PTPN6通过抑制SP1/p38 MAPK信号通路促进前列腺癌细胞的化疗敏感性

目的:研究PTPN6对前列腺癌细胞PC3的作用及其作用机制。方法:RT-PCR和Western blot实验检测前列腺癌组织和细胞以及癌旁组织和人前列腺上皮细胞中PTPN6的表达量；CCK-8和EDU染色实验检测PTPN6对前列腺癌细胞PC3增殖的影响；Western blot实验检测耐药相关蛋白P-gp和MRP-1的蛋白表达水平。结果:RT-PCR和Western blot结果显示，PTPN6在前列腺癌组织和细胞中的表达量显著低于癌旁组织和人前列腺上皮细胞中的表达量；过表达PTPN6显著抑制前列腺癌PC3细胞的增殖，并降低PC3细胞的耐药性；进一步的研究结果表明PTPN6可通过抑制SP1，并抑制p38 MAPK通路抑制PC3细胞的增殖和耐药。结论:PTPN6能够抑制前列腺癌细胞PC3的增殖和耐药，提高其化疗敏感性，作用机制是通过调控SP1/p38 MAPK信号通路来实现的，这一结果能够为临床上前列腺癌的诊断和治疗提供分子基础。     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

肿瘤干细胞的研究进展

肿瘤具有异质性的特征，随着研究的深入，越来越多的证据提示肿瘤组织中也存在少量具有干细胞性质的肿瘤干细胞，于是人们在此基础上提出了肿瘤干细胞学说，肿瘤干细胞已成为当今肿瘤研究领域的热点。目前，已经从白血病、脑肿瘤、乳腺癌、恶性黑色素瘤及前列腺癌等多种恶性肿瘤中初步分离鉴定出肿瘤干细胞。肿瘤干细胞学说的提出，使得靶向性杀伤肿瘤干细胞从而根治肿瘤成为可能。     

硒螺旋藻对大鼠肝叶切除术后肝细胞再生和抗氧化能力的影响

目的研究硒螺旋藻（Se—SP）对大鼠肝叶切除术后肝细胞再生和抗氧化能力的影响，以印证其生物利用价值。方法用Wistar大鼠复制67％肝叶切除动物模型，设Se—SP高剂量（H）和低剂量（L）治疗组，术前以Se—SP灌胃7d；另设生理盐水（C）及假手术对照组（S）。于手术前及其后24h取鼠肝细胞，检测硒（Se）、丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性；利用免疫组化方法测定肝细胞增生核抗原（PCNA）表达指数，慧星实验检测过氧化氢诱导的肝细胞DNA损伤。结果与C，S组相比，H组、L组肝细胞中MDA水平明显降低（P〈0．05），而Se，GPx和SOD明显升高（P〈0．05）；肝细胞PCNA指数明显升高（P〈0．05），过氧化氢诱导的DNA损伤程度较轻。结论Se—SP对肝切除鼠肝细胞具有一定的抗氧化和促再生作用。     

正常人颈段脊柱结构内CGRP和SP阳性神经纤维的分布

目的 为深入探讨颈肩痛的发病机理。方法 用免疫组织化学方法观察人颈段脊柱结构内CGRP和SP阳性神经末梢存在的情况。结果 人颈段脊柱结构的纤维层内均有CGRP和SP免疫反应阳性神经末梢存在，多数神经末梢独立行走，呈树枝状或念珠状，少量神经末梢交织网状。结论 CGRP和SP可能参与了人颈段脊柱结构的伤害性感觉信息的传递。当人颈段脊柱结构的神经末梢受刺激时，可能引起CGRP和SP的释放和传递，这可能是引起原发性颈肩痛的原因之一。     

电针三阴交治疗围绝经期综合征多中心随机对照研究

目的:客观评价针刺三阴交穴治疗围绝经期综合征的临床疗效。方法:采用多中心、随机、对照、单盲临床试验,将175例患者分为针刺组(90例)和西药组(85例)。针刺组采用电针双侧三阴交穴(疏密波,2/100Hz,刺激强度8~10mA),每周治疗3次,1个月为1疗程,连续3个疗程。西药组口服尼尔雌醇,每次2mg,每月2次,连续3个月。对已绝经者,第3个月开始加用甲羟孕酮,每天6mg,连用10d。疗效评价包括:症候积分量表中症状改善程度及血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)水平检测(化学发光分析法)。结果:3个中心共纳入175例病例,157例完成试验。针刺组在治疗后患者的疗效评价症状积分均极显著降低(P<0.01)。针刺组治疗后血清FSH、LH水平显著降低(P<0.01),血清E2水平显著升高(P<0.01),且针刺组在LH和E2水平的改善上与西药组相比差异有显著性意义(P<0.05)。表明电针三阴交能明显改善患者的临床症状,良性调整患者血清性激素水平。电针治疗组和西药对照组之间的显效率和有效率差异均无显著性意义(P>0.05)。结论:针刺三阴交穴治疗围绝经期综合征有较好的疗效。     

Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

亮氨酸脑啡肽样和P物质样免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布

用PAP法研究亮氨酸脑啡肽样(L—ENK—LI)和P物质样(SP—LI)免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布。证明在孤束核、迷走神经背核、外侧网状核外侧部及其外侧的区域内有大量的L-ENK样终末和纤维,在背侧和腹侧网状核之间的移行区内有中等量的分布,其余区内为少量。L-ENK样胞体在孤束核、咀侧腹外侧网状核、巨细胞网状核的腹侧部和α部、外侧旁巨细胞核以及中缝大核内均有许多分布,在迷走神经背核的尾侧部、背侧和腹侧网状核之间的移行区有中等量,其余区内为少量。SP样反应物的分布与L-ENK样物类似,但其终末和纤维的数量较L-ENK者略少,阳性胞体的数量除了在中缝核及外侧旁巨细胞核内侧端中的量较L-ENK样胞体多以外,在其余区内均较少。     

Localization of substance P- and enkephalin-like immunoreactivity in relation to catecholamine-containing cell bodies in the cat dorsolateral pontine tegmentum: an immunofluorescence study

The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.