Objective: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) had emerged as useful inflammatory biomarkers in multiple diseases. The study aimed to explore the possible relationships between NLR, PLR, MLR and methylamphetamine dependence, and explore their potential wider use in clinical research.Methods: 632 methylamphetamine-dependent patients and 325 controls were enrolled. The demographics, complication of de-pendence, and hematologic parameters were compared. The NLR, PLR, and MLR were estimated and compared between the two groups.Result: The count of white blood cell (WBC), neutrophil, monocyte, NLR, MLR, and PLR were significantly higher and the lym-phocyte count was significantly lower in methylamphetamine-dependent patients than controls (p < 0.05). Multivariate analysis showed that the NLR, MLR, monocyte, and platelet were screened as useful biomarkers to evaluate the inflammatory states of methylamphetamine dependence, respectively (NLR: OR (odds ratio) = 71.72, 95% CI (confidence interval) [27.63-186.19], p < 0.001. MLR: OR = 6.34, 95% CI [3.27-12.27], p < 0.001. Monocyte: OR = 26.34, 95% CI [3.44-206.11], p = 0.002. Platelets: OR = 3.71, 95% CI [1.97-7.02], p < 0.001). However, there were no significant differences in WBC, neutrophil cell, lymphocyte, and PLR (p > 0.05). Similar results were obtained after adjusting for age and gender. The receiver operating characteristic curve (ROC) analysis indicated that the NLR and MLR were useful parameters to identify the inflammatory states of methy-lamphetamine dependence (AUC (area under the curve): NLR = 0.89, MLR = 0.82, platelet = 0.64, monocyte = 0.77,p < 0.001). Furthermore, the NLR was significantly and positively associated with severity of dependence scale (SDS) score and hallucination in methylamphetamine-dependent patients (p < 0.05). However, the MLR was uncorrelated with those variables (p > 0.05).Conclusions: The NLR might serve as a useful clinical biomarker in inflammatory states of methylamphetamine dependence, and positively correlated with hallucination and severity of methylamphetamine dependence. [GRAPHICS]
FAK mediated tumour cell migration, invasion, survival, proliferation and regulation of tumour stem cells through its kinase-dependent enzymatic functions and kinase-independent scaffolding functions. At present, the development of FAK PROTACs has become one of the hotspots in current pharmaceutical research to solve above problems. Herein, we designed and synthesised a series of FAK-targeting PROTACs consisted of PF-562271 derivative 1 and Pomalidomide. All compounds showed significant in vitro FAK kinase inhibitory activity, the IC50 value of the optimised PROTAC A13 was 26.4 nM. Further, A13 exhibited optimal protein degradation (85% degradation at 10 nM). Meantime, compared with PF-562271, PROTAC A13 exhibited better antiproliferative activity and anti-invasion ability in A549 cells. More, A13 had excellent plasma stability with T (1/2) >194.8 min. There are various signs that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents.
目的 对亚洲兰茂牛肝菌(Lanmaoa asiatica)内生真菌Penicillium cinereoatrum Chalab.JSQ-15的次级代谢产物进行分离与鉴定,并探究其细胞毒活性.方法 采用多种色谱技术分离纯化次级代谢产物,根据理化性质和波谱数据(质谱、核磁共振谱和Marfey分析)鉴定化合物结构,并采用噻唑蓝比色法(MTT法)评价其细胞毒活性.结果 与结论从内生真菌P.cinereoatrum Chalab.JSQ-15发酵产物中分离鉴定出18个化合物,分别为9(11)-去氢过氧化麦角甾醇(1)、过氧化麦角甾醇(2)、23-甲基过氧化麦角甾醇(3)、环(L-4-羟脯氨酸-L-亮氨酸)(4)、环(L-脯氨酸-L-亮氨酸)(5)、环(L-4-羟脯氨酸-L-苯丙氨酸)(6)、3-甲氧基-环(L-脯氨酸-L-亮氨酸)(7)、环(甘氨酸-L-脯氨酸)(8)、botryolide B(9)、decarestrictine I(10)、邻苯二酚(11)、5,6-二氢尿嘧啶(12)、2-哌啶酮(13)、trans-L-4-羟脯氨酸-L-亮氨酸(14)、1-亚油酰基溶血磷脂酰胆碱(15)、油酸-α-单甘油酯(16)、油酸(17)和丁二酸(18),18个化合物均为首次从P.cinereoatrum Chalab.中分离得到.化合物对肿瘤细胞的细胞毒活性测试结果表明:甾体类化合物1、2对小鼠小胶质细胞(BV2)、人肺癌细胞(A549)和人乳腺癌细胞(MCF-7)均呈现出较强的细胞毒活性(IC50≤30 μmol·L-1),化合物3、11对BV2细胞呈现出较强的细胞毒活性(IC50≤22μmol·L-1).本研究对亚洲兰茂牛肝菌内生真菌P.cinereoatrum Chalab.JSQ-15次级代谢产物进行了较为系统的分离鉴定,为该菌种次级代谢产物的首次报道.
目的 制备盐酸非索非那定杂质G,并对其安全性进行评价,为其质量标准研究提供依据.方法 以盐酸非索非那定为起始原料,经酸降解反应得到杂质G,并研究杂质G对小鼠细胞毒性、遗传毒性及生殖毒性的影响.结果 与结论盐酸非索非那定杂质G的结构经1H-NMR、13C-NMR、MS、IR、UV谱确证,其收率为57.35％,HPLC法检测纯度为98.23％.杂质G在0.25～2.00 mg·mL-1浓度范围内,随着浓度的增大,细胞毒性也逐渐增大;杂质G在40 mg·kg-1高剂量浓度下对小鼠骨髓细胞染色体无畸变作用,未显示对小鼠骨髓细胞染色体和微核有影响,且无致雄性小鼠生殖毒性作用.制备盐酸非索非那定杂质G的方法简便可行,评价杂质G对小鼠细胞毒性、遗传毒性及生殖毒性的方法真实有效.
应激颗粒(stress granule,SG)是细胞在遇到外界环境压力时形成的一种无膜细胞器.目前已经发现SG的组装和解体与多种疾病的发生发展过程密切相关,包括神经退行性疾病、癌症、病毒感染等,因此SG被认为是一个极具开发前景的潜在药物作用靶标.本文作者介绍了 SG的生物学特征及其与疾病发生发展的关系,并在此基础上对通过不同途径与机制干预SG组装或解体的化合物进行了归纳总结与评述,以期为SG作为药物靶点的可行性探讨以及靶向SG小分子化合物的研发提供参考.
