Toward an understanding of the protein interaction network of the human liverAn extensive interaction network of human liver-expressed proteins is described, composed of 3484 interactions among 2582 proteins. Proteins associated with liver disease tend to be central and highly connected in the network.

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing–remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline. Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN–alemtuzumab), followed by additional, as-needed, alemtuzumab. Results: Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN–alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN–alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. Conclusion: This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. ClinicalTrials.gov identifiers: NCT00530348; NCT00548405; NCT00930553

Platinum-based chemotherapeutic drugs are irreplaceable for the treatment of advanced non-small cell lung cancer (NSCLC). However, acquired drug resistance has become a major obstacle for the clinical application of chemotherapy on NSCLC. In the present study, we established carboplatin-resistant NSCLC models on A549 and PC9 cell lines, which were named A549/R and PC9/R. Besides the low sensitivity of A549/R and PC9/R to carboplatin treatment, they exhibited higher metabolism rate of glucose compared to their parental A549 and PC9 cells, respectively. Mechanically, we confirmed that overexpression of PKM2 in A549/R and PC9/R was responsible for the high glucose metabolism and carboplatin resistance. Metformin, an antidiabetic drug, was observed to increase the sensitivity of carboplatin-resistant NSCLC cells to carboplatin treatment in vitro and in vivo. Mechanically, metformin decreased expression of PKM2 and subsequently inhibited the glucose uptake, lactate generation and ATP production in A549/R and PC9/R. Therefore, metformin promoted carboplatin-induced apoptosis through the mitochondria pathway. In addition, we demonstrated that metformin treatment also impaired the cross-resistance of A549/R and PC9/R to cisplatin, etoposide and 5-fluorouracil.

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Background Gestational diabetes mellitus (GDM) is defined as varying degrees of glucose intolerance with an onset or first recognition during pregnancy in women without previously diagnosed diabetes. Accumulating evidence indicates that miRNAs exert crucial roles in the pathogenesis and development of diabetes, including GDM. In the present study, we aimed to determine the clinical performance of miR‐195‐5p in GDM. Methods First, the miR‐195‐5p expressions in serum samples from healthy pregnant women and women with GDM at 25 weeks pregnancy were detected using real‐time polymerase chain reaction (RT‐qPCR). Then, receive characteristic (ROC) curve was used to determine the diagnostic value of miR‐195‐5p in GDM. Finally, the correlation analysis of miR‐195‐5p expression with related clinicopathological factors was carried out to determine the clinical value of miR‐195‐5p in GDM. Results In this study, we found that miR‐195‐5p expression was significantly increased in serum samples from GDM patients as compared with that in healthy pregnancies. Furthermore, miR‐195‐5p might be a putative biomarker for GDM diagnosis with an area under the curve (AUC) of 0.8451; the cutoff value was 1.598, sensitivity was 73.69%, specificity was 96.85%, accuracy was 81.26%, and Youden index was 70.54%. Expression of miR‐195‐5p was positively associated with fasting plasma glucose, one‐hour plasma glucose, and two‐hour plasma glucose. Conclusion miR‐195‐5p might function as a putative diagnostic biomarker for GDM and contribute to identifying at‐risk mothers in pregnancy.

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Long non-coding RNAs (lncRNAs) have involved in human malignancies and played an important role in gene regulations. The dysregulation of lncRNA MIR22HG has been reported in several cancers. However, the role of MIR22HG in esophageal adenocarcinoma (EAC) is poorly understood. Loss of function approaches were used to investigate the biological role of MIR22HG in EAC cells. The effects of MIR22HG on cell proliferation were evaluated by WST-1 and colony formation assays. The effects of MIR22HG on cell migration and invasion were examined using transwell assays. QRT-PCR and Western blot were used to evaluate the mRNA and protein expression of related genes. In this study, abrogation of MIR22HG inhibited cell proliferation, colony formation, invasion and migration in EAC 3 cell lines (OE33, OE19 and FLO-1). Mechanistically, MIR22HG silencing decreased the expression of STAT3/c-Myc/p-FAK proteins and induced apoptosis in EAC cell lines. These results delineate a novel mechanism of MIR22HG in EAC, and may provide potential targets by developing lncRNA-based therapies for EAC.

Objective. To investigate the effect of simvastatin on glucose homeostasis in streptozotocin induced type 2 diabetic rats. Methods. Forty male Wistar rats were randomly divided into four groups. Normal control rats were fed with standard diet, others were fed with high-fat diet. Diabetic rats were induced by a single intraperitoneal injection of STZ. The simvastatin intervention rats were fed with simvastatin during the experiment process, and the simvastatin treatment rats were fed with simvastatin after diabetes rats were induced. We measured body weight, fasting plasma glucose, cholesterol, high-density lipoprotein cholesterol, and triglyceride after an overnight fast. Results. The FPG was higher in diabetic rats when compared to normal control ones; the simvastatin intervention rats had a higher FPG compared to the diabetic rats and were more easily be induced to diabetes at the end of 4 weeks, FPG level of simvastatin treatment rats was increased compared with diabetic model rats after 12 weeks. Conclusion. These data indicate that simvastatin intervention rats may cause hyperglycemia by impairing the function of islet β cells and have an adverse effect on glucose homeostasis, especially on FPG level.