Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Objective

Recurrent spontaneous abortion (RSA) is a multifactor and distressing disease. There are still approximately half of the RSA patients with cause not being identified to date. Accumulating studies have confirmed that genetic polymorphisms in glutathione S-transferases (GSTs) were associated with the risk of recurrent spontaneous abortion. In this study, we aimed to investigate the relationship between the polymorphism of GSTA1, which is GSTA1 -69C/T (rs3957357), and the development of recurrent spontaneous abortion.

Methods

A case–control study of 127 cases with RSA and 112 ethnic and age matched women as controls was conducted. And measurement of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed to genotype all of samples in order to analyze the association between GSTA1 -69C/T (rs3957357) and the risk of RSA.

Results

We found that the frequencies of genotypes between cases and controls have no significant difference (P = 0.908) and GSTA1 mutant allele GSTA1 −69 T was present at a frequency of 0.122 in case group, while in controls the frequency was 0.125 (P = 0.922).

Conclusion

The polymorphism of GSTA1 (rs3957357) may not be associated with the risk of recurrent spontaneous abortion in Chinese Han population.     

Meningococcal factor H-binding protein vaccines with decreased binding to human complement factor H have enhanced immunogenicity in human factor H transgenic mice

Factor H-binding protein (fHbp) is a component of a meningococcal vaccine recently licensed in Europe for prevention of serogroup B disease, and a second vaccine in clinical development. The protein specifically binds human factor H (fH), which down-regulates complement activation and enhances resistance to bactericidal activity. There are conflicting data from studies in human fH transgenic mice on whether binding of human fH to fHbp vaccines decreases immunogenicity, and whether mutant fHbp vaccines with decreased fH binding have enhanced immunogenicity. fHbp can be classified into two sub-families based on sequence divergence and immunologic cross-reactivity. Previous studies of mutant fHbp vaccines with low fH binding were from sub-family B, which account for approximately 60% of serogroup B case isolates. In the present study, we evaluated the immunogenicity of two mutant sub-family A fHbp vaccines containing single substitutions, T221A or D211A, which resulted in 15- or 30-fold lower affinity for human fH, respectively, than the corresponding control wild-type fHbp vaccine. In transgenic mice with high serum concentrations of human fH, both mutant vaccines elicited significantly higher IgG titers and higher serum bactericidal antibody responses than the control fHbp vaccine that bound human fH. Thus, mutations introduced into a sub-family A fHbp antigen to decrease fH binding can increase protective antibody responses in human fH transgenic mice. Collectively the data suggest that mutant fHbp antigens with decreased fH binding will result in superior vaccines in humans.     

一例成骨不全家系致病变异的鉴定及胚胎植入前遗传学检测

目的:明确一例成骨不全(osteogenesis imperfecta,OI)家系的致病变异并为其提供胚胎植入前遗传学检测(preimplantation genetic testing,PGT)。方法:应用高通量测序结合Sanger测序的方法鉴定患者的候选变异,用直接检测变异的方法对胚胎进行PGT检测,同时筛查囊胚的...     

A novel apolipoprotein E5 variant with a 24-bp insertion causing hyperlipidemia

A tandem 24-bp insertion in the apolipoprotein E (apo E) gene was detected in a patient with elevated triglyceride, apolipoprotein (apo) CII, and apo CIII levels. This novel variant, apo E5ss, showed in position apo E5 by isoelectric focusing and was of larger molecular weight than apo E3 during two-dimensional gel electrophoresis. Polymerase chain reaction-single strand conformation polymorphism analysis using the primer pairs that cover all the coding regions was useful for rapid detection of the variant of the apo E allele. Apo E5ss may have a 24-bp insertion caused by slipped mispairing, resulting in a tandem duplication of amino acid residues 135–142 [APOE, 24-BP INS, DUP CODONS 135–142]. The proband was the only person with apo E5ss among the 806 Japanese males that we examined. We inspected six other reported apo E5 variants in the literature. Received: July 10, 2001 / Accepted: August 8, 2001     

