Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

Is Atrial Fibrillation a Risk Factor for Gastroesophageal Reflux Disease Occurrence?

Recent studies have reported an association between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF). The objective of the present study was to evaluate whether AF is one of the risk factors for GERD occurrence.In this hospital-based, retrospective, case–control study, the patients were classified into 2 groups. The patients diagnosed with new AF were assigned to the AF group (n = 1612); those diagnosed without AF and GERD were assigned to the control group (n = 1612). The subjects in the control group were selected from outpatients of total healthcare center without a history of AF or GERD, and matched for age and gender. We evaluated the incidence of GERD and risk factors for GERD occurrence between the 2 groups.The number of patients experiencing occurrence of GERD during the follow-up period was significantly higher in the AF group than those in the control group, respectively (129 patients vs 98 subjects, P = 0.037). The incidence of GERD was significantly higher in the AF group than in the control group by Kaplan–Meier analysis with log-rank test (P = 0.008). The AF group''s adjusted hazard ratio of GERD occurrence against that of the control group was 1.37 (95% confidence interval [CI]: 1.16–1.57; P = 0.009) according to Cox''s proportional hazard model.The presence of AF appears to increase the incidence of GERD and may be considered a risk factor for the development of GERD. Further, large prospective and cohort studies will be required to better establish the correlation of GERD with AF.     

Intravenous Thrombolysis Is Safe and Effective for the Cryptogenic Stroke in China: Data From the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)

Background

The intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) therapy is safe and efficient during the treatment of acute ischemic stroke. Nonetheless, the different outcomes among various stroke subgroups have limited data with regard to the safety and efficacy of cryptogenic stroke (CS). The present study compared the safety and efficacy when IVT with rt-PA was used for the treatment of CS and the other stroke subtypes.

Ki-67表达与原发性肝癌根治性切除术后行预防性肝动脉化疗栓塞患者预后的关系

目的:探讨Ki-67表达与原发性肝癌根治性切除术后行预防性TACE患者预后的关系。方法:采用回顾性队列研究,收集2014年12月—2016年1月福建医科大学孟超肝胆医院150例行原发性肝癌根治性切除术并在术后2个月内行预防性TACE患者的临床病理资料,根据术后肝癌组织病理Ki-67评分分为为低表达组(Ki-67评分≤20%,44例)和高表达组(Ki-67评分20%,106例);分析Ki-67表达量与患者临床病理因素及复发与生存的关系。结果:高表达组肿瘤多发、肿瘤包膜不完整及合并微血管癌栓患者比例明显高于低表达组(均P0.05)。Ki-67高表达与肿瘤多发、肿瘤直径大为影响无瘤生存期的独立危险因素(均P0.05);Ki-67高表达与肿瘤多发、肿瘤直径大、肿瘤包膜不完整、合并微血管癌栓为影响总生存期的独立危险因素(均P0.05);高表达组患者复发率明显高于低表达组(57.9%vs. 37.7%,χ~2=6.777,P0.05),总生存率明显低于低表达组(45.6%vs. 75.9%,χ~2=8.447,P0.05)。结论:Ki-67的表达量对肝癌根治性切除术后行预防性TACE患者的预后有显著影响,高表达者预后不良。