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https://www.readbyqxmd.com/read/28435471/nucleolin-targeted-extracellular-vesicles-as-a-versatile-platform-for-biologics-delivery-to-breast-cancer
#1
Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#2
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28429073/urinary-extracellular-vesicles-a-promising-shortcut-to-novel-biomarker-discoveries
#3
REVIEW
Karina Barreiro, Harry Holthofer
Proteomic and genomic techniques have reached full maturity and are providing unforeseen details for the comprehensive understanding of disease pathologies at a fraction of previous costs. However, for kidney diseases, many gaps in such information remain to inhibit major advances in the prevention, treatment and diagnostics of these devastating diseases, which have enormous global impact. The discovery of ubiquitous extracellular vesicles (EV) in all bodily fluids is rapidly increasing the fundamental knowledge of disease mechanisms and the ways in which cells communicate with distant locations in processes of cancer spread, immunological regulation, barrier functions and general modulation of cellular activity...
April 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28428068/comparative-analysis-of-gene-expression-profiles-for-several-migrating-cell-types-identifies-cell-migration-regulators
#4
Young-Kyung Bae, Frank Macabenta, Heather Leigh Curtis, Angelike Stathopoulos
Cell migration is an instrumental process that ensures cells are properly positioned to support the specification of distinct tissue types during development. To provide insight, we used fluorescence activated cell sorting (FACS) to isolate two migrating cell types from the Drosophila embryo: caudal visceral mesoderm (CVM) cells, precursors of longitudinal muscles of the gut, and hemocytes (HCs), the Drosophila equivalent of blood cells. ~350 genes were identified from each of the sorted samples using RNA-seq, and in situ hybridization was used to confirm expression within each cell type or, alternatively, within other interacting, co-sorted cell types...
April 17, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28424693/human-melanoma-derived-extracellular-vesicles-regulate-dendritic-cell-maturation
#5
Rachel L G Maus, James W Jakub, Wendy K Nevala, Trace A Christensen, Klara Noble-Orcutt, Zohar Sachs, Tina J Hieken, Svetomir N Markovic
Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown; however, evidence supporting the establishment of a pre-metastatic niche is evolving. We have previously described a dysfunctional immune profile including reduced expression of dendritic cell (DC) maturation markers in the first node draining from the primary tumor, the sentinel lymph node (SLN)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420881/reduced-biological-effect-of-e-cigarette-aerosol-compared-to-cigarette-smoke-evaluated-in-vitro-using-normalized-nicotine-dose-and-rna-seq-based-toxicogenomics
#6
Linsey E Haswell, Andrew Baxter, Anisha Banerjee, Ivan Verrastro, Jessica Mushonganono, Jason Adamson, David Thorne, Marianna Gaça, Emmanuel Minet
Electronic cigarettes (e-cigarettes) use has increased globally and could potentially offer a lower risk alternative to cigarette smoking. Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were generated with standard intense smoking regimens with careful consideration for dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions were tested for equivalent and higher nicotine delivery compared to 3R4F...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419548/detection-of-prostate-cancer-specific-transcripts-in-extracellular-vesicles-isolated-from-post-dre-urine
#7
Kathryn L Pellegrini, Dattatraya Patil, Kristen J S Douglas, Grace Lee, Kathryn Wehrmeyer, Mersiha Torlak, Jeremy Clark, Colin S Cooper, Carlos S Moreno, Martin G Sanda
BACKGROUND: The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs...
April 17, 2017: Prostate
https://www.readbyqxmd.com/read/28416318/basic-fibroblast-growth-factor-regulates-gene-and-protein-expression-related-to-proliferation-differentiation-and-matrix-production-of-human-dental-pulp-cells
#8
Ya-Ching Chang, Mei-Chi Chang, Yi-Jane Chen, Ji-Uei Liou, Hsiao-Hua Chang, Wei-Ling Huang, Wan-Chuen Liao, Chiu-Po Chan, Po-Yuan Jeng, Jiiang-Huei Jeng
INTRODUCTION: Basic fibroblast growth factor (bFGF) plays differential effects on the proliferation, differentiation, and extracellular matrix turnover in various tissues. However, limited information is known about the effect of bFGF on dental pulp cells. The purposes of this study were to investigate whether bFGF influences the cell differentiation and extracellular matrix turnover of human dental pulp cells (HDPCs) and the related gene and protein expression as well as the role of the mitogen-activated protein kinase (MEK)/extracellular-signal regulated kinase (ERK) signaling pathway...
