Causal association between cardiovascular diseases and erectile dysfunction, a Mendelian randomization study.

Background: Cardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure, ischemic heart disease (IHD), and atrial fibrillation, are prevalent in the aged. However, the influence of CVD on ED is less investigated. This study was performed to clarify the causal association between CVD and ED. Materials and methods: Genome-wide association studies (GWAS) datasets targeting CHD, heart failure, IHD, and atrial fibrillation were downloaded to retrieve single nucleotide polymorphisms (SNPs). Further, single-variable Mendelian randomization and multivariable Mendelian randomization (MVMR) were adopted to explore the causal association between CVD and ED. Results: Genetically predicted CHD and heart failure were found to increase the risks of ED (OR = 1.09, P < 0.05 and OR = 1.36, P < 0.05, respectively). However, no causal association was disclosed among IHD, atrial fibrillation and ED (all P > 0.05). These findings remained consistent in sensitivity analyses. After controlling for body mass index, alcohol, low density lipoprotein, smoking and total cholesterol levels, the results of MVMR support the causal role of CHD on ED (P < 0.05). Similarly, the direct causal effect estimates of heart failure on ED were significant in MVMR analyses (P < 0.05). Conclusion: Using genetic data, this study revealed that genetically predicted CHD and heart failure may predict better ED compared with atrial fibrillation and IHD. The results should be interpreted with caution and the insignificant causal inference of IHD still needs further verification in future studies.

Comprehensive Effects of Flowering Locus T-Mediated Stem Growth in Tobacco.

In flowering plants, Flowering locus T (FT) encodes a major florigen. It is a key flowering hormone in controlling flowering time and has a wide range of effects on plant development. Although the mechanism by which FT promotes flowering is currently clearly understood, comprehensive effects of the FT gene on plant growth have not been evaluated. Therefore, the effects of FT on vegetative growth need to be explored for a complete understanding of the molecular functions of the FT gene. In this study, the Jatropha curcas L. FT gene was overexpressed in tobacco (JcFTOE) in order to discover multiple aspects and related mechanisms of how the FT gene affects plant development. In JcFTOE plants, root, stem, and leaf development was strongly affected. Stem tissues were selected for further transcriptome analysis. In JcFTOE plants, stem growth was affected because of changes in the nucleus, cytoplasm, and cell wall. In the nucleus of JcFTOE plants, the primary effect was to weaken all aspects of DNA replication, which ultimately affected the cell cycle and cell division. The number of stem cells decreased significantly in JcFTOE plants, which decreased the thickness and height of tobacco stems. In the cell wall of JcFTOE plants, hemicellulose and cellulose contents increased, with the increase in hemicellulose associated with up-regulation of xylan synthase-related genes expression. In the cytoplasm of JcFTOE plants, the primary effects were on biogenesis of ribonucleoprotein complexes, photosynthesis, carbohydrate biosynthesis, and the cytoskeleton. In addition, in the cytoplasm of JcFTOE plants, there were changes in certain factors of the core oscillator, expression of many light-harvesting chlorophyll a/b binding proteins was down-regulated, and expression of fructose 1,6-bisphosphatase genes was up-regulated to increase starch content in tobacco stems. Changes in the xylem and phloem of JcFTOE plants were also identified, and in particular, xylem development was affected by significant increases in expression of irregular xylem genes.

High-fat diet-induced obesity primes fatty acid ß-oxidation impairment and consequent ovarian dysfunction during early pregnancy.

BACKGROUND: Obesity is associated with many adverse effects on female fertility. Obese women have a higher likelihood of developing ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. However, the effect of obesity on ovarian function during early pregnancy needs to be further assessed. METHODS: C57BL6/J mice were given a high-fat diet (HFD) for 12 weeks to induce obesity. An in vitro high-fat model was established by treating the human ovarian granulosa cell line KGN with oleic acid and palmitic acid. Ovarian morphology of obese mice in early pregnancy was assessed by hematoxylin and eosin staining and ovarian function was assessed by enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Oil Red O staining and transmission electron microscopy were used to detect fatty acid accumulation. Specific markers relating to the ovarian functional mechanism were assessed by real-time PCR, western blotting, lactate detection, adenosine triphosphate (ATP) detection, biochemical analyses, and enzyme-linked immunosorbent assay. RESULTS: The results of this study showed that during early pregnancy, the number of corpus lutea, serum estradiol and progesterone levels, and the expression of the steroid biosynthesis-related protein CYP19A1 (aromatase), CYP11A1 (cholesterol side chain cleavage enzyme), and StAR (steroidogenic acute regulatory protein), were significantly increased in HFD mice. Mice fed an HFD also showed a significant increase in ovarian lipid accumulation on day 7 of pregnancy. Genes involved in fatty acid synthesis (Acsl4 and Elovl5), and fatty acid uptake and transport (Slc27a4), together with the ß-oxidation rate-limiting enzyme Cpt1a, were significantly upregulated in HFD mice. Specifically, there was abnormal elevation of ATP and aberrant expression of tricarboxylic acid cycle (TCA)- and electron transport chain (ETC)-related genes in the ovaries of pregnant HFD mice. KGN cells treated with etomoxir targeting ß-oxidation of fatty acid showed decreased TCA cycle and ETC related gene expression. The elevation of ATP and estradiol and progesterone levels was reversed. CONCLUSIONS: During early pregnancy, HFD-induced obesity increases fatty acid ß-oxidation, which in turn increases TCA cycle and ETC related gene expression, leading to increased ATP production and ovarian dysfunction.

Dibutyl phthalate exposure disrupts the progression of meiotic prophase I by interfering with homologous recombination in fetal mouse oocytes.

