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Background & Aims A critical role of the Toll-like receptor ( TLR)-4 and its downstream mediators in the pathogenesis of small-for-size liver graft injury has been documented. Recently, the micro RNA-146 (miR-146) was identified as a potent negative regulator of the TLR4 signalling pathway. In this study, the role of miR-146a and miR-146b in the attenuation of TLR-4 signalling and small-for-size liver graft injury was investigated. Methods The expression levels of miR-146a and miR-146b during small-for-size liver graft injury were studied in vivo. In addition, the effects of miR-146a and miR-146b on the expression of IRAK1 and TRAF6 in the rat macrophage cell line NR8383 and rat liver kupffer cells were studied in vitro. The in vivo effect of miR-146a and miR-146b on small-for-size liver graft injury was studied by the tail vein injection of miR-146a mimics and miR-146b mimics. Results The levels of miR-146a and miR-146b decreased with a small-for-size liver graft. MiR-146a and miR-146b inhibited IRAK1 and TRAF6 expression by binding to the 3′ UTR of IRAK1 or TRAF6, respectively, in the rat macrophage cell line NR8383. The administration of miR-146a mimics and miR-146b mimics prevented liver graft injury in small-for-size liver graft injury via the inactivation of IRAK1 and TRAF6 in vivo. Conclusions miR-146a and miR-146b prevent liver injury in small-for-size liver graft injury via the inactivation of IRAK1 and TRAF6. [ABSTRACT FROM AUTHOR]

Three ionic liquids (ILs)(1-ethyl-2,3-dimethylimidazolium acetate, [EMMIM][AC]; tributyl-methylammonium acetate, [N4,4,4,1][AC]; and tetraethylammonium acetate, [N2,2,2,2][AC]) were chosen. The vapor–liquid equilibrium (VLE) data of ternary mixtures (acetate + ethanol + IL) were measured at 101.3 KPa. NRTL equation was used to correlate the data. From NRTL model, for [N2,2,2,2][AC], [EMMIM][AC], and [N4,4,4,1][AC], minimum mole fractions for completely eliminating azeotrope are 0.015, 0.020 and 0.022, respectively. From the average relative volatility and σ-profiles, it can be obtained that the separation ability order is [EMMIM][AC] > [N2,2,2,2][AC] > [N4,4,4,1][AC]. [ABSTRACT FROM AUTHOR]

The corresponding author explained that 10 mice were used in each group whilst performing liver ischemia/reperfusion experiments, but that two liver samples of the Ago-mir-NC group were damaged during embedding or sectioning, and as a result this group only contained 8 samples. Specifically, the Fig 6D Ago-mir-146a panel appeared similar to the Fig 6G Ago-mir-146a panel despite being used to represent different experimental conditions. They provided an updated Fig 6 with the correct Fig 6D Ago-mir-146a image obtained in the original experiment, as well as the individual level data underlying the published results (S1 File). [Extracted from the article]

Purpose: The number of neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes. Results: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes. Conclusions: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs. [ABSTRACT FROM AUTHOR]

A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor– associated factor 6(TRAF6), in the pathogenesis of liver ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and liver I/R injury invivo and invitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a invivo, protected against liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates liver ischemia/reperfusion injury invivo and hypoxia/reoxygenation injury invitro by directly suppressing IRAK1 and TRAF6. [ABSTRACT FROM AUTHOR]

Currently, more and more studies show that aberrantly expressed microRNAs (miRNAs) are important driving factors for the pathogenesis of hepatocellular carcinoma (HCC). Based on the TCGA and GEO databases, miR-660-5p was identified as a possible target for HCC in this study.In HCC tissues, miR-660-5pexpressionwasparticularly high, and this was confirmed inHCC cell lines. The upregulatedmiR-660-5p showed correlations with tumor size, tumor number, TNM stage and histological grade. In vitro experimental data, aswellas in vivo evidence showed that miR-660-5p has the ability to significantly enhance the cell proliferation rate, clone formation, migration, invasion, and tumorigenic capacity of HCC cells. YWHAH is validated that targeted by miR-660-5p using dual luciferase reporter assay. Knockdown of YWHAH has been shown to partially reverse the tumor suppressive function of miR-660-5p inhibitor. Furthermore, miR-660-5p/YWHAH axis could activate PI3K/AKT pathway, which promoted EMT and cell cycle processes. In conclusion, this study illustrated the function of miR-660-5p/YWHAH axis in HCC and provided potential targets for treating HCC. • The up-regulation of miR-660-5p showed correlations with tumor size, tumor number, TNM stage and histological grade. • MiR-660-5p enhance the cell proliferation rate, clone formation, migration, invasion, and tumorigenic capacity of HCC cells. • miR-660-5p/YWHAH axis could activate PI3K/AKT pathway, which promoted EMT and cell cycle processes. [ABSTRACT FROM AUTHOR]

Nectins are Ca2+‑independent immunoglobulin‑like cell adhesion molecules that belong to a family of four members that function in a number of biological cellular activities. Nectin‑4 is overexpressed in several types of human cancer; however, the functional and prognostic significance of Nectin‑4 in gastric cancer (GC) remains unclear. In the present study, the reverse transcription‑quantitative polymerase chain reaction and tissue microarray immunohistochemical analysis were used to investigate the expression of Nectin‑4 in GC as well as its function in the prognosis of patients with GC. The results indicated that mRNA and protein expression of Nectin‑4 were increased in tumor tissues compared with the matched non‑tumor tissues. Expression of Nectin‑4 was closely associated with differentiation (P=0.004), primary tumor (P=0.001), lymph node metastasis (P<0.001) and tumor‑node‑metastasis (TNM) stage (P<0.001). Positive Nectin‑4 expression (P=0.001) and advanced TNM stage (P<0.001) were demonstrated to be associated with overall survival time in multivariate analyses. These results suggest that Nectin‑4 may serve a significant function in GC and may serve as a novel clinic pathological biomarker and therapeutic target in GC. [ABSTRACT FROM AUTHOR]