• Nilsson Chappell posted an update 6 months, 1 week ago

    There was an increasing trend of proliferative and cell growth related genes and shutting down of immune response as the disease progress mild to moderate to advanced stage cirrhosis. The myriad of changes in gene expression showed more chances of developing liver cancer in patients infected with HCV genotype 3a in a systematic manner. The identified gene set can act as disease markers for prediction, whether the fibrosis lead to cirrhosis and its association with end stage liver disease development. © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.Metabolic syndrome (MetS) is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 diabetes. There is growing body of data showing the associations of genetic variants of the genes involved in the PI3K/AKT/mTOR pathway with diabetes and obesity. We aimed to investigate the association between MetS and its components with the genetic polymorphism in AKT1, rs1130233 (T > C). Total of 618 participants, recruited from Mashhad stroke and heart atherosclerosis disorder cohort (MASHAD study). Patients with MetS were defined by using international diabetes federation (IDF) criteria (n = 326) and those without MetS (n = 261) were recruited. Anthropometric and biochemical parameters were measured in all subjects. Genetic analysis for the rs1130233 polymorphism was performed, using the ABI-StepOne instruments with SDS version-2.0 software. Individuals with MetS had a significantly higher levels of BMI, waist-circumference, total cholesterol, triglyceride, high sensitivity-c reactive protein (hs-CRP) and blood-pressure, and lower concentrations of high density lipoprotein (HDL-C), compared to non-MetS individuals (P  C) polymorphism was associated with major components of MetS such as hs-CRP, and BMI, indicating further investigation in a multi-center setting to explore its value as an emerging biomarker of risk stratification marker. © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.EZH2 is a component of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. EZH2 mutations are associated with oncogenesis and progression of cancers. However, the relationship between the clinical outcome of patients with myeloid malignancies and EZH2 mutations is controversial. Therefore, we performed a meta-analysis of 8 studies (n = 2243 patients) that evaluates the correlation between EZH2 mutations and overall survival (OS) in patients with myeloid neoplasms. EZH2 mutations were associated with significantly worse OS (hazard ratio  = 2.37, 95% confidential interval (CI), 1.48-3.79). In a word, EZH2 mutations indicate a poor prognosis for patients with myeloid neoplasms. © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.Mesenchymal stem cells (MSCs) are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes, chondrocytes, adipocytes, tenocytes and myocytes. MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineage-specific differentiation regulated by various cellular signaling pathways, such as bone morphogenetic proteins (BMPs). As members of TGFβ superfamily, BMPs play diverse and important roles in development and adult tissues. At least 14 BMPs have been identified in mammals. Different BMPs exert distinct but overlapping biological functions. Cirtuvivint clinical trial Through a comprehensive analysis of 14 BMPs in MSCs, we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs. Nonetheless, a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated. Here, we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs. Hierarchical clustering analysis classifies 14 BMPs into three subclusters an osteo/chondrogenic/adipogenic cluster, a tenogenic cluster, and BMP3 cluster. We also demonstrate that six BMPs (e.g., BMP2, BMP3, BMP4, BMP7, BMP8, and BMP9) can induce I-Smads effectively, while BMP2, BMP3, BMP4, BMP7, and BMP11 up-regulate Smad-independent MAP kinase pathway. Furthermore, we show that many BMPs can upregulate the expression of the signal mediators of Wnt, Notch and PI3K/AKT/mTOR pathways. While the reported transcriptomic changes need to be further validated, our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs. © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.Arginine methylation is a common posttranslational modification that governs important cellular processes and impacts development, cell growth, proliferation, and differentiation. Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs), which are classified as type I and type II enzymes responsible for the formation of asymmetric and symmetric dimethylarginine, respectively. PRMT5 is the main type II enzyme that catalyzes symmetric dimethylarginine of histone proteins to induce gene silencing by generating repressive histone marks, including H2AR3me2s, H3R8me2s, and H4R3me2s. PRMT5 can also methylate nonhistone proteins such as the transcription factors p53, E2F1 and p65. Modifications of these proteins by PRMT5 are involved in diverse cellular processes, including transcription, translation, DNA repair, RNA processing, and metabolism. A growing literature demonstrates that PRMT5 expression is upregulated in hematologic malignancies, including leukemia and lymphoma, where PRMT5 regulates gene expression to promote cancer cell proliferation. Targeting PRMT5 by specific inhibitors has emerged as a potential therapeutic strategy to treat these diseases. © 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.Immune checkpoint blockade therapies (ICBs) are a prominent breakthrough in cancer immunotherapy in recent years (named the 2013 “Breakthrough of the Year” by the Science magazine). Thus far, FDA-approved ICBs primarily target immune checkpoints CTLA-4, PD-1, and PD-L1. Notwithstanding their impressive long-term therapeutic benefits, their efficacy is limited to a small subset of cancer patients. In addition, ICBs induce inadvertent immune-related adverse events (irAEs) and can be costly for long-term use. To overcome these limitations, two strategies are actively being pursued identification of predictive biomarkers for clinical response to ICBs and multi-pronged combination therapies. Biomarkers will allow clinicians to practice a precision medicine approach in ICBs (biomarker-based patient selection) such as treating triple-negative breast cancer patients that exhibit PD-L1 staining of tumor-infiltrating immune cells in ≥1% of the tumor area with nanoparticle albumin-bound (nab)-paclitaxel plus anti-PD-L1 and treating patients of MSI-H or MMR deficient unresectable or metastatic solid tumors with pembrolizumab (anti-PD-1).

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