p53 promotes peroxisomal fatty acid β-oxidation to repress purine biosynthesis and mediate tumor suppression.

The metabolic pathways through which p53 functions as a potent tumor suppressor are incompletely understood. Here we report that, by associating with the Vitamin D receptor (VDR), p53 induces numerous genes encoding enzymes for peroxisomal fatty acid β-oxidation (FAO). This leads to increased cytosolic acetyl-CoA levels and acetylation of the enzyme 5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase (ATIC), which catalyzes the last two steps in the purine biosynthetic pathway.

USP19 exacerbates lipogenesis and colorectal carcinogenesis by stabilizing ME1.

Lipogenesis plays a critical role in colorectal carcinogenesis, but precisely how remains unclear. Here, we show that ERK2 phosphorylates ME1 at T103, thereby inhibiting its polyubiquitination and proteasomal degradation and enhancing its interaction with USP19. USP19 antagonizes RNF1-mediated ME1 degradation by deubiquitination, which in turn promotes lipid metabolism and NADPH production and suppresses ROS.

The IKKβ-USP30-ACLY Axis Controls Lipogenesis and Tumorigenesis.

Background And Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death that develops as a consequence of obesity, cirrhosis, and chronic hepatitis. However, the pathways along which these changes occur remain incompletely understood.

Approach And Results: In this study, we show that the deubiquitinase USP30 is abundant in HCCs that arise in mice maintained on high-fat diets.

Role of Interleukin-17 in Pathogenesis of Intestinal Fibrosis in Mice.

Background: The level of interleukin (IL)-17 is commonly increased in serum and intestinal mucosa of patients with inflammatory bowel disease, especially Crohn's disease with intestinal stricture. However, the role of IL-17 in the pathogenesis of intestinal fibrosis and the effect of anti-IL-17 treatment on intestinal fibrosis remain unclear; these issues are studied in vivo in this study.

Method: A total of 24 wild female Balb/c mice (18-22 g) were randomly divided into three groups: (1) control group, (2) 2,4,6-trinitrobenzenesulfonic acid (TNBS) + immunoglobulin G (IgG) group, and (3) TNBS + anti-IL-17 group.

Dynamic Regulation of ME1 Phosphorylation and Acetylation Affects Lipid Metabolism and Colorectal Tumorigenesis.

PGAM5 is a mitochondrial serine/threonine phosphatase that regulates multiple metabolic pathways and contributes to tumorigenesis in a poorly understood manner. We show here that PGAM5 inhibition attenuates lipid metabolism and colorectal tumorigenesis in mice. PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation.

LINC00265 promotes colorectal tumorigenesis via ZMIZ2 and USP7-mediated stabilization of β-catenin.

Colorectal cancer (CRC) is the third most prevalent world cancer and oncogenic β-catenin is frequently dysregulated in CRC. Long noncoding RNAs (lncRNAs) play critical roles in colorectal tumorigenesis; however, the contributions of lncRNAs to human CRC remain largely unknown. In this study, we report that LINC00265 is upregulated and predicts poor clinical outcome in human patients with CRC.

miR-148a inhibits colitis and colitis-associated tumorigenesis in mice.

miR-148a has been shown to regulate inflammation, immunity and the growth of certain tumors, but its roles in colitis and colorectal tumorigenesis remain largely undetermined. Here we found miR-148a-deficient mice to be more susceptible to colitis and colitis-associated tumorigenesis. Both were associated with increased nuclear factor κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling.

Cross-species validation of cell cycle arrest markers for acute kidney injury in the rat during sepsis.

Background: The recent discovery of cell cycle arrest biomarkers, tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), has led to a newly available clinical test for acute kidney injury. The performance of these markers in preclinical studies has not been established. Therefore, we sought to evaluate the performance of TIMP-2 and IGFBP7 in rats undergoing cecal ligation and puncture.

Risk factors for initial surgery in patients with Crohn's disease in Central China.

Purposes: To establish the risk factors for initial surgery in patients with Crohn's disease (CD) in Central China.

Methods: The subjects of this study were patients with CD treated at Zhongnan Hospital of Wuhan University, an IBD center in Wuhan City, Central China, between January, 1992 and June, 2012. We conducted uni- and multivariate analyses of the risk factors for initial surgery for CD in these patients.

Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study.

