Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats

The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5 mg/kg) alone or in combination with rosuvastatin (RSU) (10 mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.     

基于三维打印的钙化层重建生物活性支架制备及其性能研究

目的初步构建基于软骨钙化层损伤重建的有机—无机复合组织工程支架,探究掺镁硅灰石含量与支架抗压性能之间的关系。方法利用质量分数分别为1%、3%、5%的高生物活性钙镁硅酸盐超细颗粒复合Ⅰ型胶原—透明质酸钠进行三维打印,经海藻酸钠—氯化钙气雾交联成型,电镜下观察表面孔隙、孔径、无机相分布,万能材料试验机测试抗压性能,并计算支架孔隙率。结果支架表面平均孔径(212.3±34.2)μm,平均孔隙率(48.3±5.9)%,不同质量分数的高生物活性钙镁硅酸盐超细颗粒复合Ⅰ型胶原—透明质酸钠支架压缩模量差异无统计学意义( P>0.05),平均压缩模量(7.2±1.2)MPa,介于软骨和软骨下骨之间。 结论利用三维打印技术成功构建出多孔钙化层仿生重建支架,可为今后研制多层次复合支架治疗骨—软骨损伤奠定基础。     

Biomaterials reinforced MSCs transplantation for spinal cord injury repair

Due to the complex pathophysiological mechanism, spinal cord injury (SCI) has become one of the most intractable central nervous system (CNS) diseases to therapy. Stem cell transplantation, mesenchymal stem cells (MSCs) particularly, appeals to more and more attention along with the encouraging therapeutic results for the functional regeneration of SCI. However, traditional cell transplantation strategies have some limitations, including the unsatisfying survival rate of MSCs and their random diffusion from the injection site to ambient tissues. The application of biomaterials in tissue engineering provides a new horizon. Biomaterials can not only confine MSCs in the injured lesions with higher cell viability, but also promote their therapeutic efficacy. This review summarizes the strategies and advantages of biomaterials reinforced MSCs transplantation to treat SCI in recent years, which are clarified in the light of various therapeutic effects in pathophysiological aspects of SCI.     

Carcinogenicity of acrylamide in B6C3F1 mice and F344/N rats from a 2-year drinking water exposure

Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F₁ mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70 mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F₁ mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F₁ mice. Male B6C3F₁ mice also had a significantly increased incidence of forestomach tumors, while female B6C3F₁ mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide.     

A trivalent vaccine candidate against hepatitis E virus,norovirus, and astrovirus

Hepatitis E virus (HEV), norovirus (NoV), and astrovirus (AstV) are enterically-transmitted viral pathogens causing epidemic or endemic hepatitis (HEV) and gastroenteritis (NoV and AstV) respectively in humans, leading to significant morbidity and mortality worldwide. While a recombinant subunit vaccine against HEVs is available in China, there is no commercial vaccine or antiviral against NoV or AstV. We report here our development of a trivalent vaccine against the three viral pathogens through our new polymer vaccine technology. All HEV, NoV, and AstV are non-enveloped RNA viruses covered by a protein capsid, featuring surface protruding (P) proteins that are responsible for virus–host interaction. These dimeric P proteins elicit neutralizing antibody and are good targets for subunit vaccine development. The trivalent subunit vaccine was developed by fusion of the dimeric P domains of the three viruses together that formed tetramers. This trivalent vaccine elicited significantly higher antibody responses in mice against all three P domains than those induced by a mixture of the three free P domains (mixed vaccine). Furthermore, the post-immune antisera of the trivalent vaccine showed significantly higher neutralizing titers against HEV infection in cell culture and higher blocking activity against NoV binding to HBGA ligands than those of the post-immune sera of the mixed vaccine. Thus, the trivalent vaccine is a promising vaccine candidate against HEV, NoV, and AstV.     

Multi-site clustering and nested feature extraction for identifying autism spectrum disorder with resting-state fMRI

Brain functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to study neuropsychiatric disorders such as autism spectrum disorder (ASD). Existing studies usually suffer from (1) significant data heterogeneity caused by different scanners or studied populations in multiple sites, (2) curse of dimensionality caused by millions of voxels in each fMRI scan and a very limited number (tens or hundreds) of training samples, and (3) poor interpretability, which hinders the identification of reproducible disease biomarkers. To this end, we propose a Multi-site Clustering and Nested Feature Extraction (MC-NFE) method for fMRI-based ASD detection. Specifically, we first divide multi-site training data into ASD and healthy control (HC) groups. To model inter-site heterogeneity within each category, we use a similarity-driven multiview linear reconstruction model to learn latent representations and perform subject clustering within each group. We then design a nested singular value decomposition (SVD) method to mitigate inter-site heterogeneity and extract FC features by learning both local cluster-shared features across sites within each category and global category-shared features across ASD and HC groups, followed by a linear support vector machine (SVM) for ASD detection. Experimental results on 609 subjects with rs-fMRI from the ABIDE database with 21 imaging sites suggest that the proposed MC-NFE outperforms several state-of-the-art methods in ASD detection. The most discriminative FCs identified by the MC-NFE are mainly located in default mode network, salience network, and cerebellum region, which could be used as potential biomarkers for fMRI-based ASD analysis.