摘要：
P>1. Adipocyte hypertrophy and hyperplasia are important processes in the development of obesity. To understand obesity and its associated diseases, it is important to elucidate the molecular mechanisms governing adipogenesis. MicroRNA-375 has been shown to inhibit differentiation of neurites, and participate in the regulation of insulin secretion and blood homeostasis. However, it is unknown whether miR-375 plays a role in adipocyte differentiation. 2. To investigate the role of miR-375 in adipocyte differentiation, we compared the miR-375 expression level between 3T3-L1 pre-adipocytes and adipocytes using miRNA microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Furthermore, we evaluated the effects of overexpression or inhibition of miR-375 on 3T3-L1 adipocyte differentiation. 3. In the present study, we found that miR-375 expression was increased after induction of adipogenic differentiation. Overexpression of miR-375 enhanced 3T3-L1 adipocyte differentiation, as evidenced by its ability to increase mRNA levels of both CCAAT/enhancer binding protein-alpha (C/EBP alpha) and peroxisome proliferator-activated receptor-gamma (PPAR gamma 2), and induction of adipocyte fatty acid-binding protein (aP2) and triglyceride (TG) accumulation. Furthermore, we found overexpression of miR-375 suppressed phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2). In contrast, anti-miR-375 increased ERK1/2 phosphorylation levels and inhibited mRNA expression of C/EBP alpha, PPAR gamma 2 and aP2 in 3T3-L1 adipocyte, accompanied by decreased adipocyte differentiation. 4. Taken together, these data suggest that miR-375 promotes 3T3-L1 adipocyte differentiation, possibly through modulating the ERK-PPAR gamma 2-aP2 pathway.
关键词：
Adult-onset type II citrullinemia (CTLN2);Aspartate-glutamate carrier (AGC);Citrin;Malate-aspartate shuttle;Neonatal intrahepatic cholestatic hepatitis (NICCD);Retrotransposal insertion;SLC25A13
摘要：
Deficiency of citrin, liver-type mitochondrial aspartate-glutamate carrier, is an autosomal recessive disorder caused by mutations of the SLC25A13 gene on chromosome 7q21.3 and has two phenotypes: neonatal intrahepatic cholestatic hepatitis (NICCD) and adult-onset type II citrullinemia (CTLN2). So far, we have described 19 SLC25A13 mutations. Here, we report 13 novel SLC25A13 mutations (one insertion, two deletion, three splice site, two nonsense, and five missense) in patients with citrin deficiency from Japan, Israel, UK, and Czech Republic. Only R360X was detected in both Japanese and Caucasian. IVS16ins3kb identified in a Japanese CTLN2 family seems to be a retrotransposal insertion, as the inserted sequence (2,667-nt) showed an antisense strand of processed complementary DNA (cDNA) from a gene on chromosome 6 (C6orf68), and the repetitive sequence (17-nt) derived from SLC25A13 was found at both ends of the insert. All together, 30 different mutations found in 334 Japanese, 47 Chinese, 11 Korean, four Vietnamese and seven non-East Asian families have been summarized. In Japan, IVS16ins3kb was relatively frequent in 22 families, in addition to known mutations IVS11 + 1G > A, 851del4, IVS13 + 1G > A, and S225X in 189, 173, 48 and 30 families, respectively; 851del4 and IVS16ins3kb were found in all East Asian patients tested, suggesting that these mutations may have occurred very early in some area of East Asia.
作者：
Ling, H. -y.;Hu, B.;Hu, X. -b.;Zhong, J.;Feng, S. -d.;Qin, L.;Liu, G.;Wen, G. -b.;Liao, D. -f.
期刊：
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association,2012年120(9):553-559 ISSN：0947-7349
通讯作者：
Liao, DF
作者机构：
[Hu, B.; Ling, H. -y.] Univ S China, Sch Med, Dept Physiol, Hengyang, Peoples R China.;[Hu, X. -b.] Univ S China, Sch Life Sci & Technol, Dept Biochem & Mol Biol, Hengyang, Peoples R China.;[Liu, G.; Qin, L.] Univ S China, Inst Pharm & Pharmacol, Key Lab Pharmacoprote Hunan Prov, Hengyang, Peoples R China.;[Liao, D. -f.] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.;[Feng, S. -d.] Univ S China, Sch Publ Hlth, Dept Epidemiol, Hengyang, Peoples R China.
