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.
摘要：
Apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Vascular smooth muscle cells express both apelin and APJ, which are important regulatory factors in the cardiovascular and nervous systems. Importantly, APJ is also involved in the pathogenesis if HIV-1 infection. We investigated whether vascular smooth muscle cell proliferation was regulated through an apelin-pERK1/2-cyclin D1 signal transduction pathway. Apelin-13 significantly stimulated vascular smooth muscle cell proliferation and increased cell cycle progression. Apelin-13 a decreased the proportion of cell in the G0/G1 phase while increasing the number of cells in S phase. Apelin-13 also increased the levels of cyclin D1, cyclin E and pERK1/2. Treatment of cells with the MEK inhibitor PD98059 attenuated the apelin-3-induced pERK1/2 activation. Similarly, treatment with PD98059 partially diminished the apelin-13-induced expression of cyclin D1 and vascular smooth muscle cell proliferation. Taken together, these data established that apelin-13 stimulates vascular smooth muscle cell proliferation by promoting the G1-S phase transition, and that this effect is mediated in part by an apelin-pERK1/2-cyclin D1 signal cascade.
期刊：
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,2012年184(4):401-410 ISSN：0820-3946
通讯作者：
Liang, FR
作者机构：
[Huang, Wen-jing; Liang, Fan-rong; Zheng, Hui; Li, Ying; Zhao, Ling; Yu, Shu-guang] Chengdu Univ Tradit Chinese Med, Chengdu, Sichuan, Peoples R China.;[Huang, Wen-jing; Roll, Stephanie; Witt, Claudia M.] Charite Univ Med Ctr, Inst Social Med, Berlin, Germany.;[Yan, Jie; Chang, Xiao-rong; Lan, Lei] Hunan Univ Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Sun, Guo-jie; Zou, Ran; Zhang, Hong-xing] Hubei Univ Tradit Chinese Med, Wuhan, Hubei, Peoples R China.;[Witt, Claudia M.] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA.
通讯机构：
[Liang, FR] Chengdu Univ Tradit Chinese Med, Chengdu, Sichuan, Peoples R China.
摘要：
BACKGROUND: Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture. METHODS: We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5-8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life. RESULTS: Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5-8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13-16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference -1.06 [95% confidence interval (CI) -1.77 to -0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference -1.22 [95% CI -1.92 to -0.52], p < 0.001; Yangming-specific acupuncture v. control: difference -0.91 [95% CI -1.61 to -0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups. INTERPRETATION: Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture. TRIAL REGISTRATION: Clinicaltrials.gov NCT00599586.
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.
作者机构：
[Zhou, Xuan; Li, Lin-Zi; Peng, Yi-Han; Zhang, Zhao-Jie; Liu, Li-Li; Yun, Jing-Ping; Lu, Shi-Xun; Zhang, Chris Zhiyi; Yang, Yuan-Zhong] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China.;[Zhou, Xuan; Li, Lin-Zi; Peng, Yi-Han; Zhang, Zhao-Jie; Liu, Li-Li; Yun, Jing-Ping; Lu, Shi-Xun; Zhang, Chris Zhiyi; Yang, Yuan-Zhong] Sun Yat Sen Univ, Ctr Canc, Dept Pathol, Guangzhou 510060, Guangdong, Peoples R China.;[Yi, Chun] Hunan Univ Chinese Med, Coll Med, Dept Pathol, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Yun, JP] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China.
摘要：
Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that microRNAs (miRNAs) are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly downregulated in primary breast cancer, with greater downregulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased expression of miR-720 was correlated with lymph node metastasis. Furthermore, reexpression of miR-720 in breast cancer cells remarkably inhibited cell invasiveness and migration both in vitro and in vivo. Mechanistically, downregulation of TWIST1, a promoter of metastasis that was identified as a direct functional target of miR-720, was attributed to the inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast cancer, reexpression of miR-720 upregulated epithelial markers (E-cadherin and beta-catenin) and downregulated mesenchymal markers (N-cadherin, fibronectin, vimentin and matrix metalloproteinase-2). Expression of miR-720 was inversely associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1 expression by small interfering RNA exhibited similar effects to reintroduction of miR-720, whereas overexpression of TWIST1 (without the 3'-untranslated region) abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate that miR-720 is frequently decreased in breast cancer and manifests antimetastatic activity by downregulating TWIST1, presenting a novel mechanism of miRNA-mediated regulation of tumor metastasis.
