Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Calcium overload in nerve terminals of cultured neurons intoxicated by alpha-latrotoxin and snake PLA2 neurotoxins

Snake presynaptic neurotoxins with phospholipase A2 (PLA2) activity cause degeneration of the neuromuscular junction. They induce depletion of synaptic vesicles and increase the membrane permeability to Ca²⁺ which fluxes from the outside into the nerve terminal. Moreover, several toxins were shown to enter the nerve terminals of cultured neurons, where they may display their PLA2 activity on internal membranes. The relative contribution of these different actions in nerve terminal degeneration remains to be established. To gather information on this point, we have compared the effects of β-bungarotoxin, taipoxin, notexin and textilotoxin with those of alpha-latrotoxin on the basis of the notion that this latter toxin is well known to cause massive Ca²⁺ influx and exocytosis of synaptic vesicles. All the parameters analysed here, including calcium imaging, are very similar for the two classes of neurotoxins. This indicates that Ca²⁺ overloading plays a major role in the degeneration of nerve terminals induced by the snake presynaptic neurotoxins.     

表面活化PLA纤维增强胶原多孔支架材料

目的用表面活化PLA纤维增强胶原海绵,制备具有良好力学性能的组织工程支架？方法用己二胺处理PLA纤维,在表面引入氨基．经过戊二醛处理制备醛基活化的PLA纤维。将表面活化PLA纤维与I型胶原溶液均匀混合,经冷冻干燥和交联得到复合多孔胶原海绵。考察其形貌．物理化学性质和细胞毒性,并评价细胞在支架上的黏附和生长情况。结果活化PLA纤维可均匀分散在胶原中,明显增强了胶原海绵的抗压缩能力,而不影响其多孔结构。制得的多孔支架材料不显示细胞毒性,L929细胞在活化PLA纤维增强支架上的粘附优于纯胶原海绵和纯PLA纤维增强胶原海绵,组织学染色显示其内部细胞增殖分布更好结论表面活化PLA纤维增强胶原海绵是一种有前景的组织工程支架材料,     

Activation of leukocyte immunoglobulin-like receptor B2 signaling pathway in cortical lesions of pediatric patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

BackgroundsFocal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC.MethodsIn this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency.ResultsThe protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker.ConclusionTaken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy.     

军队流行性出血热流行现况分析

目的 分析军队流行性出血热流行病学特征,为部队防控提供参考依据.方法 收集1991年1月至2016年7月军队流行性出血热的疫情监测数据及1949年以来的文献资料,并进行流行病学分析.结果 文献共报道23起流行性出血热暴发疫情;驻东北地区部队暴发17起,占73.91%,明显高于其他地区部队(P<0.01);1991年1月至2016年7月军队疫情监测管理信息系统和军队突发公共卫生事件和传染病疫情报告信息系统共上报暴发疫情12起,流行性出血热1666例,发病总体呈下降趋势;驻华北地区部队上报病例最多,为734例,占46.00%(P<0.01);男性明显多于女性(P<0.01);战士发病人数明显多于军官(P<0.05);营区内发病明显多于营区外发病(P<0.05).结论 军队流行性出血热总体发病情况趋于平稳,在年龄、地区、发病地点分布等方面存在显著差异,应加强监测,制定综合防控措施,提升高流行区域驻军流行性出血热卫生防控能力和水平.     

Improvement of Drug Release and Compatibility between Hydrophilic Drugs and Hydrophobic Nanofibrous Composites

Electrospinning is a flexible polymer processing method to produce nanofibres, which can be applied in the biomedical field. The current study aims to develop new electrospun hybrid nanocomposite systems to benefit the sustained release of hydrophilic drugs with hydrophobic polymers. In particular, electrospun hybrid materials consisting of polylactic acid (PLA):poly(ε-caprolactone) (PCL) blends, as well as PLA:PCL/halloysite nanotubes-3-aminopropyltriethoxysilane (HNT-ASP) nanocomposites were developed in order to achieve sustained release of hydrophilic drug tetracycline hydrochloride (TCH) using hydrophobic PLA:PCL nanocomposite membranes as a drug carrier. The impact of interaction between two commonly used drugs, namely TCH and indomethacin (IMC) and PLA:PCL blends on the drug release was examined. The drug release kinetics by fitting the experimental release data with five mathematical models for drug delivery were clearly demonstrated. The average nanofiber diameters were found to be significantly reduced when increasing the TCH concentration due to increasing solution electrical conductivity in contrast to the presence of IMC. The addition of both TCH and IMC drugs to PLA:PCL blends reduced the crystallinity level, glass transition temperature (T_g) and melting temperature (T_m) of PCL within the blends. The decrease in drug release and the impairment elimination for the interaction between polymer blends and drugs was accomplished by mobilising TCH into HNT-ASP for their embedding effect into PLA:PCL nanofibres. The typical characteristic was clearly identified with excellent agreement between our experimental data obtained and Ritger–Peppas model and Zeng model in drug release kinetics. The biodegradation behaviour of nanofibre membranes indicated the effective incorporation of TCH onto HNT-ASP.