通讯机构：
[Liao, DF] Hunan Univ Chinese Med, State Key Lab Chinese Med Powder & Med Innovat Hu, Div Stem Cell Regulat & Applicat, Changsha 410208, Hunan, Peoples R China.
关键词：
miR-21;insulin resistance;PTEN;AKT
摘要：
Aims/hypothesis: Our previous study showed there was a change of microRNA (miRNA) expression profile, and miR-21 was significantly down regulated in insulin-resistant adipocytes (IR-adipocytes). Phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, was identified to be a target gene of miR-21, which suggested miR-21 might be associated with insulin resistance (IR) or diabetes. However, it is not known whether miR-21 play any role in the development of IR in 3T3-L1 adipocytes. Methods: Normal adipocytes and adipocytes transfected with pre-miR-21(pmiR-21) or negative control (pNeg) were treated with high glucose and high insulin for 24 h, insulin-stimulated glucose uptake was determined by 2-Deoxyglucose transport assay, miR-21 expression level was measured by using quantitative real-time RT-PCR (qRT-PCR). The protein expression levels of PTEN, Akt, phospho-Akt (Ser473), IR beta, GSK3 beta, phospho-GSK3 beta (Ser9) and GLUT4 were detected by western blotting assay. Results: We further confirmed that miR-21 was down regulated in IR-adipocytes by qRT-PCR. Over-expression of miR-21 significantly increased insulin-induced glucose uptake and decreased PTEN protein expression, while it had no significant effect on PTEN mRNA expression in IR-adipocytes. Moreover, over-expressing miR-21 significantly increased insulin-induced phosphorylation of AKT (Ser473), GSK3 beta (Ser9) and the translocation of glucose transporter 4 (GLUT4) in IR-adipocytes. Conclusions: In this study, our data demonstrate that miR-21 reverses high glucose and high insulin induced IR in 3T3-L1 adipocytes, possibly through modulating the PTEN-AKT pathway, and miR-21 may be a new therapeutic target for metabolic diseases such as T2DM and obesity.
摘要：
Aldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated with tumorigenic transformation of human mammary epithelial cells. This study demonstrated that AKR1B10 was overexpressed in 20 (71.4%) of 28 ductal carcinomas in situ, 184 (83.6%) of 220 infiltrating carcinomas and 28 (87.5%) of 32 recurrent tumors. AKR1B10 expression in breast cancer was correlated positively with tumor size (p = 0.0012) and lymph node metastasis (p = 0.0123) but inversely with disease-related survival (p = 0.0120). Univariate (p = 0.0077) and multivariate (p = 0.0192) analyses both suggested that AKR1B10, alone or together with tumor size and node status, is a significant prognostic factor for breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Importantly, AKR1B10 in the serum of breast cancer patients was significantly increased to 15.18 +/- 9.08 ng/ml [n = 50; 95% confidence interval (CI), 12.6017.76], with a high level up to 58.4 ng/ml, compared to 3.34 +/- 2.27 ng/ml in healthy donors (n = 60; 95% CI, 2.783.90). In these patients, AKR1B10 levels in serum were correlated with its expression in tumors (r = 0.8066; p < 0.0001). Together our data suggests that AKR1B10 is overexpressed in breast cancer and may be a novel prognostic factor and serum marker for this deadly disease.
期刊：
Cancer immunology research,2016年4(5):419-430 ISSN：2326-6066
通讯作者：
He, AR
作者机构：
[He, Aiwu Ruth] Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia. arh29@georgetown.edu;[Gatalica, Zoran; Reddy, Sandeep] Caris Life Science, Irving, Texas;[Marshall, John; Feng, Perry; Tesfaye, Anteneh; Kachhela, Jaydeep; Loffredo, Christopher; Wang, Hongkun; Gabrielson, Andrew; Zhang, Tiger; Atkins, Michael; Jiang, Jiji; Weiner, Louis; Prins, Petra] Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia;[Kallakury, Bhaskar] Department of Pathology, Georgetown University Hospital, Washington, District of Columbia;[Fishbein, Thomas; Satoskar, Rohit; Island, Eddie] Medstar Transplant Institute, Georgetown University Hospital, Washington, District of Columbia
通讯机构：
[He, AR] MedStar Georgetown Univ Hosp, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.;Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
摘要：
Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. (c)2016 AACR.
