Amino acid transporters: Emerging roles in drug delivery for tumor-targeting therapy

Amino acid transporters,which play a vital role in transporting amino acids for the biosynthesis of mammalian cells,are highly expressed in types of tumors.Increasing studies have shown the feasibility of amino acid transporters as a component of tumortargeting therapy.In this review,we focus on tumor-related amino acid transporters and their potential use in tumor-targeting therapy.Firstly,the expression characteristics of amino acid transporters in cancer and their relationship with tumor growth are reviewed.Secondly,the recognition requirements are discussed,focusing on the“acidbase”properties,conformational isomerism and structural analogues.Finally,recent developments in amino acid transporter-targeting drug delivery strategies are highlighted,including prodrugs and nanocarriers,with special attention to the latest findings of molecular mechanisms and targeting efficiency of transporter-mediated endocytosis.We aim to offer related clues that might lead to valuable tumor-targeting strategies by the utilization of amino acid transporters.     

肌硬膜桥的研究进展

正1995年, Hack等[1]发现了肌硬膜桥(myodural bridges,MDBs),随着对其相关研究的不断深入,越来越多的学者开始关注和研究肌硬膜桥,本文通过对肌硬膜桥相关文献资料的整理总结和分析,目的在于对肌硬膜桥有更加系统和深入的认识,为今后肌硬膜桥的研究提供参考和思路。     

预防冠状动脉支架植入术术后低分子肝素皮下出血的前瞻性临床研究

目的 低分子肝素皮下注射后注射部位出血率高达34％～42％,十分影响患者就医体验及依从性,本文将探讨一种按压贴预防低分子肝素皮下出血的效果.方法 本研究采用前瞻性自身对照实验设计,研究收集2019年2月-10月某院急诊行冠状动脉支架植入术(Percutaneous coronary intervention,PCI)的急性冠脉综合征(Acute coronary syndrome,ACS)患者,对于术中发现慢血流或多支血管病变的患者,临床通常在术后会皮下注射3天(Q12h,共6针)低分子肝素,将这6针随机分为对照组和实验组(每组3针),对照组皮下注射后常规不按压,实验组采用自制按压贴在注射后进行物理按压,比较两组的皮下出血发生率及出血面积的差异.结果 本研究纳入171例患者共1026针次低分子肝素皮下注射,实验组和对照组各513针次.实验组不仅皮下出血发生率显著低于对照组(14.42％VS.44.83％,P＜0.01),且实验组皮下出血患者的平均出血面积也显著小于对照组[(56±12)mm2 VS.(719±170)mm2,P＜0.01].亚组分析中发现对照组中高龄患者(≥60岁)的皮下出血率较非高龄患者(＜60岁)高(50.81％VS.44.30％,PP＜0.05),女性患者皮下出血率高于男性(48.81％VS.44.06％,P＜0.05).围术期抗血小板方案对低分子肝素皮下出血发生率无显著影响.结论 按压贴可有效预防ACS患者PCI术后低分子肝素皮下出血的发生率及显著减少出血后的出血面积,有利于改善患者就医体验,且使 用按压贴较传统手工按压可显著降低护理工作量,有一定临床推广价值.     

Effect of high volume hemofiltration on CHOP protein from a canine model of multiple organ dysfunction syndrome

Objective To observe the effect of high volume hemofiltration (HVHF) on the expression of CCAAT enhancer binding protein(CHOP) during the treatment of multiple organ dysfunction syndrome (MODS). To investigate the role of CHOP protein act in apoptosis pathway mediated by the endoplasmic reticulum stress. Methods Twelve Beagle dogs were subjected to hemorrhagic shock plus resuscltation and endotixemia to establish MODS model, then they were randomly divided into two groups: HVHF group (n=6) and MODS group (n=6). After endotoxin injection completed, the HVHF group received HVHF treatment for 24 hours; MODS group did not receive. Vivo experiments: Blood samples were obtained at different time points(before operation, 0 h, 6 h, 12 h, 24 h after the injection of endotoxin). The dogs were killed and the tissue samples from lung, liver and kidney were took, then the expression of CHOP mRNA was determined. Vitro experiments: human umbilical vein endothelial cells (HUVECs) were induced by two groups’ blood samples to establish the apoptosis model. Gene expression, protein quantification and cell apoptosis rate were determined before and after the interference. Results Vivo experiments: The levels of CHOP mRNA from lung, liver and kidney had no significant difference between the two groups (P＞0.05). Vitro experiments: (1)The expression of CHOP mRNA: Compared with MODS group, the expression levels of CHOP mRNA were significantly decreased in HVHF group at 6 h, 24 h after the injection of endotoxin (P＜0.05). Compared with before, the expression levels of CHOP mRNA in the two groups were both significantly decreased after CHOP siRNA interference (P＜0.05). (2)The expression of CHOP protein: Compared with MODS group, the expression levels of CHOP protein were significantly decreased in HVHF group at each time points (P＜0.05). Compared with before, the expression levels of CHOP protein in the two groups were both significantly decreased after CHOP siRNA interference(P＜0.05). (3)Endothelial cell apoptosis rate: Compared with the preoperative rate, the two group’s endothelial cell apoptosis rate was decreased significantly at each time points(P＜0.05). Compared with MODS group, the endothelial cell apoptosis rate was significantly decreased in HVHF group at each time points(P＜0.05). Compared with before, the endothelial cell apoptosis rate in the two groups was both significantly decreased after CHOP siRNA interference(P＜0.05). Conclusion In the treatment of MODS process, HVHF can reduce endothelial cell apoptosis which may be related to the inhibition of CHOP mRNA expression and protein synthesis.     

