performed to achieve full resection in our endoscopy center. A fish bone was found in the lesion during the operation, and was successfully removed, and the defect was later closed with endoscopic purse-string sutures. CONCLUSION: This case report highlights the management strategies of SMTs, the importance of being familiar with diagnostic methods related to submucosal lesions, and being able to conduct effective treatment when this rare condition is highly suspected.

Regulation of lipid-induced macrophage polarization through modulating peroxisome proliferator-activated receptor-gamma activity affects hepatic lipid metabolism via a Toll-like receptor 4/NF-κB signaling pathway.

BACKGROUND AND AIM: Chronic inflammation links closely to insulin resistance and lipid metabolism in nonalcoholic fatty liver disease (NAFLD). Macrophage M1 activation plays an important role in the initiation and continuing of pro-inflammatory response of NAFLD. Our study was to investigate whether macrophage M1/M2 polarization switching would affect hepatic inflammation and lipid metabolism through modulation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) activity in vivo and in vitro. METHODS: RAW264.7 macrophages were treated with different fatty acids, and cell culture supernatants were collected to prepare conditioned media (CM). Different co-culture systems between primary hepatocytes and CM from macrophages were established. A PPAR-γ agonist or antagonist was administered to regulate PPAR-γ activity and macrophage polarization. M1/M2 phenotype markers, inflammatory signaling pathway, and lipid-related genes expression were determined. Wild-type C57BL/6 mice were fed a high-fat diet to induce NAFLD and given rosiglitazone to regulate PPAR-γ activity in vivo. RESULTS: Saturated fatty acids induced M1-polarized macrophages while polyunsaturated fatty acids induced M2-polarized macrophages. M1-polarized macrophages significantly promoted lipid synthesis and accumulation in primary hepatocytes through upregulation of a toll-like receptor 4 (TLR4)/NF-κB signaling pathway. The PPAR-γ agonist made lipid-induced M1-polarized macrophages switch to an M2-predominant phenotype, while PPAR-γ antagonist had the opposite effect. Macrophage polarization shifting subsequently affected lipid metabolism in primary hepatocytes. Administration of rosiglitazone improved high-fat diet induced hepatic steatosis and lipid metabolism through reducing hepatic TLR4/NF-κB expression and M1-polarized Kupffer cells. CONCLUSIONS: Lipid-induced macrophage M1 polarization promoted hepatic lipid metabolism. Modulation of PPAR-γ activity could shift macrophage polarization and subsequently affect lipid metabolism. Upregulation of the TLR4/NF-κB signaling pathway is closely linked to dysregulated lipid metabolism in NAFLD.

Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is among the most common chronic liver diseases. However, the pathogenesis of NAFLD is not still unclear. This study aims at evaluating the role of zinc finger and BTB domain-containing 7A (ZBTB7A) in NAFLD. METHODS: Western blotting, real-time reverse transcription PCR (RT-PCR), and immunohistochemistry were submitted to evaluate the level of ZBTB7A in the high fatty diet- (HFD-) induced NAFLD mouse model. In vitro, the expression of ZBTB7A was assessed in oleic acid- (OA-) induced HepG2 cells with western blotting and RT-PCR. The luciferase reporter assay was used to estimate the effect of ZBTB7A on the SREBP1 and NF-κB, and the ChIP assay was subjected to evaluate the direct binding to the SREBP1 promoter. Oil Red staining was used to detect lipid accumulation, and the ELISA was used to verify the levels of TG, T-CHO, and MDA. ZBTB7A was knocked down with siRNA, and RT-PCR was performed to analyze the lipogenesis-, fatty acid transporter-, and oxidation metabolism-related genes expression. The levels of ZBTB7A in primary hepatocyte, Kupffer, and hepatic stellate cells (HSCs) were tested by RT-PCR. RESULTS: The upregulation of ZBTB7A expression was assessed in NAFLD mice, and ZBTB7A expression was positively correlated with TNFα, IL-6, TG, T-CHO, and MDA. ZBTB7A was highly expressed in the hepatocytes. In vitro, OA-induced ZBTB7A expression and ZBTB7A expression were closely associated with SREBP1c. ZBTB7A could activate the promoter activity of SREBP1 and activate NF-κB activity. Interestingly, the direct binding of ZBTB7A in the SREBP1 promoter was acquired in HepG2 cells. Inhibition of ZBTB7A expression could attenuate OA-induced lipid accumulation, inhibit the expression of the lipogenesis-related genes and fatty acid transporter genes, and promote the expression of oxidation metabolism-related genes. CONCLUSION: ZBTB7A plays a significant role in the development process of NAFLD, and obesity-induced upregulation of ZBTB7A promotes lipid accumulation through activation of SREBP1 and NF-κB. ZBTB7A may be a potential novel target for the therapy of NAFLD.

Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation.

AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation. METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1ß production were measured. RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes. CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.