支气管扩张症合并感染患者血清人分泌型磷脂酶A2-X表达情况及其与炎性指标的相关性研究

背景　支气管扩张症是呼吸系统常见病、多发病，感染是引起支气管扩张症的最常见原因。人分泌型磷脂酶A2-X（sPLA2-X）在炎性反应中发挥重要作用，并可促进炎性反应的发生、发展，而支气管扩张症合并感染患者血清sPLA2-X表达情况及其与重要炎性指标如降钙素原（PCT）、C反应蛋白（CRP）、诱导型一氧化氮合酶（iNOS）、白介素（IL）-6、IL-17、IL-33是否存在相关性尚未见相关报道。目的　研究支气管扩张症合并感染患者血清sPLA2-X表达情况及其与炎性指标--PCT、CRP、iNOS、IL-6、IL-17、IL-33的相关性，并进一步研究血清sPLA2-X对支气管扩张症合并感染的影响。方法　选取2017年2月-2019年1月在贵州省人民医院呼吸与危重症医学科住院治疗的支气管扩张症合并感染患者47例为病例组，选取同期在贵州省人民医院健康体检中心体检的健康志愿者21例为健康对照组。收集研究对象一般资料，分别检测健康对照组体检当天、观察组治疗前（入院当天）与治疗后（出院前1天）血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33。比较两组治疗前后观察指标，分析病例组治疗前血清sPLA2-X与PCT、CRP、iNOS、IL-6、IL-17、IL-33的相关性。结果　病例组治疗前血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33均高于健康对照组（P<0.05）；病例组治疗后血清sPLA2-X、PCT、CRP、iNOS、IL-17均高于健康对照组（P<0.05）；两组治疗后白细胞计数、IL-6、IL-33比较，差异无统计学意义（P>0.05）。病例组治疗后血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33均低于本组治疗前（P<0.05）。病例组治疗前血清sPLA2-X与PCT、CRP、iNOS、IL-6、IL-17、IL-33均呈正相关（r=0.526 2、 0.640 1、0.550 7、0.516 8、0.609 9、0.357 4，P值均<0.01）。结论　支气管扩张症合并感染患者血清sPLA2-X升高，且其与PCT、CRP、iNOS、IL-6、IL-7、IL-33呈正相关，表明血清sPLA2-X与支气管扩张症合并感染有重要的关联，血清sPLA2-X可作为评估支气管扩张症合并感染的参考指标。     

Graphene oxide-induced neurotoxicity on neurotransmitters,AFD neurons and locomotive behavior in Caenorhabditis elegans

Graphene oxide (GO) and graphene-based nanomaterials have been widely applied in recent years, but their potential health risk and neurotoxic potentials remain poorly understood. In this study, neurotoxic potential of GO and its underlying molecular and cellular mechanism were investigated using the nematode, Caenorhabditis elegans. Deposition of GO in the head region and increased reactive oxygen species (ROS) was observed in C. elegans after exposure to GO. The neurotoxic potential of GO was then investigated, focusing on neurotransmitters contents and neuronal activity using AFD sensory neurons. The contents of all neurotransmitters, such as, tyrosine, tryptophan, dopamine, tyramine, and GABA, decreased significantly by GO exposure. Decreased fluorescence of Pgcy-8:GFP, a marker of AFD sensory neuron, by GO exposure suggested GO could cause neuronal damage on AFD neuron. GO exposure led decreased expression of ttx-1 and ceh-14, genes required for the function of AFD neurons also confirmed possible detrimental effect of GO to AFD neuron. To understand physiological meaning of AFD neuronal damage by GO exposure, locomotive behavior was then investigated in wild-type as well as in loss-of-function mutants of ttx-1 and ceh-14. GO exposure significantly altered locomotor behavior markers, such as, speed, acceleration, stop time, etc., in wild-type C. elegans, which were mostly rescued in AFD neuron mutants. The present study suggested the GO possesses neurotoxic potential, especially on neurotransmitters and AFD neuron in C. elegans. These findings provide useful information to understand the neurotoxic potential of GO and other graphene-based nanomaterials, which will guide their safe application.     

呼出气一氧化氮对哮喘的诊断作用及与过敏原sIgE的关系

目的探讨呼出气一氧化氮(FeNO)对哮喘的诊断作用及与过敏原特异性IgE抗体(sIgE)的关系。方法选取2017年8月至2019年8月收治的98例疑似哮喘患儿进行观察,收集所有患儿的临床特征指标,检测肺功能及FeNO浓度,分析FeNO对哮喘的诊断作用及其与过敏原sIgE的关系。结果哮喘组的FeNO水平高于非哮喘组(P<0.05)。血清过敏原sIgE阳性患儿的Fe NO水平高于阴性患儿(P<0.05)。经Pearson相关性分析得出,FeNO水平与血清过敏原sIgE、血清总IgE和血清过敏原种类呈显著正相关(r=0.703、0.624、0.719,P<0.05)。结论FeNO在哮喘中具有一定的诊断价值,与过敏原sIgE存在显著的相关性,可为临床诊断与治疗哮喘提供有利参考依据。     

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-Fe3O4 Nanotherapy Drugs

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe₃O₄ and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe₃O₄@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe₃O₄@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.     

