Inhibitory effects of total saponins from Ilex pubescens Hook against hydrogen peroxide-induced cardiomyocyte apoptosis

Purpose: To study the protective effects of total saponins from Ilex pubescens Hook (IPTS) against cardiomyocyte apoptosis.Methods: Response surface methodology (RSM) based on Box-Benhnken Design (BBD) was carried out to optimize the extraction of IPTS. Thereafter, H9c2 cell model prepared by hydrogen peroxide (H2O2) treatment was used to investigate the effects of IPTS on cardiomyocyte apoptosis. Cell viability was determined using MTT assay, while the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), creatine kinase (CK) and catalase (CAT) were measured as indices of oxidative stress. Expressions of proteins related to apoptosis (caspase-3, Bax and Bcl-2) were measured using Western blot assay.Results: Optimal IPTS extraction was achieved with extraction temperature of 86.6 °C, extraction time of 2.23 h and water: raw material ratio of 10.8 mL/g. IPTS extract, at doses of 200, 400, 600 and 800 μg/mL, significantly increased the viability of H2O2-treated H9c2 cells (p < 0.05), but significantly decreased LDH and CK activities (p < 0.01). It also led to significant increases in SOD and CAT activities, and significant decreases in the levels of MDA in these cells (p < 0.01). There were significant down-regulation of the protein expressions of caspase-3 and Bax (p < 0.01) in IPTS-treated H9c2 cells, as well as significant up-regulation of Bcl-2 protein expression (p < 0.01).Conclusion: These results suggest that IPTS can protect cardiomyocytes against apoptosis via the inhibition of oxidative stress and mitochondria-induced intrinsic apoptosis.Keywords: Ilex pubescens, Total saponins, Cardiomyocytes, Apoptosis, H9c2 cell

Polarized electron-beam acceleration driven by vortex laser pulses

We propose a new approach based on an all-optical set-up for generating relativistic polarized electron beams via vortex Laguerre-Gaussian (LG) laser-driven wakefield acceleration. Using a pre-polarized gas target, we find that the topology of the vortex wakefield resolves the depolarization issue of the injected electrons. In full three-dimensional particle-in-cell simulations, incorporating the spin dynamics via the Thomas-Bargmann Michel Telegdi equation, the LG laser preserves the electron spin polarization by more than 80% at high beam charge and flux. The method releases the limit on beam flux for polarized electron acceleration and promises more than an order of magnitude boost in peak flux, as compared to Gaussian beams. These results suggest a promising table-top method to produce energetic polarized electron beams.Comment: We replace some results and revise some description

De novo intestine-specific transcriptome of the brown planthopper Nilaparvata lugens revealed potential functions in digestion, detoxification and immune response

AbstractThe brown planthopper (Nilaparvata lugens, BPH) is the most serious rice plant pests in Asia. In this study, we performed transcriptome-wide analysis on BPH intestine. We obtained more than 26 million sequencing reads that were then assembled into 53,553 unigenes with a mean size of 388bp. Based on similarity search with the nucleotide sequences available at NCBI, BPH intestine-specific transcriptome analysis identified 21,405 sequences. Assembled sequences were annotated with gene description, gene ontology and clusters of orthologous group terms. The digestion-, defense- and xenobiotic metabolism-related genes were abundantly detected in the transcripts from BPH intestine. Many novel genes including 33 digestion-related genes, 25 immune responsive genes and 27 detoxification-related genes are first reported here. We investigated the gene expression patterns at the transcript levels in different tissues by quantitative real-time PCR analysis, which revealed that some genes had intestine-specific expression, implicating their potential significance for BPH management

A new score system for predicting response to cardiac resynchronization therapy

Background: The aim of this study was to establish a score system derived from clinical, echocardiographic and electrocardiographic indexes and evaluate its clinical value for cardiac resynchronization therapy (CRT) patient selection. Methods: Ninety-three patients receiving CRT were enrolled. A patient selection score system was generated by the clinical, echocardiographic and electrocardiographic parameters achieving a significant level by univariate and multivariate Cox regression model. The positive response to CRT was a left ventricular end systolic volume decrease of ≥ 15% and not reaching primary clinical endpoint (death or re-hospitalization for heart failure) at the end of follow-up. Results: Thirty-nine patients were CRT non-responders (41.94%) and 54 were responders (58.06%). A 4-point score system was generated based on tricuspid annular plane systolic ex­cursion (TAPSE), longitudinal strain (LS), and complete left bundle branch block (CLBBB) combined with a wide QRS duration (QRSd). The sensitivity and specificity for prediction of a positive response to CRT at a score > 2 were 0.823 and 0.850, respectively (AUC: 0.92295% CI 0.691–0.916, p< 0.001). Conclusions: A patient selection score system based on the integration of TAPSE, LS and CLBBB combined with a wide QRSd can help to predict positive response to CRT effectively and reliably

Effects of RNA interference-mediated gene silencing of JMJD2A on human breast cancer cell line MDA-MB-231 in vitro

