The latest medical research on Gastroenterology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about gastroenterology gathered by our medical AI research bot.

The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.

Want more personalised results?

Request Access

Protective and Detrimental Roles of p38α MAPK in Different Stages of Nonalcoholic Fatty Liver Disease.

Hepatology

Neutrophil infiltration is a hallmark of nonalcoholic steatohepatitis (NASH), but how this occurs during the progression from steatosis to NASH remains obscure. Human NASH features hepatic neutrophil infiltration and upregulation of major neutrophil-recruiting chemokines (e.g., CXCL1 and IL-8). However, mice fed a high-fat diet (HFD) only develop fatty liver without significant neutrophil infiltration or elevation of chemokines. The aim of this study was to determine why mice are resistant to NASH development and the involvement of p38 mitogen-activated protein kinase (p38) activated by neutrophil-derived oxidative stress in the pathogenesis of NASH.

Inflamed human hepatocytes attracted neutrophils more effectively than inflamed mouse hepatocytes due to the greater induction of CXCL1 and IL-8 in human hepatocytes. Hepatic overexpression of Cxcl1 and/or IL8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing liver inflammation, injury, and p38 activation. Pharmacological inhibition of p38α/β or hepatocyte-specific deletion of p38a (a predominant form in the liver) attenuated liver injury and fibrosis in the HFD+Cxcl1 -induced NASH model that is associated with strong hepatic p38α activation. In contrast, hepatocyte-specific deletion of p38a in HFD-induced fatty liver where p38α activation is relatively weak exacerbated steatosis and liver injury. Mechanistically, weak p38α activation in fatty liver upregulated the genes involved in fatty acid β-oxidation via PPARα phosphorylation, thereby reducing steatosis. Conversely, strong p38α activation in NASH promoted CASP3 cleavage, CHOP expression, and BCL2 phosphorylation, thereby exacerbating hepatocyte death.

Genetic ablation of hepatic p38a increases simple steatosis but ameliorates oxidative stress-driven NASH, indicating that p38α plays distinct roles depending on the disease stages, which may set the stage for investigating p38α as a therapeutic target for the treatment of NASH.

Genetics of HCC: Novel approaches to explore molecular diversity.

Hepatology

Hepatocellular carcinomas (HCCs) are highly heterogeneous malignancies with different risk factors, including alcohol abuse, chronic hepatitis B (H...

Roles of trained immunity in the pathogenesis of cholangiopathies: a novel therapeutic target.

Hepatology

Cholangiopathies are a group of diseases mainly including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), biliary atresia ...

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) index: a prognostic tool for children.

Hepatology

Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC.

We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1012 patients from 40 centers. We generated a multivariate risk index (SCOPE index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase and cholangiography to predict a primary outcome of liver transplantation or death (TD), and a broader secondary outcome that included portal hypertensive, biliary and cancer complications termed hepatobiliary complications (HBC). The model stratified patients as low, medium or high risk based on progression to TD at rates of <1, 3, and 9% annually, and to HBC at rates of 2, 6, and 13% annually, respectively (p<0.001). C-statistics to discriminate outcomes at 1 and 5 years was 0.95 and 0.82 for TD, and 0.80 and 0.76 for HBC, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest vs. 100% with the highest risk index, p<0.001. The model was validated in 240 children from 11 additional centers and performed well.

The SCOPE index is the first pediatric-specific prognostic tool for PSC. It uses routinely-obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Schistoma mansoni and Hepatocellular Carcinoma: is it all about c-Jun and STAT3?

Hepatology

Schistosomiasis is a chronic helminthic disease caused by parasitic flatworms called schistosomes, infecting more than 207 million people in 78 cou...

The evolution and clinical impact of hepatitis B virus genome diversity.

Nat Rev Gastroenterol

The global burden of hepatitis B virus (HBV) is enormous, with 257 million persons chronically infected, resulting in more than 880,000 deaths per ...

Reversal of anti-drug antibodies against tumor necrosis factor inhibitors with addition of immunomodulators: A systematic review and meta-analysis.

Indian Journal of Gastroenterology

The development of anti-drug antibodies (ADA) to tumor necrosis factor (TNF-α) inhibitors is a significant result contributing to the loss of clinical response in inflammatory bowel disease (IBD).