作者机构：
[Zeng, Yang; Nie, Ya-Xiong; Jing, Kai-Quan] Department of Neurology of the First Affiliated Hospital, University of South China, Hengyang, People's Republic of China;[Liao, Duan-Fang] Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha,Poeple's Republic of China;[Tong, Qiao-Zhen; Zheng, Xi-Long; Gu, Hong-Feng] Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, People's Republic of China;[Zheng, Xi-Long] Smooth Muscle Research Group, Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada;[Tang, Ya-Ling; Gu, Hong-Feng] Department of Physiology & Institute of Neuroscience, University of South China, Hengyang, People's Republic of China
摘要：
Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (A beta(1-42)) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.
期刊：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2012年420(1):17-23 ISSN：0006-291X
通讯作者：
Yi, GH
作者机构：
[Liu, Jiang-Hua; Zu, Xu-Yu; Cao, Ren-Xian; Zhang, Qing-Hai] Univ S China, Affiliated Hosp 1, Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.;[Yi, Guang-Hui; Mo, Zhong-Cheng; Zhang, Qing-Hai; Li, Yuan-Bin; Zeng, Ying; Xiong, Sheng-Lin; Liu, Xing] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yi, GH] Univ S China, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
关键词：
HDL;SR-B1;PI3K;eNOS;COX-2;PGI(2)
摘要：
It is well-known that sphingosine-l-phosphate (SIP), the phospholipid content of HDL, binding to SIP receptors can raise COX-2 expression and PGI(2) release through p38MAPK/CREB pathway. In the present study we assess the action of SR-B1 initiated PI3K-Akt-eNOS signaling in the regulation of COX-2 expression and PGI(2) production in response to HDL. We found that apoA1 could increase PGI(2) release and COX-2 expression in ECV 304 endothelial cells. Furthermore, SR-B1 was found to be involved in HDL induced up-regulation of COX-2 and PGI(2). Over-expressed SR-B1 did not significantly increase the expression of COX-2 and the PGI(2) levels, but knock-down of SR-B1 by siRNA could significantly attenuate COX-2 expression and PGI(2) release together with p38MAPK and CREB phosphorylation. Consistently, the declines of p-p38MAPK, p-CREB, COX-2 and PGI(2) were also observed after incubation with LY294002 (25 mu mol/L; PI3K special inhibitor) or L-NAME (50 mu mol/L; eNOS special inhibitor). In addition, we demonstrated the increases of PGI(2) release, COX-2 expression and p38MAPK phosphorylation, when nitric oxide level was raised through the incubation of L-arginine (10 or 20 nmol/L) in endothelial cells. Taking together, our data support that SR-B1 mediated PI3K-Akt-eNOS signaling was involved in HDL-induced COX-2 expression and PGI(2) release in endothelial cells. (C) 2012 Elsevier Inc. All rights reserved.
摘要：
Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of hearing loss. Of these, the homoplasmic A1555G and C1494T mutations at the highly conserved decoding site of the 12S rRNA gene are well documented as being associated with either aminoglycoside-induced or nonsyndromic hearing loss in many families worldwide. Moreover, five mutations associated with nonsyndromic hearing loss have been identified in the tRNA(Ser(UCN)) gene: A7445G, 7472insC, T7505C, T7510C, and T7511C. Other mtDNA mutations associated with deafness are mainly located in tRNA and protein-coding genes. Failures in mitochondrial tRNA metabolism or protein synthesis were observed from cybrid cells harboring these primary mutations, thereby causing the mitochondrial dysfunctions responsible for deafness. This review article provides a detailed summary of mtDNA mutations that have been reported in deafness and further discusses the molecular mechanisms of these mtDNA mutations in deafness expression.
