Phenothiazines alter plasma membrane properties and sensitize cancer cells to injury by inhibiting annexin-mediated repair

Repair of damaged plasma membrane in eukaryotic cells is largely dependent on the binding of annexin repair proteins to phospholipids. Changing the biophysical properties of the plasma membrane may provide means to compromise annexin-mediated repair and sensitize cells to injury. Since, cancer cells experience heightened membrane stress and are more dependent on efficient plasma membrane repair, inhibiting repair may provide approaches to sensitize cancer cells to plasma membrane damage and cell death. Here, we show that derivatives of phenothiazines, which have widespread use in the fields of psychiatry and allergy treatment, strongly sensitize cancer cells to mechanical-, chemical-, and heat-induced injury by inhibiting annexin-mediated plasma membrane repair. Using a combination of cell biology, biophysics, and computer simulations, we show that trifluoperazine acts by thinning the membrane bilayer, making it more fragile and prone to ruptures. Secondly, it decreases annexin binding by compromising the lateral diffusion of phosphatidylserine, inhibiting the ability of annexins to curve and shape membranes, which is essential for their function in plasma membrane repair. Our results reveal a novel avenue to target cancer cells by compromising plasma membrane repair in combination with noninvasive approaches that induce membrane injuries.     

超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值

摘要 目的：探讨超声造影定量分析联合血清甲胎蛋白（AFP）、血管内皮生长因子受体-2（VEGFR-2）、可溶性T细胞免疫球蛋白粘蛋白分子3（sTim-3）对原发性肝癌肝动脉化疗栓塞（TACE）治疗疗效的预测价值。方法：选择2020年1月至2022年10月海军军医大学第二附属医院收治的原发性肝癌患者94例。行TACE治疗2个月,采用改良的实体瘤疗效评价标准评估患者疗效,根据不同疗效分为疗效不良组（n=32）和疗效良好组（n=62）。所有患者均行超声造影检查,比较两组超声造影定量分析参数、治疗前血清AFP、VEGFR-2、sTim-3水平,采用受试者工作特征（ROC）曲线分析超声造影定量分析参数联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值。结果：经TACE治疗,62例患者疗效良好、32例患者疗效不良,治疗有效率为65.96%。疗效良好组术前超声造影达峰时间、等增强开始时间显著长于疗效不良组（P<0.05）。疗效良好组术前血清AFP、VEGFR-2、sTim-3水平显著低于疗效不良组（P<0.05）。ROC曲线分析结果显示,超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效预测的曲线下面积（AUC）为0.950,灵敏度为84.85%,特异度为82.12%,高于各指标单独检测。结论：超声造影定量分析参数、血清AFP、VEGFR-2、sTim-3水平可预测原发性肝癌患者TACE治疗的疗效,且联合诊断的预测效能更高。     

探讨女性盆底功能障碍性疾病的相关因素及盆底超声测定压力性尿失禁SUI的临床意义

目的:探讨女性盆底功能障碍性疾病的相关因素及盆底超声测定压力性尿失禁SUI的临床意义。方法:选取我院2019年-2020年共收治的63例盆底功能障碍性疾病患者作为研究对象,将其分为研究组,另取同期来我院进行体检的63例健康女性作为对照组,对所有女性应用盆底超声检测,对比两组女性静息状态下和Valsalva状态下的盆底超声检查指标,对通过问卷调查方式,调查两组女性的一般临床治疗,对于女性盆底功能障碍性疾病的相关因素进行单因素分析与多因素分析,最终得出盆底肌功能障碍性疾病的相关因素。结果:在静息状态下通过盆底超声发现,研究组与对照组膀胱尿道后角、肛提肌裂孔面积、尿道倾斜度对比差异显著(P<0.05),两组女性膀胱颈位置、膀胱位置对比无明显差异(P>0.05);在Valsalva状态下通过盆底超声发现,研究组与对照组膀胱尿道后角、肛提肌裂孔面积、尿道倾斜度、膀胱颈位置、膀胱位置对比差异显著(P<0.05);两组女性年龄、BMI、孕次、产次、绝经情况以及白带清洁度是否≥Ⅲ度情况对比差异显著(P<0.05),两组女性子宫肌瘤史情况对比无显著差异(P>0.05);logistic回归分析结果显示,年龄、绝经情况、子宫肌瘤史和白带清洁度≥Ⅲ度不是盆底功能障碍性疾病的独立危险因素(P>0.05),BMI、孕次、产次为盆底功能障碍性疾病的独立危险因素(P<0.05)。结论:盆底肌超声在对盆底功能障碍性疾病患者压力性尿失禁的诊断中具有重要价值,在静息状态下和Valsalva状态下发现患者的膀胱经移动情况与尿道倾斜情况。年龄、BMI、孕次、产次、绝经情况以及白带清洁度是否≥Ⅲ度可能与盆底功能障碍性疾病具有一定关系,BMI、孕次、产次为盆底功能障碍性疾病的独立危险因素。     

