通讯机构:
[Zuo, Jianhong] U;[Lei, Mingsheng] P;Univ South China, Sch Med, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Peoples Hosp Zhangjiajie City, Dept Resp & Crit Care Med, 192 Gu Yong Rd, Zhangjiajie 427000, Hunan, Peoples R China.
关键词:
laryngocarcinoma cancer;Bcl-2;Hsp90 beta
摘要:
Laryngeal carcinoma (LC) is one of the most common malignant tumors of all head and neck squamous cell carcinomas (HNSCCs). However, the molecular mechanism and genetic basis of the development of LC have not been fully elucidated. To explore the possible mechanism, targeted proteomic analysis was performed on Bcl-2-associated proteins from LC cells. According to our results, 35 proteins associated with Bcl-2 were identified and Hsp90 beta was confirmed by co-immunoprecipitation and western blot analysis. Protein-protein interaction (PPI) analysis indicated that Bcl-2-Hsp90 beta interactions may be involved in the anti-apoptotic progression of LC. Further results revealed that disruption of the Bcl-2-Hsp90 beta interaction inhibited the anti-apoptotic ability of Bcl-2 and decreased the caspase activation in LC, which has broad implications for the better understanding of tumor formation, tumor cell survival and development of metastasis due to Bcl-2. Collectively, we report the mechanism by which Bcl-2 functions in LC as an anti-apoptotic factor in relation to its association with proteins and potentially identify a Bcl-2/Hsp90 beta axis as a novel target for LC therapy.
摘要:
'Obesity Facts' publishes articles covering all aspects of obesity, in particular epidemiology, etiology and pathogenesis, treatment, and the prevention of adiposity. As obesity is related to many disease processes, the journal is also dedicated to all topics pertaining to comorbidity and covers psychological and sociocultural aspects as well as influences of nutrition and exercise on body weight. The editors carefully select papers to present only the most recent findings in clinical practice and research. All professionals concerned with obesity issues will find this journal a most valuable update to keep them abreast of the latest scientific developments.Special sections comprising a variety of subspecialties reinforce the journal's value as an exhaustive record of recent progress for all internists, gastroenterologists, endocrinologists, pediatricians, dieticians, nutritionists, bariatric surgeons, psychologists and psychiatrists, occupational health practitioners, sports medicine specialists, ecotrophologists, sociologists, and biologists as well as prevention and public health researchers. In addition, 'Obesity Facts' serves as an ideal information tool for the members of the pharmaceutical and food industry as well as those active in nutritional research and medicine.
摘要:
Chemotherapy is the most common therapeutic strategy for the treatment of unresectable hepatocellular carcinoma. However, the therapeutic efficacy is limited by the low delivery efficiency of chemotherapeutics and severe toxicity towards healthy tissues. To address these challenges, active-targeting mesoporous silica nanoparticles conjugating a platinum(IV) prodrug were developed as a therapy for liver cancer for the first time. Taking advantage of liver-targeting lactobionic acid (LA), the smart nano-carriers not only enhanced the circulation time, but also effectively concentrated at the liver tumor site. Moreover, the conjugated platinum(IV) could be reduced in the reductive tumor environment for the fast release of active platinum(II). The novel targeting and self-responsive drug-loading system offers new prospects for liver cancer chemotherapy.
摘要:
Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence. We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1. At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E2) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines. Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.
