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1.
Obesogens are a subset of endocrine disruptor chemicals (EDCs) that cause obesity. The typical EDC 4-nonylphenol (4-NP) has been identified as an obesogen. However, the in vitro effects of 4-NP on adipogenesis remain unclear. In this study, 3T3-L1 preadipocytes and C3H/10T1/2 mesenchymal stem cells (MSCs) were used to investigate the influence of 4-NP on adipogenesis. The differentiation protocols for 3T3-L1 preadipocytes and C3H/10T1/2 MSCs took 8 and 12 days, respectively, beginning at Day 0. In differentiated 3T3-L1 preadipocytes, 20 μM 4-NP decreased cell viability on Days 4 and 8. Exposure to 4-NP inhibited triglyceride (TG) accumulation and adipogenic marker expression on Days 0–8, but the inhibitory effects were weaker on Days 2–8. The protein expression of pSTAT3 or STAT3 decreased on Days 0–8 and 2–8. Conversely, 4-NP promoted TG accumulation and the adipogenic marker expression in C3H/10T1/2 adipocytes. The opposing effects were attributed to physiological differences between the two cell lines. The 3T3-L1 preadipocytes are dependent on mitotic clonal expansion (MCE) to drive differentiation, while C3H/10T1/2MSCs and human preadipocytes are not. Additionally, 4-NP downregulated β-catenin expression in C3H/10T1/2 adipocytes. Accordingly, we hypothesized that 4-NP promotes adipogenesis. The role of the canonical Wnt pathway in the promotion of adipogenesis by 4-NP requires further validation. This study provides new insights into the mechanisms and appropriate risk management of 4-NP.  相似文献   
2.
Background: The current disadvantages (high cost, toxicity, resistance) of chemotherapy for gastric cancer opted people for alternative therapy from natural source. Curcumin (natural product) possess multiple biological activities but low bio-availability limits their uses as therapeutic. The Nano-formulation of curcumin increased the bioavailability and productivity of anti-cancer and anti-bacterial properties. The present study was initiated to determine the anti-cancer and anti-bacterial effect of Nano curcumin against gastric cancer and H. pylori. Methods: Curcumin loaded PLGA nanoparticles (CUR-NPs) was prepared by single emulsion solvent evaporation method. The MIC were determined using agar dilution method to find the anti-H. Pylori activity of Nano curcumin. The cytotoxicity of Nano curcumin was evaluated by MTT assay and the apoptotic effect (cell cycle arrest and morphology change) was shown by PI staining and microscopy. Results: The MIC of nanocurcumin and curcumin for all four H. pylori strains were 8 µg/ml and 16 µg/ml respectively. The inhibition rate of gastric cancer cells after treatment with curcumin was increased from 6% to 67% for 24h, from 8% to 75% for 48h, from 10% to 83% for 72h. In case of nanocurcumin, the inhibition rate increased from 7% to 69% for 24h, 11% to 87% for 48h and 16% to 97% for 72h. The IC50 of curcumin and Nano-curcumin were 24.20 µM and 18.78 µM respectively for 72 h. The population of cells in sub-G0 population increased from 4.1% in the control group to 24.5% and 57.8% when treated with curcumin and nanocurcumin respectively. After 72h of treatment with nanocurcumin, the apoptotic cells population increased as compared to native curcumin treated cells. Conclusion: The Nano curcumin might be used as a potential therapeutics against gastric cancer and H. Pylori. There is need of further in vivo study in order to validate CUR-NPs activity.  相似文献   
3.
N6甲基腺苷化(N6-methyladenosine,m6A)mRNA修饰在细胞分化和肿瘤发生中具有重要作用,也是近几年表观转录组学的研究热点。ZC3H13(zinc finger CCCH domain-containing protein 13)是m6A甲基转移酶复合体中的新型调控蛋白,其介导的m6A修饰在肿瘤的发生发展中起着重要作用,因此可能成为新的肿瘤表观遗传调节剂。本文将阐述一种新的mRNA m6A甲基化修饰酶ZC3H13的结构、功能及其在肿瘤中的研究进展,旨在为基础医学及临床治疗中m6A修饰的研究提供新的研究思路和治疗靶点。  相似文献   
4.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.  相似文献   
5.
