Although the autophagic effect and mechanism of spermidine have been reported, the role of spermidine-induced autophay in cancer cell survival has not been fully elucidated yet. In the present study, we aim to investigate the effect and toxic mechanism of spermidine on cell survival using Hela cells, a cervical cancer cell line as a model. Cell viability was assessed by MTT assay. LDH leakage was determined using a LDH assay kit. Mitochondria membrane potential (MMP) was measured by flow cytometry. LC3 conversion and p62 expression were evaluated by western blot analysis. MTT assay revealed that spermidine decreased the viability of Hela cells in a dose-dependent manner in conjunction with disrupted morphology. Moreover, spermidine caused cell damage as evidenced by elevated LDH leakage and compromised MMP as demonstrated by flow cytometry. Concomitantly, western blot analysis showed that spermidine induced autophagy by activating the LC3 conversion and p62 degradation at different concentrations and durations. However, inhibition of autophagy by 3-MA rescued the survival of Hela cells. This study demonstrated that the potential effect of spermidine on decreasing the survival of Hela India cells is attributable to autophagy induction.
Background Mitomycin (MMC) has been frequently used as the compound for intravesical treatment. The relatively new pyrimidine analog gemcitabine (GEM) has exhibited anticancer effect on various solid cancers, such as the advanced bladder cancer. In this study, the GEM and MMC in treating non-muscle invasive bladder cancer (NMIBC) cases was compared through systemic review. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the electronic databases, including Embase, PubMed, Chinese biomedicine literature database, the Cochrane Library, the National Institute for Health and Clinical Excellence, NHS Evidence, Chinese technological periodical full-text database, and Chinese periodical full-text database, were systemically reviewed from inception to October 2018. Then, the RevMan 5.0 software was applied for data analysis. Five randomized controlled trials (RCTs) involving a total of 335 patients were included. Results For MMC group, the recurrence rate in the mitomycin arm increased compared with that in GEM group (OR = 0.44 95% CI [0.24, 0.78]), and the difference was statistically significant between the two groups. GEM was associated with reduced incidence of chemical cystitis compared with that of MMC (OR = 0.23 95% CI [0.12, 0.44]). Differences in hematuria (OR = 0.46 95% CI [0.16, 1.31]), skin reaction (OR = 0.49 95% CI [0.14, 1.70]) and liver and kidney function damage (OR = 0.51 95% CI [0.09, 2.85]) displayed no statistical significance between the two groups. Conclusion Findings in our study demonstrate the superior efficacy of GEM over MMC in reducing the relapse rate among NMIBC patients following transurethral resection (TUR). In addition, GEM is associated with reduced local toxic effects on the bladder compared with those of MMC. However, more future studies are needed to examine GEM safety when used as the monotherapy or polytherapy for bladder patients. More RCTs with high quality are also required to validate our findings due to the limitations of the current meta-analysis.
It is well-documented that lead (Pb) toxicity can affect almost all systems in living organisms. It can induce selective autophagy of mitochondria (mitophagy) by triggering reactive oxygen species production. Emerging evidence has suggested that Pb-induced autophagy can also be activated by the endoplasmic reticulum (ER) stress pathway. However, the interplay between ER stress and mitophagy remains to be elucidated. In this study, human embryonic kidney HEK293 cells were employed to investigate the role of ER stress in Pb-induced mitophagy. The results showed that the cell viability was decreased and cell damage was induced after exposure to Pb (0, 0.5, 1, 2, and 4 mM) for 24 h in a dose-dependent manner. Moreover, the expression of LC3-Ⅱ was significantly increased, and the expression of HSP60 was dramatically decreased after exposure to 1 mM and 2 mM Pb, indicating the induction of mitophagy following Pb exposure. Meanwhile, the expressions of activating transcription factor 6, inositol-requiring protein-1α, CCAAT/enhancer binding protein homologous protein, and glucose-regulated protein 78 were dramatically increased after Pb treatment, signifying the initiation of ER stress. Notably, the mitophagic effect was significantly compromised when ER stress was inhibited by 0.5 mM 4-phenylbutyrate, which was evidenced by lesser decreases in HSP60 expression and level of LC3-Ⅱ, suggesting Pb-induced mitophagy may be activated by the ER stress. Taken together, these findings provide a better understanding of Pb toxicity and suggest that Pb-induced ER stress may play a regulatory role in the upstream of mitophagy.