期刊：
Journal of ethnopharmacology,2009年121(3):412-418 ISSN：0378-8741
通讯作者：
Deng, CQ
作者机构：
[Deng, Chang-Qing; Liang, Yan; Zhang, Shu-Ping] Hunan Univ Tradit Chinese Med, Lab Pathophysiol, Changsha, Hunan, Peoples R China.;[Chen, Bei-Yang; Li, Hua] Hunan Univ Tradit Chinese Med, Dept Histol & Embryol, Changsha, Hunan, Peoples R China.;[Luo, Xue-Gang; Li, Hua] Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha, Hunan, Peoples R China.
通讯机构：
[Deng, CQ] Hunan Univ Tradit Chinese Med, Lab Pathophysiol, Changsha, Hunan, Peoples R China.
关键词：
Total saponins of Panax notoginseng;Cerebral ischemia-reperfusion;TUNEL;Caspase-1;Caspase-3;Caspase-8
摘要：
Ethnopharmacological relevance: Total saponins of Panax notoginseng (TSPN), main constituents extracted from Panax Notoginseng, a highly valued traditional Chinese medicine, have been shown to be an effective agent on cerebral infarction. Aim of the study: The effects of TSPN on apoptosis and expressions of caspase-1, caspase-3 and caspase-8 were studied after cerebral ischemia for 2 h followed by reperfusion for 46 h in rats. Materials and methods: Rats were subjected to transient middle cerebral artery occlusion (MCAO) model using the intraluminal thread. TSPN was administered intraperitoneally at 5 min before and 12 h, 24 h and 36 h after MCAO, respectively. Results: TSPN (at the dose of 25 mg/kg) significantly attenuated TUNEL-positive cells and reduced the expression of caspase-1 and caspase-3 compared to the model group, while it had no obvious effect on the expression of caspase-8. Conclusions: The neuroprotective effect of TSPN on focal ischemia may be related to inhibition of apoptosis and caspases activation. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
摘要：
BACKGROUND: Numerous man-made pollutants activate the aryl hydrocarbon receptor (AhR) and are risk factors for type 2 diabetes. AhR signaling also affects molecular clock genes to influence glucose metabolism. OBJECTIVE: We investigated mechanisms by which AhR activation affects glucose metabolism. METHODS: Glucose tolerance, insulin resistance, and expression of peroxisome proliferator activated receptor-alpha (PPAR-alpha) and genes affecting glucose metabolism or fatty acid oxidation and clock gene rhythms were investigated in wild-type (WT) and AhR-deficient [knockout (KO)] mice. AhR agonists and small interfering RNA (siRNA) were used to examine the effect of AhR on PPAR-alpha expression and glycolysis in the liver cell line Hepa-1c1c7 (c7) and its c12 and c4 derivatives. Brain, muscle ARNT-like protein 1 (Bmal1) siRNA and Ahr or Bmal1 expression plasmids were used to analyze the effect of BMAL1 on PPAR-alpha expression in c7 cells. RESULTS: KO mice displayed enhanced insulin sensitivity and improved glucose tolerance, accompanied by decreased PPAR-alpha and key gluconeogenic and fatty acid oxidation enzymes. AhR agonists increased PPAR-alpha expression in c7 cells. Both Ahr and Bmal1 siRNA reduced PPAR-alpha and metabolism genes. Moreover, rhythms of BMAL1 and blood glucose were altered in KO mice. CONCLUSIONS: These results indicate a link between AhR signaling, circadian rhythms, and glucose metabolism. Furthermore, hepatic activation of the PPAR-alpha pathway provides a mechanism underlying AhR-mediated insulin resistance.