Background: Genetic variants make some contributions to inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). More than 100 susceptibility loci were identified in Western IBD studies, but susceptibility gene has not been found in Chinese IBD patients till now. Sequencing of individuals with an IBD family history is a powerful approach toward our understanding of the genetics and pathogenesis of IBD.

The utility of platelet, mean platelet volume, and red cell distribution width in the diagnosis of active Crohn's disease and intestinal tuberculosis.

Objective: To evaluate the diagnostic utility of platelet count (PLT), mean platelet volume (MPV), and red cell distribution width (RDW) in patients with active Crohn's disease (CD) and intestinal tuberculosis (ITB).

Methods: This study was conducted in the Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. Sixty-eight patients with active CD, 35 with ITB, and 22 as control group were recruited.

Effects of sinomenine on the expression of microRNA-155 in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice.

Background: Sinomenine, a pure alkaloid isolated in Chinese medicine from the root of Sinomenium acutum, has been demonstrated to have anti-inflammatory and immunosuppressive effects. MicroRNAs (miRNAs) are gradually being recognized as critical mediators of disease pathogenesis via coordinated regulation of molecular effector pathways.

Methodology/findings: After colitis was induced in mice by instillation of 5% (w/v) 2,4,6-trinitrobenzenesulfonic acid (TNBS), sinomenine at a dose of 100 or 200 mg/kg was orally administered once daily for 7 days.

Total glucosides of peony attenuates 2,4,6-trinitrobenzene sulfonic acid/ethanol-induced colitis in rats through adjustment of TH1/TH2 cytokines polarization.

The present study is to investigate effects of total glucosides of peony (TGP) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol-induced colitis in rats and to explore potential clinical use of TGP for treatment of inflammatory bowel disease. Sixty Sprague-Dawley rats were randomly grouped into normal controls, model controls, sulfasalazine (SASP) controls (100 mg/kg/day), and low, medium, and high-dose TGP groups (25, 50, and 100 mg/kg/day, respectively). 24 h following colonic instillation of TNBS, TGP, and SASP were given by gastric gavage three times a day for 7 days.

[Serum screening of celiac disease in Chinese adults with diarrhea-predominant irritable bowel syndrome in Hubei, China].

Objective: To screen the prevalence of celiac disease with serologic markers in the central Chinese population, specifically in patients with chronic diarrhea-predominant irritable bowel syndrome (D-IBS).

Methods: A total of 282 adult patients with D-IBS were selected based on ROME III criteria with 296 age and sex matched consecutive healthy individuals as controls. A gluten-free diet (GFD) was advised in subjects positive for IgA/IgG anti-htTG/DGP antibodies and the serologic antibodies were retested after the GFD.

Increased expression of the spindle checkpoint protein BubR1 is associated with high cell proliferation in primary gastrointestinal diffuse large B cell lymphoma.

Primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) is a relatively rare malignancy with limited results on clinical characteristics and carcinogenesis. Chromosome instability (CIN) is a hallmark of cancer cells, including lymphoma. As a key component of spindle assembly checkpoint (SAC), BubR1 plays a crucial role in maintaining genome stability.

The prevalence and risk factors of cytomegalovirus infection in inflammatory bowel disease in Wuhan, Central China.

Background: The etiology of inflammatory bowel disease (IBD) is not clear and cytomegalovirus (CMV) infection is often associated with IBD patients. The etiologic link between IBD and CMV infection needs to be studied. The objective of the present study is to investigate the prevalence and risk factors of CMV in a cohort of IBD patients from Central China.

Meta-analysis: total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis.

Background: Total parenteral nutrition (TPN) as a traditional mode of treatment in severe acute pancreatitis was still used widely in clinical work. In addition, enteral nutrition treatment methods have developed; early enteral nutrition has already been highlighted for severe acute pancreatitis, but the therapeutic risks versus benefits need to be studied.

Aims And Objective: To compare total parenteral nutrition with total enteral nutrition (TEN) in patients with severe acute pancreatitis by performing a meta-analysis.

Epigenetic regulation of death-associated protein kinase expression in primary gastric cancers from Chinese patients.

Death-associated protein kinase (DAPK) is a novel serine/threonine kinase involved in apoptosis and tumor suppression. Promoter methylation is an important mechanism by which tumor suppressor gene transcription is repressed in cancer cells. Although reduced expression and aberrant methylation of DAPK has been reported in various human cancers, including gastric cancer (GC), the results remain discrepant.