A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low‐density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium‐dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC‐induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC‐inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC‐triggered Ca2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC‐induced caspase 3 activation and alleviate LPC‐inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation. 相似文献
背景与目的:甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和桥本甲状腺炎(Hashimoto’s thyroiditis,HT)的发病率均呈上升趋势,两者之间的关系已成为目前研究的热点。探讨PTC和HT之间的关系。方法:回顾性分析2014—2015年期间在中国科学院大学附属肿瘤医院头颈肿瘤外科行甲状腺癌手术治疗的首诊患者306例,术后病理学检查均明确诊断为PTC,其中术后病理学确诊伴发HT者42例,比较伴发HT与未伴发HT患者的临床病理学特征。结果:PTC患者女性发病年龄高于男性(46.2岁 vs 41.9岁)。相较于与未伴发HT的PTC患者,伴发HT的患者中女性比例更高(93% vs77%),中央区淋巴结数目较多[(5.0±3.4)枚 vs (2.5±2.7)枚],术前促甲状腺激素(thyroid-stimulating hormone,TSH)水平较高[(3.28±1.91)μU/mL vs (2.12±1.29)μU/mL],术前抗甲状腺过氧化物酶抗体(thyroid peroxidaseantibody,TPOAb)阳性率较高(55% vs 14%),术前甲状腺球蛋白抗体(thyroglobulin antibodies,TgAb)阳性率较高(69% vs 13%)。发生中央区淋巴结转移的患者中,中央区淋巴结转移数目与中央区淋巴结总数显著相关(Pearson相关系数=0.582)。多因素logistic回归分析发现,男性、低龄、被膜侵犯是PTC患者中央区淋巴结转移的独立危险因素。结论:伴发HT对PTC患者的预后无显著影响。伴发HT的PTC患者TSH水平显著偏高,提示HT可能是PTC发病风险因素之一。中央区淋巴结转移数目与中央区淋巴结总数相关,推测PTC淋巴结转移可能与淋巴结炎症反应相关。 相似文献
OBJECTIVE: Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS: Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS: The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS: Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering. 相似文献
Summary: Linear unsaturated nylons 6 u18 and 18 u18 have been made containing a double bond in the center of the diacid segment with potential for additional functionalization. Solution state NMR showed the presence of a small portion of cis amide units. Solid state NMR verified the presence of the double bond in the bulk, and that the polyamides were present in the α‐crystalline form. Thermal stability was comparable to linear saturated nylons, and the melting and crystallization temperatures of the unsaturated nylons were lower compared to the saturated analogs.
DSC heating and cooling thermograms for nylons 6 u18 and 18 u18. 相似文献
Chronic pelvic pain (CPP) is a common condition in women that is difficult to diagnose. Although heritability estimates have been published for some conditions potentially underlying pelvic pain, the heritability of CPP itself has never been investigated. Using data from 623 MZ and 377 DZ female twin pairs aged 29–50 from an Australian twin cohort, we found an increased CPP concordance among MZs compared to DZs, with tetrachoric correlations of 0.43 (95% CI: 0.26–0.58) and 0.11 (95% CI: –0.16–0.38), respectively. This corresponded to a heritability of 0.41 (95% CI: 0.25–0.56). Lack of correlations with environmental indicators suggested that violation of the equal environments assumption was not responsible for this effect. Multivariate Cholesky decomposition models incorporating CPP and significantly correlated phenotypes showed that the entire CPP heritability could be explained by genetic variance underlying endometriosis (38%), dysmenorrhoea (23%), fibroids (24%), and somatic distress (15%), the latter a possible indicator of increased nociception. CPP itself is unlikely to be a useful independent phenotype to conduct genetic aetiological studies; contributing conditions such as endometriosis and variation in nociception are likely to provide more useful phenotypes. 相似文献