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Xiaoxing Kou, Xingtian Xu, Chider Chen, Maria Laura Sanmillan, Tao Cai, Yanheng Zhou, Claudio Giraudo, Anh Le, Songtao Shi
Mesenchymal stem cells (MSCs) are capable of secreting exosomes, extracellular vesicles, and cytokines to regulate cell and tissue homeostasis. However, it is unknown whether MSCs use a specific exocytotic fusion mechanism to secrete exosomes and cytokines. We show that Fas binds with Fas-associated phosphatase-1 (Fap-1) and caveolin-1 (Cav-1) to activate a common soluble N -ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)-mediated membrane fusion mechanism to release small extracellular vesicles (sEVs) in MSCs...
March 14, 2018: Science Translational Medicine
Asokan Devarajan, Feng Su, Victor Grijalva, Meghna Yalamanchi, Ashna Yalamanchi, Feng Gao, Hannah Trost, Josephine Nwokedi, Gina Farias-Eisner, Robin Farias-Eisner, Alan M Fogelman, Srinivasa T Reddy
Ovarian cancer (OC) is most lethal malignancy among all gynecological cancer. Large bodies of evidences suggest that mitochondrial-derived ROS play a critical role in the development and progression of OC. Paraoxonase 2 (PON2) is a membrane-associated lactonase with anti-oxidant properties. PON2 deficiency aggravates mitochondrial ROS formation, systemic inflammation, and atherosclerosis. The role of PON2 in cancer development remains unknown. In this report, in human, we identified that PON2 expression is higher in early stages (but not in late stages) of OC when compared to normal tissue...
March 12, 2018: Cell Death & Disease
Priscila E Kobayashi, Carlos E Fonseca-Alves, Luis G Rivera-Calderón, Márcio Carvalho, Hellen Kuasne, Silvia R Rogatto, Renée Laufer-Amorim
Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated...
March 5, 2018: Research in Veterinary Science
Aernoud A van Batenburg, Karin M Kazemier, Ton Peeters, Matthijs F M van Oosterhout, Joanne J van der Vis, Jan C Grutters, Roel Goldschmeding, Coline H M van Moorsel
Telomeres are small repetitive DNA sequences at the ends of chromosomes which act as a buffer in age-dependent DNA shortening. Insufficient telomere repeats will be recognized as double-strand breaks. Presently, it is becoming more evident that telomere attrition, whether or not caused by mutations in telomere maintenance genes, plays an important role in many inflammatory and age-associated diseases. In this report, a method to (semi)quantitatively assess telomere length and DNA double-strand breaks in formalin-fixed paraffin-embedded (FFPE) tissue is described...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Qing Hu, Qing Chen, Xiuyun Yan, Bomei Ding, Dawei Chen, Lifang Cheng
AIM: To develop a nanocarrier for targeted delivery of agents to the cartilage. MATERIALS & METHODS: Chondrocyte affinity peptide modified PEGylated polyamidoamine conjugates (CAP-PEG-PAMAM) were prepared and rhodamine B isothiocyanate (RB) fluorophore was linked on them for comparative biological tracing and profiling. RESULTS: CAP4-PP-RB exhibited much more efficient cellular uptake in vitro than that of PEG-PAMAM-RB. Both the conjugates were likely internalized by chondrocytes via clathrin and caveolin co-mediated endocytosis, and delivered to lysosomes...
March 12, 2018: Nanomedicine
Zahra Tahmasebi Fard, Nahid Nafisi
BACKGROUND: Caveolae play a role in cell signal transduction, kinetic regulation of transport vesicles, and cellular physiology. In this study, we evaluated the role of caveolin-1 (CAV-1) genotypes in the risk of breast cancer. PATIENTS AND METHODS: We evaluated 6 single nucleotide polymorphisms of the CAV-1 gene in a sample size of 406 participants. Six polymorphisms-G32124A (rs3807992), T29107A (rs7804372), T28608A (rs3757733), G21985A (rs12672038), G14713A (rs3807987), and C521A (rs1997623)-were assessed using restriction fragment length polymorphism polymerase chain reaction...