期刊：
DNA and cell biology,2013年32(6):302-309 ISSN：1044-5498
通讯作者：
Peng, D
作者机构：
[Jin, Yi; Peng, Dan; Shen, Yi; Xu, Min] Cent S Univ, Xiangya Hosp 2, Dept Orthoped, Changsha 410000, Hunan, Peoples R China.;[Liang, Ying] Cent South Univ Forestry & Technol, Natl Engn Lab Rice & Byprod Deep Proc, Changsha, Hunan, Peoples R China.;[Lu, Jing] Hunan Univ Chinese Med, Sch Med, Changsha, Hunan, Peoples R China.;[Xiao, Bowen] Cent Hosp Changsha, Thorac & Cardiovasc Surg Ward, Changsha, Hunan, Peoples R China.
通讯机构：
[Peng, D] Cent S Univ, Xiangya Hosp 2, Dept Orthoped, Changsha 410000, Hunan, Peoples R China.
摘要：
MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-376c expression level was decreased while transforming growth factor-alpha (TGFA) mRNA expression levels were increased in osteosarcoma tissues and cell lines, and we identified TGFA as a novel direct target of miR-376c. Overexpression of miR-376c suppressed TGFA expression and the expression of its downstream signaling molecule such as epidermal growth factor receptor, and attenuated cell proliferation and invasion. Forced expression of TGFA could partly rescue the inhibitory effect of miR-376c in the cells. Taken together, these findings will shed light on the role and mechanism of miR-376c in regulating osteosarcoma cell growth via miR-376c/TGFA axis, and miR-376c may serve as a potential therapeutic target in osteosarcoma in the future.
摘要：
The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)-dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and beta-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants.
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.
摘要：
Resident microglia are the major immune cells in the brain, acting as the first defense of the central nervous system. Following cerebral ischemia, microglia respond to this injury at first and transform from surveying microglia to active state. The activated microglia play a dual role in the ischemic injury, due to distinct microglia phenotypes, including deleterious M1 and neuroprotective M2. However, microglia show transient M2 phenotype followed by a shift to M1. The high ratio of M1 to M2 is significantly related to ischemic injury. Many signal pathways participate in the alternation of microglial phenotype, presenting potential therapeutic targets for selectively modulating M2 polarization of microglia. In this review, we discuss how the M2 phenotype mediates neuroprotective effects and summarize the alternation of signaling cascades that control microglial phenotype after ischemic stroke. (C) 2015 Elsevier B.V. All rights reserved.
摘要：
AKR1B10 (aldo-keto reductase family 1, member B10) protein is primarily expressed in normal human small intestine and colon, but overexpressed in several types of human cancers and considered as a tumour marker. In the present study, we found that AKR1B10 protein is secreted from normal intestinal epithelium and cultured cancer cells, as detected by a newly developed sandwich ELISA and Western blotting. The secretion of AKR1B10 was not affected by the protein-synthesis inhibitor cycloheximide and the classical protein-secretion pathway inhibitor brefeldin A, but was stimulated by temperature, ATP, Ca(2+) and the Ca(2+) carrier ionomycin, lysosomotropic NH(4)Cl, the G-protein activator GTP gamma S and the G-protein coupling receptor N-formylmethionyl-leucyl-phenylalanine. The ADP-ribosylation factor inhibitor 2-(4-fluorobenzoylamino)-benzoic acid methyl ester and the phospholipase C inhibitor U73122 inhibited the secretion of AKR1B10. In cultured cells, AKR1B10 was present in lysosomes and was secreted with cathepsin D, a lysosomal marker. In the intestine, AKR1B10 was specifically expressed in mature epithelial cells and secreted into the lumen at 188.6-535.7 ng/ml of Heal fluids (mean = 298.1 ng/ml, 17 = 11). Taken together, our results demonstrate that AKR1B10 is a new secretory protein belonging to a lysosome-mediated non-classical protein-secretion pathway and is a potential serum marker.