We performed a systematic review and meta-analysis to assess whether the addition of immunomodulators to TNF-α inhibitors lead to reversal of antibody formation in TNF-α inhibitor-treated IBD patients.

We conducted a comprehensive search of electronic databases from inception through October 2018 in order to identify specific studies describing clinical response in IBD patients following the addition of immunomodulators (methotrexate or thiopurines) to TNF-α inhibitors. Clinical response was expressed as an improvement of symptoms, with a noted decrease or complete elimination of ADA against TNF-α inhibitors. The meta-analysis was performed using the DerSimonian and Laird random-effect model.

Four studies were included in our final meta-analysis, which reported outcomes in 72 patients receiving TNF-α inhibitors. Forty-nine of the seventy-two (68%) patients received either methotrexate (19) or thiopurines (30). The average follow up period was 13.5 months. The overall pooled clinical response was 73.86% (95% confidence interval [CI] = 47.36-94.38, I2 = 60.77%).

In our meta-analysis, addition of immunomodulators to TNF-α inhibitors was shown to restore the clinical response in 74% of the patients by either decreasing or completely eliminating anti-drug antibody levels. Further long-term multicenter studies are needed to validate these findings.

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3.

Am J Physiol

Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In t...

Lipid droplets disrupt mechanosensing in human hepatocytes.

Am J Physiol

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and ...

Alterations in Pancreatic Islet Cell Function in Response to Small Bowel Resection.

Am J Physiol

Background - After massive small bowel resection (SBR), mice exhibit hepatic steatosis, impaired glucose metabolism without insulin resistance, and...

Lipid remodelling in hepatocyte proliferation and hepatocellular carcinoma.

Hepatology

Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically- and genetically-activated cell proliferation, and HCC.

Integrating metabolomics, lipidomics and transcriptomics, we link changes in the lipidome of proliferating hepatocytes to altered metabolic pathways including lipogenesis, fatty acid desaturation, and generation of phosphatidylcholine (PC). We confirm this altered lipid signature in human HCC and show a positive correlation of monounsaturated-PC with hallmarks of cell proliferation and hepatic carcinogenesis.

Overall, we demonstrate that specific lipid metabolic pathways are coherently altered when hepatocytes switch to proliferation. These represent a source of targets for the development of new therapeutic strategies and prognostic biomarkers of HCC.

YAP1 withdrawal in hepatoblastoma drives therapeutic differentiation of tumor cells to functional hepatocyte-like cells.

Hepatology

Despite surgical and chemotherapeutic advances, the five-year survival rate for Stage IV Hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. YAP1 and β-Catenin co-activation occurs in 80% of children's HB; however, a lack of conditional genetic models precludes tumor maintenance exploration. Thus, the need for a targeted therapy remains unmet. Given the predominance of YAP1 and β-Catenin activation in HB, we sought to evaluate YAP1 as a therapeutic target in HB.

We engineered the first conditional HB murine model using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A , constitutive β-CateninDelN90 , and a luciferase reporter to murine liver. Tumor regression was evaluated using bioluminescent imaging, and tumor landscape characterized using RNA and ATAC sequencing, and DNA foot-printing. Here we show that YAP1S127A withdrawal mediates >90% tumor regression with survival for 230+ days in mice. YAP1 S127A withdrawal promotes apoptosis in a subset of tumor cells and in remaining cells induces a cell fate switch driving therapeutic differentiation of HB tumors into Ki-67 negative "hbHep cells" with hepatocyte-like morphology and mature hepatocyte gene expression. YAP1 S127A withdrawal drives formation of hbHeps by modulating liver differentiation transcription factor (TF) occupancy. Indeed, tumor-derived hbHeps, consistent with their reprogrammed transcriptional landscape, regain partial hepatocyte function and rescue liver damage in mice.

YAP1S127A withdrawal, without silencing oncogenic β-Catenin, significantly regresses hepatoblastoma, providing the first in vivo data to support YAP1 as a therapeutic target for HB. YAP1S127A withdrawal alone sufficiently drives long-term regression in hepatoblastoma because it promotes cell death in a subset of tumor cells and modulates transcription factor occupancy to reverse the fate of residual tumor cells to mimic functional hepatocytes.