April 14, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28415825/recombinant-human-erythropoietin-stimulates-melanoma-tumor-growth-through-activation-of-initiation-factor-eif4e
#9
Annabelle Julius, Anjali Desai, Raymond L Yung
Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer patients. Recent clinical trials suggest that EPO may accelerate tumor progression and increase mortality. However, the evidence supporting a growth-promoting effect of EPO has remained controversial. Employing an in vivo model of B16 murine melanoma, we observed that administration of EPO to tumor bearing C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro studies demonstrate that B16 murine melanoma cells express EPOR, both at the protein and mRNA levels...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415760/binding-of-galectin-1-to-integrin-%C3%AE-1-potentiates-drug-resistance-by-promoting-survivin-expression-in-breast-cancer-cells
#10
KeeSoo Nam, Seog-Ho Son, Sunhwa Oh, Donghwan Jeon, Hyungjoo Kim, Dong-Young Noh, Sangmin Kim, Incheol Shin
Galectin-1 is a β-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413458/mir-9-functions-as-a-tumor-inhibitor-of-cell-proliferation-in-epithelial-ovarian-cancer-through-targeting-the-sdf-1-cxcr4-pathway
#11
Lin He, Li Zhang, Mengfei Wang, Wenrong Wang
The current study aimed to investigate the potential role of miR-9 in the inhibition of ovarian cancer progression through the stromal cell-derived factor-1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) pathway and to provide a theoretical basis for the diagnosis and treatment of ovarian cancer. Human ovarian cancer OVCAR-3 cells were transfected with miR-9 short hairpin RNA (shRNA). The effect of miR-9 on the mRNA expression levels of CXCR4 were analyzed using reverse transcription-quantitative polymerase chain reaction...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410004/rna-in-salivary-extracellular-vesicles-as-a-possible-tool-for-systemic-disease-diagnosis
#12
J Kim, H Shin, J Park
Saliva contains biological information as blood and is recognized as a valuable diagnostic medium for their noninvasiveness. Although "-omics" researches have tried to investigate saliva, the origin and significance of its contents are not clear, and its usage is largely confined to oral disease in the diagnostic and prognostic field. In an attempt to broaden the applicability of saliva and to find systemic disease-derived RNA in saliva, we made mouse models that had human melanoma and isolated extracellular vesicles (EVs) from their saliva by an aqueous 2-phase system (ATPS), then identified and evaluated their expression of human melan-A RNA, which is associated with melanoma on skin...
April 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28408748/the-microbiome-of-the-lung-and-its-extracellular-vesicles-in-nonsmokers-healthy-smokers-and-copd-patients
#13
Hyun Jung Kim, You-Sun Kim, Kang-Hyun Kim, Jun-Pyo Choi, Yoon-Keun Kim, Sunmi Yun, Lokesh Sharma, Charles S Dela Cruz, Jae Seung Lee, Yeon-Mok Oh, Sang-Do Lee, Sei Won Lee
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28406140/spicule-formation-in-calcareous-sponges-coordinated-expression-of-biomineralization-genes-and-spicule-type-specific-genes
#14
Oliver Voigt, Maja Adamska, Marcin Adamski, André Kittelmann, Lukardis Wencker, Gert Wörheide
The ability to form mineral structures under biological control is widespread among animals. In several species, specific proteins have been shown to be involved in biomineralization, but it is uncertain how they influence the shape of the growing biomineral and the resulting skeleton. Calcareous sponges are the only sponges that form calcitic spicules, which, based on the number of rays (actines) are distinguished in diactines, triactines and tetractines. Each actine is formed by only two cells, called sclerocytes...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28404980/hiv-1-tat-inhibits-eaat-2-through-aeg-1-upregulation-in-models-of-hiv-associated-neurocognitive-disorder
#15
Xiang Ye, Yu Zhang, Qiping Xu, Honghua Zheng, Xiaoyan Wu, Jinhua Qiu, Zhou Zhang, Wei Wang, Yiming Shao, Hui Qin Xing
During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate the molecular mechanisms underlying the decreased EAAT-2 expression during HAND at the tissue and cellular levels. We used simian immunodeficiency virus-human immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo model of HAND...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403796/riboswitches-as-potential-targets-for-the-development-of-anti-biofilm-drugs
#16
José A Reyes-Darias, Tino Krell
In nature, bacteria can exist as single motile cells or as sessile cellular community, known as microbial biofilms. Bacteria within biofilms are embedded in a self-produced extracellular matrix that makes them more resistant to antibiotic treatment and responses of the host immune system. Microbial biofilms are very important in medicine since they are associated with several human diseases such as dental caries, periodontitis, otitis media, infective endocarditis, infectious kidney stones, osteomyelitis or prostatitis...
