摘要：
Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional therapies are limited due to the human liver being such a unique organ and easily showing side-effects. The unclear molecular mechanisms are tough challenges for scientists searching for new and effective anti-HCC targeting drugs. We identified that the nuclear receptor NR4A2 is a novel oncogene in HCC progression. In this study, we show that NR4A2 and the notch recceptor Notch1 were expressed highly in primary HCC tissues and immortal HCC cells by using qPCR, western blot and immuno-histochemistry assays. Both genes were observed to stimulate HCC cell proliferation, anti-apoptosis and cell cycle arrest by using cell proliferation assays and FACS assays. We also observed that the four notch receptor subtypes (Notch1-4) displayed different effects on HCC cell growth. The over-expression of Notch1 by transiently transfecting the intracellular domain of Notch1 (ICN1, Notch1 active form) increased the expression of NR4A2, with the knockdown of Notch1 decreasing NR4A2. This indicates that NR4A2 is one of the Notch-mediated downstream genes. Moreover, both NR4A2 and Notch1 suppressed the expression of tumor suppressors p21 and p63. These findings support that Notch1/NR4A2 co-regulate HCC cell functions by playing oncogenic roles and regulating the associated downstream signaling pathways. Novel Notch1/NR4A2-mediated oncogenic signaling may provide us a great opportunity for anti-HCC drug development.
摘要：
Formaldehyde (FA), a common environmental contaminant, has toxic effects on the central nervous system (CNS). We have previously found that hydrogen sulphide (H2S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA. However, the underlying mechanism is poor. Aldehyde-dehydrogenase-2 (ALDH2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H2S antagonizes FA-induced neurotoxicity by modulating ALDH2. In the present study, we found that the exposure of PC12 cells to FA causes increase in ALDH2 expression and activity. Daidzin, an inhibitor of ALDH2, significantly antagonizes FA-exerted cytotoxicity and oxidative stress including the accumulation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-trans-nonenal (4-HNE), and malondialdehyde (MDA), in PC12 cells. We also showed that daidzin markedly attenuated FA-induced apoptosis in PC12 cells. Furthermore, we found that H2S reverses FA-elicited upregulation of ALDH2 in PC12 cells. Our results demonstrated the involvement of downregulation of ALDH2 in the protection of H2S against FA neurotoxicity.
期刊：
Journal of the American College of Cardiology,2017年69(11, Supplement):1881-1881 ISSN：0735-1097
作者机构：
Hunan Childrens Hosp, Dept Cardiol, Changsha, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Xiao, Yunbin; Peng, Hongyan; Qin, Xuping; Chen, Zhi; Hong, Chenliang; Deng, Xicheng; Luo, Jinwen] Department of Cardiology, Hunan Children's Hospital, Changsha, People's Republic of China<&wdkj&>Institute of Pharmacy and Pharmacology, University of South China, Hengyang, People's Republic of China
会议名称：
66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)
摘要：
Hepatocellular carcinoma (HCC), a disease that is a major health care issue across the globe, includes the deviant expression of miRNAs in its development, progression, and resistance to treatment. We focused our study on miR-503 expression and its role in HCC. miR-503 was found in HCC tissues and cell lines using quantitative real-time PCR (RT-qPCR). Western blot analyses and the luciferase reporter assay were used to determine the miR-503 potential target in the HCC cells. We used MTT to analyze cell proliferation activity and noted that there was a considerable decrease of miR-503 in HCC tissues and cell lines when measured against the controls. miR-503 upregulation decreased expression of eukaryotic translation initiation factor 4E (EIF4E), and reduced HCC cell proliferation and sensitized HCC cells to anticancer drugs. miR-503 overexpression hindered luciferase activity of EIF4E 3' untranslated region-based reporter construct among HepG2, BEL-7402, and SMMC-7721 cells, revealing that miR-503 may increase sensitivity to therapies at least partially through targeting EIF4E suppression of HCC proliferation.
