Elevated red blood cell distribution width (RDW) may correlate with a worse prognosis in pulmonary hypertension (PH), though results to date are inconsistent. The goal of this study is to detect the impact of RDW on the prognosis of PH.PubMed and EMBASE databases were searched from their inception to July 22, 2019 for relevant publications reporting the relationship between RDW and the prognosis of PH. A meta-analysis was performed, and the heterogeneity across the included studies was evaluated using I and Q statistics. We conducted sensitivity and subgroup analyses to detect sources of heterogeneity. In addition, potential publication bias was evaluated by Begg's and Egger's tests.In total, 1236 publications were retrieved, and 7 eligible publications with 666 PH patients were included in our meta-analysis. The results suggested that increased RDW can predict worse prognosis in PH (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.11-1.45). According to subgroup analysis, study design, region, various endpoints, time of follow-up, and patient age were not sources of heterogeneity. In addition, RDW showed prognostic value in retrospective studies (HR = 1.32, 95%CI 1.15-1.51) but not in prospective studies (HR = 1.14, 95%CI 0.78-1.67). Additionally, RDW may serve as a predictive biomarker of PH in Europe (HR = 1.33, 95%CI 1.18-1.49) but not in Asia (HR = 1.20, 95%CI 0.90-1.58). Further analysis indicated that the prognostic value of RDW was influenced by patient age (>44 years: HR = 1.34, 95%CI 1.17-1.55; ≤44 years: HR = 1.20, 95%CI 0.90-1.58) and follow-up (<3 years, HR = 1.36, 95%CI 0.53-3.47; ≥3 years, HR = 1.29, 95%CI 1.14-1.45).RDW provides important prognostic information for PH patients, and this measure may be used to optimize patient management and guide clinical treatment.PROSPERO registration number: CRD42019122636.

Lupus nephritis (LN) is one of most common types of secondary glomerulonephritis, which is characterized by longitudinal pathological changes. Microstructural lesions of LN will impact the motion of water molecules, which can be detected by diffusion-weighted imaging (DWI). There are few reported measurements of water diffusion in patients with LN, and the nature of water diffusion across the entire depth of the renal parenchyma remains largely unknown.

Although colchicine (COL) has been used to treat gout for more than a thousand years, it has been shrouded in a dark history for a long time due to its high toxicity, especially for the gastrointestinal tract. With the widespread clinical application of COL, COL's toxicity to the gastrointestinal tract has raised concerns. This study's objective was to address the exact intestinal toxicity of COL, with particular attention to the effects of COL on gut microbiota homeostasis. The mice were exposed to various dosages of COL (0.1, 0.5, and 2.5 mg kg-1 body weight per day) for a week, and the results showed that COL exposure caused serious intestinal injuries, reducing the relative expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and tight junction proteins (zo-1, claudin-1, and occludin) in the ileum and colon tissue. The 16S rRNA gene sequencing analysis of mice feces samples revealed that the composition and diversity of intestinal microbiome underwent a profound remodeling at the dosage of 2.5 mg kg-1 body weight per day, which may increase the toxic load in the gut. In addition, elevated levels of diamine oxidase (DAO) and lipopolysaccharide (LPS) in serum indicated that COL increased intestinal permeability, impairing intestinal barrier. In conclusion, our results demonstrate that COL's toxicity to the gut microbiome is compatible with intestinal injuries, inflammatory pathway inhibition, and increased intestinal permeability; our results also represent a novel insight to uncover the adverse reactions of COL in the gastrointestinal tract.

