BackgroundBrain derived neurotrophic factor (BDNF) is one of the most important regulatory proteins in the pathophysiology of major depressive disorder (MDD). Increasing numbers of studies have reported the relationship between serum/plasma BDNF and antidepressants (ADs). However, the potential effects of several classes of antidepressants on BDNF concentrations are not well known. Hence, our meta-analyses aims to review the effects of differential antidepressant drugs on peripheral BDNF levels in MDD and make some recommendations for future research.MethodsElectronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, and PsycINFO were searched from 1980 to June 2016. The change in BDNF levels were compared between baseline and post-antidepressants treatment by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.ResultsWe identified 20 eligible trials of antidepressants treatments for BDNF in MDD. The overall effect size for all drug classes showed that BDNF levels were elevated following a course of antidepressants use. For between-study heterogeneity by stratification analyses, we detect that length of treatment and blood samples are significant effect modifiers for BDNF levels during antidepressants treatment. While both SSRIs and SNRIs could increase the BDNF levels after a period of antidepressant medication treatment, sertraline was superior to other three drugs (venlafaxine, paroxetine or escitalopram) in the early increase of BDNF concentrations with SMD 0.53(95% CI = 0.13–0.93; P = 0.009).ConclusionsThere is some evidence that treatment of antidepressants appears to be effective in the increase of peripheral BDNF levels. More robust evidence indicates that different types of antidepressants appear to induce differential effects on the BDNF levels. Since sertraline makes a particular effect on BDNF concentration within a short amount of time, there is potential value in exploring its relationship with BDNF and its pharmacological mechanism concerning peripheral blood BDNF. Further confirmatory trials are required for both observations.

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods—the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.

BackgroundA low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is associated with cardiovascular risk. A key cardioprotective property of HDL is cholesterol efflux capacity (CEC), the ability of HDL to accept cholesterol from macrophages. In this study, we aimed to identify the predictive value of CEC for cardiovascular risk.MethodsThe relative risks (RRs) and 95% confidence intervals (CIs) were pooled to analyze the association between CEC and the incidence of cardiovascular events and all-cause mortality. The odds ratios (ORs) and 95% CIs were pooled to estimate the association of CEC and the prevalence of cardiovascular events.ResultsA total of 15 studies were included. Results showed that the highest CEC was significantly associated with a reduced risk of cardiovascular events incidents compared to the lowest CEC (RR, 0.56; 95% CI, 0.37 to 0.85; I 2, 89%); the pooled RR of cardiovascular risk for per unit SD increase was 0.87 (95% CI, 0.73 to 1.04; I 2, 67%). Dose-response curve indicated that cardiovascular risk decreased by 39% (RR, 0.61; 95% CI, 0.51 to 0.74) for per unit CEC increase. Similarly, an inverse association was observed between CEC and the prevalence of cardiovascular events (highest vs. lowest, OR, 0.30; 95% CI, 0.17 to 0.5; I 2 = 63%; per unit SD increase, OR, 0.94; 95% CI, 0.90 to 0.98; I 2 = 71%). However, based on the current data, CEC was not significantly associated with all-cause mortality.ConclusionsFindings from this meta-analysis suggest that HDL-mediated CEC is inversely associated with cardiovascular risk, which appears to be independent of HDL concentration. The growing understanding of CEC and its role in cardiovascular risk decrease may improve the accuracy of cardiovascular risk prediction and also open important avenues to develop novel therapeutic targeting HDL metabolism.Electronic supplementary materialThe online version of this article (doi: 10.1186/s12944-017-0604-5) contains supplementary material, which is available to authorized users.

The promise of single-objective light-sheet microscopy is to combine the convenience of standard single-objective microscopes with the speed, coverage, resolution and gentleness of light-sheet microscopes. We present DaXi, a single-objective light-sheet microscope design based on oblique plane illumination that achieves: (1) a wider field of view and high-resolution imaging via a custom remote focusing objective; (2) fast volumetric imaging over larger volumes without compromising image quality or necessitating tiled acquisition; (3) fuller image coverage for large samples via multi-view imaging and (4) higher throughput multi-well imaging via remote coverslip placement. Our instrument achieves a resolution of 450 nm laterally and 2 μm axially over an imaging volume of 3,000 × 800 × 300 μm. We demonstrate the speed, field of view, resolution and versatility of our instrument by imaging various systems, including Drosophila egg chamber development, zebrafish whole-brain activity and zebrafish embryonic development – up to nine embryos at a time.

Hmgb1 (high mobility group box-1; amphoterin) is highly expressed in brain during early development of vertebrate and nonvertebrate species. However, its role in brain development remains elusive. Here we have cloned the zebrafish Hmgb1 and specifically manipulated Hmgb1 expression using injection of morpholino antisense oligonucleotides or Hmgb1 cRNA. The HMGB1 knockdown morphants produced by injection of three different morpholino oligonucleotides display a characteristic phenotype with smaller size, smaller brain width, and shorter distance between the eyes. Closer examination of the phenotype reveals severe defects in the development of the forebrain that largely lacks catecholaminergic neural networks. The HMGB1 morphant is deficient in survival and proliferation of neural progenitors and displays fewer cell groups expressing the transcription factor Pax6a in the forebrain and aberrant Wnt8 signaling. The mechanism of HMGB1-dependent progenitor survival involves the neuronal transmembrane protein AMIGO (amphoterin-induced gene and orf), the expression of which is regulated by HMGB1 in vivo. Our data demonstrate that HMGB1 is a critical factor for brain development, enabling survival and proliferation of neural progenitors that will form the forebrain structures.The high mobility group box-1 protein (HMGB1 3 ; also designated as HMG1 and amphoterin) is an abundantly occurring parental form of the HMG proteins (for review, see Ref. 1). HMGB1 is an exceptional member in the family of HMG-box proteins; depending on the cell type and its activation state, HMGB1 displays a nonnuclear localization and is secreted from cells, in contrast to most HMG-box proteins that are strictly bound to the cell nuclei (for recent reviews, see Refs. 2 and 3). During the last few years, the extensive literature dealing with HMGB1 functions has mainly focused on extracellular regulation of cells by HMGB1. HMGB1 can be passively released from injured cells, but it is also actively secreted due to several types of stimuli such as cell contact with extracellular matrix and cytokine stimulation of cells (2). Acetylation of lysine residues of HMGB1 has been shown to act as a signal leading to extracellular export via a non-classical secretory pathway (4). HMGB1 functions are currently mainly associated with binding to the cell surface receptor RAGE (receptor for advanced glycation end products), but Toll-like receptors have been increasingly suggested as membrane receptors of HMGB1 (for review, see Ref. 2).Compared with the extensive recent literature dealing with the pathophysiological roles of HMGB1 in inflammation, much less attention has been paid to its physiological roles. The Hmgb1 knock-out mouse survives until early postnatal age, and problems in glucose homeostasis have been suggested to cause multiorgan failure in these mice (5).HMGB1 was isolated from developing rat brain using neurite outgrowth in embryonic forebrain neurons as a readout in protein fractionation (6). These studies provided the initial evidence of HMGB1 as a...