MicroRNA-876-5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2

Aberrant expression of microRNA-876-5p (miR-876-5p) is implicated in the progression of multiple human cancers. However, the potential role of miR-876-5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR-876-5p in colorectal cancer. miR-876-5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain-of-function assays revealed that miR-876-5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR-876-5p target gene. A luciferase reporter assay confirmed that miR-876-5p directly binds to the 3′-untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR-876-5p in colorectal cancer cells. Notably, there was an inverse correlation between miR-876-5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR-876-5p was involved in regulating the activation of Yes-associated protein (YAP) signalling through inhibiting RASAL2. However, the miR-876-5p-mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR-876-5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR-876-5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR-876-5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR-876-5p is a potential therapeutic target for treating colorectal cancer.     

Autologous fat as a rectal–prostate spacer for prostate brachytherapy: Results at 6 months

PurposeImplanted rectal spacers (IRS) have been developed to increase the distance between the prostate and the rectum, thus optimizing dose escalation. Cost is a disadvantage and there are still uncertainties as to their durability. We have developed an autologous fat transfer (AFT) technique to use as an IRS. We aim to present the feasibility and durability at 6 months of AFT placed immediately after the implant of the seeds in low-dose-rate brachytherapy (BT).Methods and MaterialsThirty-five patients underwent AFT (12 were treated with primary BT, 7 with a combined primary treatment of external beam radiotherapy + BT, 16 with salvage BT). The isodose used for primary BT was 14400 cGy, 11,000 cGy after 4600 cGy of external beam radiotherapy in the combined group, and 14400 cGy for the salvage group. Patients underwent a CT scan at 1, 3, and 6 months to measure the distance between the rectum and the prostate.ResultsAn average of 32.7 cc (20–40) of fat was transferred successfully in 100% of cases. The mean distance to the rectum at the level of the base, middle, and apex at 1 and 6 months were 11.2, 9.7, and 7.6 mm; 8.3, 8.1, and 5.9 mm, respectively. No rectal toxicity or major complications were reported.ConclusionsThe use of fat as an IRS seems to be a valid alternative to reduce rectal toxicity after BT, achieving equivalent distances to synthetic IRS. It is feasible, safe, and the loss of distance at 6 months is small. Cost is lower than other alternatives.     

MiR-129-5p靶向抑制高迁移率族蛋白B1表达增加甲状腺髓样细胞MZ-CRC-1放射敏感性的实验研究

目的 探讨miR-129-5p靶向抑制高迁移率族蛋白B1（HMGB1）对甲状腺髓样细胞MZ-CRC-1放射敏感性的影响机制。方法 建立抗辐射细胞株MZ-CRC-1/R;克隆形成实验分析细胞存活分数;qRT-qPCR检测miR-129-5p在MZ-CRC-1和MZ-CRC-1/R细胞中的表达;噻唑蓝（MTT）法检测细胞活力;流式细胞术检测细胞凋亡;双荧光酶报告基因实验验证miR-129-5p与高迁移率族蛋白B1（HMGB1）之间的靶向关系;Western blot检测HMGB1和p-AKt的蛋白表达。结果 与MZ-CRC-1细胞相比,MZ-CRC-1/R细胞的细胞存活分数显著提高（t=3.038、4.330、4.885、4.568,P<0.05）;细胞活力增加（t=3.637、7.734、11.896、14.522,P<0.05）;与MZ-CRC-1细胞（1.00±0.06）相比,miR-129-5p在MZ-CRC-1/R细胞中的表达（0.26±0.03）显著降低（t=19.107,P<0.05）;与miR-NC-inhibitor组细胞相比,miR-129-5p-inhibitor组细胞的细胞活力显著增加（t=5.156、6.005、9.649,P<0.05）,细胞凋亡率降低（t=8.659,P<0.05）。与miR-NC组细胞相比,miR-129-5p mimic组细胞的细胞活力显著降低（t=3.118、5.034、6.005、7.488,P<0.05）,细胞凋亡率升高（t=6.362,P<0.05）;过表达miR-129-5p可抑制HMGB1及p-AKt信号通路的表达（t=9.325、10.614,P<0.05）;与miR-129-5p inhibitor组细胞相比,miR-129-5p inhibitor+si-HMGB1组细胞的细胞凋亡率显著升高（t=6.700,P<0.05）;与miR-129-5p mimic组细胞相比,miR-129-5p mimic+si-HMGB1组细胞的细胞凋亡率显著降低（t=7.073,P<0.05）。结论 miR-129-5p可靶向抑制HMGB1增加甲状腺髓样细胞MZ-CRC-1的放射敏感性。     