Dibutyl phthalate (DBP), one of the most widely used plasticizers, is a known environmental endocrine disruptor that impairs male and female fertility. In this study, oral administration of DBP was given to pregnant mice on 14.5 days post coitus (dpc) for 3 days; and additionally, DBP was added into the culture of 14.5 dpc fetal ovaries for 3 days. DBP exposure during gestation disturbed the progression of meiotic prophase I of mouse oocytes, specifically from the zygotene to pachytene stages. Meanwhile, the DBP-exposed pachytene oocytes showed increased homologous recombination sites and unrepaired DNA damage. Furthermore, DBP caused DNA damage by increasing oxidative stress, decreased the expression of multiple critical meiotic regulators, and consequently induced oocyte apoptosis. Moreover, the effect of DBP on meiosis I prophase involved estrogen receptors α and ß. Collectively, these results demonstrated a set of meiotic defects in DBP-exposed fetal oocytes. As aberrations in homologous recombination can result in aneuploid gametes and embryos, this study provides new support for the deleterious effects of phthalates.

A novel DNA biosensor integrated with Polypyrrole/streptavidin and Au-PAMAM-CP bionanocomposite probes to detect the rs4839469 locus of the vangl1 gene for dysontogenesis prediction.

The single nucleotide polymorphism (SNP) of the vangl1 gene is highly correlated with Neural Tube Defects (NTDs), a group of severe congenital malformations. It is hindered by the lack of a quantitative detection method. We first propose the use of a DNA biosensor to detect the missense single nucleotide polymorphism (rs4839469 c.346G>A p.Ala116Thr) of the vangl1 gene in this work. Polypyrrole (PPy) and streptavidin were integrated to modify a gold electrode. We took advantage of the PPy's good biocompatibility and excellent conductivity. To further accelerate the electron transfer process at the electrode surface, polyamidoamine dendrimer-encapsulated gold nanoparticles (Au-PAMAM) were used, because Au-PAMAM possess a large number of amino groups to load capture probes (CP). Using the biotin-streptavidin system, the Au-PAMAM-CP bionanocomposite probe, which can detect the target DNA, was conjugated to the electrode surface. Under optimal conditions, the DNA biosensor exhibited a wide linear range of 0.1-100 nM with a low detection limit of 0.033 nM (S/N=3). The results suggest that this approach has the potential to be used in clinical research.

A switched catalysis qualified sealers capped one-step synthesis biocompatibility bimetallic scaffold film for Neu5Acα(2-6)Gal ß MP Glycoside specific detection.

In this work, a novel label-free biosensor was designed for the sensitive and selective determination of Neu5Acα(2-6)Gal ß MP Glycoside using AuPt-PPy(polypyrrole) conductive nanocomposite film as the sensor platform. The introduced AuPt-PPy nanocomposite provided a large surface area for the immobilization of Sambucus nigra agglutinis (SNA) through a coupling agent for specifically recognizing analytes and exhibited high electrocatalytic activity toward the reduction of hydrogen peroxide (H2O2) as an analytical signal. Subsequently, to block the non-specific sites of the modified electrode, GOx was employed instead of the usual sealers. Most importantly, in the presence of glucose, these localized GOx further enhanced the electrochemical signal, which was achieved by the efficient catalysis of glucose. This study is the first that demonstrates the specific detection of Neu5Acα(2-6)Gal ß MP Glycoside using AuPt-PPy as the electrocatalytic. Under optimal conditions, the electrochemical biosensor exhibited a wide linear range of 0.01 pgmL(-1)-800 ngmL(-1) with a low detection limit of 0.003 pgmL(-1) (S/N=3), due to the affinity between SNA and Neu5Acα(2-6)Gal ß MP Glycoside. Therefore, the co-catalysis signal amplification approach has considerable potential in clinical applications and is suitable for the quantification of other biomarkers.

MiR-378 Plays an Important Role in the Differentiation of Bovine Preadipocytes.

BACKGROUND: Adipocyte, the main cellular component of white adipose tissue, plays a vital role in energy balance in higher eukaryotes. In recent years, adipocytes have also been identified as a major endocrine organ involved in immunological responses, vascular diseases, and appetite regulation. In farm animals, fat content and categories are closely correlated with meat quality. MicroRNAs (miRNAs), a class of endogenous single-stranded non-coding RNA molecules, participate in the regulation of adipocyte differentiation and adipogenesis through regulating the transcription or translation of target mRNAs. MiR-378 plays an important role in a number of biological processes, including cell growth, cell differentiation, tumor cell survival and angiogenesis. METHODS: In the present study, bioinformatics analysis and dual-luciferase reporter assay were used to identify and validate the target genes of miR-378. In vitro cell transfection, quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot analysis, Oil Red O staining, and triglyceride content measurement were conducted to analyze the effects of miR-378 on bovine preadipocyte differentiation. RESULTS: MiR-378 was induced during adipocyte differentiation. In the differentiated adipocytes overexpressing miR- 378, the volume of lipid droplets was enlarged, and the triglyceride content was increased. Moreover, the mRNA expression levels of the adipocyte differentiation marker genes, peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein (SREBP), were significantly elevated in the differentiated, mature adipocytes. In contrast, the mRNA expression level of preadipocyte factor 1 (Pref-1) was markedly reduced. E2F transcription factor 2 (E2F2) and Ras-related nuclear (RAN)-binding protein 10 (RANBP10) were the two target genes of miR-378. The mRNA expression levels of E2F2 and RANBP10 did not significantly change in bovine preadipocytes overexpressing miR-378. However, the protein expression levels of E2F2 and RANBP10 were markedly reduced. CONCLUSION: MiR-378 promoted the differentiation of bovine preadipocytes. E2F2 and RANBP10 were the two target genes of miR-378, and might involve in the effects of miR-378 on the bovine preadipocyte differentiation.