January 31, 2018: Clinical Breast Cancer
Shuai Zhang, Qier An, Tianfu Wang, Shuping Gao, Guangqian Zhou
Post-stroke hyperglycemia during early reperfusion increases blood-brain barrier (BBB) permeability and subsequently aggravates brain injury and clinical prognosis. The decreased level of tight junction proteins (TJPs) has been reported but the underlying mechanism remains largely elusive. Herein we designed to investigate the detailed molecular events in brain microvascular endothelial cells (BMECs) ex and in vivo. After oxygen-glucose deprivation (OGD) for 90 min and reperfusion with 8 or 16 mM glucose for 30 min, glucose at 16 mM caused significant decrease of the TJP expression and particularly ZO-1 redistribution from membrane to cytoplasm of BMECs...
March 7, 2018: Neuroscience
Julia Ketteler, Diana Klein
Resistance of solid tumors to chemo- and radiotherapy remains a major obstacle in anti-cancer treatment. Herein, the membrane protein Caveolin-1 (CAV1) came into focus as it is highly expressed in many tumors and high CAV1 levels were correlated with tumor progression, invasion and metastasis, and thus, a worse clinical outcome. Increasing evidence further indicates that the heterogeneous tumor microenvironment, also known as the tumor stroma, contributes to therapy resistance resulting in poor clinical outcome...
March 9, 2018: International Journal of Cancer. Journal International du Cancer
Chi-Han Wu, Fon-Chang Liu, Chun-Hsu Pan, Ming-Tsung Lai, Shou-Jen Lan, Chieh-Hsi Wu, Ming-Jyh Sheu
The purpose of this study was to investigate the inhibitory activities of ethanolic extracts from Antrodia cinnamomea (EEAC) on lung cancer. Cell proliferation and cell cycle distribution were analyzed using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and flow cytometry, respectively. Wound-healing assay, Western blotting, and a murine tumor model were separately used to examine cell migration, protein expression, and tumor repression. Our results showed that EEAC induced cell cycle arrest at the G0/G1 phase resulting decreased cell viability in A549 cells...
March 9, 2018: International Journal of Molecular Sciences
Lasse Jørgensen Cehofski, Anders Kruse, Sigriður Olga Magnusdottir, Alexander Nørgård Alsing, Svend Kirkeby, Bent Honoré, Henrik Vorum
A dexamethasone intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a dexamethasone (DEX) implant this study combined an experimental model of BRVO with proteomic techniques. In six Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser...
March 2, 2018: Experimental Eye Research
Hsiu-Kuan Lin, Hsi-Hui Lin, Yu-Wei Chiou, Ching-Lung Wu, Wen-Tai Chiu, Ming-Jer Tang
Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-RasV12 gene) transformation by Ha-RasV12 . Cav1 overexpression abrogates the Ha-RasV12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells...
March 4, 2018: Journal of Cellular and Molecular Medicine
Dariusz Zakrzewicz, Miroslava Didiasova, Marcus Krüger, Benedetto Daniele Giaimo, Tilman Borggrefe, Maren Mieth, Andreas C Hocke, Anna Zakrzewicz, Liliana Schaefer, Klaus T Preissner, Malgorzata Wygrecka
OBJECTIVES: Enolase-1-dependent cell surface proteolysis plays an important role in cell invasion. Although enolase-1 (Eno-1), a glycolytic enzyme, has been found on the surface of various cells, the mechanism responsible for its exteriorization remains elusive. Here, we investigated the involvement of post-translational modifications (PTMs) of Eno-1 in its lipopolysaccharide (LPS)-triggered trafficking to the cell surface. RESULTS: We found that stimulation of human lung adenocarcinoma cells with LPS triggered the monomethylation of arginine 50 (R50me) within Eno-1...
March 1, 2018: Biochimica et Biophysica Acta
Rabih Darwiche, Fernanda Lugo, Claire Drurey, Koen Varossieau, Geert Smant, Ruud H P Wilbers, Rick M Maizels, Roger Schneiter, Oluwatoyin A Asojo
Brugia malayi is a causative agent of lymphatic filariasis, a major tropical disease. The infective L3 parasite stage releases immunomodulatory proteins including the venom allergen-like proteins (VALs), which are members of the SCP/TAPS (Sperm-coating protein / Tpx / antigen 5 / pathogenesis related-1 / Sc7) superfamily. BmVAL-1 is a major target of host immunity with >90% of infected B. malayi microfilaraemic cases being seropositive for antibodies to BmVAL-1. This study is part of ongoing efforts to characterize the structures and functions of important B...