摘要：
Sirtuin 6 (SIRT6) is an important modulator of cardiovascular functions in health and diseases. However, the exact role of SIRT6 in heart disease is poorly defined. We hypothesized that SIRT6 is a negative regulator of angiotensin II (Ang II)-mediated myocardial remodeling, fibrosis and injury. The male Sprague-Dawley rats were randomized to Ang II (200 ng/kg/min) infusion with an osmotic minipump and pretreated with recombinant plasmids adeno-associated viral vector (AAV)-SIRT6 (pAAV-SIRT6) or pAAV-GFP for 4 weeks. Ang II triggered downregulated levels of SIRT6 and angiotensin-converting enzyme 2 (ACE2) and upregulated expression of connective tissue growth factor (CTGF) and proinflammatory chemokine fractalkine (FKN), contributing to enhanced cardiac fibrosis and ultrastructural injury. Reduced levels of phosphorylated pAMPK-alpha, increased myocardial hypertrophy and impaired heart dysfunction were observed in both Ang II-induced hypertensive rats and ACE2 knockout rats, characterized with increases in heart weight and left ventricular (LV) posterior wall thickness and decreases in LV ejection fraction and LV fractional shortening. More importantly, pAAV-SIRT6 treatment strikingly potentiated cardiac levels of pAMPKalpha and ACE2 as well as decreased levels of CTGF, FKN, TGFbeta1, collagen I and collagen III, resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats. In conclusion, our findings confirmed cardioprotective effects of SIRT6 on pathological remodeling, fibrosis and myocardial injury through activation of AMPK-ACE2 signaling and suppression of CTGF-FKN pathway, indicating that SIRT6 functions as a partial agonist of ACE2 and targeting SIRT6 has potential therapeutic importance for cardiac fibrosis and heart disease.
作者：
Li, Shuihong;Mou, Qianqian;Leung, Polly H. M.*
期刊：
Nanoscience and Nanotechnology Letters,2017年9(10):1514-1519 ISSN：1941-4900
通讯作者：
Leung, Polly H. M.
作者机构：
[Li, Shuihong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Li, Shuihong] Univ South China, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Peoples R China.;[Mou, Qianqian; Leung, Polly H. M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong 999077, Hong Kong, Peoples R China.
通讯机构：
[Leung, Polly H. M.] H;Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong 999077, Hong Kong, Peoples R China.
摘要：
The applications of zinc oxide (ZnO) nanostructures have gained increasing research interests in the past decades. However, limited progress has been made in developing ZnO NP-based multimodality tumor-imaging agents. This work presented synthesis and in vitro bioimaging effect of ethanol dispersed ZnO quantum dots (QDs). The synthesis of ZnO QDs is based on the water-induced protonation of amines. The synthesis pathway was simple and less cost because the preparation process was under routine conditions (room temperature, atmosphere pressure and neutral pH). The synthesized ZnO QDs (mean diameters of 4.5 nm) exhibited a broad and strong ultraviolet emission peak centered near 385 nm under ultraviolet excitation (lambda(ex): 325 nm). The results of fourier transform infrared (FTIR) spectra indicated that the surface of ZnO nanocluster were capped by amine/PVP, and formed ZnO@amine/PVP core-shell. The unanticipated bright blue fluorescence signals were generated when the ZnO QDs entered into the bacterial and cancer cells. This raised the possibility that ZnO QDs can be used for fluorescence bio-imaging.
摘要：
The aim of this study was to investigate the relationship between endothelial-mesenchymal transition (EndoMT) and the progression of infantile hemangioma (IH) and to provide references for clinical. Sixty-five patients were enrolled in this study. Tissues obtained from these patients were analyzed by tissue microarray (TMA). Serial sections from TMA blocks underwent immunohistochemistry with the primary antibodies for EndoMT markers (Twist, Zeb1, Smad, N-cadherin, Vimentin, and alpha-SMA). Intensity and extent points were counted to quantitate the markers expression. All sixty-five patients were diagnosed as IH, which distributes all over the body from head to planta pedis. Progressive phases could be distinguished with H&E staining. The expressionof Twist, Zeb1, Smad, a-SMA, Vimentin and N-cadherin in the abnormal endothelial cells were significantly increased compared with normal controls (***P < 0.01). Average expression points (intensity + extent) in proliferating and involuting phases were 7.69 and 7.80 for Twist; 8 and 7.90 for Zeb1; 4.43 and 3.80 for N-cadherin; 6.72 and 6.85 for Smad; 7.31 and 6.87 for alpha-SMA, and 6.42 and 7.00 for Vimentin. EndoMT involves in the tumorigenesis of IH. The endothelial cells have the capacity to transdifferentiate into mesenchymal cells when IH proliferates and these mesenchymal cells may further transdifferentiate into adipocytes or fibroblasts in involuting phase.