Different profiles of circulating arginase 2 in subtypes of preeclampsia pregnant women

Background and aimsPreeclampsia (PE) is a gestational hypertensive disease responsible for high maternal and fetal morbidity and mortality. The increase in blood pressure is associated with a decrease in the bioavailability of nitric oxide (NO). Arginase interferes with NO production consuming L-arginine, a substrate required by endothelial NO synthase to NO formation. No previous study has quantified the circulating levels of the two arginase isoforms (arginase 1 and arginase 2) in the plasma of pregnant women with PE. Therefore, our objective is to evaluate these plasma levels in healthy pregnant women and PE with or without severe features and who respond or not to antihypertensive therapy.MethodsWe compared 29 healthy pregnant women with 56 pregnant women with PE, who were also divided into with severe features (n = 24) or without severe features (n = 32) and into responsive (n = 29) or nonresponsive to antihypertensive therapy (n = 27). We quantified the plasmatic expression of arginase 1 and arginase 2 by ELISA kits.ResultsWhile similar levels of arginase 1 were found among groups, lower arginase 2 plasma levels were found in PE without severe features and responsive to antihypertensive drugs when compared to healthy pregnant women. There was no difference between arginase 2 levels in PE with severe features and nonresponsive group when compared to healthy pregnant women.ConclusionThis shows different circulation profiles of arginase 2 among groups, suggesting the existence of mechanisms of arginase 2 modulation in pregnant women with PE associated with the severity of the disease and responsiveness to antihypertensive treatment.     

Chlamydia trachomatis: Cell biology,immunology and vaccination

Chlamydia trachomatis is the causative agent of a highly prevalent sexually transmitted bacterial disease and is associated with a number of severe disease complications. Current therapy options are successful at treating disease, but patients are left without protective immunity and do not benefit the majority asymptomatic patients who do not seek treatment. As such, there is a clear need for a broad acting, protective vaccine that can prevent transmission and protect against symptomatic disease presentation. There are three key elements that underlie successful vaccine development: 1) Chlamydia biology and immune-evasion adaptations, 2) the correlates of protection that prevent disease in natural and experimental infection, 3) reflection upon the evidence provided by previous vaccine attempts. In this review, we give an overview of the unique intra-cellular biology of C. trachomatis and give insight into the dynamic combination of adaptations that allow Chlamydia to subvert host immunity and survive within the cell. We explore the current understanding of chlamydial immunity in animal models and in humans and characterise the key immune correlates of protection against infection. We discuss in detail the specific immune interactions involved in protection, with relevance placed on the CD4+ T lymphocyte and B lymphocyte responses that are key to pathogen clearance. Finally, we provide a timeline of C. trachomatis vaccine research to date and evaluate the successes and failures in development so far. With insight from these three key elements of research, we suggest potential solutions for chlamydial vaccine development and promising avenues for further exploration.     

Single-dose combination nanovaccine induces both rapid and durable humoral immunity and toxin neutralizing antibody responses against Bacillus anthracis

Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event. Identification of more effective adjuvants and novel delivery platforms is necessary to improve not only the effectiveness of the anthrax vaccine, but also enhance its shelf stability and ease-of-use. Polyanhydride particles have proven to be an effective platform at adjuvanting the vaccine-associated adaptive immune response as well as enhancing stability of encapsulated antigens. Another class of adjuvants, the STING pathway-targeting cyclic dinucleotides, have proven to be uniquely effective at inducing a beneficial inflammatory response that leads to the rapid induction of high titer antibodies post-vaccination capable of providing protection against bacterial pathogens. In this work, we evaluate the individual contributions of cyclic di-GMP (CDG), polyanhydride nanoparticles, and a combination thereof towards inducing neutralizing antibody (nAb) against the secreted protective antigen (PA) from B. anthracis. Our results show that the combination nanovaccine elicited rapid, high titer, and neutralizing IgG anti-PA antibody following single dose immunization that persisted for at least 108 DPI.     

Black beans and red kidney beans induce positive postprandial vascular responses in healthy adults: A pilot randomized cross-over study

Background and aimsConsuming pulses (dry beans, dry peas, chickpeas, lentils) over several weeks can improve vascular function and decrease cardiovascular disease risk; however, it is unknown whether pulses can modulate postprandial vascular responses. The objective of this study was to compare different bean varieties (black, navy, pinto, red kidney) and white rice for their acute postprandial effects on vascular and metabolic responses in healthy individuals.Methods and resultsThe study was designed as a single-blinded, randomized crossover trial with a minimum 6 days between consumption of the food articles. Vascular tone (primary endpoint), haemodynamics and serum biochemistry (secondary endpoints) were measured in 8 healthy adults before and at 1, 2, and 6 h after eating ¾ cup of beans or rice. Blood pressure and pulse wave velocity (PWV) were lower at 2 h following red kidney bean and pinto bean consumption compared to rice and navy bean, respectively (p < 0.05). There was greater vasorelaxation 6 h following consumption of darker-coloured beans, as shown by decreased vascular tone: PWV was lower after consuming black bean compared to pinto bean, augmentation pressure was lower after consuming black bean compared to rice and pinto bean, and wave reflection magnitude was lower after consuming red kidney bean and black bean compared to rice, navy bean, and pinto bean (p < 0.05). LDL-cholesterol concentrations were lower 6 h after black bean consumption compared to rice (p < 0.05).ConclusionOverall, red kidney and black beans, the darker-coloured beans, elicited a positive effect on the tensile properties of blood vessels, and this acute response may provide insight for how pulses modify vascular function.