• Erichsen Hampton posted an update 6 months, 3 weeks ago

    Hepatitis E virus (HEV) causes 14 million infections and 60,000 deaths per year globally, with immunocompromised persons and pregnant women experiencing severe symptoms. Although ribavirin can be used to treat chronic hepatitis E, toxicity in pregnant patients and the emergence of resistant strains are major concerns. Therefore there is an imminent need for effective HEV antiviral agents. The aims of this study were to develop a drug screening platform and to discover novel approaches to targeting steps within the viral life cycle. We developed a screening platform for molecules inhibiting HEV replication and selected a candidate, isocotoin. Isocotoin inhibits HEV replication through interference with heat shock protein 90 (HSP90), a host factor not previously known to be involved in HEV replication. Additional work is required to understand the compound’s translational potential, however this suggests that HSP90-modulating molecules, which are in clinical development as anti-cancer agents, may be promising therapies against HEV.β-adrenergic receptor antagonists (β-blockers) are extensively used to improve cardiac performance in heart failure (HF), but the electrical improvements with these clinical treatments are not fully understood. The aim of this study was to analyze the electrophysiological effects of β-adrenergic system remodeling in heart failure with reduced ejection fraction and the underlying mechanisms. We used a combined mathematical model that integrated β-adrenergic signaling with electrophysiology and calcium cycling in human ventricular myocytes. HF remodeling, both in the electrophysiological and signaling systems, was introduced to quantitatively analyze changes in electrophysiological properties due to the stimulation of β-adrenergic receptors in failing myocytes. We found that the inotropic effect of β-adrenergic stimulation was reduced in HF due to the altered Ca2+ dynamics resulting from the combination of structural, electrophysiological and signaling remodeling. Isolated cells showed proarrhythmic risk after sympathetic stimulation because early afterdepolarizations appeared, and the vulnerability was greater in failing myocytes. When analyzing coupled cells, β-adrenergic stimulation reduced transmural repolarization gradients between endocardium and epicardium in normal tissue, but was less effective at reducing these gradients after HF remodeling. The comparison of the selective activation of β-adrenergic isoforms revealed that the response to β2-adrenergic receptors stimulation was blunted in HF while β1-adrenergic receptors downstream effectors regulated most of the changes observed after sympathetic stimulation. In conclusion, this study was able to reproduce an altered β-adrenergic activity on failing myocytes and to explain the mechanisms involved. The derived predictions could help in the treatment of HF and guide in the design of future experiments.

    As a class of endogenous non-coding RNAs with closed-loop structure, circular RNAs (circRNAs) are receiving more and more attention. CircRNAs have been reported to be widely expressed in various human cancers and are implicated in tumorigenesis and progression. The present study aimed to systematically evaluate the clinicopathological, diagnostic and prognostic values of circRNAs in lung cancer.

    We searched literature from PubMed, Web of science, Cochrane Library, EMBASE and Ovid online databases up to May 29, 2020. this website Statistical analyses were undertaken based on Stata 11.0, Meta-DiSc 1.4, and RevMan 5.3 software.

    Finally, a total of 63 eligible articles were included in our meta-analysis, including 18 studies for diagnosis, 22 studies for prognosis and 57 studies for clinicopathological features. In terms of diagnostic values, circRNAs could discriminate between lung cancer patients and the normal individuals with a relatively high pooled area under the curve (AUC) of 0.83 (95%CI, 0.80-0.86). For the pro diagnosis, prognosis and clinicopathological features in lung cancer.

    Our meta-analysis demonstrated that circRNAs could be used as feasible and important biomarkers for diagnosis, prognosis and clinicopathological features in lung cancer.

    Genetic factor is a risk factor in glioma occurrence. This study was designed to detect the effect of ADCY9 polymorphisms on glioma risk and prognosis.

    We performed a case-control study of 1080 participants (584 cases and 496 controls) to assess the relationship of ADCY9 polymorphisms with the risk and prognosis of glioma among the Chinses Han population. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the relationship between ADCY9 variants and glioma risk. The correlation of SNPs with survival was analyzed by the Cox regression model.

    Our study showed that rs2230742 and rs2531992 polymorphisms played protective roles in glioma susceptibility (OR 0.65, p=0.001; OR 0.73, p=0.038, respectively). While rs2230742 significantly increased the susceptibility of III-V grade glioma patients (OR 1.50, p=0.036). Haplotype analysis revealed that C

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    haplotype was related to a significantly decreased glioma risk (OR 0.65, p=0.002). Notably, rs2531995 and rs879620 polymorphisms significantly enhanced death risk in high-grade glioma patients (hazard ratio 1.36, p=0.041; HR 1.37, p=0.042; respectively). For rs2230742 and rs2531992 SNPs, glioma patients had a worse prognosis (HR 2.30, p=0.021; HR 2.30, p=0.021; respectively). We further observed that age, chemotherapy, and surgical scope can affect the glioma prognosis.

    We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.

    We firstly studied the association of ADCY9 variants with glioma risk and prognosis, which might give scientific evidence for exploring the molecular mechanism of glioma.Chloroplast (cp) genomes are considered important for the study of lineage-specific molecular evolution, population genetics, and phylogenetics. Our aim here was to elucidate the molecular evolution in cp genomes of species in the Dracunculus clade (Aroideae, Araceae). We report de novo assembled cp genomes for eight species from eight genera and also retrieved cp genomes of four species from the National Center for Biotechnology Information (NCBI). The cp genomes varied in size from 162,424 bp to 176,835 bp. Large Single Copy (LSC) region ranged in size from 87,141 bp to 95,475 bp; Small Single Copy (SSC) from 14,338 bp to 23,981 bp; and Inverted Repeats (IRa and IRb) from 25,131 bp to 32,708 bp. The expansion in inverted repeats led to duplication of ycf1 genes in four species. The genera showed high similarity in gene content and yielded 113 unique genes (79 protein-coding, 4 rRNA, and 30 tRNA genes). Codon usage, amino acid frequency, RNA editing sites, microsatellites repeats, transition and transversion substitutions, and synonymous and non-synonymous substitutions were also similar across the clade.

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