康复新液联合美沙拉嗪对溃疡性结肠炎活动期患者HMGB1、MCP-1、SOCS-3和Beclin1表达的影响

目的探讨康复新液联合美沙拉嗪对溃疡性结肠炎（UC）活动期患者高迁移率族蛋白B1（HMGB1）、单核细胞趋化蛋白-1（MCP-1）、细胞因子信号传导抑制蛋白-3（SOCS-3）和Beclin1表达的影响。 方法选择2019年2月至2021年2月亳州市人民医院UC活动期患者120例,按1∶1比例随机分为对照组和治疗组,各60例。2组患者均给予补液、营养支持、纠正电解质和酸碱平衡紊乱等基础治疗。对照组口服美沙拉嗪肠溶片1 g/次,4 次/d,连续治疗2周。治疗组在美沙拉嗪肠溶片基础上给予康复新液,30 ml加入150 ml 0.9%生理盐水稀释并加温至37℃后灌肠,每次灌肠时间20～30 min,每日2次,连续治疗2周。比较2组治疗效果、主要症状积分、肠道黏膜病变程度（改良Mayo评分和Geboes指数）、HMGB1、MCP-1、SOSC-3、Beclin1水平及炎症性肠病问卷（IBDQ）评分。 结果治疗组UC活动期患者治疗总有效率显著高于对照组（93.33% vs 78.33%,P＜0.05）。治疗前2组症状积分差异无统计学意义（P＞0.05）,治疗后2组各症状积分均显著降低（P＜0.05）,且治疗组显著低于对照组（P＜0.05）。治疗前2组改良Mayo评分和Geboes指数差异无统计学意义（P＞0.05）,治疗后2组指标均降低（P＜0.05）,且治疗组显著低于对照组（P＜0.05）。治疗前2组血清HMGB1、MCP-1、SOSC-3和Beclin1水平、蛋白表达水平差异无统计学意义（P＞0.05）,治疗后2组HMGB1、MCP-1、Beclin1水平均下降,SOSC-3水平均升高,且治疗组各指标水平显著优于对照组（P＜0.05）。治疗前2组IBDQ评分差异无统计学意义（P＞0.05）,治疗后2组评分均升高（P＜0.05）,且治疗组显著高于对照组（P＜0.05）。 结论康复新液联合美沙拉嗪对UC活动期患者治疗效果显著,机制可能与HMGB1、MCP-1、Beclin1的下调及SOSC-3的上调有关。     

百秋李醇对幽门螺杆菌致小鼠胃炎的保护作用

目的: 探讨百秋李醇对幽门螺杆菌(Helicobacter pylori)感染小鼠胃炎的保护作用及其作用机制。方法: 采用化学致癌剂和幽门螺杆菌联合诱导法建立胃炎模型, 将C57BL/6小鼠分为正常组、模型组、阳性对照组(铋剂四联疗法)、百秋李醇高剂量组(40 mg·kg^-1)、百秋李醇低剂量组(20 mg·kg^-1)。灌胃给药, 连续治疗4周后, 行快速尿素酶试验, 评价胃组织中幽门螺杆菌的定植程度; 酶联免疫吸附法测定血清中白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)浓度, 免疫组织化学法和实时定量聚合酶链反应法测定胃黏膜Wnt2、β联蛋白(β-catenin)及核因子κB(NF-κB)的蛋白及基因表达。结果: 各给药组小鼠胃黏膜的腺体排列、炎性细胞浸润及不典型增生等病变现象均有显著减轻, 百秋李醇高、低剂量组对幽门螺杆菌根除率分别为78%、70%, 与模型组相比组间差异均有统计学意义(P＜0.01);与模型组相比, 百秋李醇高、低剂量组小鼠血清IL-8和TNF-α水平均有显著降低(P＜0.01);与模型组相比, 百秋李醇高、低剂量组小鼠胃黏膜Wnt2、β-catenin和NF-κB蛋白及基因表达均有显著降低(P＜0.05或P＜0.01)。结论: 百秋李醇可通过抑制NF-κB信号转导通路及Wnt/β-catenin信号转导通路的持续活化及相关炎性细胞因子的高表达, 减轻胃黏膜炎症反应, 防止胃黏膜细胞上皮-间质样转化的发生, 从而阻止或延缓胃肠癌前病变的进程。     

