摘要:
Aims: Diabetic macroangiopathy is the main cause of morbidity and mortality in patients with diabetes. Endothelial cell injury is a pathological precondition for diabetic macroangiopathy. Fibroblast growth factor 21 (FGF21) is a key metabolic regulator which has recently been suggested to protect cardiac myocytes and vascular cells against oxidative stress-induced injury in vitro and vivo. In this study, we aimed to investigate the protective capacity of FGF21 in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced apoptosis via phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway. Methods: The cell viability was examined by CCK-8 assay, Intracellular ROS levels were measured by the detection of the fluorescent product formed by the oxidation of DCFH-DA, Apoptosis was analyzed using Hoechst 33258 nuclear staining and Flow Cytometry Analysis (FCA), the expression of protein were detected by Western blot. Results: Results show that pretreating HUVECs with FGF21 before exposure to HG increases cell viability, while decreasing apoptosis and the generation of reactive oxygen species. Western blot analysis shows that HG reduces the phosphorylation of Akt and FoxO3a, and induces nuclear localization of FoxO3a. The effects were significantly reversed by FGF21 pre-treatment. Furthermore, the protective effects of FGF21 were prevented by PI3K/Akt inhibitor LY294002. Conclusions: Our data demonstrates that FGF21 protects HUVECs from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.
摘要:
Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super ability of carbon source biosynthesis and catabolism. The comparative transcriptome analysis from three culture conditions revealed the landscape of gene-altered expressions responsible for lipid accumulation. The LD proteomes further identified the proteins that mediate lipid synthesis, storage and other biological functions. Integrating these three omics uncovered 177 proteins that may be involved in lipid metabolism and LD dynamics. A LD structure-like protein LPD06283 was further verified to affect the LD morphology. Our omics studies provide not only a first integrated omics study of prokaryotic LD organelle, but also a systematic platform for facilitating further prokaryotic LD research and biofuel development.
期刊:
Journal of Orthopaedic Research,2013年31(10):1514-1519 ISSN:0736-0266
通讯作者:
Li, Kanghua
作者机构:
[Li, Kanghua; Dai, Zhu] Cent S Univ, Xiangya Hosp, Dept Orthoped, Changsha 410078, Hunan, Peoples R China.;[Chen, Zhiwei; Dai, Zhu; Liu, Chunlei; Yang, Lezhong; Liao, Ying] South China Univ, Affiliated Hosp 1, Dept Orthoped, Hengyang 421001, Hunan, Peoples R China.;[Ding, Wenjun] South China Univ, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Li, Kanghua] Cent S Univ, Xiangya Hosp, Dept Orthoped, 87 Xiangya Rd, Changsha 410078, Hunan, Peoples R China.
通讯机构:
[Li, Kanghua] C;Cent S Univ, Xiangya Hosp, Dept Orthoped, 87 Xiangya Rd, Changsha 410078, Hunan, Peoples R China.
关键词:
in vitro;injury;integrative repair;meniscus;organ culture
摘要:
We investigated whether the implantation of juvenile allograft and minced meniscal fragments could improve the healing of avascular meniscal injuries, which cannot heal spontaneously. Concentric cylindrical explants were excised from the inner two-thirds of swine medial menisci. The inner cylinder consisted of a "sandwich" structure, with minced juvenile meniscal fragments, juvenile meniscal columns, minced mature meniscal fragments, or mature meniscal columns implanted in the middle. The explants were cultured in vitro for 2, 4, or 6 weeks. Interfacial meniscal repair was assessed by histology, immunohistochemistry, biomechanical testing, and confocal laser scanning microscopy. Histology and confocal microscopy results revealed that tissue repair and cell accumulation at the interface were best at all time points in the juvenile meniscal fragments group, followed by the juvenile columns, minced mature fragments, and mature columns groups, respectively. At 6 weeks, the implantation of juvenile allograft and minced meniscal fragments increased the shear strength, peak force, and energy to failure in the peripheral interface. Picosirius red/polarized light microscopy and immunohistochemistry results showed concurrent expression of type I and II collagen in the interfacial repair tissue. In conclusion, implantation of juvenile allograft and minced meniscal fragments could increase the healing of avascular meniscal injury in vitro.