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION,2017年317(24):2502-2514 ISSN：0098-7484
通讯作者：
Wu, XK
作者机构：
[Liu, Jian-Ping] Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China;[Ding, Cai-Fei] Centre for Reproductive Medicine, Zhejiang Province Hospital of Integrative Medicine, Hangzhou, China;[Fu, Ping] Department of Gynecology, Hangzhou City Hospital of Chinese Medicine, Hangzhou, China;[Sun, Yun] Department of Gynecology, Wenzhou City Hospital of Chinese Medicine, Wenzhou, China;[Hou, Li-Hui; Xie, Liang-Zhen; Kuang, Hong-Ying; Gao, Jing-Shu; Ma, Hong-Li] Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
通讯机构：
[Wu, XK] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Dept Obstet & Gynecol, Harbin 150040, Peoples R China.
摘要：
Importance: Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective: To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants: A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions: Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures: The primary outcome was live birth. Secondary outcomes included adverse events. Results: Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, -0.6%; 95% CI, -5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance: Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration: clinicaltrials.gov Identifier: NCT01573858.
作者：
Xu, C-X;Wang, C.;Zhang, Z-M;Jaeger, C. D.;Krager, S. L.;Bottum, K. M.;Liu, J.;Liao, D-F;Tischkau, S. A.
期刊：
International journal of obesity (2005),2015年39(8):1300-1309 ISSN：0307-0565
通讯作者：
Tischkau, SA
作者机构：
[Wang, C.; Tischkau, S. A.; Jaeger, C. D.; Xu, C-X] Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA;[Zhang, Z-M] 1;[Krager, S. L.; Bottum, K. M.] Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA;[Liu, J.] Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, China;[Liao, D-F] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha, China
通讯机构：
[Tischkau, SA] So Illinois Univ, Sch Med, Dept Pharmacol, 801N Rutledge St, Springfield, IL 62702 USA.
摘要：
BACKGROUND/OBJECTIVES: Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined. METHODS: Male wild-type (WT), AhR null (AhR(-/-)) and AhR heterozygote (AhR(+/-)) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed. RESULTS: AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared with WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial beta-oxidation genes in muscle were significantly higher in AhR(-/-) and AhR(+/-) mice compared with WT. CONCLUSIONS: This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders.
摘要：
BACKGROUND: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-gamma (SNCG). MATERIALS AND METHODS: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. RESULTS: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. CONCLUSIONS: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.
期刊：
Journal of ethnopharmacology,2016年192:382-389 ISSN：0378-8741
通讯作者：
Dai, Bing;Xiao, Zizeng
作者机构：
[Zhang, Jiani; Cao, Luting; Wu, Qinxuan] Changsha Medical University, Changsha, Hunan 410219, China;[Zeng, Chengxi] Changsha Social Work College, Changsha, Hunan 410000, China;[Xiao, Zizeng] Changsha Social Work College, Changsha, Hunan 410000, China. Electronic address: 15570883815@163.com;[Yang, Menglin] Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410208;[Dai, Bing] The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shaoshan Road, Changsha, Hunan 410007, China. Electronic address: db0223@163.com
通讯机构：
[Xiao, Zizeng] Changsha Social Work College, Changsha, Hunan 410000, China. Electronic address:;[Dai, Bing] The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Shaoshan Road, Changsha, Hunan 410007, China. Electronic address:
关键词：
Type 2 diabetes mellitus;Liuwei Dihuang decoction;PI3K/Akt signaling pathway
摘要：
Ethnopharmacological relevance: Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. Materials and methods: T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group-vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. Results: Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI31<, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI31</Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI31<, and Akt protein had no obvious changes. Conclusions: The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
摘要：
Essential hypertension (EH) is a frequent, chronic, age-related disorder, which remains a major modifiable risk factor for cardiovascular disease despite important advances in our understanding of its pathophysiology. Previous studies have noted a consistent maternal effect on blood pressure (BP). Consequently, mutations in mitochondrial DNA (mtDNA) have become an additional target of investigations on the missing BP heritability. Among these mutations, mt-transfer RNA (tRNA) is a hot mutational spot for pathogenic mutations associated with EH. Mutant mtDNA aggravates mitochondrial dysfunction, pivotally contributing to the clinical phenotype. Moreover, the damaged mitochondria, due to their inability to provide the high-energy requirements for cells, generate reactive oxygen species (ROS) and induce mitochondrial-mediated cell death pathways. Therefore, mitochondrial dysfunction plays a critical role in the pathogenesis of EH. This review summarizes the basic knowledge of mitochondrial genetics and EH-associated mtDNA mutations and further discusses the molecular mechanisms behind these mtDNA mutations in clinical manifestations of EH.