摘要:
Minimally modified low-density lipoprotein (mmLDL) is a well-known risk factor for cardiovascular diseases. The present study was designed to investigate the role of mmLDL in the endothelium-dependent relaxation of mouse mesenteric arteries. A sensitive myograph system was employed to examine the endothelial function of mesenteric arteries. mRNA and protein expression levels were determined using real-time PCR and Western blotting, respectively. The ultra-microstructure of mesenteric vascular beds was investigated using a transmission electron microscope. The results showed that mmLDL significantly impaired the acetylcholine-induced (3 x 10(-10) to 1 x 10(-4) M) endothelium-dependent relaxation of mouse mesenteric arteries with markedly reduced plC(50) (p < 0.05) and R-max values (p < 0.001). In addition, mmLDL increased the levels of superoxide production and nitrotyrosine concentration and impaired the endothelial microstructure with decreased K(ca)3.1 and K(ca)2.3 expression. In conclusion, mmLDL increases superoxide and nitro-tyrosine levels, damages endothelial microstructure with decreased K(ca)3.1 and K(ca)2.3 expression, and ultimately attenuates relaxation mediated by nitric oxide- and endothelium-derived hyperpolarizing factor. (C) 2016 S. Karger AG, Basel
摘要:
Lung cancer is the leading cause of cancer-related mortality in humans worldwide. Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80% of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) have been found to exist in a large number of NSCLCs. CAFs have been proven to promote tumor progression, metastasis and resistance to therapy through paracrine effects in most solid tumors. In the present study, firstly we isolated CAFs from patient tissues and demonstrated that they promoted cell proliferation and chemoresistance to cisplatin in the lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA and quantative PCR, we found that a higher amount of stromal cell derived factor 1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation and drug resistance via the CXCR4-mediated signaling pathway which involved NF-kappa B and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1 in the CAFs was negatively regulated by microRNA mir-1 through microRNA overexpression and quantitative PCR. Overall, our data provide one explanation for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest CAFs as a potential therapeutic target in tumor treatment.
摘要:
Resveratrol is a polyphenolic compound found in wine, which is mainly produced by the grapevine and exerts chemopreventive effects against hepatocellular carcinoma. However, the underlying molecular mechanisms have remained to be fully elucidated. The present study assessed whether resveratrol-induced apoptosis was mediated via the activation of the forkhead box O3a (FoxO3a) transcription factor. It was demonstrated that resveratrol treatment induced apoptosis in HepG2 cells, and that this pro-apoptotic effect was accompanied with increases in the expression of apoptotic protein Bim. Following resveratrol treatment, Akt-mediated phosphorylation of FoxO3a was observed to be diminished in HepG2 cells. Furthermore, resveratrol enhanced the nuclear levels of FoxO3a and mediated neuronal death via Bim. The present study demonstrated that resveratrol induced apoptosis in HepG2 cells through activation of the transcription factor FoxO3a and increasing the expression of Bim protein.
作者机构:
[Feng Guo; Hongyan Peng; Jingfei Luo; Haiyang Quan; Yanmei Liu; Jie Li; Zhisheng Jiang; Xuping Qin] Institute of Pharmacy & Pharmacology, Key Laboratory for Arteriosclerology of Hunan Province, University of South China
摘要:
Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX-induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX-induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX-induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N-acetyl-L-cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-gamma-lyase were examined by western blotting.
期刊:
RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY,2016年11(2):184-196 ISSN:1574-8928
通讯作者:
Hu, Zheng;Luo, Dixian
作者机构:
[Hu, Z; Luo, DX; Li, Jia; Huang, Li; Hu, Zheng; He, Rongzhang; Luo, Weihao; Zhang, Xi; Luo, Dixian; Tan, Tan] Univ South China, Natl & Local Joint Engn Lab High Mol Diag Technol, Collaborat Res Ctr Postdoctoral Mobile Stn, Translat Med Inst,Affiliated Peoples Hosp Chenzho, Chenzhou 432000, Peoples R China.;[Huang, Li; Zhang, Xi; Luo, Dixian; Tan, Tan] Univ South China, Affiliated Peoples Hosp Chenzhou 1, Ctr Clin Pathol, Chenzhou 432000, Peoples R China.;[Zhu, Yuan-Shan; Hu, Zheng] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410078, Hunan, Peoples R China.;[Zhu, Yuan-Shan; Hu, Zheng] Cent S Univ, Inst Clin Pharmacol, Changsha 410078, Hunan, Peoples R China.;[Zhu, Yuan-Shan; Hu, Zheng] Hunan Key Lab Pharmacogenet, Changsha 410078, Hunan, Peoples R China.
通讯机构:
[Hu, Z; Luo, DX] U;Univ South China, Natl & Local Joint Engn Lab High Mol Diag Technol, Collaborat Res Ctr Postdoctoral Mobile Stn, Translat Med Inst,Affiliated Peoples Hosp Chenzho, Chenzhou 432000, Peoples R China.
摘要:
Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function.