Previous data demonstrate that JMJD2A is a cancer-associated gene and may be involved in human breast cancer by demethylation of H3K9me3. The aim of this study was to investigate depressive effects on JMJD2A by transfection with JMJD2A-sepcific siRNA in human breast cancer cell line MDA-MB-231 and effects on cell proliferation, invasion and migration. JMJD2A-specific siRNA was chemically synthesised and transfected into human breast cancer cell line MDA-MB-231. Expression levels of JMJD2A were detected by quantitative real-time PCR and Western blot analysis. Cells proliferation was evaluated by using flow cytometric anlysis and MTT assay. The abilities of invasion and migration were evaluated by cell migration and invasion assay with Boyden chambers. The results showed that the transfection was successful and expression levels of JMJD2A mRNA and protein in siRNA group were both down-regulated. By MTT assay, the mean actual absorbance in siRNA group was significantly lower than that in blank control group (P < 0.05) and negative control group (P < 0.05). In addition, the percentage of cells in G0/G1 phase in siRNA group was significantly more than that in blank control group (P < 0.05) and negative control group (P < 0.05). Furthermore, by cell invasion and migration assay, the decreased number of migrated cells in siRNA group was observed (P < 0.05). These data imply that silencing JMJD2A gene could result in cell cycle change and proliferation inhibition, and lead to suppress tumor cell invasion and migration. It provides a new perspective in understanding the pleiotropic functions of JMJD2A and its contribution to human breast cancer

Identification of LncRNA Linc00513 Containing Lupus-Associated Genetic Variants as a Novel Regulator of Interferon Signaling Pathway

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility single-nucleotide polymorphisms (SNPs) yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in non-coding regions. Long non-coding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA containing functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in SLE patients. Linc00513 expression was higher in active disease patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and extends the role of lncRNAs in the pathogenesis of SLE

A possible 250-second X-ray quasi-periodicity in the fast blue optical transient AT2018cow

The fast blue optical transients (FBOTs) are a new population of extragalactic transients of unclear physical origin. A variety of mechanisms have been proposed including failed supernova explosion, shock interaction with a dense medium, young magnetar, accretion onto a compact object, and stellar tidal disruption event, but none is conclusive. Here we report the discovery of a possible X-ray quasi-periodicity signal with a period of $\sim$250 second (at a significance level of 99.76%) in the brightest FBOT AT2018cow through the analysis of XMM-Newton/PN data. The signal is independently detected at the same frequency in the average power density spectrum from data taken from the Swift telescope, with observations covering from 6 to 37 days after the optical discovery, though the significance level is lower (94.26%). This suggests that the QPO frequency may be stable over at least 1.1$\times$ 10$^{4}$ cycles. Assuming the $\sim$250 second QPO to be a scaled-down analogue of that typically seen in stellar mass black holes, a black hole mass of $\sim10^{3}-10^{5}$ solar masses could be inferred. The overall X-ray luminosity evolution could be modeled with the stellar tidal disruption by a black hole of $\sim10^4$ solar masses, providing a viable mechanism to produce AT2018cow. Our findings suggest that other bright FBOTs may also harbor intermediate-mass black holes.Comment: 18 pages, 10 figures. Accepted for publication in Research in Astronomy and Astrophysic

Assessment of the impact of intravenous antibiotics treatment on gut microbiota in patients: Clinical data from pre-and post-cardiac surgery

Background and aimsSurgical site infection is a common complication after surgery. Periprocedural antibiotics are necessary to prescribe for preventing or treating infections. The present study aimed to explore the effect of intravenous antibiotics on gut microbiota and menaquinone biosynthesis in patients, especially in elderly patients undergoing cardiac surgery.MethodsA total of 388 fecal samples were collected from 154 cardiac surgery patients. The V3–V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced on a MiSeq PE300. The gut microbiota diversity of samples was analyzed in terms of α- and β-diversity at the OTU level. The different groups were classified according to antibiotics in combinations and single antibiotics. PICRUSt2 was used for preliminary prediction of the gut microbiota function for menaquinone biosynthesis.ResultsThe intravenously administered antibiotics which are excreted via bile represents the main antibiotics that could disturb the gut microbiota’s composition in cardiac surgery patients, especially for elderly patients. The effect of antibiotics on gut microbiota is produced after antibiotics treatments over one week. The recovery of gut microbiota to the state of pre-antibiotics may require over two weeks of antibiotics withdrawal. Sex factor doesn’t represent as an influencer in gut microbiota composition. Long-term use of cefoperazone-sulbactam may affect coagulation function.ConclusionsThe composition of the gut microbiota had a significant change post-intravenous antibiotics treatment in cardiac surgery patients. The richness and diversity of gut microbiota are increased in elderly patients

NCAM mimetic peptide P2 synergizes with bone marrow mesenchymal stem cells in promoting functional recovery after stroke

The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation