不同胃癌前病变中医证型PG、G-17、CEA和叶酸水平变化及相关性研究

目的:对不同胃癌前病变中医证型和血清胃蛋白酶原(pepsinogen,PG)、胃泌素-17(gastrin-17,G-17)、癌胚抗原(carcinoembryonic antigen,CEA)和叶酸水平变化的关系进行探讨,为胃癌前病变的诊断提供一定的依据。方法:以80例胃癌前病变(precancerous lesion of gastric cancer,PLGC)患者研究组,80例健康者为对照组,对研究组患者进行中医临床辨证分型,对两组研究对象的血清PG、G-17、CEA和叶酸进行测定比较。结果:研究组PLGC患者中医证型分布不均匀,差异显著(P<0.05),由多到少依次为湿热蕴胃并/兼脾胃虚寒证>胃络瘀阻并/兼气阴两虚证>痰湿中阻并/兼脾胃气虚证>肝胃气滞并/兼气阴两虚证>肝胃气滞并/兼脾胃虚寒证>湿热蕴胃并/兼胃阴不足证。PLGC不同中医证型患者血清PG I和PG II水平差异显著(P<0.05);与对照组比较,各证型PG I水平均显著降低,PG II水平均显著升高(P<0.05)。且湿热蕴胃并/兼脾胃虚寒证和胃络瘀阻并/兼气阴两虚证的PG I水平显著低于其他证候,血清PG II水平显著高于其他(P<0.05)。与对照组比较,研究组不同证候的G-17、CEA水平显著升高,叶酸水平显著降低(P<0.05);观察组中湿热蕴胃并/兼脾胃虚寒证和胃络瘀阻并/兼气阴两虚证G-17、CEA显著高于其他证候,叶酸水平显著低于其他证候(P<0.05)。结论:胃癌前病变不同中医证型血清PG、G-17、CEA和叶酸存在明显差异。     

长链非编码RNA KCNQ1OT1影响脂多糖诱导的血管内皮细胞凋亡及其炎性因子表达的机制

该研究探讨了长链非编码RNA KCNQ1OT1对脂多糖(LPS)诱导的血管内皮细胞(VEC)凋亡和炎性因子表达的影响以及其可能机制。通过体外培养VEC,分别转染KCNQ1OT1过表达载体、miR-223抑制剂或共转染KCNQ1OT1过表达载体与miR-223模拟物后,用1.0 mg/mL LPS干预24 h,然后采用RT-qPCR法检测细胞中KCNQ1OT1和miR-223的表达水平,流式细胞仪检测细胞凋亡,Western blot检测细胞中Bcl-2和Bax蛋白表达,ELISA试剂盒检测细胞培养上清中TNF-α、IL-1和IL-6水平。双荧光素酶报告基因实验验证KCNQ1OT1与miR-223的调控关系。结果显示,LPS可抑制VEC中KCNQ1OT1的表达,而促进miR-223表达;上调KCNQ1OT1或下调miR-223后均可降低LPS诱导的VEC凋亡率、Bax蛋白及TNF-α、IL-1和IL-6表达(P<0.05),而促进Bcl-2蛋白表达(P<0.05)。KCNQ1OT1靶向负调控miR-223表达,上调miR-223则逆转上调KCNQ1OT1对LPS诱导的VEC凋亡及炎性因子表达的抑制作用。这表明,上调KCNQ1OT1抑制LPS诱导的VEC凋亡及炎性因子表达,其作用机制可能与靶向负调控miR-223有关,KCNQ1OT1/miR-223轴可能为血管内皮细胞损伤的治疗提供了新靶点。     

Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease

Alzheimer's disease (AD), a severe age‐related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ‐induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD‐related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ‐induced synaptic dysfunction and neuronal death through MKP7‐dependent suppression of JNK3, a brain‐specific JNK isoform related to neurodegeneration. The results showed PBM‐attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug‐free therapeutic strategy to impede AD progression.     

The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I

RIG-I and MDA5 are cytoplasmic RNA sensors that mediate cell intrinsic immunity against viral pathogens. While it has been well-established that RIG-I and MDA5 recognize RNA viruses, their interactive network with DNA viruses, including herpes simplex virus 1 (HSV-1), remains less clear. Using a combination of RNA-deep sequencing and genetic studies, we show that the γ₁34.5 gene product, a virus-encoded virulence factor, enables HSV growth by neutralization of RIG-I dependent restriction. When expressed in mammalian cells, HSV-1 γ₁34.5 targets RIG-I, which cripples cytosolic RNA sensing and subsequently suppresses antiviral gene expression. Rather than inhibition of RIG-I K63-linked ubiquitination, the γ₁34.5 protein precludes the assembly of RIG-I and cellular chaperone 14-3-3ε into an active complex for mitochondrial translocation. The γ₁34.5-mediated inhibition of RIG-I-14-3-3ε binding abrogates the access of RIG-I to mitochondrial antiviral-signaling protein (MAVS) and activation of interferon regulatory factor 3. As such, unlike wild type virus HSV-1, a recombinant HSV-1 in which γ₁34.5 is deleted elicits efficient cytokine induction and replicates poorly, while genetic ablation of RIG-I expression, but not of MDA5 expression, rescues viral growth. Collectively, these findings suggest that viral suppression of cytosolic RNA sensing is a key determinant in the evolutionary arms race of a large DNA virus and its host.     