赵文  赵斐  李敏  叶慧芳 《眼科新进展》2022,(12):962-966
目的 探讨补体因子H(CFH)基因多态性与玻璃体液血管内皮生长因子(VEGF)对年龄相关性黄斑变性(AMD)患者抗VEGF疗效影响的交互作用。方法 选取2020年5月~2022年1月广州医科大学附属第三医院眼科149例(149眼)AMD患者为研究对象,根据抗VEGF治疗是否有应答,分为应答组(111例)、无应答组(38例)。比较两组患者CFH基因多态性、玻璃体液VEGF表达水平,比较CFH位点rs1061170不同基因型患者玻璃体液VEGF表达水平,采用Logistic分析抗VEGF疗效的相关影响因素,采用交互作用系数γ分析CFH基因多态性、玻璃体液VEGF的交互作用是否存在及其作用类型。结果 无应答组患者CFH位点rs1061170基因型分布与应答组比较,差异有统计学意义(P<0.05)。无应答组患者玻璃体液VEGF高于应答组(P<0.05)。在全部AMD患者中,玻璃体液VEGF高水平患者CFH位点rs1061170基因型分布与低水平患者比较,差异有统计学意义(P<0.05)。在全部AMD患者中,玻璃体液VEGF、CFH位点rs1061170 CC基因型均是抗VEGF疗效的独立相关影响因素(均为P<0.05)。在全部AMD患者中,单独玻璃体液VEGF的OR值为41.250,单独rs1061170基因型CC的OR值为22.000,两者共存时的OR值为759.000,且γ为1.068,提示患者玻璃体液VEGF升高与CFH位点rs1061170 CC基因型在抗VEGF疗效中呈正向交互作用;同时交互作用<两单独因素OR值的乘积,则患者玻璃体液VEGF升高与CFH位点rs1061170 CC基因型交互作用符合次相乘模型。结论 玻璃体液VEGF升高与CFH位点rs1061170 CC基因型在AMD抗VEGF疗效中呈正向交互作用,且交互作用符合次相乘模型,为临床抗VEGF药物精准使用提供参考。  相似文献   
6.
Base catalysed exchange with sodium hydroxide, calcium oxide or N,N,N,N-tetramethylguanidine in deuterium oxide is a viable procedure for the preparation of terminally deuterated alkynes for those alkynes stable to strong base. The use of silver perchlorate as a catalyst is an alternative practical option when labelling alkynes which are sensitive to base or contain functionalities which would lead to labelling elsewhere in the molecule. Labelling with this catalyst takes place smoothly at ambient temperature in a mixture of N,N-dimethylformamide and deuterium oxide.  相似文献   
7.
Objective: We aimed to identify gastric cancer-related risk factors and evaluate the efficacy of screening ABC(D) method in determining high risk  gastric cancer individuals in Mongolian population. Methods: A total of 240 participants (120 gastric cancer patients and 120 healthy individuals) were included in this study. Data were collecting using a structured questionnaire consisting of 56 questions covering 5 categories. Serum Helicobacter pylori IgG (H. pylori IgG), pepsinogen I (PGI), and pepsinogen II (PGII) were tested in one third of all the participants (40 gastric cancer patients and 40 controls).  PGI, PGII, and H. pylori IgG levels were measured using GastroPanel enzyme-linked immunosorbent assay kit (Biohit, Helsinki, Finland). Results: Habits of having leftover meals (OR 2.22, 95%CI 1.27-3.86, p<0.01), daily consumption of tea with salt (OR 1.97, 95%CI 1.18-3.30, p<0.01), smoking on an empty stomach (OR 2.44, 95%CI 1.11-5.37, p<0.05), daily consumption of vegetables (OR 0.45, 95%CI 0.27-0.76, p<0.01), and daily consumption of fruit juice (OR 0.36, 95%CI 0.15-0.85, p<0.05), family history of gastric cancer (parents OR 2.88, 95%CI 1.07-7.78, p<0.05, siblings (OR 3.09, 95%CI 1.09-8.81, p<0.05), and history of gastric diseases (OR 3.65, 95%CI 2.10-6.35, p<0.0001) were identified as protective factors. A low PGI level (<35.25ng/ml) and low PGI/II ratio (<4) were associated with gastric cancer risk. According to ABC(D) method, groups C and D had higher proportion of gastric cancer cases than group A and B (group C, OR 7.50, 95%CI 1.20-47.05, p<0.05; group D, OR 8.3, 95%CI 1.33-51.26, p<0.05). Conclusion: Our findings suggested that gastric cancer risk was more closely related to eating habits, smoking, family history, and precancerous lesions. ABC(D) method seems to be a plausible alternative or supplementary method for stratifying patients at high risk of gastric cancer in this country.  相似文献   
8.
目的为研究DNA条形码技术在中成药鉴定中的应用,以三七片为研究对象,对方法的适用性、专属性与精密度进行考察。方法收集15批次市售三七片样品,考察三七片DNA提取条件,并对"中药材DNA条形码分子鉴定法指导原则"中PCR扩增、序列获得、结果判定等方法适用性进行确认;收集三七、人参、西洋参,制作三七片及其掺伪品,考察方法的专属性和重现性。结果三七片取样量100 mg,56℃水浴8 h所获得DNA的质量浓度平均值为60.7 ng/μL,PCR扩增、序列获得和结果判定均可获成功;三七、人参和西洋参的ITS2序列长度均为230bp,三七与人参、三七与西洋参的序列间均存在7个稳定的SNP位点,自制三七片和掺伪三七片均可成功获得ITS2序列,不同比例三七与人参、三七与西洋参的测序峰图在SNP位点处呈现相应峰高比的SNP套峰具备专属性;重复性、中间精密度和重现性考察符合《中国药典》2015年版(通则9101)相关要求。结论 ITS2序列作为DNA条形码能够稳定、准确鉴定三七片的原料药材,具备良好的专属性和精密度,三七片DNA条形码分子鉴定法将为保障三七片临床用药安全提供新的技术手段,并对《中国药典》其他收载单方制剂的鉴定提供参考。  相似文献   
9.
吴秀稳  杨秀伟 《中草药》2020,51(13):3383-3392
目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7~10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50~35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。  相似文献   
10.
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