Effect of glutathione peroxidase mimic ebselen (PZ51) on endothelium and vascular structure of stroke-prone spontaneously hypertensive rats

BACKGROUND: To investigate whether extrinsic antioxidant seleno-glutathione peroxidase mimic ebselen (PZ51) can protect endothelium and vascular structure of stroke-prone spontaneously hypertensive rats (SHRsp) during the chronic process of hypertension. METHODS: Twenty-two 8-week-old SHRsp were randomized into a PZ51 group and a control group, and administered by gavage for 6 weeks. We examined the level of nitric oxide (NO) and malonaldehyde (MDA) in plasma. The intima-media thickness (IMT) of the common carotid artery (CCA) was measured by an image-analysis system. The endothelium of the CCA was observed by scanning electron microscopy. The eNOS protein of the major artery was assayed by immunohistochemistry and western blotting. RESULTS: Compared with the control group, PZ51 decreased plasma MDA (7.88+/-1.06 vs 10.88+/-1.73 nmol/l, p<0.001) and increased plasma NO (40.02+/-9.74 vs 22.22+/-10.05 micromol/l, p<0.001), increased eNOS protein expression (8.25+/-2.36 vs 4.46+/-3.14, p=0.026), decreased IMT (69.85+/-5.47 vs 76.60+/-6.53 microm, p<0.05) significantly and alleviated the damage to the endothelium of the CCA. CONCLUSION: Administration of PZ51 for 6 weeks can protect the endothelium and inhibit vascular remodeling, maybe due to its suppression of lipid peroxide formation and increase in eNOS protein expression.     

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.     

Management of bisphosphonate‐related osteonecrosis of the jaw: a literature review

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non‐bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high‐dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate‐related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.     

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.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

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.