目的 研究甘肃地区不育男性患者的精液质量状况.方法 采用计算机辅助精液分析技术,参照《人类精液及精子-宫颈粘液相互作用实验室检验手册》5版标准,回顾性分析2009年7月至2014年10月来我院就诊的6325例男性不育患者的精液进行分析.结果 6325份精液标本中,精液量(2.96±1.27)ml,pH值(7.44±0.33),精子浓度(75.01±65.58)×106/mL,精子活力(63.06±27.19)%,前向运动(PR)精子百分率为(46.14±23.07)%.参数正常的精液标本有3971份,约占62.78%;参数异常的精液标本有2354份,约占37.22%.结论 甘肃地区男性不育患者精液参数异常主要表现为弱精子症、少精子症和畸精子症,对不育男性进行精液分析,可以为男性不育的病因诊断和治疗提供有力的参考.
Inhalable environmental pollutants induce pulmonary malfunction, which alters thoracoabdominal respiratory conditions. Traditional methods of recording pressure differences or existing machine vision analyses for detecting respiratory abnormalities are not suitable for synchronous thoracic and abdominal respiratory detections. The present study provides a new method that combines a model of thoracoabdominal localization and distribution based on respiratory physiological characteristics and a machine vision analysis on respiratory conditions in mice exposed to aqueous aerosol containing cadmium with classical symptoms. Thoracoabdominal respirations of mice were similar to male humans based on thoracic and abdominal composite respiration and the primarily presented abdominal respiration. Under environmental inhalable cadmium doses (1, 3, 5 mM CdCl2 in solution respectively atomized to be 112.41, 337.23, 562.05 μg/g Cd/Aerosol), the pathological thoracoabdominal respirations of mice showed that abdominal respiration contributed more to respiratory compensation and presented greater adaptive adjustments and more obvious fluctuations during lung injury than thoracic respiration, which suggests that toxic aerosol from a high-risk work environment quickly induces discernible respiratory clinical manifestations in occupational groups, as a warning for health, and abdominal obesity is unfavorable for male respiratory compensation. The respiratory abnormality shown in machine vision analysis was verified in pulmonary structural changes and hypoxia stress. Conclusively, the present method may be used to test the effects of aerosols on respiratory state and provides new prospects for toxicity determinations and risk evaluations of aerosols in the respiratory system in vivo.
1 病例报告 患者男性,38岁,主因"间断性全程肉眼血尿3月"于2009年10月入院,有条索状血凝块,并伴有排尿不畅.查体无明显阳性体征.肾 CT (computed tomography ,CT )见:右肾中上级混杂密度影实质部分呈不均匀中度强化,静脉期强化更明显;仍低于正常肾皮质.尿液有形成分分析:红细胞4 558个/μL ,正常红细胞100%.术前诊断为右肾肿瘤,行根治性右肾切除术.术后病理示:(右)肾乳头状肾细胞癌(papillary renal cell carcinoma ,PRCC)2型,大小约6 cm×4 cm .侵及肾盂,未突破被膜,输尿管断端未见肿瘤.术后使用人白介素半年并定期复查. 2015年3月复查CT :右肾缺如,右侧第十二肋可见骨质破坏并局部软组织肿块,下腔静脉后软组织密度影并腹主动脉旁及腹股沟增大的淋巴结影,多考虑转移.追问病史患者右侧腰部疼痛5月.右肾区可触及一约6 cm×4 cm大小肿物,遂入院行肿物穿刺活检.活检病理:腹壁肿物为纤维、脂肪及横纹肌组织,其间有少量慢性炎症细胞浸润.其后患者拒绝进一步诊疗,也未定期随访.