摘要：
It has been reported that the effect of inflammatory cytokines on beta-cell destruction in type 1 diabetes is concentration-dependent. However, the underlying mechanisms remain unclear. In the present study, we found that a high concentration of cytokines promoted apoptosis in the rat beta-cell line INS-1, whereas a low concentration of cytokines had no effect. We also found that cytokines at a low concentration stimulated neutral ceramidase (NCDase) release via exosomes from INS-1 cells, whereas cytokines at a high concentration inhibited NCDase release. Furthermore, the results showed that the NCDase-containing exosomes isolated from the culture medium of INS-1 cells treated with cytokines at a low concentration inhibited apoptosis induced by a high concentration of cytokines. Finally, the results also showed that the protective action of NCDase in the exosomes on apoptosis was mediated by the generation of sphingosine 1-phosphate (S1P) and its interaction with S1P receptor 2. Taken together, these findings revealed a novel NCDase-S1P-phosphate-S1P receptor 2-dependent mechanism by which a low level of inflammatory cytokines protects pancreatic beta-cells from apoptosis induced by a high level of inflammatory cytokines.
期刊：
International immunopharmacology,2015年25(1):49-54 ISSN：1567-5769
通讯作者：
Wang, Haibin;Song, Houpan
作者机构：
[Liu, Wengang] The 2nd Traditional Chinese Medicine Hospital of Guangdong Province, Guangdong Province, China;[Song, Houpan] Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, Hunan 410007, China. Electronic address: houpan_song@163.com;[He, Wei; Zhou, Chi; Chen, Qunqun] The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China;[Wang, Haibin] The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: haibin_wanggz@163.com
通讯机构：
[Wang, Haibin] The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address:;[Song, Houpan] Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, Hunan 410007, China. Electronic address:
摘要：
Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin a (SSa) possesses anti-inflammatory activity. However, the role of SSa in osteoporosis is still unclear. Therefore, the objective of this study was to investigate the effects of SSa on receptor activator of the nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro assay. In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus macrophage colony-stimulating factor (M-CSF)-induced osteodast differentiation in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related marker proteins expression, including NFATcl, c-fos and cathepsin K At molecular levels, SSa inhibited RANKL-induced I kappa B alpha phosphotylation, p65 phosphorylation and NF-kappa B luciferase activity in RAW264.7 cells. And SSa also suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these findings suggest that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38, ERK, JNK and NF-kappa B activation. SSa is a novel agent in the treatment of osteodast-related diseases, such as osteoporosis. (C) 2015 Elsevier B.V. All rights reserved.
期刊：
LIFE SCIENCES,2014年117(1):19-23 ISSN：0024-3205
通讯作者：
Wang, Wei
作者机构：
[Jian, Zijuan; Guo, Jingjing] Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, PR China;[Wang, Wei] Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address: weiweiwang1983@163.com;[Ning, Xingwang] Department of Clinical Laboratory, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, PR China
通讯机构：
[Wang, Wei] Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address:
摘要：
Aims: The clinical significance of myeloperoxidase (MPO) has been the focus of investigation because it may contribute to the chronic, non-microbial inflammatory process in various diseases. Here, we determined serum MPO levels in rheumatoid arthritis (RA) and other autoimmune or inflammatory conditions, and investigated the associations between MPO levels and disease activity indicators in RA. Main methods: The distribution of MPO was determined in serum samples from patients with RA, systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), dermatomyositis (DM), or ankylosing spondylitis (AS) and from healthy controls using commercial ELISA kits. Associations of serum MPO levels with the disease variables of RA patients were evaluated. Key findings: All patient samples analyzed showed higher serum levels of MPO than healthy controls. Furthermore, MPO levels in RA were significantly higher than those in the other diseases with the exception of DM. Higher MPO levels were observed in RA patients with increased C-reactive protein (p = 0.005) or neutrophil percentage (p < 0.001), as well as in those with highly active disease (p < 0.001). Moderate positive correlations between MPO levels and IgM (r = 0.334, p = 0.001),C-reactive protein (r = 0.293, p = 0.003), erythrocyte sedimentation rate (r = 0.240, p = 0.016), or DAS28 (r = 0.350, p < 0.001) were also demonstrated. Significance: The MPO concentration is likely to increase in patients with chronic inflammation. The associations between MPO and the disease variables of RA patients support a role for MPO in the inflammatory process of the disease. (C) 2014 Elsevier Inc. All rights reserved.
