Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Chinese Library Classification No.R456; R741; Q344+.14     

大鼠脑缺血后脑内MPO、NSE活性变化

目的 通过测定大鼠局灶性脑缺血-再灌流后不同时点脑组织中髓过氧化物酶(MPO)和神经元特异性烯醇化酶(NSE)活性的变化,探讨炎症反应与脑缺血损伤的关系.方法 用线栓法制备大鼠左侧大脑中动脉缺血-再灌流模型,检测缺血3h再灌流后6h、12h、24h、48h、72h和7d脑组织中MPO和NSE活性、脑梗死体积的变化.结果 缺血组脑组织中NSE和MPO活性升高,再灌流后48h的NSE为(5.44±0.95)ng/ml,MPO为4.49±0.22;72h分别为(5.36±0.65)ng/l和5.96±0.19,升高最为明显.脑梗死体积随再灌流时间延长而增加,第7d梗死体积百分比为(39.18±0.63)%.局灶性缺血脑组织中MPO活性与组织损伤(NSE活性)间具有高度正相关性.结论 炎症反应是加重脑缺血损伤的重要因素.     

芍药苷对大鼠术后肠粘连影响及其作用机制探讨

目的 探讨芍药苷对SD大鼠术后肠粘连的作用效果。方法 选取40只雄性SD大鼠,采用电脑抽号随机分配成4组：空白对照组（Sham组）、对照组（Control组）、透明质酸钠盐阳性对照组（hyaluronate,HA组）以及芍药苷（paeoniflorin）组,每组10只大鼠。Sham组正常开腹后找到盲肠向外拉出然后放回;其余各组均采用盲肠摩擦+对应腹壁损伤模型进行肠粘连造模。芍药苷组术后给予芍药苷灌胃;透明质酸钠组术中腹腔放置透明质酸钠。造模成功后第10天处死所有动物,评估并比较4组大鼠形成粘连的程度及范围,进而进行粘连评分;病理学分析炎症渗出;取粘连组织进行蛋白质印迹（Western blot）分析肿瘤生长因子β（TGF-β）、白细胞介素8（IL-8）的表达;通过ELISA试剂盒检测各组血TGF-β、IL-8的表达水平。结果 术后第10天开腹后肉眼宏观评估粘连程度及范围,与对照组比较,芍药苷组中粘连等级及评分均降低,差异有统计学意义（P<0.50）;HE病理学分析显示芍药苷组炎症渗出显著降低;ELISA检测结果显示,芍药苷组TGF-β、IL-8低于Control组,差异有统计学（P<0.05）;进一步Western blot定量分析检测TGF-β、IL-8的表达在芍药苷组中显著降低（P<0.05）。结论 芍药苷可显著降低术后TGF-β、IL-8的表达,较临床常用的透明质酸钠效果更显著,有望成为术后用于预防肠粘连的药之一。     

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma

Clinical and Experimental Medicine - The poor prognosis of hepatocellular carcinoma (HCC) patients is mainly due to cancer metastasis. Methionine adenosyltransferase 2β (MAT2B) encodes a...     

The role of glutamate receptors in attention‐deficit/hyperactivity disorder: From physiology to disease

Attention‐deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents, which is characterized by behavioral problems such as attention deficit, hyperactivity, and impulsivity. As the receptors of the major excitatory neurotransmitter in the mammalian central nervous system (CNS), glutamate receptors (GluRs) are strongly linked to normal brain functioning and pathological processes. Extensive investigations have been made about the structure, function, and regulation of GluR family, describing evidences that support the disruption of these mechanisms in mental disorders, including ADHD. In this review, we briefly described the family and function of GluRs in the CNS, and discussed what is recently known about the role of GluRs in ADHD, that including GluR genes, animal models, and the treatment, which would help us further elucidate the etiology of ADHD.     

Three additional de novo CTCF mutations in Chinese patients help to define an emerging neurodevelopmental disorder

CCCTC‐binding factor (CTCF) is an important regulator for global genomic organization and gene expression. CTCF gene had been implicated in a novel disorder characterized by intellectual disability, feeding difficulty, developmental delay and microcephaly. So far, four patients have been reported with de novo CTCF mutations. We reported three additional Chinese patients with de novo variants in CTCF. The new evidence helped to establish the clinical validity between CTCF and the emerging disorder. We described the consistent phenotypes shared by all patients and revealed additional clinical features such as delayed or abnormal teeth development and a unique pattern of the eyebrow that may help to define a potential recognizable neurodevelopmental disorder. We also reported the first CTCF patient treated with recombinant human growth hormone. Follow‐up and more case studies will further our understanding to the clinical presentations of this novel disorder and the prognosis of patients with this disorder.     

血管生成的调节在瘢痕形成过程中的作用

血管生成的调节主要发生在创面愈合过程中的后2个阶段,即增生期、重塑期。正常情况下,创面形成大量排列紊乱的毛细血管床,但随着创面逐渐愈合,大部分血管凋亡、退化,并重新排列,最终恢复正常皮肤毛细血管结构与密度。该过程受一系列复杂分子及信号通路的调控,主要包括促血管生成和抗血管生成2方面因子的刺激,但关于创面血管功能和毛细血管增生如何影响瘢痕形成的关键问题仍未得到解答。本综述总结国内外现有研究成果,全面阐述创面血管生成的调控机制,深入探讨血管生成和瘢痕形成之间的关系以及血管异常生长影响瘢痕形成的潜在机制,介绍针对血管形成的相关治疗方案,为减少创面瘢痕形成提供新的思路。     

社区常见恶性肿瘤筛查研究

目的探寻一种简便的恶性肿瘤初筛自查方法。方法将人体肿瘤分为三类:体表肿瘤约占15％;空腔脏器肿瘤占65％;深层实体脏器肿瘤20％。通过科普宣传教育,让群众学会自查体表部位肿瘤,每年用自查盒助查各空腔脏器有无微量出血,隐血阳性时,去医院进一步精查。北京部分大学选40～70岁居民1万人,分成试验组、对照组各5千人。结果试验四年后:试验组共查出79例癌,年平均癌检出率482.5人/10万,癌死亡率为12.2/10万;对照组癌死亡率206.2人/10万,两组有显著性差异。在癌症高发区,同时作扩大普查试验:广东四会市肿瘤所,在门诊普查1669人,检出25例癌,鼻咽癌占24例。1999～2000年,江苏省食管胃癌高发区,普查近8万人,检出480例癌。加上“九五”以前的普查统计,用秦氏自查盒已筛查431075人,检出1272例癌,癌前病变1万多例。结论试验证明该方案设计合理,在当前是一种最简便的恶性肿瘤初筛自查方法。