Synaptic connections from large afferents of wrist flexor and extensor muscles to synergistic motoneurones in man

 Short-latency excitatory Ia reflex connections were determined between pairs of human wrist flexor and extensor muscles. Spindle Ia afferents were stimulated by either tendon tap or electrical stimulation. The activity of voluntarily activated single motor units was recorded intramuscularly from pairs of wrist flexor or extensor muscles. Cross-correlation between stimuli and the discharge of the motor units provided a measure of the homonymous or heteronymous excitatory input to a motoneurone. Homonymous motoneurone facilitation was generally stronger than that of the heteronymous motoneurones. The principal wrist flexors, flexor carpi radialis (FCR) and flexor carpi ulnaris (FCU), were tightly connected through a bidirectional short-latency reflex pathway. In contrast, the extensor carpi ulnaris (ECU) and the extensor carpi radialis (ECR) did not have similar connections. ECU motoneurones received no short-latency excitatory Ia input from the ECR. ECR motoneurones did receive excitatory Ia input from ECU Ia afferents; however, its latency was delayed by several milliseconds compared with other heteronymous Ia excitatory effects observed. The wrist and finger extensors were linked through heteronymous Ia excitatory reflexes. The reflex connections observed in humans are largely similar to those observed in the cat, with the exception of heteronymous effects from the ECU to the ECR and from the extensor digitorum communis (EDC) to the ECU, which are present only in humans. The differences in the reflex organization of the wrist flexors versus the extensors probably reflects the importance of grasping. Received: 19 August 1996 / Accepted: 6 March 1997     

Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients

The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.     

Hydrogen peroxide-induced Ca responses in CNS pericytes

Objective: The aims of the present study were to elucidate the interaction of reactive oxygen species (ROS) and Ca²⁺ response in central nervous system (CNS) pericytes. Methods: The intracellular Ca²⁺ concentration was measured using fluorescent Ca²⁺ indicator, fura-2, in cultured CNS pericytes. Results: Hydrogen peroxide evoked a dose-dependent increase in cytosolic Ca²⁺, which was completely inhibited by catalase. Removal of external Ca²⁺ or addition of nicardipine (1 μM) during application of hydrogen peroxide did not affect Ca²⁺ response. Incubation of the cells in Ca²⁺ free solution did not abolish but slightly reduced Ca²⁺ response by hydrogen peroxide. Ca²⁺ response to hydrogen peroxide was not altered by the depletion of intracellular Ca²⁺ by thapsigargin (1 μM). Pretreatment of the cells with tyrosine kinase inhibitor genistein (100 μM) or tyrphostin A47 (30 μM) significantly reduced Ca²⁺ increase by hydrogen peroxide. Conclusions: These results indicate that hydrogen peroxide evokes Ca²⁺ increase predominantly by release from intracellular Ca²⁺ store, which may be regulated by tyrosine kinases.     

A possible paracellular route for the resolution of hydrocephalic edema

Summary Considering the possibility of a paracellular route for edema resolution we studied the microvasculature of the subependymal and subcortical white matter in hydrocephalic rats. Normal adult rats were used as controls. After injection of kaolin suspension into the cisterna magna, the animals were killed at intervals of 1, 2, 4, and 8 weeks. In hydrocephalic rats at 1 week after kaolin injection, widening of the interendothelical cleft between the tight junction (dehiscence) was seen in 27 of 76 (35%) vessels. At 2 weeks after kaolin injection, the number of the dehiscences had increased (39/7:56%) and some were enlarged, forming interendothelial blisters. At 4 weeks in hydrocephalic rats, both dehiscences and blisters were still prominent (45/7363%) and at 8 weeks the dehiscences were still prominent, but the number of the blisters had decreased (25/8131%). The blisters and dehiscences were most pronounced in the corpus callosum and occipital regions. Following i.v. injection of horseradish peroxidase, the interendothelial dehiscences and blisters were completely devoid of the marker substance. These findings indicate that in obstructive hydrocephalus the tight junctions may constitute part of a paracellular pathway for the resorption of interstitial edema fluid.     

