Prader–Willi syndrome: From genetics to behaviour,with special focus on appetite treatments

Prader–Willi syndrome (PWS) is a neurodevelopmental disorder resulting from a deletion in the expression of the paternally derived alleles in the region of 15q11–q13. PWS has a prevalence rate of 1:10,000–1:30,000 and is characterized by marked endocrine abnormalities including growth hormone deficiency and raised ghrelin levels.The hyperphagic phenotype in PWS is established over a number of phases and is exacerbated by impaired satiety, low energy expenditure and intellectual difficulties including obsessive–compulsive disorder and/or autistic behaviours. Clinical management in PWS typically includes familial/carer restriction and close supervision of food intake. If the supervision of food is left unmanaged, morbid obesity eventuates, central to the risk of cardiorespiratory disorder. None of the current appetite management/intervention strategies for PWS include pharmacological treatment, though recent research shows some promise.We review the established aberrant genetics and the endocrine and neuronal attributes which may determine disturbed regulatory processes in PWS. Focusing on clinical trials for appetite behaviours in PWS, we define the effectiveness of pharmacological treatments with a view to initiating and focusing research towards possible targets for modulating appetite in PWS.     

miR-30c negatively regulates the migration and invasion by targeting the immediate early response protein 2 in SMMC-7721 and HepG2 cells

miR-30c has been reported to act as a tumor suppressor and negatively regulate cancer metastasis by directly targeting metastasis associated genes; however, miR-30c has also been shown to promote the invasion of metastatic breast cancer cells, suggesting that miR-30c might be involved in cancer cell metastasis in different ways via targeting different genes. In this study, we demonstrated that over-expression and knockdown of immediate early response protein 2 (IER2) modulated the general capacity of the migration and invasion in hepatocellular carcinoma cell line SMMC-7721 and HepG2, whereas overexpression and knockdown of miR-30c decreased and promoted cell motility, respectively. Further studies revealed that miR-30c overexpression down-regulated the expression of IER2 protein but not its mRNA level, and miR-30c can directly target the 3’ untranslated region (3’UTR) of IER2, and subsequently reducing its expression. Moreover, we also showed that suppression of cell motility by miR-30c was partially rescued by IER2 re-expression. Our results indicated that miR-30c may function as a negative regulator in cell motility, with IER2 as a direct and functional target in SMMC-7721 and HepG2 cells.     

间充质干细胞外泌体在创伤修复再生中作用的研究进展

间充质干细胞（MSCs）外泌体能够通过旁分泌作用,发挥类似干细胞的促进组织器官修复再生的功能,避免了直接移植MSCs的风险,如致瘤、伦理、免疫排斥反应等。MSCs外泌体参与细胞通讯,维持微环境的稳态,促进细胞的增殖、迁移及细胞外基质的修复再生,且能够在不同物种之间传递,却不会引起明显的免疫反应,在组织器官的修复与再生方...     

Celastrus orbiculatus Extracts Inhibit Human Hepatocellular Carcinoma Growth by Targeting mTOR Signaling Pathways

Objective: To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts(COE). Methods: The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin(mT OR) knockdown expressed(HepG 2/mT OR-) were constructed using molecular biological technology. In vitro, the HepG 2/mT OR-cells were treated with COE at various concentrations(10, 20, 40, 80, 160 and 320 μg/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assays. According to the half-maximal inhibitory concentration(IC50) value(140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG 2/mT OR-cells were divided into 5 groups: negative control(untreated), COE treatment groups(40, 80, 120 mg/L COE) and positive control group(cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG 2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy(TEM), respectively. The protein expression levels of mT OR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR-cells(2×10~6 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight(6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group(BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules(10 mg/kg) treated group, and different dosages of COE(10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues. Results: COE inhibited the proliferation significantly in a concentration-dependent manner in HepG 2/mT OR-cells(P0.01). COE significantly induced the apoptosis of HepG 2/mT OR-cells(P0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mT ORrelated signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice(P0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein(P0.01). Conclusion: COE was a potential chemotherapeutic drug in HCC treatments via targeting mT OR signal pathway.     