岩藻黄质调控TGF-β/Smad3信号通路减轻CCl4诱导的大鼠肝纤维化和氧化应激

目的： 探究岩藻黄质对肝纤维化模型大鼠氧化应激和纤维化的保护作用及可能机制。方法： 将雄性SD大鼠随机分为空白、模型、岩藻黄质和水飞蓟宾组。除空白组外,其余各组大鼠均皮下注射CCl₄溶液,2次/周,连续8周。造模同时,各组给予相应药物,空白和模型2组均给予等体积无菌水。8周后处死大鼠,检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（T-BIL）、直接胆红素（D-BIL）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽-过氧化物酶（GSH-Px）、透明质酸（HA）、羟脯氨酸（HYP）、层粘连蛋白（LN）含量以及α-SMA、TGF-β/Smad3通路主要mRNA和蛋白表达;并检测肝组织病理变化和纤维化。结果： 与空白组比较,模型组大鼠血清AST、ALT、T-BIL、D-BIL、HA、HYP、LN、MDA,肝组织α-SMA mRNA和α-SMA、TGF-β、p-Smad3蛋白水平显著上调,而SOD和GSH-Px含量降低,肝脏可见细胞结构破坏,大量炎症细胞浸润,胶原沉积和纤维增生;与模型组相比,岩藻黄质和水飞蓟宾可显著逆转大鼠血清ALT、AST、T-BIL、D-BIL、HA、HYP、LN和MDA的升高及SOD和GSH-Px的降低,并缓解肝组织炎症和纤维化程度;此外,岩藻黄质可显著抑制肝组织α-SMA、TGF-β mRNA和α-SMA、TGF-β、p-Smad3蛋白表达水平。结论： 岩藻黄质通过抑制TGF-β/p-Smad3通路缓解大鼠肝纤维化水平,调节氧化应激状态。     

活性氧与上皮性卵巢癌转移的相关性研究进展

活性氧(reactive oxygen species,ROS)是近年来基础医学和生命科学的研究热点。大量研究结果显示活性氧参与肿瘤的发生发展过程,并参与到肿瘤的进展、转移过程中[1-2]。而上皮性卵巢癌(epithelial ovarian carcinoma,EOC)是妇科癌症中恶性程度最高、死亡率最高的疾病,目前认为其转移是造成其5年生存率低的主要原因之一。因此,深入探讨EOC侵袭转移的机制,寻求有效的抑制转移的方法,是当前亟待解决的问题。而活性氧是否与上皮性卵巢癌转移存在一定相关性?如果存在相关性,是通过何     

Thapsigargin对SLE患者T细胞TCR／CD3复合物介导的[Ca^2＋]i反应的影响

目的证实SLE患者T细胞功能异常是否与TCR/CD3复合物介导的[Ca2+]i反应异常有关,以及[Ca2+]i反应异常的原因.方法用CD3单抗与羊抗鼠二抗IgG相关联刺激T细胞,并用Thapsigargin干预后,分别用粘附细胞仪连续观察10 min T细胞[Ca2+]i的变化,并评价[Ca2+]i反应与CD3分子表达的相关性.结果正常人和SLE患者T细胞[Ca2+]i反应的基准值相似(P=0.105);SLE患者T细胞的[Ca2+]i反应高峰值、平台值明显高于正常对照(P＜0.001,P＜0.001);加入Thapsigargin后二者[Ca2+]i反应无显著差异,二者的T细胞CD3阳性率无差异(P=0.665).结论SLE患者T细胞TCR/CD3介导的[Ca2+]i反应存在异常,并且这种异常不是因为胞内Ca2+库排空后跨膜Ca2+内流不同所致.     

Growth factors,signal transduction,and cellular responses

The extraordinary advances in the field of growth factors and signal transduction have created new and promising therapeutic interventions. We intend to explain the difficult nomenclatures associated with growth factors and their mechanisms of action.     