Kluyvera is a genus within the family Enterobacteriaceae and can cause various human infections but remains poorly studied. A carbapenem-resistant bla NDM- 1-carrying Kluyvera strain 090646T was isolated from a hospital sink in Chengdu, Sichuan province, China. Whole genome sequencing of the strain revealed that it had 28.2 to 42.3% in silico DNA-DNA hybridization (isDDH) scores and 84.15 to 90.10% average nucleotide identity (ANI) values with other Kluyvera species. Both values are well below the ≥ 70.0% isDDH and ≥ 95-96% ANI cutoffs to define bacterial species, suggesting that the strain represents a novel species of the genus Kluyvera, for which the name Kluyvera sichuanensis. nov. is proposed. Type strain of K. sichuanensis is 090646T (=GDMCC 1.1872T =KCTC 82166T). Strain 090646T can be differentiated from other Kluyvera species by its ability to utilize D-sorbitol but not β-galactosidase (ONPG), D-mannose, glycerin, raffinose, nor sucrose. There were 47 genome sequences labeled as Kluyvera in GenBank, which were curated for precise species identification. Only 33 of the 47 genomes were indeed of Kluyvera and four novel Kluyvera genomospecies were identified, highlighting that the species assignation of bacterial genomes in GenBank need to be curated. Genome sequencing for more strains is required to understand the genus Kluyvera.

Myocyte apoptosis plays a critical role in the development of doxorubicin- (DOX-) induced cardiotoxicity. In addition to its cardiotonic effect, laboratory evidence indicates that levosimendan can inhibit apoptosis, but its role in DOX-induced cardiac injury remains unclear. Therefore, the present study is aimed at exploring whether levosimendan could attenuate DOX-induced cardiotoxicity.

Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.

Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology.

Untreated pathological cardiac hypertrophy, which can be caused by sustained systemic hypertension, may lead to heart failure. In the present study, we investigated whether AS-1 had attenuating effects on hypertension-induced cardiac hypertrophy, and whether this process was mediated by the regulation of miRNA-143. To induce the hypertrophic response in vitro, cardiomyocytes were stimulated with Ang II for 24hs. AS-1 administration strongly attenuated Ang II-induced hypertrophic response of cardiomyocytes. Chronical infusion of Ang II via implanted osmotic mini-pump induced increased blood pressure and cardiac hypertrophy in vivo. AS-1 administration attenuated hypertension-induced cardiac hypertrophy by, at least in part, inhibin of MAPK signaling. We observed, for the first time, upregulated expression of miRNA-143 in Ang II-induced cardiomyocytes, and inhibition of miRNA-143 significantly reduced the Ang II-induced hypertrophic responses. Importantly, AS-1 administration diminished the Ang II-induced upregulation of miRNA-143. Overexpression of miRNA-143 abolished the attenuating effects of AS-1 on Ang II-induced hypertrophic response of cardiomyocytes. Additionally, AS-1 administration abrogates Ang II-induced nuclear translocation of p50 NF-κB subunit in hypertrophic cardiomyocytes. Application of NF-κB inhibitor significantly suppressed Ang II-induced upregulation of miRNA-143. Our data suggest a novel mechanism by which AS-1 attenuates Ang II-induced hypertrophic response through downregulation miRNA-143 expression in a NF-κB-dependent manner.

In this study, we investigated the neural changes and their relationships with interstitial cells (ICs) in the rumen of pre-weaning goats by transmission electron microscopy, western blot and immunofluorescence (antibody: general neuronal marker-Protein Gene Product (PGP9.5)/ IC marker-vimentin). The immunofluorescence results showed that PGP9.5-positive reaction was widely distributed in neuronal soma (NS) and nerve fibre (NF). The NSs were observed in the ganglia of the myenteric plexus (MP) but not in the submucosal plexus. The mean optical density (MOD) of the whole of PGP9.5-positive nerves and the protein expression level of PGP.5 in the rumen wall both decreased significantly with age. However an obvious increase MOD of PGP.5-positive NFs within the rumen epithelium were observed. In the MP, the nerves and ICs were interwoven to form two complex networks that gradually tightened with age. Furthermore, NSs and nerve trunks were surrounded by a ring-boundary layer consisting of several ICs that became physically closer with aging. Moreover, ICs were located nearby NFs within the ML, forming connections between ICs, smooth muscle cells and axons. This study describes the pattern of neural distribution and its association with ICs in the developing rumen which shed light on the postpartum development of ruminants.

