Prognostic Utility of Monocyte to High-Density Lipoprotein Ratio in Patients With Acute Coronary Syndrome: A Meta-Analysis

BackgroundThe monocyte to high-density lipoprotein ratio (MHR) has been used to predict adverse clinical outcomes in patients with acute coronary syndrome (ACS). This meta-analysis aimed to evaluate the prognostic utility of MHR in patients with ACS.Materials and MethodsWe comprehensively searched for relevant studies in Pubmed, Embase, CNKI, WanFang and VIP databases until March 12, 2019. Epidemiologic studies investigating the association between MHR and major adverse cardiovascular events (MACE) or all-cause mortality in patients with ACS were included. Pooled effect was expressed as risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the reference lower MHR group.ResultsEight studies involving 6,480 patients with ACS were included and analyzed. Meta-analysis indicated that the highest MHR was significantly associated with higher risk of MACE (RR 1.65; 95%CI 1.36-2.02) and all-cause mortality (RR 2.61; 95%CI 1.29-4.89) after adjusting for the conventional confounders. The prognostic values of MACE with the highest MHR caused no significant changes in the in-hospital follow-up (RR 1.76; 95%CI 1.34-2.32) and >6 months follow-up (RR 1.68; 95%CI 1.08-2.62) subgroups. Furthermore, ST elevation myocardial infarction patients with the highest MHR had a 2.07-fold higher risk of in-hospital MACE (RR 2.07; 95%CI 1.52-2.80).ConclusionsElevated MHR is independently associated with an increased risk of MACE and all-cause mortality in patients with ACS. MHR may serve as a potential prognostic indicator for ACS prognosis.     

Genetic diversity of subgenotype 2.1 isolates of classical swine fever virus

As the causative agent of classical swine fever, the economically devastating swine disease worldwide, classical swine fever virus (CSFV) is currently classified into the 11 subgenotypes, of which subgenotype 2.1 is distributed worldwide and showing more genetic diversity than other subgenotypes. Prior to this report, subgenotype 2.1 was divided into three sub-subgenotypes (2.1a–2.1c). To further analyze the genetic diversity of CSFV isolates in China, 39 CSFV isolates collected between 2004 and 2012 in two Chinese provinces Guangxi and Guangdong were sequenced and subjected to phylogenetic analysis together with reference sequences retrieved from GenBank. Phylogenetic analyses based on the 190-nt and/or 1119-nt full length E2 gene fragments showed that current CSFV subgenotype 2.1 virus isolates in the world could be divided into 10 sub-subgenotypes (2.1a–2.1j) and the 39 isolates collected in this study were grouped into 7 of them (2.1a–2.1c and 2.1g–2.1j). Among the 10 sub-subgenotypes, 2.1d–2.1j were newly identified. Sub-subgenotype 2.1d isolates were circulated only in India, however the rest 9 sub-subgenotypes were from China with some of them closely related to isolates from European and neighboring Asian countries. According to the temporal and spatial distribution of CSFV subgenotype 2.1 isolates, the newly classified 10 sub-subgenotypes were further categorized into three groups: dominant sub-subgenotype, minor sub-subgenotype and silent sub-subgenotype, and each sub-subgenotype can be found only in certain geographical areas. Taken together, this study reveals the complex genetic diversity of CSFV subgenotype 2.1 and improves our understanding about the epidemiological trends of CSFV subgenotype 2.1 in the world, particularly in China.     

Cardiac molecular markers of programmed cell death are activated in end-stage heart failure patients supported by left ventricular assist device

BackgroundCardiomyocyte apoptosis increases in heart failure (HF) and is implicated in disease progression. The apoptotic cell is not inevitably committed to death, and appropriate therapy like left ventricular assist device (LVAD) support could offer a rescue of cellular functions. Literature data regarding the modulation of the apoptotic process during LVAD support are still controversial.MethodsTo assess whether LVAD implantation modifies the apoptotic profile in the heart, cardiac tissue was collected from end-stage HF patients before LVAD implant (pre-LVAD, n=22) and at LVAD removal (post-LVAD, n=6) and from stable HF patients on medical therapy without prior circulatory support (HTx, n=7) at heart transplantation as control. Caspase (Casp)-3, Bax, Bcl-2, and Hsp72 cardiac mRNA and protein expression were evaluated by real-time polymerase chain reaction and Western blotting (WB) in the three groups of patients. Immunohistochemical analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and DNA laddering analysis were performed; cellular size and interstitial fibrosis content were also determined.ResultsAll the apoptotic indices were increased in the post-LVAD group compared to pre-LVAD, specially antiapoptotic Hsp72 and proapoptotic Bax (Hsp72: 3.27±0.41 vs. 0.76±0.14, P<.001; Bax: 2.15±0.38 vs. 1.10 ± 0.29, P=.035; post-LVAD vs. pre-LVAD, respectively). The significant increase in Hsp72 was confirmed by WB and immunohistochemical analysis.ConclusionLVAD appears to induce an activation of apoptotic mediators, mainly at the mitochondrial level, while the following activation of Casp-3 is reduced by the significant increase of Hsp72, whose enhancement could be an important factor in cardiac remodeling associated with LVAD support.     

Sciadopitysin suppresses RANKL-mediated osteoclastogenesis and prevents bone loss in LPS-treated mice

Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects reactive oxygen species (ROS)-mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteoclast-specific genes expression, including cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1. Meanwhile, Sc also strikingly inhibited the activation of NF-κB without altering the phosphorylation of MAPKs (p38, JNK and ERK1/2). Finally, our study demonstrated that Sc administration could reverse the bone loss in LPS-induced mice model. This study suggests that Sc inhibits RANKL-induced osteoclastogenesis and bone loss by inhibiting NF-κB activation and reducing the expression of c-Fos and NFATc1. Therefore, Sc might be benefit for RANKL-mediated osteolytic bone diseases.     