作者机构：
[He, Bixiu; Lu, Xiaoxiao; Chen, Qiong; Xiao, Jian] Cent S Univ, Xiangya Hosp, Dept Geriatr, Resp Med, Changsha, Hunan, Peoples R China.;[Liu, Aibin] Cent S Univ, Xiangya Hosp, Dept Geriatr, Changsha, Hunan, Peoples R China.;[Chen, Xi] Cent S Univ, Xiangya Hosp, Dept Resp Med, Changsha, Hunan, Peoples R China.;[Li, Wei] Cent S Univ, Xiangya Hosp, Dept Geriatr, Clin Lab, Changsha, Hunan, Peoples R China.;[He, Shuya] Univ South China, Dept Biochem & Biol, Hengyang, Peoples R China.
通讯机构：
[Chen, Qiong] C;Cent S Univ, Xiangya Hosp, Dept Geriatr, Resp Med, Changsha, Hunan, Peoples R China.
摘要：
Several prognostic indicators have shown inconsistencies in patients of different genders with lung adenocarcinoma, indicating that these variations may be due to the different genetic background of males and females with lung adenocarcinoma. In this study, we first used the Gene-Cloud of Biotechnology Information (GCBI) bioinformatics platform to identify differentially expressed genes (DEGs) that eliminated gender differences between lung adenocarcinoma and normal lung tissues. Then, we screened out that transcription factor 21 (TCF21) is a hub gene among these DEGs by creating a gene co-expression network on the GCBI platform. Furthermore, we used the comprehensive survival analysis platforms Kaplan-Meier plotter and PrognoScan to assess the prognostic value of TCF21 expression in lung adenocarcinoma patients. Finally, we concluded that decreased mRNA expression of TCF21 is a predictor for poor prognosis in patients with lung adenocarcinoma.
摘要：
Diallyl disulfide (DADS) is a primary component of garlic, which has chemopreventive potential. We previously found that moderate doses (15-120 microM) of DADS induced apoptosis and G2/M phase cell cycle arrest. In this study, we observed the effect of low doses (8 microM) of DADS on human leukemia HL-60 cells. We found that DADS could inhibit proliferation, migration and invasion in HL-60 cells, and arrested cells at G0/G1 stage. Then, cell differentiation was displayed by morphologic observation, NBT reduction activity and CD11b evaluation of cytometric flow. It showed that DADS induced differentiation, reduced the ability of NBT and increased CD11b expression. Likewise, DADS inhibited xenograft tumor growth and induced differentiation in vivo. In order to make sure how DADS induced differentiation, we compared the protein expression profile of DADS-treated cells with that of untreated control. Using high resolution mass spectrometry, we identified 18 differentially expressed proteins after treatment with DADS, including four upregulated and 14 downregulated proteins. RT-PCR and western blot assay showed that DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), Calreticulin (CTR) and PCNA were decreased by DADS. These data suggest that the effects of DADS on leukemia may be due to multiple targets for intervention.
作者机构：
[Yi, Lan; Mu, Hongxiang; Sun, Jing] Univ South China, Coll Pharm & Biol Sci, Biol Res Inst, Hengyang, Hunan, Peoples R China.;[Yi, Lan; Dai, Keren] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Hunan, Peoples R China.
通讯机构：
[Yi, Lan] U;Univ South China, Coll Pharm & Biol Sci, Biol Res Inst, Hengyang, Hunan, Peoples R China.
