Scientific reports
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While aging is unavoidable, the aging mechanism is still unclear because of its complexity. Smoking causes premature death and is considered as an environmental aging accelerator. In the present study, we focused on the influence of smoking to the serum concentration of anti-aging protein α-klotho (αKl) and the β-klotho-associated protein fibroblast growth factor (FGF)-21 in men. ⋯ In aged men (60.3 ± 1.7 years), although the serum levels of sαKl in never-smokers were low, smokers showed highly increased serum levels of sαKl. Serum levels of sαKl was correlated with IL-6 in middle-aged never-smokers, suggesting sαKl regulates IL-6. However, this correlation was disrupted in smokers and aged men.
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The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. ⋯ This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation.
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Review Meta Analysis
Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update.
Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. ⋯ Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.
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Meta Analysis
Association between vitamin C intake and the risk of pancreatic cancer: a meta-analysis of observational studies.
Quantification of the association between the intake of vitamin C and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed and Web of Knowledge throughSeptember of 2014. ⋯ The associations were also significant both in Caucasian [summary RR = 0.741, 95% CI = 0.626-0.876], Asian [summary RR = 0.455, 95% CI = 0.275-0.754] and Mixed population [summary RR = 0.677, 95% CI = 0.508-0.901]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might reduce the risk of pancreatic cancer.
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P2X7 receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mechanisms are largely unclear. ⋯ Prolonged application of ATP caused macrophage apoptosis, while the presence of rhein suppressed this cell cytotoxicity. Such ATP/BzATP-induced cellular reactions were also inhibited by a well-known rat P2X7 receptor antagonist, brilliant blue G, in a similar way to rhein. Together, our results demonstrate that rhein inhibit ATP/BzATP-induced [Ca(2+)]c increase, pore formation, ROS production, phagocytosis attenuation, IL-1β release and cell apoptosis by antagonizing the P2X7 receptor in rat peritoneal macrophages.