芍药汤及其加减方治疗溃疡性结肠炎的研究进展

芍药汤由黄连、黄芩、大黄、白芍、当归、木香、槟榔、肉桂,甘草构成。因其具有清热利湿、调气活血功效,后世医家皆推此方为治疗湿热泄痢之主方。现代临床应用中,除芍药汤原方,其加减方亦用于溃疡性结肠炎治疗,并可与其他方剂（痛泄要方、白头翁汤、参苓白术散等）、西药（美沙拉嗪、柳氮磺吡啶、英夫利昔单抗等）、中医针刺或艾灸等特色疗法联用。临床疗效结果显示芍药汤及其加减方能明显降低梅奥内镜（Mayo）评分、结肠黏膜病变（Baron）评分、中医证候积分等疾病评分,改善患者肠道症状效果显著且不良反应少。实验药理学研究显示芍药汤可通过抑制肿瘤坏死因子-α(TNF-α)、核转录因子-κB(NF-κB)、白细胞介素-1β(IL-1β)等促炎因子表达,上调白细胞介素-10(IL-10)等抑炎因子来减轻炎症反应;可通过调节炎症信号通路,阻断连环反应,减少细胞凋亡;可通过调节免疫轴平衡、调节免疫蛋白修复异常免疫屏障;可调节肠道菌群平衡、促进肠上皮细胞再生、改善黏膜通透性,从而恢复肠道内环境平衡以达到治疗溃疡性结肠炎的效果;其药物单体黄芩苷、芍药苷、黄连素等可起到抗炎、抗菌、调节代谢等作用。该文就芍药汤治疗溃疡性结肠炎...     

枳实-白术调节PINK1/Parkin信号通路介导的线粒体自噬改善慢传输型便秘大鼠结肠动力障碍

目的：基于线粒体自噬及磷酸酶及张力蛋白同源物诱导的蛋白激酶1(PINK1)/帕金蛋白(Parkin)通路观察枳实、白术及其配伍对慢传输型便秘大鼠结肠动力障碍的改善作用,为临床精准用药提供理论参考。方法：将56只雄性SD大鼠按体质量随机分成正常组、模型组、自然恢复组、枳实组、白术组、枳实-白术组和莫沙必利组,每组各8只。除正常组外,采用洛哌丁胺连续14 d灌胃(3 mg·kg^-1·d^-1)构建慢传输型便秘大鼠模型。造模成功后,除模型组继续洛哌丁胺诱导外,正常组和自然恢复组采用0.9%生理盐水灌胃,枳实组(1.35 g·kg^-1·d^-1)、白术组(2.7 g·kg^-1·d^-1)、枳实-白术组(4.05 g·kg^-1·d^-1)和莫沙必利组(1.56 mg·kg^-1·d^-1)大鼠分别给予相应的药物灌胃,连续7 d。观察药物对大鼠粪便数量、粪便含水率及小肠推进率的影响;苏木素-伊...     

薏苡附子败酱散对结肠癌细胞HCT116凋亡的影响及机制

目的：探究薏苡附子败酱散对结肠癌细胞HCT116凋亡的影响,并探讨其相关的细胞凋亡机制。方法：不同质量浓度(0.5、1、2、4、6、8、10、12、14、16 g·L^-1 )薏苡附子败酱散干预结肠癌细胞24、48、72 h,细胞增殖与活性检测-8(CCK-8)法检测细胞体外增殖的影响;设空白组、卡培他滨组(1.8 g·L^-1 )和薏苡附子败酱散组(6、10、14 g·L^-1 ),分别处理48 h,采用流式细胞技术检测细胞凋亡率,Hochest 33342荧光染色观察细胞凋亡形态,线粒体红色荧光探针(Mito-Tracker Red CMXRos)分析线粒体膜电位(MMP)变化,蛋白免疫印迹法(Western blot)检测线粒体凋亡途径相关蛋白B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、细胞色素C(Cyt C)、胱天蛋白酶(Caspase)-9、Caspase-3、活化的(cleaved) Caspase-9、cleaved Caspase-3的表达水平,实时荧光定量聚合酶链式反应(Real-time...     