赤芍通过抗神经胶质增生及抗氧化保护局部短暂性脑缺血小鼠海马部位神经的研究

目的：卒中是全球第二大死亡原因。本研究探究赤芍（Paeoniae Radix Rubra， PRR）对缺血性脑卒中小鼠的神经保护作用。方法：使用小鼠大脑中动脉堵塞法构建局部脑缺血模型。将实验动物分为4组，假手术组（Sham 组）、假手术给药组（PRR-sham组）、手术组（Isch组）、手术给药组（PRR-Isch组）。采用TTC染色法测量各组小鼠脑梗死体积；免疫组织化学染色观察各组之间小鼠缺血侧大脑海马区神经元细胞的凋亡情况以及星形胶质细胞和小胶质细胞的活化程度；采用蛋白印迹法观察小鼠缺血侧海马超氧化物歧化酶1（SOD1）、超氧化物歧化酶2（SOD2）、过氧化氢酶抗体（Catalase）表达水平。结果：赤芍可以明显减少局部脑缺血小鼠的脑梗死体积，并能抑制海马CA1区星形胶质细胞和小胶质细胞的活化程度，同时可以改善由缺血再灌注损伤引起的SOD1、SOD2和Catalase的表达水平下降情况。结论：赤芍可以通过抗胶质增生以及抗氧化作用改善局部短暂性脑缺血小鼠的神经损伤情况。     

汉黄芩素调控Ywhaz蛋白抑制结肠癌细胞增殖及侵袭转移

目的:探讨汉黄芩素对人结肠癌细胞HCT116和HT29细胞系的增殖、侵袭能力的影响,并研究汉黄芩素对酪氨酸3/色氨酸5-单加氧酶激活蛋白(Ywhaz)蛋白水平的影响。方法:体外培养HCT116和HT29细胞系,设空白组、汉黄芩素不同浓度组(浓度分别为5,10,20,40μmol·L-1)作用不同时间后,采用细胞计数试剂盒(CCK-8)法检测汉黄芩素对结肠癌细胞增殖的影响,并用Annexin V-FITC/PI双标后流式细胞仪检测结肠癌细胞的凋亡率;穿透小室(Transwell)小室法检测处理24 h后细胞侵袭和迁移力的变化;实时荧光定量-聚合酶链式反应(q PCR)检测不同浓度汉黄芩素作用24 h后Ywhaz mRNA的水平,并运用蛋白质免疫印迹(Western blot)检测该蛋白及其磷酸化水平。结果:与空白组比较,汉黄芩素可明显抑制结肠癌细胞系的增殖,具有浓度和时间依赖性,并促进结肠癌细胞系的凋亡率,其中20和40μmol·L-1的汉黄芩素抑制细胞增殖作用显著(P0.01),且不同浓度的汉黄芩素(10,20,40μmol·L-1)作用于结肠癌细胞后,明显降低肿瘤细胞的穿膜数(P0.05,P0.01),汉黄芩素可下调Ywhaz mRNA水平和蛋白水平的表达,并降低Ywhaz的磷酸化水平(P0.05,P0.01)。结论:汉黄芩素可显著抑制HCT116和HT29细胞系的增殖、侵袭和迁移能力,并诱导细胞凋亡,其抗肿瘤机制可能与下调Ywhaz的蛋白水平及其蛋白的磷酸化水平有关。     

Quinoline alkaloids isolated from Scolopendra subspinipes mutilans

Objective To study the quinoline alkaloids from the ethanol extract of Scolopendra subspinipes mutilans (SSM). Methods The chemical constituents were isolated and purified by macroporous resin column, medium pressure preparation chromatography, and semi-preparative HPLC. Their structures were elucidated by IR, MS, and NMR experiments. Results Three quinolone alkaloids were obtained and identified as 3-hydroxy-4-methoxyquinolin-8-yl hydrogen sulfate (1), jineol-8-sulfate (2), and jineol (3), respectively. Conclusion Compound 1 is a new compound from SSM.     

黄花三宝木中香豆素类成分研究

目的对黄花三宝木Trigonostemon lutescens枝叶的95%乙醇提取物中的化学成分进行研究。方法利用硅胶柱色谱、MCI和Sephadex LH-20柱色谱及半制备型高效液相等色谱方法分离纯化,结合理化性质和MS、NMR等波谱学数据对化学结构进行解析。结果从黄花三宝木醋酸乙酯萃取物中发现并鉴定了11个化合物,分别为7个香豆素类:酸橙素烯醇(1)、水合橘皮内酯(2)、花椒毒素(3)、佛手柑内酯(4)、异茴芹内酯(5)、别异欧芹属素乙(6)、异去甲基呋喃羽叶芸香素(7);2个苯丙素糖苷:3,4-dihydroxyallylbenzene-4-O-β-D-glucopyranoside(8)、1-O-β-D-glucopyranosyl-4-allylbenzene(9);1个苯乙醇类:1-(2-ethylphenyl)-1,2-ethanediol(10);1个生物碱类:8-hydroxy-3-methoxy-5H-pyrido [2,1-c] pyrazin-5-one(11)。结论化合物1～11均为首次从三宝木属植物中分离得到。