miR-124靶向STAT3改善脑恶性胶质瘤细胞辐射敏感性

目的 研究miR-124在放射敏感及耐受的脑恶性胶质瘤细胞LN229和LN229R中的表达以及miR-124对细胞放射敏感性的影响,并深入探讨miR-124调控LN229R细胞放射敏感性的作用机制。方法 将miR-124模拟物（miR-124）及阴性对照（miR-NC）,STAT3过表达质粒（STAT3）及pcDNA3.1质粒（pcDNA）单独或共转染到放射抵抗的胶质瘤细胞LN229R中。qRT-PCR检测LN229和LN229R细胞中miR-124的表达;克隆形成实验分析不同放射剂量下LN229R细胞的生存率以及敏感性相关参数值;流式细胞术分析LN229R细胞的凋亡情况;生物信息学预测miR-124和STAT3的靶向关系,并利用双荧光素酶报告分析加以验证;Western blot分析STAT3的蛋白表达水平。结果 与LN229组（1.02±0.09）相比,miR-124在LN229R细胞中的表达水平（0.32±0.03）显著降低,差异有统计学意义（t=12.780,P<0.05）;与miR-NC组（0.95±0.06）相比,转染miR-124模拟物可促进LN229R细胞中miR-124的表达（4.02±0.39）（t=13.476,P<0.05）;8 Gy照射条件下,miR-124过表达组癌细胞的生存率（0.003±0.000 4）显著低于miR-NC组（0.033±0.005 0）（t=5.655,P<0.05）,细胞凋亡率（22.34±2.42）%显著高于miR-NC组（4.69±0.51）%（t=12.361,P<0.05）;STAT3是miR-124的靶基因;外源回补STAT3可逆转miR-124对LN229R细胞生存的抑制作用。结论 miR-124通过靶向STAT3改善LN229R细胞的放射敏感性。     

HPLC法同时测定乙肝益气解郁颗粒中的11种成分

目的建立HPLC法同时测定乙肝益气解郁颗粒中柴胡皂苷a、柚皮苷、芍药苷、毛蕊异黄酮苷、丹参酮IIA、桂皮醛、五味子醇甲、紫丁香苷、盐酸小檗碱、大黄酚和橙皮苷的含量,并采用主成分分析(PCA)法对其质量进行综合评价。方法采用HPLC法,色谱柱为Caprisil C18-AQ(250 mm×4.6 mm,5.0μm);流动相为0.1%磷酸水溶液-乙腈,梯度洗脱,体积流量0.8mL/min;柱温45℃。最后将定量结果与PCA法相结合对不同批次药物进行科学的质量评价分析。结果乙肝益气解郁颗粒中柴胡皂苷a、柚皮苷、芍药苷、毛蕊异黄酮苷、丹参酮IIA、桂皮醛、五味子醇甲、紫丁香苷、盐酸小檗碱、大黄酚和橙皮苷11种成分分别在1.6～80.0、14～700、10～500、1.6～80.0、1.6～80.0、2.4～120.0、1.2～60.0、1.2～60.0、8.0～400.0、2.0～100.0、2.0～100.0μg/m L线性关系良好;平均加样回收率分别为98.3%、99.2%、98.8%、99.3%、101.9%、97.5%、99.8%、101.7%、101.1%、102.5%、100.9%,RSD均2.0%;16批样品中11种有效成分的质量分数分别为0.233～0.322、3.007～3.142、2.201～2.273、0.320～0.355、0.317～0.399、0.451～0.523、0.265～0.297、0.209～0.226、1.848～1.873、0.380～0.425、0.615～0.647mg/g。结论实验建立的方法简便准确、重复性好,可用于乙肝益气解郁颗粒的质量控制,为乙肝益气解郁颗粒后续质量提高提供参考。     

Hemodynamic alterations following a cerebellar arteriovenous malformation resection: Case report and densitometric quantitative analysis from CT imaging

BackgroundCerebellar arteriovenous malformations (cAVMs) are rare and challenging lesions with an aggressive natural history. The mechanisms whereby a patient can worsen clinically after a supratentorial AVM resection include an acute alteration in cerebral hemodynamics, which is a known cause of postoperative hyperemia, edema and/or hemorrhage. These phenomena has not been described for cAVMS. Moreover, the underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial.MethodsWe report a patient that presented an abrupt neurological deterioration after cAVM surgical resection. Emergent external ventricular drainage to treat incipient hydrocephalus only partially reverted the patient's deterioration. Consecutive post-surgery CT images revealed fourth ventricle compression secondary to cerebellar swelling that concurred with a new neurological deterioration. Densitometric analysis was performed in these CT images to reveal the nature of these changes as well as their evolution over time.ResultsImportantly, we demonstrated a dynamic increase in the cerebellum mean density at the interval of Hounsfield values which correspond to hyperemia values. These changes were dynamic, and when hyperemia resolved and cerebellar density returned to basal levels, the fourth ventricle re-expanded and the patient neurologically recovered.ConclusionsThis study demonstrated the utility of quantitative CT image analysis in the context of hemodynamic alterations following cAVM resection. Densitometric CT analysis demonstrated that hyperemic changes, but not ischemic ones, were time-dependent and were responsible for swelling and hemorrhage that conditioned neurological status and patient's evolution.     

MiR-663a Inhibits Radiation-Induced Epithelium-to-Mesenchymal Transition by Targeting TGF-β1

Objective miR-663 a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of mi R-663 a during radiation-induced Epithelium-to-mesenchymal transition(EMT).Methods TGF-β1 or IR was used to induce EMT. After mi R-663 a transfection, cell migration and cell morphological changes were detected and the expression levels of mi R-663 a, TGF-β1, and EMT-related factors were quantified.R...     

MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia

ObjectiveMost acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.MethodsBased on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.ResultsMiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.ConclusionThis study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.