Telocytes (TCs) have been identified as a distinct type of interstitial cells, but have not yet been reported in the gastrointestinal tract (GIT) of ruminants. In this study, we used transmission electron microscopy (TEM) and double-labelling immunofluorescence (IF) (antibodies: CD34, vimentin and PGP9.5) to seek TCs and investigate their potential functions in the muscle layers of the goat rumen. TCs were distributed widely in the myenteric plexus (TC-MYs) between the circular and longitudinal muscle layers, within circular muscle layers (TC-CMs) as well as in longitudinal muscle layers (TC-LMs). Ultrastructurally, TCs displayed small cell bodies with several long prolongations-telopodes-harboring alternate thin segments (podomers) and dilated segments (podoms). The podoms contained mitochondria, rough endoplasmic reticulum, and caveolae. Telopodes frequently established close physical interactions with near telopodes, collagen fibers (CFs), nerve fibers (NFs), smooth muscle cells (SMCs), nerve tracts, and smooth muscle bundles, as well as with blood vessels (BVs). Furthermore, both homo- and heterotypic connections were observed. In addition, telopodes were capable of releasing extracellular vesicles (EVs). IF analyses proved that TCs were reliably labeled as CD34+/vimentin+ cells, displaying spindle- or triangle-shaped bodies with long prolongations, consistent with TEM results. Specifically, podoms were visible as obvious bright spots. These positive cells covered entire muscular layers, surrounding ganglions, intermuscular BVs as well as entire smooth muscle bundles, forming a network. TC-MYs were distributed as clusters in the external ganglion, encompassing the entire ganglion and spreading to the muscle layers where TC-CMs and TC-LMs seemingly surround whole smooth muscle bundles. TC-MYs were also scattered within the interior of the ganglion, surrounding each ganglionic neuron, following the glial cells layer. We speculate that TCs support the muscle layer structure of the goat rumen and facilitate intercellular signaling directly or indirectly via the TC network.

Hematopoietic development occurs in the bone marrow, and this process begins with hematopoietic stem cells (HSCs). Ubc9 is a unique E2-conjugating enzyme required for SUMOylation, an evolutionarily conserved post-translational modification system. We herein show that a conditional Ubc9 deletion in the hematopoietic system caused decreased thymus weight and reduced lymphocyte to myeloid cell ratio. Importantly, Ubc9 deletion in the hematopoietic system only selectively impaired the development of common lymphoid progenitors (CLPs) in the bone marrow and perturbed their potential to differentiate into lymphocytes, thereby decreasing the number of T/B cells in the periphery. Ubc9 was found to be required for CLP viability, and therefore, Ubc9 deficiency rendered CLPs to undergo apoptosis and attenuated their proliferation. Thus, Ubc9 plays a critical role in the regulation of CLP function during hematopoietic development in the bone marrow.

Ovarian cancer (OC) is one of the most common types of cancer among women worldwide. The majority of patients with OC respond to current chemotherapy approaches initially; however, patients are likely to experience cancer recurrence and become resistant to the chemotherapy. Therefore, novel agents for the treatment of OC are urgently required. Chaetocin, a natural product isolated from Chaetomium fungi, has been reported to exhibit anticancer activity against various types of cancer; however, the pharmacological action and detailed mechanism underlying the effects of chaetocin on OC cells remain unclear. Therefore, the present study investigated the cytotoxic effects of chaetocin on OC cells. A Cell Counting kit-8 assay was used to study cell viability, a colony formation assay was used to assess cell proliferation, flow cytometry was used to detect apoptosis, cell cycle and reactive oxygen species (ROS) generation, and western blotting was used to determine the protein levels of poly (ADP-ribose) polymerase, caspase-3 and cleaved-caspase-3. The results demonstrated that chaetocin significantly decreased the viability of OC cells. Chaetocin inhibited the proliferation and induced G2/M phase arrest of the OVCAR-3 OC cell line. Additionally, chaetocin induced apoptotic cell death in OVCAR-3 cells via the caspase pathway. It was observed that chaetocin induced the accumulation of ROS in OVCAR-3 cells. Treatment with the ROS scavenger N-acetyl-L-cysteine reversed the apoptotic effects and activation of the caspase pathway induced by chaetocin. Collectively, these results revealed that chaetocin suppressed the proliferation and promoted the caspase-dependent apoptosis of OC cells by increasing the levels of ROS. Therefore, chaetocin may serve as a potential therapeutic agent for the treatment of OC.

