Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma

Objective: Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma(LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein(JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD.Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect ...     

基于复方抑瘤机制的新型纳米中药胶束剂型设计

临床实践证明中药复方具有明显的抗肿瘤作用,深入探讨中药复方有效成分的抗肿瘤作用及其对靶细胞的作用机制,对开发新的纳米中药制剂和临床中西医结合治疗肿瘤有着重要意义。本文概述了中药复方的抗肿瘤研究进展及单味中药的抗肿瘤机制,并在此基础上总结分析了目前传统纳米中药剂型的研究进展,然后以中药紫草中的紫草素为例阐述如何根据单味中药的作用机制,利用纳米材料和纳米自组装技术,围绕临床治疗中的难点设计新型纳米高分子中药剂型。     

Structural characterization,in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

Objective: The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.Methods: The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrol...     

利用CRISPR/Cas9系统建立叉头框G1基因敲除的人胚胎干细胞系

目的 采用成簇的规律间隔的短回文重复序列及其相关蛋白9（CRISPR/Cas9）基因编辑技术构建叉头框G1（FOXG1）基因敲除的人胚胎干细胞系,研究FOXG1基因在人胚胎干细胞早期神经诱导过程中的作用。方法 利用CRISPR/Cas9基因编辑技术,通过转染2个向导RNA（gRNA）诱导人胚胎干细胞FOXG1基因的大片段敲除,经单克隆筛选、测序分析和蛋白质印迹分析验证获得FOXG1基因敲除的人胚胎干细胞;通过细胞免疫荧光染色、qRT-PCR检测FOXG1基因敲除前后细胞在早期神经诱导过程中关键标志物配对框基因6（PAX6）、性别决定区Y框蛋白2（SOX2）和正小齿同源物2（OTX2）的表达。结果 利用CRISPR/Cas9基因编辑技术成功获得FOXG1基因大片段缺失的人胚胎干细胞,细胞免疫荧光染色、qRT-PCR结果均显示人胚胎干细胞早期神经诱导过程中的关键标志物PAX6、SOX2和OTX2的表达并未受FOXG1缺失的影响。结论 通过2个gRNA共转染可以快捷地诱导人胚胎干细胞FOXG1基因的大片段敲除。FOXG1基因缺失并不影响人胚胎干细胞的早期神经诱导。     

Momordica charantia fruit extract with antioxidant capacity improves the expression of tyrosine-phosphorylated proteins in epididymal fluid of chronic stress rats

ObjectiveAlthough the protective effects of Momordica charantia L. (MC) extract on chemical-induced testicular damage have been studied, the preventive effects of MC extract on functional proteins in the epididymis under chronic stress have never been reported. This study investigated the protective effects of MC fruit extract on protein secretion, especially tyrosine-phosphorylated proteins, in the epididymis of rats exposed to chronic unpredictable stress (CUS).MethodsTotal phenolic compounds (TPC), total flavonoid compounds (TFC) and antioxidant capacities of MC extract were measured. Adult male rats were divided into 4 groups: control group, CUS group, and 2 groups of CUS that received different doses of MC extract (40 or 80 mg/kg). In treated groups, rats were given MC daily, followed by induction of CUS (1 stressor was randomly applied from a battery of 9 potential stressors) for 60 consecutive days. Plasma corticosterone and testosterone levels were analyzed after the end of experiment. Expressions of heat-shock protein 70 (HSP-70) and tyrosine-phosphorylated proteins present in the fluid of the head and tail of the epididymis were quantified using Western blot.ResultsMC extract contained TPC of (19.005 ± 0.270) mg gallic acid equivalents and TFC of (0.306 ± 0.012) mg catechin equivalents per gram, and had 2,2-diphenyl-1-picrylhydrazyl antioxidant capacity of (4.985 ± 0.086) mg trolox equivalents per gram, radical 50% inhibitory concentration of (2.011 ± 0.008) mg/mL and ferric reducing antioxidant power of (23.697 ± 0.819) µmol Fe(II) per gram. Testosterone level in the epididymis was significantly increased, while the corticosterone level was significantly improved in groups treated with MC extract, compared to the CUS animals. Particularly, an 80 mg/kg dose of MC extract prevented the impairments of HSP-70 and tyrosine-phosphorylated protein expressions in the luminal fluid of the epididymis of CUS rats.ConclusionMC fruit extract had antioxidant activities and improved the functional proteins secreted from the head and tail of the epididymis. It is possible to develop the MC fruit extract as a male fertility supplement for enhancing functional sperm maturation in stressed men.     

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress,inflammation and apoptosis in rats

ObjectiveSalvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.MethodsIn a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5′-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.ResultsLiver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.ConclusionThis study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.     

头孢拉定微透析体外回收率及影响因素的研究

目的 测定头孢拉定微透析体外回收率及影响因素。方法 采用微透析浓度差法（减量法、增量法）和液质联用技术（LC-MS/MS）测定头孢拉定的体外回收率,并考察流速、浓度对回收率的影响,以探讨微透析技术用于头孢拉定体内药动学研究的可行性。结果 所建立的方法在要求范围内线性关系良好,方法灵敏可靠。增、减量法测得的回收率无显著性差异。相同条件下,探针体外回收率随流速增大而减小,不受探针周围药物浓度的影响。结论 微透析技术可用于头孢拉定药动学研究,减量法可用于头孢拉定微透析体内回收率和药动学参数的测定。