TIPE-2 ameliorates inflammatory bowel disease in mice via inhibiting STAT3 and NF-kB activation.

TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the immune inhibition mechanism of TIPE-2 involved in inflammatory bowel disease has not been well studied. Therefore, the aim of this study was to investigate whether TIPE-2 improved experimental colitis by reducing high levels of inflammation in the intestine. Lentivirus encoding TIPE-2 was administered to mice by intrarectal injection after colitis induction. Histological analysis was used to analyze sections of the intestine. Protein expression induced by STAT3 and NF-κB signaling was analyzed by western blot. We found that TIPE-2 reduced the colitis activity index score and the histological score of the intestine. TIPE-2 also decreased inflammatory cytokine levels in the intestine. Additionally, TIPE-2 inhibited STAT3 and NF-kB activation. These results suggested that TIPE-2 might attenuate inflammation of colitis via inhibiting of STAT3 and NF-kB activation.

Impact of the De Ritis Ratio on the Prognosis of Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND The aim of this study was to emphasize the impact of the aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) on the prognosis of patients with stable coronary artery disease (SCAD) undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS Patients with SCAD who underwent elective PCI at Shinonoi General Hospital were included. SCAD was defined as epicardial coronary artery diameter stenosis ≥90% or epicardial coronary artery diameter stenosis ≥75% accompanied by symptoms or stress-induced myocardial ischemia. Clinical data were collected, and cardiovascular events were followed after discharge. One-way Cox proportional risk analysis was performed to assess the risk stratification value of the De Ritis ratio, using major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality as the primary and secondary endpoints, respectively. The independent risk stratification value was evaluated by multivariate Cox proportional risk analysis. RESULTS Among 204 patients with SCAD undergoing PCI, during a median follow-up period of 706 days (24 months), 13.7% (28/204) patients experienced MACCE, and 8.8% (18/204) experienced all-cause mortality. Multifactorial Cox regression analysis revealed that a high De Ritis ratio was an independent risk factor for MACCE (HR=2.96, 95% CI: 1.29-6.78, P=0.01) and all-cause mortality (HR=3.61, 95% Cl: 1.31-9.86, P=0.012). The sensitivity analysis further confirmed the incremental value of the De Ritis ratio for adverse cardiovascular events. CONCLUSIONS A high De Ritis ratio was an independent and valuable risk stratification factor for MACCE and all-cause mortality in patients with SCAD after PCI.

Role of the Aryl Hydrocarbon Receptor and Gut Microbiota-Derived Metabolites Indole-3-Acetic Acid in Sulforaphane Alleviates Hepatic Steatosis in Mice.

Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD). Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells. Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.

Bicyclol Alleviates Signs of BDL-Induced Cholestasis by Regulating Bile Acids and Autophagy-Mediated HMGB1/p62/Nrf2 Pathway.

Cholestasis is a liver disease characterized by the accumulation of toxic bile salts, bilirubin, and cholesterol, resulting in hepatocellular damage. Recent findings have revealed several key steps of cholestasis liver injury including the toxicity of bile acids and accumulation of proinflammatory mediator. In this study, we investigated the protective effect of bicyclol in cholestasis caused by bile duct ligation (BDL), as well as relevant mechanisms. Bicyclol attenuated liver damage in BDL mice by increasing the levels of hydrophilic bile acid such as α-MCA and ß-MCA, regulating bile acid-related pathways and improving histopathological indexes. High-mobility group box 1 (HMGB1) is an extracellular damage-associated molecular pattern molecule which can be used as biomarkers of cells and host defense. Bicyclol treatment decreased extracellular release of HMGB1. In addition, HMGB1 is also involved in regulating autophagy in response to oxidative stress. Bicyclol promoted the lipidation of LC3 (microtubule-associated protein 1 light chain 3)-Ⅱ to activate autophagy. The nuclear factor, E2-related factor 2 (Nrf2) and its antioxidant downstream genes were also activated. Our results indicate that bicyclol is a promising therapeutic strategy for cholestasis by regulating the bile acids and autophagy-mediated HMGB1/p62/Nrf2 pathway.

The Enlargement of Abdominal Lymph Nodes Is a Characteristic of Autoimmune Liver Disease.

BACKGROUND: The enlargement of lymph nodes is a common clinical sign in connective tissue disease (CTD) and viral hepatitis. In this research, we evaluated the incidence of enlarged lymph nodes in autoimmune liver diseases (AILD). Moreover, we identified the clinical significance of abdominal lymph node enlargement in AILD. METHODS: The characteristics of abdominal lymph nodes, including their morphology and distribution, were assessed by ultrasonography and computed tomography in 125 patients with AILD, 54 with viral hepatitis, 135 with CTD, and 80 healthy controls. The pathological and laboratory results of 106 AILD patients were collected to analyze the association between lymphadenectasis and disease activity. RESULTS: Enlargement of abdominal lymph nodes was found in 69.6% of patients with AILD, 63% of patients with viral hepatitis, 29.6% of patients with CTD, and 2% of healthy controls. Alkaline phosphatase (ALP), glutamate transpeptidase (GGT), and immunoglobulin M (IgM) levels were significantly increased in AILD patients with lymphadenectasis (LA) in contrast to patients without lymphadenectasis (NLA) (P < 0.05). The pathological characteristics of inflammation, cholestasis, and focal necrosis were more common in the LA group than in the NLA group (P < 0.05). As shown by multivariate logistic regression analysis, interface hepatitis (OR = 3.651, P < 0.05), cholestasis (OR = 8.137, P < 0.05), and focal necrosis (OR = 5.212, P < 0.05) were related to LA. CONCLUSIONS: The percentage of abdominal lymph node enlargement in AILD subjects was significantly higher than that in CTD subjects. Therefore, the enlargement of lymph nodes can represent a noninvasive indicator of histological and biochemical inflammation activity in AILD.

Long non-coding RNA LINC00857 promotes gastric cancer cell proliferation and predicts poor patient survival.

Gastric cancer (GC) is a common malignancy worldwide and its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) serve an important function in cancer development, therefore identification of functional lncRNAs in GC is required. The results of the present study demonstrate that an lncRNA, LINC00857, was increased in GC tissues compared with adjacent non-tumor tissues. Overexpression of LINC00857 was positively associated with poor survival rate, as well as with the tumor size of patients with GC. LINC00857 knockdown induced by specific small interfering RNAs significantly inhibited GC cell proliferation in vitro. Genome-wide analysis revealed that LINC00857 knockdown deregulated the cell cycle. Western blot analysis confirmed that LINC00857 knockdown decreased protein expression of cyclin D1 and cyclin E1 in GC cells. Taken together, the results indicated that LINC00857 knockdown suppressed GC cell proliferation through deregulating the cell cycle, resulting in the downregulation of cyclin D1 and cyclin E1. Therefore, LINC00857 expression may be an independent biomarker for the diagnosis and prognosis of GC.