妊娠早期流产的阴道超声影像表现及与血清瘦素、ADAM12、CA-125水平的相关性研究

摘要 目的：探讨妊娠早期流产的阴道超声影像表现及与血清瘦素、融合素 -α（ADAM12）、糖类抗原 -125（CA-125）的相关性。方法：选取 2017年 7月 -2020年 9月于我院就诊的 419例具有早期先兆流产征象的孕妇患者,按妊娠结局分为妊娠早期流产组（流产组,61例）和正常早期妊娠组（正常组,358例）。所有患者均进行阴道超声检查,观察卵黄囊的大小和形态。测定胎儿冠臀长（CRL）、胎囊直径（GSD）、卵黄囊直径（YSD）和胎心率（FHR）。同时检测患者血清瘦素、ADAM12、CA-125水平。采用 Spearman秩相关分析评价阴道超声影像学表现与血清瘦素、ADAM12、CA-125水平的相关性。结果：正常组孕妇超声影像表现可见孕囊形态饱满,孕周和胎芽大小相符,可清晰显示原始心管、卵黄囊和胎心波动。流产组孕妇部分超声影像表现可见卵黄囊过大、过小或未见显示,胎芽略小,卵囊位置位于宫腔中下段,孕囊外形稍欠规则,同时可见原始心管或胎心波动。流产组孕妇平均 CRL、GSD、FHR均显著低于正常组,差异均有统计学意义（P＜0.05）;流产组患者平均 YSD稍低于常组,差异有统计学意义（P＜0.05）。流产组孕妇各孕周 CRL、GSD、FHR均显著低于正常组,差异均有统计学意义（P＜0.05）;流产组患者第 6-7周 YSD高于正常组、第8-9周和第 10-11周 YSD低于正常组,差异均有统计学意义（P＜0.05）。流产组患者血清瘦素、ADAM12水平明显低于正常妊娠组,差异有统计学意义（P＜0.05）,流产组患者血清 CA-125水平明显高于正常妊娠组,差异有统计学意义（P＜0.05）。妊娠早期流产患者阴道超声参数 CRL、GSD、FHR与血清瘦素、ADAM12呈正相关（P＜0.05）,与 CA-125水平呈负相关（P＜0.05）。结论：妊娠早期阴道超声及血清瘦素、ADAM12、CA-125可作为早期流产的有效预测因素,阴道超声参数 CRL、GSD、FHR与血清瘦素、ADAM12、CA-125水平具有相关性,临床可通过测定这些指标以提高妊娠早期流产预测的准确性。     

Fetal ultrasonography: Normal biometric ranges in the baboon (Papio hamadryas)

Normal biometric ranges for fetal growth in a captive breeding baboon (Papio hamadryas) colony are described. Measurements include crown-rump length, biparietal diameter, binocular distance, head circumference, abdominal circumference, femur length and amniotic fluid index. The pattern of fetal growth is compared with other baboon subspecies and man. The uses and limitations of such data for breeding colony management and optimum utilisation of experimentally derived data are discussed.     

柑橘凤蝶蛹发声器的显微结构及防御作用(英文)

【目的】动物界存在多种用于对抗捕食者的防御机制。一些鳞翅目昆虫的蛹在受到机械刺激时会发出蠕动的声音。【方法】在扫描电镜下对柑橘凤蝶Papilio xuthus蛹的发声器形态特征进行观察,并使用Audacity软件对捕获的声音进行特征分析。【结果】柑橘凤蝶蛹在腹部第4-5节和第5-6节之间的节间膜上存在发声器,有规律地发出嘶嘶声。发声器由多层甲壳素构成的刮器和板组成,刮器和板上有 50~90个突起。当蛹的腹部被寄生蜂触角刺激30 s以上时,刮器和板会迅速相互摩擦,腹部反复摆动发出声音。蛹发出的声音是由一系列每2 000~3 000 ms发生3次的短脉冲组成的。频带很宽,主要分布在5~20kHz范围内。新鲜蛹和越冬蛹的活性不同,声强也不同。【结论】本研究首先描述了柑橘蝴蝶蛹发声器的结构,结果支持了一些蝴蝶蛹对寄生生物进化出一种特殊的防御机制(声学防御)的假说。此外,通过比较两种生境的柑橘凤蝶蛹的声波特征,我们提出了同一物种在不同地理区域可以产生方言的假说。 关键词:     