Avian metapneumovirus subtype C (aMPV/C) causes an acute respiratory disease that has caused serious economic losses in the Chinese poultry industry. In the present study, we first explored the protein profile in aMPV/C-infected Vero cells using iTRAQ quantitative proteomics. A total of 921 of 7034 proteins were identified as significantly altered by aMPV/C infection. Three selected proteins were confirmed by Western blot analysis. Bioinformatics GO analysis revealed multiple signaling pathways involving cell cycle, endocytosis, and PI3K-Akt, mTOR, MAPK and p53 signaling pathways, which might participate in viral infection. In this analysis, we found that PLK2 expression was upregulated by aMPV/C infection and investigated whether it contributed to aMPV/C-mediated cellular dysfunction. Suppressing PLK2 attenuated aMPV/C-induced reactive oxygen species (ROS) production and p53-dependent apoptosis and reduced virus release. These results in a mammalian cell line suggest that high PLK2 expression correlates with aMPV/C-induced apoptosis and viral replication, providing new insight into the potential avian host cellular response to aMPV/C infection and antiviral targets.

Under nitrogen deficiency situation, Nannochloropsis spp. accumulate large amounts of lipids in the form of triacylglycerides (TAG). Mechanisms of this process from the perspective of transcriptome and metabolome have been obtained previously, yet proteome analysis is still sparse which hinders the analysis of dynamic adaption to nitrogen deficiency. Here, proteomes for 3 h, 6 h, 12 h, 24 h, 48 h and 10th day of nitrogen deplete (N-) and replete (N+) conditions were obtained and integrated with previous transcriptome data for N. oceanica.

Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor-associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR-195 was reported to be hypermethylated at its promoter CpG island and down-regulated in hepatocellular carcinoma. However, the function of miR-195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down-regulation of microRNA-195 (miR-195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR-195 significantly suppressed cell proliferation, migration, invasion and epithelial-mesenchymal transition (increased E-cadherin and decreased N-cadherin) in PCa cells. We further demonstrated that transfection with a miR-195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5-azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR-195 may function as a crucial tumor suppressor in PCa.

EZH2 acts as an oncogene through canonical pathway EZH2/H3K27Me3 and uncanonical pathway pAkt1/pS21EZH2 in many solid tumors including ovarian cancer. However, the clinical value of EZH2/H3K27Me3 and pAkt1/pS21EZH2 remain unclear. In the current study, we aim to investigate the correlation between these two pathways to clinical-pathological parameters and prognosis.