期刊：
JOURNAL OF TRADITIONAL CHINESE MEDICINE,2009年29(01):50-53 ISSN：0255-2922
通讯作者：
Chen, MR
作者机构：
[魏高文; 陈美仁; 郭翔; 王萍] Hunan TCM Profess Training Coll, Zhuzhou 412012, Peoples R China.;[成钢; 成旭辉] Hunan TCM Profess Training Coll, Affiliated Hosp 1, Hunan, Peoples R China.
通讯机构：
[Chen, MR] Hunan TCM Profess Training Coll, Zhuzhou 412012, Peoples R China.
关键词：
坐骨神经痛;针刺治疗;升温;温针灸治疗;痛阈测定;治疗效果;穴位注射;临床症状
摘要：
Objective: To observe the relation between the pain threshold and the therapeutic effects of acupuncture for sciatica. Methods: 90 sciatica patients were equally divided at random into the following 3 groups: a warming acupuncture group treated with the needles warmed by burning moxa, a western medicine group administered Nimesulide tablets and a point-injection group with Anisodamine injected. The pain threshold was tested before treatment and after the first, second and third treatment courses. Results: The warming acupuncture therapy showed better therapeutic effects than the other two groups with significant differences in the change of pain threshold and the improvement of clinical symptoms and signs (P<0.01). Conclusion: Acupuncture can relieve the symptoms of sciatica with the increase of pain threshold.
作者：
Xu Zhaojun;Zhang Caiping;Cheng Lijuan;Hu Mei;Tao Huai;Song Lan
期刊：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2014年445(1):48-53 ISSN：0006-291X
通讯作者：
Song, Lan
作者机构：
[Tao Huai; Song Lan; Cheng Lijuan; Hu Mei] Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Song Lan] Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (Incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Song Lan] University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China. Electronic address: songlan311492@163.com;[Zhang Caiping] University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China;[Xu Zhaojun] Cardiothoracic Surgery of the First Affiliated Hospital, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 41007, China
通讯机构：
[Song, Lan] University of South China, College of Life Science, Department of Biochemistry and Molecular Biology, Hengyang, Hunan 421001, China. Electronic address:
关键词：
Acute lung injury;Alveolar type II epithelial cells;FoxA1;miR-17;Gene expression
摘要：
Acute lung injury (ALI) is a severe pulmonary disease that causes a high number of fatalities worldwide. Studies have shown that FoxA1 expression is upregulated during ALI and may play an important role in ALI by promoting the apoptosis of alveolar type II epithelial cells. However, the mechanism of FoxA1 overexpression in ALI is unclear. In this study, an in vivo murine model of ALI and alveolar type II epithelial cells injury was induced using lipopolysaccharide (LPS). LPS upregulated FoxA1 in the lung tissue of the in vivo ALI model and in LPS-challenged type II epithelial cells. In contrast, miR-17 was significantly downregulated in these models. After miR-17 antagomir injection, the expression of FoxA1 was significantly increased in ALI mice. MiR-17 mimics could significantly inhibit FoxA1 mRNA and protein expression, whereas the miR-17 inhibitor could significantly increase FoxA1 mRNA and protein expression in LPS-induced type II epithelial cells. Thus, our results suggest that the downregulation of miR-17 expression could lead to FoxA1 overexpression in ALI. (C) 2014 Elsevier Inc. All rights reserved.