作者机构：
[ Yin, Shuang-Feng ; Au, Chak-Tong ; Chen, Yi ; Qiu, Renhua ; Xu, Xinhua ] State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China;[ Chen, Yi ] College of Basic Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[ Au, Chak-Tong ] Department of Chemistry, Hong Kong Baptist University, Waterloo Road, Kowloon Tong, Hong Kong
摘要：
Bipolar disorder and unipolar depressive disorder (UD) may be different in brain structure. In the present study, we performed voxel-based morphometry (VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder (BP1) and 23 patients with UD, and 23 age-, gender-, and education-matched healthy controls (HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups, the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus, while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition, correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together, the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD, and decreased grey matter volume in the right middle cingulate gyrus may be specific to BP1.
作者机构：
[Dong, Mingkai; Yang, Jie; Gao, Yujie; Li, Ying; Wu, Feng; Guo, Taipin; Li, Zhengjie; Liang, Fanrong; Lan, Lei; Zeng, Fang] Chengdu Univ Tradit Chinese Med, Teaching Hosp 3, Chengdu, Sichuan, Peoples R China.;[Makris, Nikos; Kong, Jian] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.;[Makris, Nikos; Kong, Jian] Harvard Univ, Sch Med, Charlestown, MA USA.;[Makris, Nikos; Kong, Jian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.;[Liang, Yilin] Wellesley Coll, Neurosci Program, Wellesley, MA 02181 USA.
通讯机构：
[Liang, FR] Chengdu Univ Tradit Chinese Med, Teaching Hosp 3, Chengdu, Sichuan, Peoples R China.
摘要：
The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment.
作者机构：
[Cao, Deliang] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China. dcao@siumed.edu;[Liao, Duan-Fang] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China. dfliao66@aliyun.com;[He, Ying-Chun] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China. yingchunhe@aliyun.com;[Zhou, Fang-Liang] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China. zhoufangliang305@163.com;[Shen, Yi] Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N, Rutledge Street, Springfield, IL 62702, USA. yshen@siumed.edu
通讯机构：
[He, Ying-Chun; Liao, Duan-Fang; Zhou, Fang-Liang; Cao, Deliang] Division of Stem Cell Regulation and Application, College of Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410208, China.;[Shen, Yi] Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, 913 N, Rutledge Street, Springfield, IL 62702, USA.
关键词：
cancer stem cells;side population;apoptosis;apoptotic inducers;apoptotic death pathways;cancer therapy
摘要：
Cancer stem cells (CSCs) play crucial roles in tumor progression, chemo- and radiotherapy resistance, and recurrence. Recent studies on CSCs have advanced understanding of molecular oncology and development of novel therapeutic strategies. This review article updates the hypothesis and paradigm of CSCs with a focus on major signaling pathways and effectors that regulate CSC apoptosis. Selective CSC apoptotic inducers are introduced and their therapeutic potentials are discussed. These include synthetic and natural compounds, antibodies and recombinant proteins, and oligonucleotides.
摘要：
Although draft genome sequences of two of the major human schistosomes, Schistosoma japonicum and Schistosoma mansoni are available, the structures and characteristics of most genes and the influence of exogenous genes on the metabolism of schistosomes remain uncharacterized. Furthermore, which functional genomics approaches will be tractable for schistosomes are not yet apparent. Here, the vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped pantropic retroviral vector pBABE-puro was modified to incorporate the human telomerase reverse transcriptase gene (hTERT) as a reporter, under the control of the retroviral long terminal repeat (LTR). Pseudotyped virions were employed to transduce S. japonicum to investigate the utility of retrovirus-mediated transgenesis of S japonicum and the activity of human telomerase reverse transcriptase as a reporter transgene in schistosomes. Schistosomules perfused from experimentally infected rabbits were cultured for 6 days after exposure to the virions after which genomic DNAs from virus exposed and control worms were extracted. Analysis of RNA from transduced parasites and immunohistochemistry of thin parasite sections revealed expression of hTERT in the transduced worms. Expression of hTERT was also confirmed by immunoblot analysis. These findings indicated that S. japonicum could be effectively transduced by VSVG-pseudotyped retrovirus carrying the hTERT gene. Given the potential of hTERT to aid in derivation of immortalized cells, these findings suggest that this pantropic retroviral approach can be employed to transduce cells from specific tissues and organs of schistosomes to investigate the influence of transgene hTERT on growth and proliferation of schistosome cells. (C) 2010 Elsevier B.V. All rights reserved.