Changes in activity of striato-thalamo-cortical network precede generalized spike wave discharges

The pathophysiology of generalized spike wave discharges (GSW) is not completely understood. Thalamus, basal ganglia and neocortex have been implicated in the generation of GSW, yet the specific role of each structure remains to be clarified. In six children with idiopathic generalized epilepsy (IGE), we performed combined EEG-fMRI to identify GSW-related changes in blood oxygen level-dependent (BOLD) signal in the striato-thalamo-cortical network. In all patients, within-subject analysis demonstrated BOLD signal changes that preceded the GSW. An increase in BOLD signal in the medial thalamus started 6 s before the onset of the GSW. Decreases in cortical BOLD signal were mainly found in frontoparietal areas and precuneus starting 6 to 3 s before the GSW. All patients showed a decrease in BOLD signal in the head of the caudate nucleus with a variable onset. The temporospatial pattern of BOLD signal changes suggests that GSW on the cortical surface is preceded by a sequence of neuronal events in the thalamo-cortical-striatal network. Approximately 6 s before the GSW, the thalamus shows an increase in neuronal activity along with regional decreases in cortical activity. These changes in thalamo-cortical activity are followed by a deactivation of the caudate nucleus. These early changes in BOLD signal may reflect changes in neuronal activity that contribute to the generation of GSW and may contribute to the transition from a normal to a generalized hypersynchronous pattern of neuronal activity. Our preliminary findings warrant further studies on a larger number of patients to explore the influence of age, medication and type of epileptic syndrome.     

High dose antithrombin III inhibits HMGB1 and improves endotoxin-induced acute lung injury in rats

Objective High mobility group box 1 (HMGB1) is an important factor in the development of sepsis. Previous work suggests that antithrombin III (ATIII) inhibits inflammation, but the mechanism of action is still poorly understood. Design and setting Prospective controlled animal study in a university laboratory. Materials Rats were randomly divided into a lipopolysaccharide (LPS)-induced sepsis control group and an ATIII-treated experimental group. Animals in the experimental group received a bolus of 250 units/kg of ATIII injected into the tail vein. Measurements and results Animals receiving high-dose ATIII (250 units/kg) had significantly improved lung histopathology and survival compared to the control rats. We measured serum and lung levels of various cytokines and HMGB1 at regular intervals from 0 to 12 h after the induction of sepsis and demonstrated lower HMGB1 levels over time in ATIII-treated animals. In an in vitro experiment, we stimulated the mouse macrophage cell line RAW 264.7 with LPS in the presence or absence of ATIII. Subsequent measurement of HMGB1 concentrations in the supernatant and cell signaling molecules in cell lysates revealed an ATIII dose-dependent decrease in HMGB1 release. Furthermore, inhibition of IkB and p42 phosphorylation was observed with the administration of ATIII, suggestive of downstream signaling pathways. Conclusions High-dose ATIII decreases lung pathology and reduces mortality in a rat sepsis model. This finding may be mediated by the inhibition of HMGB1. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Platelets Strongly Induce Hepatocyte Proliferation with IGF-1 and HGF In Vitro

BACKGROUND: It is well known that platelets have a thrombotic effect. However, platelets play an important role not only in hemostasis but also in wound healing and tissue regeneration. Platelets have been reported to accumulate in the liver and promote liver regeneration after an extended hepatectomy, but the mechanism is unclear. The present study was designed to clarify the mechanism by which platelets have a direct proliferative effect on hepatocytes in vitro. MATERIALS AND METHODS: Hepatocytes obtained from male BALB/c mice by collagenase digestion and immortalized hepatocytes (TLR2) were used. To elucidate the mechanism of the proliferative effect of platelets, DNA synthesis of hepatocytes was measured under various conditions and the related cellular signals were analyzed. Chromatographic analysis was also performed to clarify which elements of platelets have mitogenic activity. RESULTS: DNA synthesis significantly increased in the hepatocytes cultured with platelets (P < 0.001). However, when the platelets and hepatocytes were separated, the platelets did not have a proliferative effect. Whole disrupted platelets, the supernatant fraction, and fresh isolated platelets had a similar proliferative effect, while the membrane fraction did not. After the addition of platelets, both Akt and extracellular signal-regulated kinases ERK1/2 were activated, but extracellular signal-regulated kinase STAT3 was not activated. Some mitogenic fractions were obtained from the platelet extracts by gel exclusion chromatography; the fractions were rich in hepatocyte growth factor and IGF-1. CONCLUSIONS: Direct contact between platelets and hepatocytes was necessary for the proliferative effect. The direct contact initiated signal transduction involved in growth factor activation. Hepatocyte growth factor, vascular endothelial growth factor, and insulin-like growth factor-1, rather than platelet-derived growth factor, mainly contributed to hepatocyte proliferation.