关键词：
Pancreatic cancer;RNA interference (RNAi);X-linked apoptosis inhibiting protein (XIAP);Survivin;Lentivirus;Proliferation;Apoptosis;Chemosensitivity
摘要：
At present, classic therapies provide limited benefits to the survival of patients with pancreatic cancer. However, clinically available gene therapy strategies have not been well established. This study investigates the effect of shRNA-mediated inhibition of XIAP and survivin expression on the proliferation, apoptosis, and chemosensitivity of pancreatic cancer cells. Stable inhibition of XIAP and survivin expression in SW1990 and Panc-1 pancreatic cancer cells was established by lentivirus-carried shRNAs. The mRNA and protein expression of XIAP and survivin were detected by real-time PCR and Western blot, respectively. Cell proliferation was measured by MTT assay, and apoptosis was detected by caspase-3/7 activity and Hoechst33342 staining. The lentivirus-carried shRNA significantly inhibited XIAP and survivin expression. Simultaneous inhibition of XIAP and survivin expression in pancreatic cells significantly reduced cell proliferation, increased caspase-3/7 activity, and increased cell sensitization to 5-FU and gemcitabine treatments compared to inhibition of XIAP or survivin expression alone. However, simultaneous silencing of XIAP and survivin showed no significant difference in inducing cell apoptosis compared to silencing of XIAP or survivin expression alone. Simultaneous inhibition of XIAP and survivin expression may be an effective strategy for gene therapy of pancreatic cancer.
作者机构：
[Zheng, Hua-Bin] Chengdu Univ Tradit Chinese Med, Teaching Hosp, Chengdu, Sichuan, Peoples R China.;[Liu, Zhi-Shun; Zhang, Wei] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing, Peoples R China.;[Zheng, Hui; Li, Ying; Zhou, Si-Yuan; Zeng, Fang] Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Coll, Chengdu, Sichuan, Peoples R China.;[Wang, Shi-Jun] Shandong Univ Tradit Chinese Med, Jinan, Shandong, Peoples R China.;[Tang, Chun-Zhi] Guangzhou Univ Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China.
通讯机构：
[Zhu, B] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China.;[Liu, ZS] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing, Peoples R China.
摘要：
Diarrhea-predominant irritable bowel syndrome (IBS-D) and functional diarrhea (FD) are highly prevalent, and the effectiveness of acupuncture for managing IBS-D and FD is still unknown. The aim of this study was to compare the effectiveness of electroacupuncture with loperamide. It was a prospective, randomized, parallel group controlled trial. A total of 448 participants were randomly assigned to He electroacupuncture group (n = 113), Shu-Mu electroacupuncture group (n = 111), He-Shu-Mu electroacupuncture group (n = 112), or loperamide group (n=112). Participants in the 3 acupuncture groups received 16 sessions of electroacupuncture during a 4-week treatment phase, whereas participants in the loperamide group received oral loperamide 2 mg thrice daily. The primary outcome was the change from baseline in stool frequency at the end of the 4-weeks treatment. The secondary outcomes were the Bristol scale, the MOS 36-item short form health survey (SF-36), the weekly average number of days with normal defecations and the proportion of adverse events. Stool frequency was significantly reduced at the end of the 4-week treatment in the 4 groups (mean change from baseline, 5.35 times/week). No significant difference was found between the 3 electroacupuncture groups and the loperamide group in the primary outcome (He vs. loperamide group [mean difference 0.6, 95% CI, -1.2 to 2.4]; Shu-Mu vs. loperamide group [0.4, 95% CI, -1.4 to 2.3]; He-Shu-Mu vs. loperamide group [0.0, 95% CI, -1.8 to 1.8]). Both electroacupuncture and loperamide significantly improved the mean score of Bristol scale and increased the weekly average number of days with normal defecations and the mean scores of SF-36; they were equivalent in these outcomes. However, the participants in electroacupuncture groups did not report fewer adverse events than those in the loperamide group. Similar results were found in a subgroup analysis of separating patients with IBS-D and FD patients.