Ultrasound promoted green synthesis,anticancer evaluation,and molecular docking studies of hydrazines: a pilot trial

We reported herein an efficient, environmentally friendly synthesis of hydrazine carboxamides (6a–l) in a water-glycerol (6:4) solvent system using ultrasonic irradiation. Ultrasonicated reactions were found to be much faster and more productive than conventional synthesis. The prepared compounds (6a–l) were tested against nine panels of 60 cancer cell lines according to the National Cancer Institute (NCI US) protocol. N-(4-Chlorophenyl)-2-(2-oxoindolin-3-ylidene)hydrazine-1-carboxamide (6b) was discovered to be promising anticancer agents with higher sensitivity against CCRF-CEM, HOP-92, UO-31, RMPI-8226, HL-60(TB), and MDA-MB-468 with percent growth inhibitions (%GIs) of 143.44, 33.46, 33.21, 33.09, 29.81, and 29.55 respectively. Compounds (6a–l) tested showed greater anticancer activity than Imatinib, except for compound 6k. Compounds 6b and 6c were found to be lethal on the CCRF-CEM leukaemia cell line, with %GIs of 143.44 and 108.91, respectively. Furthermore, molecular docking analysis was performed to investigate ligand binding affinity at the active site of epidermal growth factor (EGFR).     

Simpler is better: fewer non‐target insects trapped with a four‐component chemical lure vs. a chemically more complex food‐type bait for Drosophila suzukii

Baits – fermented food products – are generally attractive to many types of insects, which makes it difficult to sort through non‐target insects to monitor a pest species of interest. We test the hypothesis that a chemically simpler and more defined attractant developed for a target insect is more specific and attracts fewer non‐target insects than a chemically more complex food‐type bait. A four‐component chemical lure isolated from a food bait and optimized for the spotted wing drosophila (SWD), Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), was compared to the original wine/vinegar bait to assess the relative responses of non‐target insects. In several field experiments in Washington State, USA, it was shown that numbers of pest muscid flies, cutworm and armyworm moths, and pest yellowjackets were reduced in traps baited with the chemical lure compared to the wine/vinegar bait. In other field experiments in the states of Washington, Oregon, and New York, numbers of non‐target drosophilid flies were also reduced in traps baited with the chemical lure relative to wine/vinegar bait. In Washington, numbers of Drosophila melanogaster Meigen and Drosophila obscura Fallen species groups and Drosophila immigrans Sturtevant were reduced in the chemical lure traps, whereas in New York, D. melanogaster and D. obscura species groups, D. immigrans, Drosophila putrida Sturtevant, Drosophila simulans Sturtevant, Drosophila tripunctata Loew, and Chymomyza spp. numbers were reduced. In Oregon, this same effect was observed with the D. melanogaster species group. Taken together, these results indicate that the four‐component SWD chemical lure will be more selective for SWD compared to fermentation baits, which should reduce time and cost involved in trapping in order to monitor SWD.     

聚焦超声消融治疗子宫小肌瘤的疗效评价

摘要 目的：探讨聚焦超声消融治疗无症状子宫小肌瘤的临床价值。方法：采用对照回顾性研究,将2011年03月至2018年03月在遂宁市中心医院妇科收治入院行聚焦超声消融治疗的无症状的子宫小肌瘤患者设置为治疗组,将同期未经任何治疗的门诊随访的无症状子宫小肌瘤患者设置为对照组,比较两组在6个月、12个月、18个月、24个月后子宫肌瘤的体积变化、是否出现临床症状及妊娠情况。结果：治疗组在聚焦超声消融治疗后6个月、12个月、18个月、24个月,随着时间的推移,子宫小肌瘤的体积较治疗前逐渐缩小,均未出现临床症状;对照组子宫小肌瘤的体积逐渐增大,并出现临床症状;治疗组和对照组24个月内的妊娠率分别为17.48%和8.42%,比较两组差异有统计学意义(P＜0.05)。聚焦超声消融治疗后无严重并发症发生。结论：对于孕龄期有生育要求的黏膜下或肌壁间的无症状子宫小肌瘤患者,可行聚焦超声消融手术缩小病灶,维持子宫腔的正常形态,避免或延迟临床症状的出现,提高妊娠率。