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the salvage pathway of nicotinamide adenine dinucleotide synthesis. NAMPT can also be secreted and functions as a cytokine. We have previously shown that in the brain, NAMPT expression and secretion can be induced in microglia upon neuroinflammation and injury. Yet the mechanism for NAMPT secretion remains unclear. Here we show that NAMPT can be actively secreted from microglia upon the treatment of ischemia-like injury - oxygen-glucose deprivation and recovery (OGD/R). We confirmed that classical ER-Golgi pathway is not involved in NAMPT secretion. NAMPT secretion was further enhanced by ATP, and the secretion was mediated by P2X7 receptor and by intracellular Ca2+ . Importantly, we found that phospholipase D inhibitor, n-butanol, phospholipase D siRNA, and wortmannin significantly decreased OGD/R-induced and ATP-enhanced release of NAMPT in microglia. After excluding the mechanisms of involving secretory autophagy, endosomes, and secretory lysosome, we have concluded that microglial NAMPT is secreted mainly via exosome. Immune-electron microscopy identifies NAMPT in extracellular vesicles with the size and morphology characteristic of exosome. With the vesicles harvested by ultra-centrifugation, exosomal NAMPT is further confirmed by Western blotting analysis. Intriguingly, the amount of NAMPT relative to exosomal protein markers remains unchanged upon the treatment of OGD/R, suggesting a constant load of exosomal NAMPT in microglia. Taken together, we have identified NAMPT is actively secreted via exosome from microglia during neuroinflammation of ischemic injury.

Atrial Fibrillation (AF) is the most common supraventricular tachyarrhythmia that is typically associated with cardiovascular disease (CVD) and poor cardiovascular health. Paradoxically, endurance athletes are also at risk for AF. While it is well-established that persistent AF is associated with atrial fibrosis, hypertrophy and inflammation, intensely exercised mice showed similar adverse atrial changes and increased AF vulnerability, which required tumor necrosis factor (TNF) signaling, even though ventricular structure and function improved. To identify some of the molecular factors underlying the chamber-specific and TNF-dependent atrial changes induced by exercise, we performed transcriptome analyses of hearts from wild-type and TNF-knockout mice following exercise for 2 days, 2 or 6 weeks of exercise. Consistent with the central role of atrial stretch arising from elevated venous pressure in AF promotion, all 3 time points were associated with differential regulation of genes in atria linked to mechanosensing (focal adhesion kinase, integrins and cell-cell communications), extracellular matrix (ECM) and TNF pathways, with TNF appearing to play a permissive, rather than causal, role in gene changes. Importantly, mechanosensing/ECM genes were only enriched, along with tubulin- and hypertrophy-related genes after 2 days of exercise while being downregulated at 2 and 6 weeks, suggesting that early reactive strain-dependent remodeling with exercise yields to compensatory adjustments. Moreover, at the later time points, there was also downregulation of both collagen genes and genes involved in collagen turnover, a pattern mirroring aging-related fibrosis. By comparison, twofold fewer genes were differentially regulated in ventricles vs. atria, independently of TNF. Our findings reveal that exercise promotes TNF-dependent atrial transcriptome remodeling of ECM/mechanosensing pathways, consistent with increased preload and atrial stretch seen with exercise. We propose that similar preload-dependent mechanisms are responsible for atrial changes and AF in both CVD patients and athletes.

The WHO Comprehensive Mental Health Action Plan 2013-2030 encourages routine collection and reporting of a set of essential mental health indicators, including the availability of psychotropic medicines. The global monitoring of country-level psychotropic medicine consumption trends can provide information on the extent of the availability of psychotropic medicines. The primary objective of this study was to investigate global trends in psychotropic medicines consumption from 2008 to 2019 across 65 countries and regions according to country income level and geographical region.

Omega-3 fatty acid prescription drugs, Vascepa (≥96% eicosapentaenoic acid [EPA] ethyl ester) and Lovaza (46.5% EPA and 37.5% docosahexaenoic acid ethyl ester) are known therapeutic regimens to treat hypertriglyceridemia. However, their impact on glucose homeostasis, progression to type 2 diabetes, and pancreatic beta cell function are not well understood. In the present study, mice were treated with Vascepa or Lovaza for one week prior to six weeks of high-fat diet feeding. Vascepa but not Lovaza led to reduced insulin resistance, reduced fasting insulin and glucose, and improved glucose intolerance. Vascepa improved beta cell function, reduced liver triglycerides with enhanced expression of hepatic fatty acid oxidation genes, and altered microbiota composition. Vascepa has protective effects on diet-induced insulin resistance and glucose intolerance in mice.