国际糖尿病联盟最新数据显示,2014年全世界有3.87亿糖尿病患者.其中在高收入国家,2型糖尿病占85%~95%,在中等收入和低收入国家可能更高.预计到2035年,糖尿病患病人数将增长55%,达到6亿[1].近年来许多研究发现,男性迟发性性腺功能减退症(late-onset hypogonadism,LOH)在2型糖尿病患者中的患病率明显高于非糖尿病人群,尤其在身体质量指数(body mass index,BMI)高的人群[2].LOH是指中老年男性随着年龄增加而睾酮水平进行性下降,血清睾酮水平低于健康青年男性的正常范围,并出现一系列雄激素部分缺乏的相应临床症状和体征的综合征[3].
阴茎勃起功能障碍(erectile dysfunction,ED)是指阴茎不能达到和(或)维持足够的勃起以获得满意的性生活,并且时间持续3个月以上者[1],已逐渐成为困扰全球男性的重要疾病之一.近年来,对阴茎勃起的基础研究取得了很大的突破,其中一氧化氮-环鸟苷磷酸(NO/cGMP)通路是目前与阴茎勃起相关最为经典、研究最为深入的分子信号通路,以NO/cGMP通路调控作用为基础的5型磷酸二酯酶(phosphodiesterase type 5,PDE5)抑制剂药物治疗ED已经应用到临床并且取得了很好的疗效.然而,尽管在这一领域的相关研究已经取得了显著的进步,但是充分的认识和理解一氧化氮(nitric oxide, NO)、一氧化氮合酶(NO synthase,NOS)在勃起功能的生理状态和病理状态的作用及相关调节机制仍然具有一定的意义,即在探索这些机制的过程中,发现潜在的治疗靶点,并将之充分的利用到临床,达到治疗的目的,为广大男性ED患者带来更加多元的治疗手段.现将NO及NOS在勃起功能中的作用和相关调节机制做一综述,为进一步的研究阐明理论基础.
淋病是一种由淋病奈瑟菌感染引起的性传播疾病,临床表现主要为泌尿生殖道感染,如不及时诊断和治疗往往会引起严重的并发症.实验室的检测在淋病的诊断和治疗中具有十分重要的作用.近年来,随着PCR技术的迅速发展,快速、敏感、特异性高的核酸扩增试验已经成为实验室检测的重要手段.本文就核酸扩增试验在淋病诊断和治疗后诊断的最新研究进展加以综述,期盼能够为淋病的诊疗提供新的方法.
Approximately 2,300 genes are found to be associated with spermiogenesis and their expressions play important roles in the regulation of spermiogenesis. In recent years, more and more attention has been focused on the studies of the genes associated with oligospermia, asthenospermia and teratospermia and their molecular mechanisms. Some genes, such as GSTM1, DNMT3L, and CYP1A1, have been shown to be potentially associated with oligospermia; some, such as CATSPER1, CRISP2, SEPT4, TCTE3, TEKT4, and DNAH1, with asthenospermia; and still others, such as DPY19L2 and AURKC, with teratospermia. These findings have provided a molecular basis for the studies of the pathogenesis of oligospermia, asthenospermia and teratospermia, as well as a new approach to the exploration of new diagnostic and therapeutic techniques.
迟发性性腺功能减退(late-onset hypogonadism, LOH)是一种与年龄增长相关的临床和生物化学综合征,又称为年龄相关的睾酮缺乏综合征,是指老年男性血睾酮水平低于正常年轻男性参考值,伴随有体能下降、性功能障碍及心理障碍等睾酮不足的临床表现,并逐渐导致生活质量下降和多器官的损害[1]。随着我国步入老龄化社会,作为严重影响中老年男性生活质量和健康的重要疾病之一,LOH已成为研究的热点和难点,近年来LOH的相关研究取得许多进展。