Presenilin mediates neuroprotective functions of ephrinB and brain-derived neurotrophic factor and regulates ligand-induced internalization and metabolism of EphB2 and TrkB receptors

Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface regulates important functions, including neurite outgrowth, axonal guidance, and synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal cultures from necrotic cell death induced by glutamate excitotoxicity and that this function depends on EphB receptors. Importantly, the neuroprotective function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore, absence of one PS1 allele results in significantly decreased neuroprotection, indicating that both PS1 alleles are necessary for full expression of the neuroprotective activity of the efnB/EphB system. We also show that the ability of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from glutamate-induced cell death depends on PS1. Neuroprotective functions of both efnB and BDNF, however, were independent of γ-secretase activity. Absence of PS1 decreases cell surface expression of neuronal TrkB and EphB2 without affecting total cellular levels of the receptors. Furthermore, PS1-knockout neurons show defective ligand-dependent internalization and decreased ligand-induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates the neuroprotective activities of efnB and BDNF against excitotoxicity and regulates surface expression and ligand-induced metabolism of their cognate receptors. Together, our observations indicate that PS1 promotes neuronal survival by regulating neuroprotective functions of ligand-receptor systems.     

Is it possible to rapidly and noninvasively identify different plants from Asteraceae using electronic nose with multiple mathematical algorithms?

Many plants originating from the Asteraceae family are applied as herbal medicines and also beverage ingredients in Asian areas, particularly in China. However, they may be confused due to their similar odor, especially when ground into powder, losing their typical macroscopic characteristics. In this paper, 11 different multiple mathematical algorithms, which are commonly used in data processing, were utilized and compared to analyze the electronic nose (E-nose) response signals of different plants from Asteraceae family. Results demonstrate that three-dimensional plot scatter figure of principal component analysis with less extracted components could offer the identification results more visually; simultaneously, all nine kinds of artificial neural network could give classification accuracies at 100%. This paper presents a rapid, accurate, and effective method to distinguish Asteraceae plants based on their response signals in E-nose. It also gives insights to further studies, such as to find unique sensors that are more sensitive and exclusive to volatile components in Chinese herbal medicines and to improve the identification ability of E-nose. Screening sensors made by other novel materials would be also an interesting way to improve identification capability of E-nose.     

The pathogenic potential of autoreactive antibodies in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease affecting ～1 % of the population. Although major advances have been made in the treatment of RA, relatively little is known about disease pathogenesis. Autoantibodies, present in approximately 60 % of the patients with early disease, might provide indications for immunological mechanisms underlying RA. Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade. The discovery of ACPAs resulted into novel insight in RA pathogenesis and allowed division of the heterogeneous entity of RA into an ACPA-positive and ACPA-negative subset of disease. Other autoantibodies discovered in the serum of RA patients, including rheumatoid factors (RFs) targeting human IgG and anti-peptidylarginine deiminase (PAD)3/4 antibodies reactive against and activating the enzyme involved in citrullination, might contribute in collaboration with ACPAs to a feed-forward loop to aggravate erosive outcome of disease. Recently, a novel autoantibody system associated with RA was identified. These autoantibodies recognize carbamylated proteins (anti-CarP antibodies) and are detected in approximately 20 % of ACPA-negative patients, suggesting another parameter to sub-classify RA. In this review, the implication of autoantibodies in RA pathogenesis, diagnosis, prognosis and as biomarker for personalized medicine is discussed.     

Lack of association of antihypertensive drugs with the risk and severity of COVID-19: A meta-analysis

BackgroundThe association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown.Methods and ResultsWe systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), β-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes.The literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, β-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66?0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66?0.91, p < 0.01).ConclusionsTaken together, usage of antihypertensive drugs is not associated with the risk and severity of COVID-19. Based on the current available literature, it is not recommended to abstain from the usage of these drugs in COVID-19 patients.RegistrationThe meta-analysis was registered on OSF (https://osf.io/ynd5g).     

软骨下骨局部注射常山酮抑制转化生长因子β1信号通路缓解犬骨关节炎

文题释义： Micro-CT：即微型计算机断层扫描,遵循的是与用于医疗的计算机断层扫描相同的原理,但可提供更高分辨率,Micro-CT和高分辨率外周定量计算机断层扫描系统是目前最有用的且拥有高分辨率的骨小梁和皮质骨超微结构成像,目前用于评估骨形态特征,作为传统组织学分析的补充替代方案。 X型胶原蛋白α1链(COL10A1)：为X型胶原蛋白的特异性裂解片段,X型胶原蛋白是软骨细胞肥大分化的典型标志,在骨关节炎进展过程中,软骨细胞肥大及其合成的促炎细胞因子助软骨破坏。 背景：研究表明随着破骨细胞骨吸收的增加,过度激活了的转化生长因子β1使骨吸收和骨形成解偶联,最终导致骨关节炎动物模型中软骨下骨的硬化表型,且可通过抑制转化生长因子β1信号传导减弱骨关节炎的进展。 目的：检测前十字韧带横切比格犬骨关节炎模型中局部注射常山酮是否可以延缓骨关节炎进展。 方法：将18只雄性比格犬分为假手术(对照组)、骨性关节炎组及治疗组,后两组通过前十字韧带横切构建骨关节炎模型,治疗组造模后于软骨下骨局部注射常山酮37.8 ng。在造模术后4,8,12,16周纵向测量血清Ⅱ型胶原C端肽(CTX-Ⅱ)和X型胶原蛋白α1链血清标志物的水平;术后16周Micro-CT扫描观察软骨下骨微结构;番红固绿染色及OARSI-Modified Manking评分评估关节软骨退变程度;免疫组织化学染色对比转化生长因子β1、基质金属蛋白酶13的表达情况。实验方案经新疆医科大学第一附属医院动物实验伦理委员会批准(批准号为IACUC20160304-07)。 结果与结论：①造模后8,12周,骨关节炎组X型胶原蛋白α1链水平高于治疗组和对照组(均P < 0.01);②造模后8,12,16周,骨关节炎组CTX-Ⅱ水平均高于对照组和治疗组(均P < 0.05);③骨关节炎组软骨下骨的骨体积分数较治疗组和对照组增加,骨小梁分离度降低,骨小梁模式因子减小(均P < 0.05);④骨关节炎组OARSI-Modified Manking评分较对照组和治疗组更高(均P < 0.01);⑤骨关节炎组基质金属蛋白酶13及转化生长因子β1的表达量较对照组和治疗组更高(均P < 0.01);⑥对照组与治疗组上述各指标比较差异均无显著性意义(均P > 0.05);⑦结果说明,局部注射常山酮可通过抑制软骨下骨中异常升高的转化生长因子β1,阻断异常骨重塑来减轻前十字韧带横切诱导的骨关节炎,表明这可能是骨关节炎的一种新的治疗选择。 ORCID: 0000-0003-1388-5541(任姜栋) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程