V-val突变型EB病毒核抗原1的功能研究

背景与目的:EB病毒核抗原1(Epstein-Barr viral nuclear antigen 1,EBNA 1)对于维持EB病毒的潜伏感染有重要作用。V-val变异型的EBNA1与鼻咽癌有密切的相关性。本研究旨在比较原型和V-val变异型的EBNA1基因在上皮细胞中的功能的差异。方法:用PCR方法扩增出原型和V-val变异型EBNA1基因的全长并克隆到pGFP载体上,转染HEK293细胞,检测两种亚型的EBNA1蛋白的表达对细胞生物学性状的影响。以含有EB病毒增强子FR序列的荧光素酶载体作为报告基因,比较两种亚型的EBNA1基因对质粒的转录激活能力。结果:原型和V-val变异型EBNA1基因的表达对HEK293细胞的生长速度没有明显影响,但表达原型EBNA1的细胞的克隆形成能力明显低于V-val亚型。在裸鼠致瘤实验中,接种表达原型和V-val变异型EBNA1细胞的实验组均未见肿瘤形成。但是在瞬时转染实验中,表达V-val变异型EBNA1基因的HEK293细胞的荧光素酶活性明显高于原型EBNA1基因。结论:原型和变异型EBNA1均未发现有明显的转化细胞的能力,但是V-val变异型EBNA1蛋白与原型相比,其转录激活的功能明显增强。     

Coronary vasospasm: A narrative review

Coronary artery vasospasm (CAVS) plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries. Pathophysiology of the disease remains incompletely understood, with autonomic and endothelial dysfunction thought to play an important role. Due to the dynamic nature of the disease, its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population. Cigarette smoking remains a prominent risk factor, although CAVS does not follow traditional coronary artery disease risk factors. Many triggers continue to be identified, with recent findings identifying chemotherapeutics, allergens, and inflammatory mediators as playing some role in the exacerbation of CAVS. Provocative testing with direct visualization is currently the gold-standard for diagnosis, but non-invasive tests, including the use of biomarkers, are being increasingly studied to aid in the diagnosis. Treatment of the CAVS is an area of active research. Apart from risk factor modification, calcium channel blockers are currently the first line treatment, with nitrates playing an important adjunct role. High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator (ICD), although timing criteria for escalated therapy require further investigation. The role of pharmaceuticals targeting oxidative stress remains incompletely understood.     

Contribution of bladder cancer pathology assessment in planning clinical trials

Bladder cancer is a heterogeneous disease that demonstrates a wide spectrum of histologic features. The modern classification of bladder cancer is largely based on pathologic analysis, which assesses tumor grade, stage, type, size, and other features that are essential for understanding the biological behavior of bladder cancer. Bladder cancers with similar histologic features are likely to show comparable responses to a new therapeutic agent in clinical trial. Furthermore, pathologic analysis also evaluates the quality of tissue samples in clinical trial to ensure the integrity of various molecular tests. In spite of the emerging role of genomic and molecular studies, pathology remains the cornerstone in the diagnosis, prognosis, and treatment of bladder cancer. Herein, the pathologic considerations for bladder cancer clinical trial planning are reviewed.     

SARS-COV-2 recombinant Receptor-Binding-Domain (RBD) induces neutralizing antibodies against variant strains of SARS-CoV-2 and SARS-CoV-1

SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them target the spike protein in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested SARS-CoV-2 spike RBD as a vaccine antigen and explored the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results show that RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralization of variants B.1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.     

Vaccine effectiveness against transmission of alpha,delta and omicron SARS-COV-2-infection,Belgian contact tracing, 2021–2022

ObjectivesVaccine effectiveness against transmission (VET) of SARS-CoV-2-infection can be estimated from secondary attack rates observed during contact tracing. We estimated VET, the vaccine-effect on infectiousness of the index case and susceptibility of the high-risk exposure contact (HREC).MethodsWe fitted RT-PCR-test results from HREC to immunity status (vaccine schedule, prior infection, time since last immunity-conferring event), age, sex, calendar week of sampling, household, background positivity rate and dominant VOC using a multilevel Bayesian regression-model. We included Belgian data collected between January 2021 and January 2022.ResultsFor primary BNT162b2-vaccination we estimated initial VET at 96% (95%CI 95–97) against Alpha, 87% (95%CI 84–88) against Delta and 31% (95%CI 25–37) against Omicron. Initial VET of booster-vaccination (mRNA primary and booster-vaccination) was 87% (95%CI 86–89) against Delta and 68% (95%CI 65–70) against Omicron. The VET-estimate against Delta and Omicron decreased to 71% (95%CI 64–78) and 55% (95%CI 46–62) respectively, 150–200 days after booster-vaccination. Hybrid immunity, defined as vaccination and documented prior infection, was associated with durable and higher or comparable (by number of antigen exposures) protection against transmission.ConclusionsWhile we observed VOC-specific immune-escape, especially by Omicron, and waning over time since immunization, vaccination remained associated with a reduced risk of SARS-CoV-2-transmission.