雷公藤内酯醇结构修饰和构效关系研究进展

雷公藤中的雷公藤内酯醇具有抗肿瘤、免疫抑制等多种生物活性,但是副作用大等特点限制了临床的使用。为了获得高效低毒的雷公藤内酯醇衍生物,对其结构进行了改造。近5年来对雷公藤内酯醇的结构改造又有了新进展,包括对其14位羟基、不饱和五元内酯环、B环、13位异丙基和10位甲基的结构改造,得到一系列衍生物。其中对14位羟基进行前药设计,从而降低了雷公藤内酯醇的毒性,14位羟基改造为α-羟基衍生物后发现了与雷公藤内酯醇活性相当的衍生物。综述了近5年来对雷公藤内酯醇的结构改造及构效关系研究进展。     

Nanog siRNA plus Cisplatin may enhance the sensitivity of chemotherapy in esophageal cancer

Background

Cancer stem cells are regarded as the origin of tumors that can proliferate, relapse, and metastasize. Nanog, with its capacity to maintain the pluripotency and regulate proliferation and prevent differentiation, is one of the most important core markers of cancer stem cells. Studying the role of Nanog in esophageal squamous cell carcinoma (ESCC), therefore, has important implications.

Methods

In the present study, we first detected the expression of Nanog in the ESCC and cell lines by RT-PCR, immunofluorescence, and immunohistochemisty. Then, we used small interfering RNA (siRNA) to block Nanog expression while evaluating the effect of Nanog siRNA on cell apoptosis and the combined effects with Cisplatin in ESCC cell lines.

Results

The results showed that both mRNA and protein-level Nanog are overexpressed in ESCC tissues compared with their normal counterparts, and the increased occurrence of Nanog expression was positively correlated with TNM stages and histopathological differentiation of ESCC patients (p?Conclusion The present study’s results suggest that detecting Nanog might be helpful for diagnosing ESCC, and Nanog siRNA combined with Cisplatin may be a feasible strategy to enhance the sensitivity of chemotherapy in patients with ESCC.     

Dynamic cultural modulation of neural responses to one's own and friend's faces

Long-term cultural experiences influence neural response to one''s own and friend''s faces. The present study investigated whether an individual''s culturally specific pattern of neural activity to faces can be modulated by temporary access to other cultural frameworks using a self-construal priming paradigm. Event-related potentials were recorded from British and Chinese adults during judgments of orientations of one''s own and friend''s faces after they were primed with independent and interdependent self-construals. We found that an early frontal negative activity at 220–340 ms (the anterior N2) differentiated between one''s own and friend''s faces in both cultural groups. Most remarkably, for British participants, priming an interdependent self-construal reduced the default anterior N2 to their own faces. For Chinese participants, however, priming an independent self-construal suppressed the default anterior N2 to their friend''s faces. These findings indicate fast modulations of culturally specific neural responses induced by temporary access to other cultural frameworks.     

Multiple introductions of HIV into men who have sex with men were found in Zhengzhou City, China

Zhengzhou is the capital of Henan province, where severe HIV prevalence was found in former paid plasma donors. In recent years, the HIV epidemic in men who have sex with men (MSM) increased rapidly in the city. To explore the subtype distribution and genetic characterization of HIV in MSM in Zhengzhou city, phylogenetic analysis was fulfilled based on the full-length gag, pol, and partial env gene. A total of 31 HIV-1-seropositive MSM individuals were enrolled. The full length gag, pol, and partial env gene were amplified and sequenced. Multiple subtypes, including CRF01_AE (45.2%), subtype B (38.7%), and CRF07_BC (16.1%), were identified. Close phylogenetic relationships among our strains with strains from the Henan local area, Hebei MSM population, Beijing area, and Liaoning area were found, suggesting a multiple introduction of HIV into the population. The results will provide clues for prevention and for changes in behavior in the Henan MSM population and also detailed sequence data for vaccine design.     

Influence of molecular weight and concentration of carboxymethyl chitosan on biomimetic mineralization of collagen

The objective of the present study was to systematically investigate the influence of molecular weight (MW) and concentration of carboxymethyl chitosan (CMC), which served as non-collagenous protein (NCP) surrogates, on biomimetic mineralization of type I collagen. Supersaturated CMC-stabilized amorphous calcium-phosphate (CMC-ACP) dispersions containing different MWs (20 kDa, 60 kDa, 150 kDa) and concentrations (25, 50, 100, 200, 400 μg ml⁻¹) of CMC were prepared. After mineralization in the aforementioned dispersions for 7 days, the pattern and extent of biomimetic mineralization of collagen scaffolds were investigated. Our study showed that increasing CMC concentration resulted in increasing stability and decreasing particle size of CMC-ACP dispersions. Images from scanning and transmission electron microscopy revealed that intrafibrillar mineralization of collagen was obtained with 20k-200, 60k-100, 60k-200 and 150k-200 CMC-ACP dispersions, with hydroxyapatite (HAp) formation confirmed by Fourier transform infrared spectroscopy and X-ray diffraction measurements, whereas HAp formed extrafibrillar clusters in other collagen scaffolds. Thermogravimetric analysis showed that the combined effect of MW and concentration of CMC contributed to different extents of biomimetic mineralization, and was correlated with the stability and particle size of CMC-ACP dispersions, and the size-exclusion characteristics of type I collagen. The results of this work support the effective function of CMC as NCP analogs, and provide parameters of MWs and concentrations of CMC for applications in hard tissue engineering as well as insights into intersections of mechanisms in biomimetic mineralization.

The study systematically investigated the influence of molecular weight and concentration of CMC on CMC-ACP nanoparticles and biomimetic mineralization.