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    Genome editing: Bioethics shows the way

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    Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

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    Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed.) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. gene was predicted as pathogenic by the PolyPhen prediction tool. metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent

    Clinical outcomes of patients with and without diabetes mellitus after hepatectomy: A systematic review and meta-analysis

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    Clinical data regarding the influence of diabetes mellitus (DM) on the outcomes of patients undergoing hepatectomy are conflicting. To determine the impact of DM on the clinical outcomes of patients undergoing hepatectomy, we systematically reviewed published studies and carried out a meta-analysis.A systematic literature search of Pubmed, Sciencedirect, Web of Science, and Chinese Biomedical Database was conducted from their inception through February 2, 2016. The combined relative risk (RR) or hazard ratio (HR) with 95% confidence intervals (95% CI) was calculated.A total of 16 observational studies with 15710 subjects were eligible for meta-analysis. The pooled results showed that DM significantly increased the risk of overall postoperative complications (RR 1.34; 95% CI 1.19–1.51; P<0.001), DM-associated complications (RR 1.8; 95% CI 1.29–2.53; P<0.001), liver failure (RR 2.21; 95% CI 1.3–3.76; P = 0.028) and post-operative infections (RR 1.59; 95% CI 1.01–2.5; P = 0.045). In addition, DM was also found to be significantly associated with unfavorable overall survival and disease free survival after liver resection. The pooled HR was 1.63 (95% CI 1.33–1.99; P<0.001) for overall survival and 1.55 (95% CI 1.07–2.25; P = 0.019) for disease free survival.DM is associated with poor outcomes in patients undergoing hepatectomy. DM should be taken into account cautiously in the management of patients undergoing hepatectomy. Further prospective studies are warranted to explore effective interventions to improve the poor outcomes of diabetic patients undergoing hepatectomy

    The association between autonomic dysfunction, inflammation and atherosclerosis in men under investigation for carotid plaques

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    Autonomic dysfunction is a risk factor for cardiovascular disease (CVD), however, the exact mechanism linking autonomic dysfunction to cardiovascular disease is not known. In this study we hypothesized that autonomic dysfunction increases inflammation, which subsequently accelerates atherosclerosis. The aim of the current study was to investigate the association between autonomic tone, inflammation and atherosclerosis.124 men under investigation for carotid atherosclerosis were examined for autonomic function (heart rate variability; HRV and baroreflex sensitivity; BRS), inflammatory markers (white blood cell count; WBCC and C-reactive protein; CRP) and degree of carotid atherosclerosis. The direct or indirect associations between autonomic function, inflammatory parameters and carotid plaque area were investigated with multiple linear regressions.Male subjects with prevalent CVD showed larger carotid plaque area, higher WBCC, and reduced BRS compared to subjects with no history of CVD. Further, BRS was inversely associated with carotid plaque area (r = -0.21, p = 0.018) as well as inflammatory parameters WBCC and CRP (r = -0.29, p = 0.001, and r = -0.23, p = 0.009, respectively), whereas HRV only was inversely associated with WBCC (r = -0.22, p = 0.014). To investigate if inflammation could provide a link between autonomic function and carotid atherosclerosis we adjusted the associations accordingly. After adjusting for WBCC and CRP the inverse association between BRS and carotid plaque area was attenuated and did not remain significant, while both WBCC and CRP remained significantly associated with carotid plaque area, indicating that low-grade inflammation can possibly link BRS to atherosclerosis. Also, after adjusting for age, antihypertensive treatment and cardiovascular risk factors, BRS was independently inversely associated with both WBCC and CRP, and HRV independently inversely associated with WBCC. WBCC was the only inflammatory marker independently associated with carotid plaque area after adjustment.We demonstrate that autonomic dysfunction is associated with atherosclerosis and that inflammation could play an important role in mediating this relationship

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    Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data

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    )-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data.-induced liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot.<0.05).-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH

    that contributes to larval growth and development

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    cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. A population of stem cell-like cells, the germinative cells, is considered to drive the larval growth and development within the host. The molecular mechanisms controlling the behavior of germinative cells are largely unknown. cultivation systems we show here that the EGFR/ERK signaling in the parasite can promote germinative cell proliferation in response to addition of human EGF, resulting in stimulated growth and development of the metacestode larvae. Inhibition of the signaling by either the EGFR inhibitors CI-1033 and BIBW2992 or the MEK/ERK inhibitor U0126 impairs germinative cell proliferation and larval growth., and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis

    10-40 Peptide Force Field Dependent?

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