摘要：
Calreticulin (CRT) is an endoplasmic reticulum luminal calcium-binding protein with multiple cellular functions, including intracellular Ca2+ homeostasis, oxidative stress responses, and lectin binding. CRT can also modulate cell adhesion, cell-cell interactions, migration, phagocytosis, integrin-dependent Ca2+ signaling, and immune responses, and plays an important role in cellular proliferation, differentiation, and apoptosis. Given these roles, it is not surprising that CRT function has important implications in health and disease. Considerable evidence in recent years suggests that CRT dysfunction is associated with cancer and that CRT could be a diagnostic marker and a target for cancer therapy. These topics are discussed in depth in this review.
摘要：
The present study aimed to explore the effect of hydrogen sulfide (H2S) on renal tissue fibrosis and its mechanism in diabetic rats. Rats were randomly divided into four groups (n=13/group): Control group; induced diabetes mellitus group (STZ); induced diabetes mellitus treated with H2S group (STZ + H2S); normal rats treated with H2S group (H2S). The diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg body weight streptozotocin (STZ); the control group was treated with saline every day (i.p); NaHS (100 mu mol/kg i.p.) was administered to rats of STZ + H2S group and H2S group. After 8 weeks, rat body weight and 24 h proteinuria levels were determined in each group, renal pathological morphology was analyzed by Masson's trichrome staining, collagen IV content was detected by immunohistochemistry, and periodic acid-Schiff (PAS) staining was performed on renal glomerular and tubular basement membranes. The expression levels of matrix metalloproteinase 9 (MMP9), MMP7, tissue inhibitor of metalloproteinase 1 (TIMP1), superoxide dismutase (SOD), serine/threonine kinase AKT, transforming growth factor (TGF) -beta 1, nuclear factor (NF)-kappa B and several autophagy related proteins were assessed by western blot analysis. Compared with the control group, renal tissue fibrosis was observed, collagen IV expression and the 24 h proteinuria quantity was markedly increased and the amount of PAS positive material in renal glomerular and tubular basement membranes was notably increased in STZ-treated rats. Furthermore, the expression levels of MMP9, MMP7, TIMP1, autophagy-associated proteins, AKT, TGF-beta 1 and NF-kappa B protein were significantly increased, and SOD expression levels were significantly decreased in the STZ group compared with the control (P<0.05). In the H2S + STZ group, renal tissue fibrosis and the expression of collagen IV were improved, 24 h proteinuria was decreased, the amount of PAS positive material in renal glomerular and tubular basement membranes was decreased, the expression levels MMP9, MMP7, TIMP1, autophagy-associated proteins, AKT, TGF-beta 1 and NF-kappa B protein were significantly decreased, and the expression levels of SOD were significantly increased compared with the STZ group (P<0.05). In conclusion, H2S may improve renal tissue fibrosis by inhibiting autophagy, upregulating SOD and downregulating AKT, TGF-beta 1 and NF-kappa B.
摘要：
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001–2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.
摘要：
Deinococcus radiodurans has attracted a great interest in the past decades due to its extraordinary resistance to ionizing radiation and highly efficient DNA repair system. Recent studies indicated that pprM is a putative pleiotropic gene in D. radiodurans and plays an important role in radioresistance and antioxidation, but its underlying mechanisms are poorly elucidated. In this study, pprM mutation was generated to investigate resistance to desiccation and oxidative stress. The result showed that the survival of pprM mutant under desiccation was markedly retarded compared to the wild strain from day 7–28. Furthermore, knockout of pprM increases the intercellular accumulation of ROS and the sensibility to H2O2 stress in the bacterial growth inhibition assay. The absorbance spectrum experiment for detecting the carotenoid showed that deinoxanthin, a carotenoid that peculiarly exists in Deinococcus, was reduced in the pprM mutant in the pprM mutant. Quantitative real time PCR showed decreased expression of three genes viz. CrtI (DR0861, 50%),CrtB (DR0862, 40%) and CrtO (DR0093, 50%), which are involved in deinoxanthin synthesis, and of Dps (DNA protection during starving) gene (DRB0092) relevant to ion combining and DNA protection in cells. Our results suggest that pprM may affect antioxidative ability of D. radiodurans by regulating the synthesis of deinoxanthin and the concentration of metal ions. This may provide new clues for the treatment of antioxidants.