杜仲及其有效成分治疗膝骨关节炎的作用机制研究现状

膝骨关节炎（KOA）是中老年常见的退行性关节疾病,发病率随着人口老龄化程度加深及肥胖人群增加而不断增加,严重影响患者健康及日常生活。目前采用的非甾体类抗炎药、软骨保护类药物、阿片类镇痛药等对症治疗手段作用有限,且药物不良反应明显。杜仲是治疗KOA常用且有效的中药之一,但其作用机制和药效物质基础尚未明确,限制了其在临床更为广泛的运用。杜仲在KOA治疗领域的有效成分主要为环烯醚萜类（京尼平苷、杜仲苷/桃叶珊瑚苷）、木脂素类（松脂醇二葡萄糖苷）、黄酮类（槲皮素、紫云英苷、黄芩素、金丝桃苷、山柰酚）、苯丙素类（绿原酸）、杜仲多糖等化合物,他们主要通过丝裂原活化蛋白激酶、核转录因子-κB、磷脂酰肌醇3-激酶/蛋白激酶B及等Janus激酶1/信号转导和转录激活因子3等信号通路,来调节炎性因子水平、抗氧化应激反应、保护软骨细胞、平衡细胞外基质合成与降解等,控制KOA病情进展。该文对杜仲及其有效成分在KOA治疗方面的作用机制进行了综述,以期为KOA新药研发提供理论依据。     

中药调控膝骨关节炎相关信号通路的研究进展

随着中医药对膝骨关节炎（KOA）研究的不断深入,现代学者发现诸多中药可从分子层面干预信号通路延缓膝骨关节炎的进展。文中所述中药及其活性成分在干预膝骨关节炎的机制中与信号通路有着密切关系。中药及有效成分可在不同信号通路的传导下调控相应的靶向分子水平,抑制软骨炎性因子、细胞凋亡、软骨基质降解及促进软骨细胞自噬,以达到减轻滑膜炎性水肿和延缓软骨退变的目的。现对国内外中药干预KOA的研究进行系统性总结：黄芩素等可通过阻断磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路,减少软骨细胞炎性因子、凋亡及促进自噬;山茱萸新苷Ⅰ等成分降低Janus激酶2/信号转导和转录激活因子3（JAK2/STAT3）通路磷酸化活性改善滑膜炎症、延缓软骨基质退变;丹酚酸A等中药活性成分可通过抑制核转录因子-κB（NF-κB）通路磷酸化,减轻炎症与软骨基质降解;大黄素等有效成分可降低Wnt/β-连环蛋白（Wnt/β-catenin）通路活性,抑制胶原蛋白与蛋白多糖分解;肉豆蔻苷等通过阻断p38丝裂原活化蛋白激酶（p38 MAPK）信号传导,抑制细胞凋亡;木通皂苷D等可增强核因子E₂相关因子2/血红素加氧酶1（Nrf2/HO-1）通路活性,抑制软骨细胞氧化应激;牛膝总皂苷等通过增强转化生长因子-β（TGF-β）/Smad信号传导,减少软骨基质降解;藏红花素通过激发河马/Yes相关蛋白（Hippo/YAP）活性抑制软骨炎症与凋亡因子增加;川芎嗪阻断Notch通路改善软骨细胞形态与异常;齐墩果酸等通过发挥雌激素信号通路,减轻软骨基质破坏与退变。以上总结旨在为今后开展KOA临床与实验研究提供借鉴。