February 28, 2018: International Journal for Parasitology
Yuan-Chiang Chung, Ching-Ming Chang, Wan-Chen Wei, Ting-Wei Chang, King-Jen Chang, Wei-Ting Chao
Trastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application...
March 2, 2018: Scientific Reports
Bo Yang, Xuefeng Qi, Hui Guo, Peilong Jia, Shuying Chen, Zhijie Chen, Ting Wang, Jingyu Wang, Qinghong Xue
Peste des petits ruminants virus (PPRV) causes an acute and highly contagious disease of sheep and goats and has spread with alarming speed around the world. The pathology of Peste des petits ruminants is linked to retrogressive changes and necrotic lesions in lymphoid tissues and epithelial cells. However, the process of PPRV entry into host epithelial cells remains largely unknown. Here, we performed a comprehensive study of the entry mechanism of PPRV into caprine endometrial epithelial cells (EECs). We clearly demonstrated that PPRV internalization was inhibited by chloroquine and ammonium chloride, which elevate the pH of various organelles...
2018: Frontiers in Microbiology
Yu Cheng, Yongxi Song, Jinglei Qu, Xiaofang Che, Na Song, Yibo Fan, Ti Wen, Ling Xu, Jing Gong, Xiaoxun Wang, Chenlu Zhang, Xiujuan Qu, Yunpeng Liu
The C-X-C motif chemokine receptor 4 (CXCR4) pathway can promote tumor metastasis but is dependent on cross talk with other signaling pathways. The MET proto-oncogene (c-MET) participates in metastasis and is highly expressed in gastric cancer. However, the relationship between CXCR4 and c-MET signaling and their mechanisms of action in gastric cancer metastasis remain unclear. In this study, in vitro experiments demonstrated that C-X-C motif chemokine ligand 12 (CXCL12)/CXCR4 induces epithelial-mesenchymal transition (EMT) and promotes migration in gastric cancer cells, which is accompanied by c-MET activation...
February 26, 2018: Translational Oncology
Yan Wu, Xiaobian Wang, Qing Zhou, Yi Wang, Jiali Zhou, Qiaoling Jiang, Yuan Wang, Huaqing Zhu
The aim of the present study was to explore the protective effects and possible mechanisms of all‑trans‑retinoic acid (ATRA) against atherosclerosis (AS). Rabbits were randomly allocated for standard or high‑fat diet with or without ATRA. After 12 weeks, the aortic rings of the rabbits were removed. Endothelium‑dependent relaxation (EDR) induced by acetylcholine and non‑endothelium‑dependent relaxation induced by sodium nitroprusside in the thoracic aorta were evaluated. NO level and eNOS activity were measured according to the protocol of NO and eNOS ELISA kits...
February 27, 2018: Molecular Medicine Reports
Lu Zhang, Hongli Yin, Lei Jiao, Tianyi Liu, Yuqiu Gao, Yingchun Shao, Yuanyuan Zhang, Hongli Shan, Ying Zhang, Baofeng Yang
BACKGROUND/AIMS: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms. METHODS: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model...
February 21, 2018: Cellular Physiology and Biochemistry
Jie Wu, Dingxin Di, Chen Zhao, Qi Pan, Yingyi Liu, Xue Zhang, Xianda Zhao, Honglei Chen
Background: Lung cancer is the leading causes of cancer-related deaths around the world. Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be involved in the occurrence, invasion, and metastasis of cancers. Autophagy also plays a significant role in the growth and metastasis of cancers. However, the correlation between the Hh signaling pathway and autophagy in small cell lung cancer (SCLC) is still poorly understood. This study aimed to investigate the significance of Hh signaling pathway and autophagy in SCLC...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Simon M Bryant, Cherrie H T Kong, Judy J Watson, Hanne C Gadeberg, Andrew F James, Mark B Cannell, Clive H Orchard
BACKGROUND: Previous work has shown redistribution of L-type Ca current (ICa ) from the t-tubules to the surface membrane of rat ventricular myocytes following myocardial infarction. However, whether this occurs in all species and in response to other insults, the relationship of this redistribution to the severity of the pathology, and the underlying mechanism, are unknown. We have therefore investigated the response of mouse hearts and myocytes to pressure overload induced by transverse aortic constriction (TAC)...
February 23, 2018: Experimental Physiology
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