MHC捕获测序探寻慢性肾功能衰竭的致病基因

目的 研究慢性肾功能衰竭患者人类白细胞抗原(HLA)基因,以获得慢性肾功能衰竭的致病突变.方法 使用新的MHC捕获技术结合新一代高通量测序技术对15例慢性肾功能衰竭患者和15名健康对照的HLA区域基因进行捕获测序.结果 慢性肾功能衰竭的致病与HLA-A* 02∶01∶01、B*15∶01∶01和DRB1* 09∶01∶02关联,且这三个基因相互独立与慢性肾功能衰竭关联.结论 HLA-A*02∶01∶01、B* 15∶01∶01和DRB1* 09∶01∶02与慢性肾功能衰竭相关.采用MHC基因捕获技术结合下一代高通量测序技术研究慢性肾功能衰竭的基因易感性是可行的.     

Body mass index as a predictor of hypertension incidence among initially healthy normotensive women

BACKGROUND: Few prospective studies have evaluated the risk for incident hypertension (HTN) across the normal range of body mass index (BMI). Even fewer studies included body composition and fat distribution measurements in their analyses. In the Aerobics Center Longitudinal Study, we examined HTN risk in women across a wide spectrum of baseline BMI (kg/m(2)) values and also studied waist circumference (WC, cm), percent body fat, fat mass (FM, kg), and fat-free mass (FFM, kg) on incident HTN in subgroup analyses. METHODS: A total of 5,296 healthy normotensive women between 20 and 77 years of age completed a baseline examination during 1971-2004, and were followed for HTN incidence. Incident HTN was identified using mail-back surveys. RESULTS: A total of 592 women reported HTN during a mean 16.7 years of follow-up. Higher BMI, even within the "normal" range, was associated with greater risk of HTN. Compared with women in the lowest fifth of BMI (18.5-20.0 kg/m(2)), the hazard ratios (HRs) (95% confidence interval (CI)) of developing HTN for women with a BMI of 20.1-21.2, 21.3-22.5, 22.6-24.7, and >24.7 were 1.19 (0.89-1.60), 1.33 (0.99-1.78), 1.36 (1.03-1.81), and 2.01 (1.52-2.66), respectively (P(trend) < 0.001). In a subgroup (n = 3,189) with complete data on all the five adiposity measures, significant positive associations with HTN were seen across incremental fifths of BMI, percent body fat, and FM (P(trend) < 0.05 each), but not WC and FFM. CONCLUSIONS: Clinicians should emphasize the importance of weight management for the primary prevention of HTN in women.     

Upregulation of cell surface estrogen receptor alpha is associated with the mitogen-activated protein kinase/extracellular signal-regulated kinase activity and promotes autophagy maturation

Recently, accumulating evidence has implicated the dysregulation of autophagy as underlying the pathophysiology of several neurodegenerative diseases. The human neuronal cell line SH-SY5Y was exposed to 1-Methyl-4-phenylpyridinium (MPP⁺). The mechanism is that the sustained activation of the MAPK/ERK pathway by MPP⁺ alters autophagy selectively at the maturation step, significant increasing in autophagy formation and delaying in autophagy degradation in SHSY5Y cells. In this study, we provided evidences that estrogen was capable of promoting SHSY5Y cells survival in MPP⁺-treated group. In particular, the up-regulation of mERα, but not mERβ, was associated with a rapid and transient activation of ERK phosphorylation compatible with promoting autophagy maturation. The up-regulation of mERα changed the sustained activation of ERK phosphorylation in MPP⁺-treated group into a temporary activation. Taken together, these findings strongly support that the expression of mERα promotes the maturation of autophagosomes into functional autolysosomes by regulating ERK, determining SHSY5Y cells survival.