期刊:
Cancer Letters,2013年340(1):72-81 ISSN:0304-3835
通讯作者:
Su, Qi
作者机构:
[Tang, Hailin; Xie, Xinhua; Yang, Lu; Xie, Xiaoming; Kong, Yanan; Guo, Jiaoli] Sun Yat Sen Univ, Ctr Canc, Dept Breast Oncol, Guangzhou 510060, Guangdong, Peoples R China.;[Tang, Hailin; Xie, Xinhua; Yang, Lu; Xie, Xiaoming; Kong, Yanan; Guo, Jiaoli] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China.;[Tang, Hailin; Su, Qi; Tang, Yi] Univ South China, Canc Res Inst, Hengyang, Hunan, Peoples R China.;[Su, Qi] Sun Yat Sen Univ, Ctr Canc, Dept Breast Oncol, State Key Lab Oncol South China, 651 East Dongfeng Rd, Guangzhou 510060, Guangdong, Peoples R China.
通讯机构:
[Su, Qi] S;Sun Yat Sen Univ, Ctr Canc, Dept Breast Oncol, State Key Lab Oncol South China, 651 East Dongfeng Rd, Guangzhou 510060, Guangdong, Peoples R China.
摘要:
Numerous microRNAs (miRNAs) play crucial roles in cancer development. In this study, we report that hsa-miR-96 is expressed at higher levels in human bladder urothelial carcinomas compared to normal tissues. We found that hsa-miR-96 increased invasion and differentiation of human bladder T24 cells and promoted their growth. Downregulation of hsa-miR-96 significantly affected the phenotype of bladder cancer T24 cells. The mRNA and protein levels of insulin receptor substrate 1 (IRS1) and MAP4K1 were significantly reduced in cells transfected with the hsa-miR-96 inhibitor when compared with levels in cells transfected with the empty plasmid vector or the negative control miRNA inhibitor. Altogether, these results suggest that hsa-miR-96 may affect the growth of bladder cancer cells by up-regulating IRS1 and MAP4K1 levels, functioning as a promising diagnostic marker in human bladder urothelial carcinomas.
摘要:
Storage of cellular triacylglycerols (TAGs) in lipid droplets (LDs) has been linked to the progression of many metabolic diseases in humans, and to the development of biofuels from plants and microorganisms. However, the biogenesis and dynamics of LDs are poorly understood. Compared with other organisms, bacteria seem to be a better model system for studying LD biology, because they are relatively simple and are highly efficient in converting biomass to TAG. We obtained highly purified LDs from Rhodococcus sp. RHA1, a bacterium that can produce TAG from many carbon sources, and then comprehensively characterized the LD proteome. Of the 228 LD-associated proteins identified, two major proteins, ro02104 and PspA, constituted about 15% of the total LD protein. The structure predicted for ro02104 resembles that of apolipoproteins, the structural proteins of plasma lipoproteins in mammals. Deletion of ro02104 resulted in the formation of supersized LDs, indicating that ro02104 plays a critical role in cellular LD dynamics. The putative α helix of the ro02104 LD-targeting domain (amino acids 83-146) is also similar to that of apolipoproteins. We report the identification of 228 proteins in the proteome of prokaryotic LDs, identify a putative structural protein of this organelle, and suggest that apolipoproteins may have an evolutionarily conserved role in the storage and trafficking of neutral lipids.
通讯机构:
[Yang, Luoyan] C;Cent S Univ, Xiangya Hosp 2, Dept Urol, Changsha 410011, Hunan, Peoples R China.
关键词:
beta-elemene;survivin;Bcl-xL;Mta-1;human bladder cancer
摘要:
β-elemene, a non-cellular antineoplastic agent, may be used to effectively inhibit the growth and proliferation of various types of tumor cells by inhibiting the nucleic acid synthesis or inducing their apoptosis and differentiation. The aim of this study was to investigate the expression, as well as the effects, of Mta-1, survivin and Bcl-xL in T24 bladder cancer cells following β-elemene treatment. The expression of the three proteins in T24 cells following β-elemene treatment was analyzed by immunocytochemistry staining and western blot analysis. The survival rate and apoptosis of T24 cells following β-elemene treatment was detected by MTT assay and TUNEL staining. We analyzed the internal corelations between apoptosis-associated genes, tumor metastasis-associated genes (cancer genes) and cell apoptosis, and investigated the mechanism of action by which β-elemene induces the apoptosis of T24 cells at a molecular level. These results provide scientific evidence for further study on the anticancer effect of β-elemene in carcinoma of the urinary bladder. In this study, it is shown that β-elemene downregulates the expression of survivin, Bcl-xL and Mta-1 in tumor cells. The apoptosis of T24 cells is dependent on the dosage and length of incubation time of β-elemene.