Systemic sclerosis stimulates angiogenesis in the chick embryo chorioallantoic membrane

Skin biopsies from patients with systemic sclerosis (SSc) were investigated for their angiogenic activity by using the chick embryo chorioallantoic membrane (CAM) assay. Ten samples of SSc and 10 of normal skin from age- and sex-matched subjects were grafted onto the CAM, and the angiogenic response in pathological and control implants was assessed on histological sections by a planimetric point-count method 4 days after grafting. The vascular counts in the area underlying the SSc were significantly higher than those of normal skin and a dense mononuclear cell infiltrate was detectable around the blood vessels in pathological specimens. These results suggest that SSc may promote angiogenesis, perhaps leading to the release of several angiogenic factors. Moreover, the role played in the angiogenic response by the inflammatory cells forming the cellular infiltrate is suggested by this study.     

Pin1抑制剂胡桃醌对乳腺癌细胞株MCF7Adr增殖、迁移及血管新生能力的影响

目的研究Pin1抑制剂胡桃醌对乳腺癌细胞株MCF7Adr增殖、迁移及血管新生能力的影响。方法培养乳腺癌细胞株MCF7Adr,分别用不含药物的DMEM(对照组)、Pin1抑制剂胡桃醌处理(处理组),采用流式细胞法检测细胞周期、划痕实验检测细胞的迁移能力、Western-blot检测Cyclin E的蛋白含量、酶联免疫吸附法检测细胞上清液中血管内皮生长因子(VEGF)的水平。结果处理组的G2/M期比例高于对照组(t=21.848,P<0.01),G0/G1比例、S期比例低于对照组(t=6.234,6.658,均P<0.05),Cyclin E蛋白含量、(A0-A24)/A0值低于对照组(t=17.586,26.679,均P<0.01),处理组细胞的上清液中VEGFA、VEGFB、VEGFC水平低于对照组(t=15.237,13.894,16.382,均P<0.01)。结论 Pin1抑制剂胡桃醌能有效抑制乳腺癌细胞株MCF7Adr的增殖、迁移和血管新生能力,Pin1抑制剂可作为乳腺癌治疗的备选药物。     

VHL-deficient vasculogenesis in hemangioblastoma

Hemangioblasts are capable of differentiation into vascular structures and blood. Patients with von Hippel–Lindau (VHL) disease develop hemangioblastomas which are composed of VHL-deficient tumor cells with protracted hemangioblastic differentiation potential. In a subset of these tumors, hemangioblastic differentiation is characterized by different stages of red blood cell formation. It has remained controversial, however, whether VHL-deficient hemangioblastic cells are similarly capable of differentiating into vascular cells and functioning vascular structures in vivo.     

敷和备化方联合肝动脉化疗栓塞术治疗肝郁脾虚型原发性肝癌患者的近期疗效及其对血浆血管生成因子水平的影响研究

背景　肝动脉化疗栓塞（TACE）术虽是目前中晚期不可手术的原发性肝癌患者的首选局部治疗措施,但TACE术后仍存在较多问题亟待解决,中医药治疗作为重要的辅助手段,联合TACE术能使原发性肝癌患者获得更大的治疗收益。目的　探讨敷和备化方联合TACE术治疗肝郁脾虚型原发性肝癌患者的近期疗效及其对血浆血管生成因子水平的影响。方法　选取2018年1-6月广西中医药大学第一附属医院肿瘤科及肝病科收治的肝郁脾虚型原发性肝癌患者90例,采用随机数字表法分为对照组和治疗组,每组45例。在常规对症支持治疗基础上,两组患者均行亚肝段动脉末梢水平TACE术,治疗组患者连续服用敷和备化方12周。比较两组患者近期（治疗12周后）疗效、无进展生存时间（PFS）及治疗前后血清甲胎蛋白水平、Karnofsky（KPS）评分、中医症候积分、血浆血管生成因子〔包括血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子（PDGF）〕,并观察两组患者毒副作用和/或并发症发生情况。TACE术后当天开始进行电话随访,随访截止时间为患者出现疾病进展或完成整个疗程（12周）。结果　两组患者均完成整个疗程及随访,无一例脱落或失访。两组患者总有效率（ORR）、疾病控制率（DCR）比较,差异无统计学意义（P>0.05）。平均随访（207.5±28.4）d,两组患者PFS的Kaplan-Meier生存曲线比较,差异有统计学意义（P<0.05）。治疗组患者治疗后血清甲胎蛋白水平,腹痛腹胀、纳呆食少、情志抑郁、恶心呕吐、神疲乏力、口苦咽干评分及中医症候积分,血浆VEGF、bFGF、PDGF水平均低于对照组,而KPS评分高于对照组（P<0.05）。两组患者毒副作用和/或并发症发生率比较,差异无统计学意义（P>0.05）。结论　敷和备化方联合TACE术能在一定程度上延长肝郁脾虚型原发性肝癌患者PFS,同时能有效改善患者临床症状及肿瘤相关血管微环境,降低血清肿瘤标志物及血浆血管生成因子水平,有利于提高患者生活质量,且安全性较高。     

