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.
期刊:
Die Pharmazie,2017年72(9):503-510 ISSN:0031-7144
通讯作者:
Yi, Lan
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.
期刊:
The Journal of Organic Chemistry,2017年82(15):8273-8281 ISSN:0022-3263
通讯作者:
Xiao, Ji-Chang;Zheng, Xing;Lin, Jin-Hong
作者机构:
[Xiao, Ji-Chang; Zheng, Xing; Huang, Qiu-xia; Zheng, Qu-tong] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Lin, JH; Xiao, Ji-Chang; Zheng, Xing; Huang, Qiu-xia; Duan, Yaya; Lin, Jin-Hong; Zheng, Qu-tong] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China.
通讯机构:
[Xiao, JC; Zheng, X; Lin, JH] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China.
摘要:
The highly diastereoselective synthesis of CF3-containing vicinal diamines by a convenient two-step procedure without the need to isolate the intermediate products is described.
摘要:
Apelin acts as the endogenous ligand of G protein coupled receptors APJ. The apelin/APJ systemis responsible for the occurrence and development of cardiovascular diseases. In recent years, apelin/APJ has been considered to play an important role in cardiac hypertrophy, but whether that role is beneficial or aggravating remains controversial. Apelin/APJ alleviates cardiac hypertrophy which is triggered by angiotensin II, oxidative stress and exercise. However, central administration of apelin induces cardiac hypertrophy. Peripheral administration of apelin also promotes the development of cardiac hypertrophy under non-pathological conditions. Furthermore, our laboratory discovers that apelin/APJ is able to induce hypertrophy of cardiomyocytes in vitro. The exact mechanism of apelin/APJ's dual effects in cardiac hypertrophy requires further study. In this paper, we review the controversies associated with apelin/APJ in cardiac hypertrophy and we elaborate the role of apelin/APJ in cardiac hypertrophy related-diseases including obesity, diabetes, hypertension, myocarditis and myocardial infarction. We conclude that further studies should emphasize more about the relationship between apelin/APJ and pathological hypertrophy especially in clinical patients. Moreover, apelin/APJ can be a promising therapeutic target for cardiac hypertrophy. (C) 2016 Published by Elsevier Ireland Ltd.
作者机构:
[Tang, Dan; Ou, Weiwei; Wang, Deming; Chen, Quan; Wang, Jiazheng; Xiao, Ji] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Mo, Zhongcheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, Deming; Peng, Liangyu] U;Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
关键词:
liver X receptor;cytokine;mRNA decay;tristetraprolin;mitogen-activated protein kinase
摘要:
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.
摘要:
The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received <50, 50-500, and 500-1000 muGy/h of 137Cs radiation for 180 d. We found that the pathological changes in liver tissues were more obvious as the irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had >/= 1.5-fold changes in expression. Twenty-three proteins were selected based on >/=2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.