Preventive effect of non-mitogenic acidic fibroblast growth factor on diabetes-induced testicular cell death

Fibroblast growth factor (FGF)-1 was found to protect the heart from oxidative damage, but clinically its long-term use was restricted for its undesirable proliferating activity on cells. Thus a cluster of amino acids responsible for the proliferation were deleted in the native FGF-1 to create a non-mitogenic FGF-1 (nmFGF-1). Whether the nmFGF-1 protects male germ cells from diabetes-induced apoptotic death was examined in diabetic mice induced with multiple low-doses of streptozotocin, followed by nmFGF-1 treatment for 6 months. Diabetic mice showed a decrease in testicular weight and an increase in apoptotic cell death. Treatment with nmFGF-1 alleviated the diabetic effects on testicular weight and apoptotic cell death. Mechanistically, nmFGF-1 may alleviate diabetes-induced germ cell death by decreasing the BAX/Bcl-2 ratio and endoplasmic reticulum stress as well as associated cell death, which is associated with Nrf-2 activation.     

Rasch analysis of a Spanish language-screening parent survey

The purpose of this study was to evaluate and refine items from a parent survey designed to screen the language skills of Spanish-speaking preschoolers. This investigation applied Rasch modeling to systematically evaluate and identify items that demonstrated favorable qualities.A set of 124 parent survey items was administered to 107 Spanish-speaking parents of preschool age children. Parents completed survey items intended to provide a global measure of preschool language abilities. Rasch analyses of the survey items were conducted using WINSTEPS.Results indicated that 59 items, all vocabulary items, fit the Rasch model. Sufficient unidimensionality was obtained, with the model accounting for 58% of the variance. Item difficulty estimates ranged from −7.43 to 4.12, with a shortage of items at both the lower ability level and at the higher ability level. Analyses of pruned and remaining items identified the type of items that may be most useful for a refined item bank. These results will inform the development of new items for a Spanish language-screening parent survey for preschool age children.     

A preliminary study of expression of human neonatal Fc-receptor (FcRn) in Escherichia coli

IntroductionHuman neonatal Fc-receptor is a potential novel antibody binding protein for development of immunoassay. Previous studies had shown that this human protein has high affinity to Ig G either in vivo or in vitro. However, none of the studies had attempted exploring the utility of human FcRn in antibody immobilisation strategy. In this study, we are in the direction towards development of a novel antibody binding protein by using human FcRn as an immobilisation platform. The three-dimensional structure of the protein was analysed. This protein was successful expressed in bacteria E. coli BL21 (DE3) by using expression vector pET-28b. The pET-28b vector contains poly-histidine tagged which allows detection and purification of expressed proteins.Objectives(1) To study the three dimensional structure of human FcRn, (2) To clone the human FcRn into pET-28b expression vector, (3) To express human FcRn in bacteria E. coli BL21 (DE3).MethodsHuman FcRn cDNA was ligated into pET-28b vector through EcoRI restriction site. The successful clone was transformed into E. coli BL21 (DE3) for expression. Expression in bacteria was induced by IPTG. Induction was conducted under 30°C and 37°C. Expression products were analysed by performing SDS-Page and Western Blot. The 3D structure of human FcRn was studied by using ViewerLite program.Results & DiscussionHuman FcRN was expressed under two sets of temperature, 30°C and 37°C, in 1 hour, 2 hours, 3 hours, and 6 hours. The induction for 3 hours showed highest amount of expressed products, under the above mentioned temperature. The amount of protein expressed in 6 hours of induction showed almost same thickness of band in SDS-PAGE compare to the induction under 3 hours period.ConclusionExpression of human FcRn can be conducted using bacteria expression system, instead of mammalian cell expression system which requires longer time and complicated process. Further study will be conducted to determine the antibody-binding activity and stability of the expressed protein.     

Development of a high-growth enterovirus 71 vaccine candidate inducing cross-reactive neutralizing antibody responses

Although Enterovirus 71 (EV71) has only one serotype based on serum neutralization tests using hyperimmune animal antisera, three major genogroups (A, B and C) including eleven genotypes (A, B1-B2, and C1-C5) can be well classified based on phylogenetic analysis. Since 1997, large-scale EV71 epidemics occurred cyclically with different genotypes in the Asia-Pacific region. Therefore, development of EV71 vaccines is a national priority in several Asian countries. Currently, five vaccine candidates have been evaluated in clinical trials in China (three C4 candidates), Singapore (one B2 candidate), and Taiwan (one B4 candidate). Overall, the peak viral titers of these 5 vaccine candidates could only reach about 10⁷ TCID₅₀/mL. Moreover, genotypes of these 5 candidates are different from the current predominant genotype B5 in Taiwan and South-Eastern Asia. We adapted a high-growth EV71 genotype B5 (HG-B5) virus after multiple passages and plaque selections in Vero cells and the HG-B5 virus could reach high titers (>10⁸ TCID₅₀/mL) in a microcarrier-based cell culture system. The viral particles were further purified and formulated with alum adjuvant. After two doses of intramuscular immunization in rabbits, the HG-B5 vaccine candidate could induce cross-reactive neutralizing antibodies against the three major EV71 genogroups. In conclusion, a high-growth EV71 virus was successfully adapted in Vero cells and could induce broad spectrum neutralizing antibody titers against three (A, B5, and C4) genotypes in rabbits.