Baicalein alleviates osteoarthritis by protecting subchondral bone,inhibiting angiogenesis and synovial proliferation

Osteoarthritis (OA) is one of the most frequent chronic joint diseases with the increasing life expectancy. The main characteristics of the disease are loss of articular cartilage, subchondral bone sclerosis and synovium inflammation. Physical measures, drug therapy and surgery are the mainstay of treatments for OA, whereas drug therapies are mainly limited to analgesics, glucocorticoids, hyaluronic acids and some alternative therapies because of single therapeutic target of OA joints. Baicalein, a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been widely used in anti-inflammatory therapies. Previous studies revealed that baicalein could alleviate cartilage degeneration effectively by acting on articular chondrocytes. However, the mechanisms involved in baicalein-mediated protection of the OA are not completely understood in consideration of integrality of arthrosis. In this study, we found that intra-articular injection of baicalein ameliorated subchondral bone remodelling. Further studies showed that baicalein could decrease the number of differentiated osteoblasts by inhibiting pre-osteoblasts proliferation and promoting pre-osteoblasts apoptosis. In addition, baicalein impaired angiogenesis of endothelial cells and inhibited proliferation of synovial cells. Taken together, these results implicated that baicalein might be an effective medicine for treating OA by regulating multiple targets.     

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

Adenosine triphosphate (ATP) and its metabolites adenosine diphosphate, adenosine monophosphate, and adenosine in purinergic signaling pathway play important roles in many diseases. Activation of P2 receptors (P2R) channels and subsequent membrane depolarization can induce accumulation of extracellular ATP, and furtherly cause kinds of diseases, such as pain- and immune-related diseases, cardiac dysfunction, and tumorigenesis. Active ingredients of traditional Chinese herbals which exhibit superior pharmacological activities on diversified P2R channels have been considered as an alternative strategy of disease treatment. Experimental evidence of potential ingredients in Chinese herbs targeting P2R and their pharmacological activities were outlined in the study.

     

β-Carboline-Based pH Fluorescent Probe and Its Application for Monitoring Enzymatic Ester Hydrolysis

A novel pH-activatable fluorescent probe, 1-(propan-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid ( L-1 ), based on β-carboline derivatives, has been developed, which displays significant fluorescent response toward pH variation with high selectivity, good photo-stability and favorable pKa value. Moreover, L-1 can dynamically monitor the release of protons during ester hydrolysis reaction in consistent with enzymatic kinetics manner.     

3D biomechanical properties of the layered esophagus: Fung-type SEF and new constitutive model

Biomechanics and Modeling in Mechanobiology - Background and Purpose: Most current studies on the passive biomechanical properties of esophageal tissues directly use the exponential strain energy...     

格氏栲天然林林窗植物物种多样性与系统发育多样性

林窗环境异质性导致群落物种多样性与系统发育多样性(phylogenetic diversity, PD)存在差异, 研究不同大小的林窗中群落的物种多样性与系统发育多样性有助于揭示林下生物多样性的形成及维持机制。本文以格氏栲(Castanopsis kawakamii)天然林为研究对象, 通过Pearson相关性分析与广义线性模型探讨了林窗内物种多样性与系统发育多样性间的相互关系及其环境影响因素。结果表明: (1)大林窗(面积 > 200 m²)植物种类及多度均高于中林窗(50 m² ≤ 面积 < 100 m²)、小林窗(30 m² ≤ 面积 < 50 m²)和非林窗(面积 = 100 m²)。大林窗群落系统发育结构趋于发散, 中、小林窗和非林窗群落系统发育结构受到生境过滤和竞争排斥综合作用。(2)群落系统发育多样性指数与物种丰富度(species richness, SR)、Margalef丰富度指数和Shannon-Wiener指数均呈显著正相关, 这与林窗内稀有种种类组成多于优势种有关。(3)林窗面积对物种多样性存在显著正效应; 土壤全氮含量对系统发育多样性和系统发育结构存在显著正效应。林窗形成提高了格氏栲天然林群落物种多样性和系统发育多样性, 林窗面积与土壤全氮共同驱动了格氏栲天然林林窗物种多样性和系统发育多样性的变化。     

隆水蚤科多样性与生态学研究进展

隆水蚤科以其丰富的个体数和多样性成为海洋水体生态系统中极为重要的小型桡足类, 但其分类学和多样性研究仍有较大不足, 其生态功能及在生态系统中的地位存在被低估的可能。为了提升对隆水蚤科的认识, 本文对国际隆水蚤科分类学和物种多样性研究进展、隆水蚤科的物种多样性研究难点和技术发展趋势、隆水蚤科的分布和生态等方面研究进行概述。19世纪末Giesbrecht创建隆水蚤科, 随后该科的新物种不断被发现和描述, 目前已描述115种。中国海仅记录到隆水蚤科物种11种, 相关生态学研究较薄弱。隆水蚤科由于个体小, 许多物种间具有高度的形态相似性, 并且包含很多姐妹种及种内分型, 因此许多研究将传统分类鉴定手段与分子生物学技术相结合, 以提高物种的发现和描述效率。随着研究的不断深入, 有关隆水蚤科物种的分布特征、食性特征、种群特征和行为学特征等均得到不同程度的关注, 这都将提高隆水蚤科研究的广度和深度。随着研究技术的迅速发展以及许多设备先进的科学考察船和载人潜水器被用于海洋研究, 从近海、边缘海到深远海研究的协同发展, 海洋生物样品资源不断丰富, 这将带动我国分类和多样性研究快速发展, 使隆水蚤科的分类学研究不断深入。