脑动脉粥样硬化与肝细胞生长因子-转化生长因子-β1平衡关联性研究进展

脑动脉粥样硬化以颅内动脉管壁增厚、僵硬、狭窄及闭塞为主要病理发展过程,以缺血性脑血管病为主要临床表现,近年来其呈现高发病率、高致残率,给患者、家庭及社会医疗资源带来巨大负担;脑动脉粥样硬化所致颅内血管分支减少也成为血管性痴呆主要致病因素。肝细胞生长因子(HGF)作为一种来源于间质细胞的分泌型肝素亲和糖蛋白,具有促进细胞增殖、迁移、分化、形态发生、抗凋亡等多种生物活性功能,目前其促血管新生机制成为研究热点。转化生长因子-β1(TGF-β1)是一种调节多种细胞生长和分化的信号分子,前期研究表明TGF-β1与HGF相互作用间存在互逆平衡关系,该平衡对维持机体正常内环境稳态发挥重要作用。本文就脑动脉粥样硬化与HGF-TGF-β1平衡关联性相关研究进行综述,总结HGF-TGF-β1平衡的维持对颅内动脉粥样硬化发生发展的影响,分析给予外源性HGF以达到促血管新生从而治疗缺血性脑血管病的临床可行性。     

Medication-related osteonecrosis of the jaw: A literature review

BackgroundAntiresorptive agents such as bisphosphonates and denosumab, as well as angiogenesis inhibitors, may induce medication-related osteonecrosis of the jaw (MRONJ). However, the exact mechanisms of MRONJ are unclear and definitive treatment strategies have not yet been developed. Moreover, the aging population requiring antiresorptive agents and angiogenesis inhibitors has been increasing worldwide. Therefore, the aim of this literature review was to introduce the latest information on MRONJ. The epidemiology, triggering factors, risk factors, drug holiday, pathoetiology and treatment strategies for each drug-induced ONJ were investigated by conducting a PubMed search.HighlightThe prevalence and incidence of ONJ were very low. Some mechanisms of ONJ have been identified, although they were not definitive. Novel treatment strategies have been proposed in basic and clinical research. Several factors, including age and the administration duration of bisphosphonates, are risks for the development of bisphosphonate-related ONJ (BRONJ). Dental implant therapy and peri-implantitis could become risk factors of BRONJ, regardless of the onset timing of bisphosphonates. No reliable information about ONJ induced by denosumab and angiogenesis inhibitors was found.ConclusionCaution should be taken when dental treatment including implant therapy is performed in patients receiving bisphosphonates, denosumab, and angiogenesis inhibitors. There is limited scientific evidence regarding the relationship between MRONJ and older age. Further ONJ-related research on the aging population is required to manage the treatment of such diseases in older people in the future.     

Isthmin 对博来霉素诱导肺纤维化小鼠胶原沉积及血管生成的影响

目的探讨Isthmin（ISM）对肺纤维模型小鼠肺部胶原沉积、血管新生的影响,为肺纤维化的防治提供理论依据。方法将昆明小鼠随机分成：对照组、模型组、ISM组3组,每组16只。博来霉素（BLM）气管内滴人制作小鼠肺纤维化模型,对照组（气管内注射0．9％NS＋尾静脉注入0．9％NS）、模型组（气管内注射BLM＋尾静脉注入0．9％NS）、ISM组（气管内注射BLM＋尾静脉注入Isthmin蛋白）。分别于第7天、14天、21天、28天取实验小鼠肺组织,病理切片苏木精-伊红染色（HE）染色观察肺结构变化,Masson染色了解肺部胶原沉积情况,CD31免疫组化观察对血管内皮细胞数目的影响。结果给予ISM蛋白可减轻小鼠肺结构破坏,减少肺部胶原沉积,血管内皮细胞数目增加。肺组织胶原纤维Masson染色经平均光密度比较,模型组与对照组第7、14、21和28天差异具有统计学意义（P〈0．01）;Isthmin组与模型组比较,第21天和28天差异具有统计学意义（P〈0．01）;肺组织CD31蛋白平均光密度比较,模型组与对照组第14天、21天和28天差异显著（P〈0．05）、第7天差异具有统计学意义（P〈0．01）,Isthmin组与模型组比较,第21天和28天差异具有统计学意义（P〈0．05）。结论ISM蛋白可减轻肺纤维化程度,但不是通过抑制血管形成实现的。     

Low level laser therapy (830nm) improves bone repair in osteoporotic rats: similar outcomes at two different dosages

Background and objective

The goal of this study was to investigate the effects of low level laser therapy (LLLT) in osteoporotic rats by means of subjective histopathological analysis, deposition of collagen at the site of fracture, biomechanical properties and immunohistochemistry for COX-2, Cbfa-1 and VEGF.

Material and methods

A total of 30 female Wistar rats (12 weeks-old, ± 250 g) were submitted to ovariectomy (OVX). Eight weeks after the OVX, a tibial bone defect was created in all animals and they were randomly divided into 3 groups (n = 10): control bone defect group (CG): bone defects without any treatment; laser 60 J/cm² group (L60): animals irradiated with LLLT, at 60 J/cm² and laser 120 J/cm² group (L120): animals irradiated with LLLT, at 120 J/cm².

Results

In the laser treated groups, at both fluences, a higher amount of newly formed bone was evidenced as well as granulation tissue compared to control. Picrosirius analysis demonstrated that irradiated animals presented a higher deposition of collagen fibers and a better organization of these fibers when compared to other groups, mainly at 120 J/cm². COX-2, Cbfa-1 or VEGF immunoreactivity was detected in a similar manner either 60 J/cm² or 120 J/cm² fluences. However, no differences were shown in the biomechanical analysis.

Conclusion

Taken together, our results support the notion that LLLT improves bone repair in the tibia of osteoporotic rats as a result of stimulation of the newly formed bone, fibrovascularization and angiogenesis.