April 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28402522/gene-expression-profiling-of-acute-type-a-aortic-dissection-combined-with-in-vitroassessment%C3%A2
#17
Naoyuki Kimura, Kyoko Futamura, Mamoru Arakawa, Naoko Okada, Fabian Emrich, Homare Okamura, Tetsuya Sato, Yasuhiro Shudo, Tiffany K Koyano, Atsushi Yamaguchi, Hideo Adachi, Akio Matsuda, Koji Kawahito, Kenji Matsumoto, Michael P Fischbein
OBJECTIVES: The mechanisms underlying aortic dissection remain to be fully elucidated. We aimed to identify key molecules driving dissection through gene expression profiling achieved by microarray analysis and subsequent in vitro experiments using human aortic endothelial cells (HAECs) and aortic vascular smooth muscle cells (AoSMCs). METHODS: Total RNA, including microRNA (miRNA), was isolated from the intima-media layer of dissected ascending aorta obtained intraoperatively from acute type A aortic dissection (ATAAD) patients without familial thoracic aortic disease ( n  = 8) and that of non-dissected ascending aorta obtained from transplant donors ( n  = 9)...
April 11, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28396358/extracellular-matrix-integrin-signaling-promotes-resistance-to-combined-inhibition-of-her2-and-pi3k-in-her2-breast-cancer
#18
Ariella B Hanker, Monica Valeria Estrada, Giampaolo Bianchini, Preston D Moore, Junfei Zhao, Feixiong Cheng, Luca Gianni, James P Koch, Darren R Tyson, Violeta Sanchez, Brent N Rexer, Melinda Sanders, Zhongming Zhao, Thomas Stricker, Carlos L Arteaga
PIK3CA mutations are associated with resistance to HER2-targeted therapies. We previously showed that HER2+/PIK3CA(H1047R) transgenic mammary tumors are resistant to the HER2 antibodies trastuzumab and pertuzumab but respond to PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of resistance to combined inhibition of HER2 and PI3K. TPB-resistant tumors were generated by treating HER2+/PIK3CA(H1047R) mice long-term with the drug combination. RNA-sequencing of TPB-resistant tumors revealed that extracellular matrix (ECM) and cell adhesion genes, including collagen II (Col2a1), were markedly upregulated, accompanied by activation of integrin β1/Src...
April 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28395182/sensitive-luminescent-reporter-viruses-reveal-appreciable-release-of-hepatitis-c-virus-ns5a-protein-into-the-extracellular-environment
#19
Nicholas S Eyre, Amanda L Aloia, Michael A Joyce, Monrat Chulanetra, D Lorne Tyrrell, Michael R Beard
The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles...
April 7, 2017: Virology
https://www.readbyqxmd.com/read/28393195/induction-of-mmp%C3%A2-1-and-%C3%A2-3-by-cyclical-mechanical-stretch-is-mediated-by-il%C3%A2-6-in-cultured-fibroblasts-of-keratoconus
#20
Gen-Lai Du, Wei-Yi Chen, Xiao-Na Li, Rui He, Peng-Fei Feng
In order to understand the effect of mechanical stretch on corneal extracellular matrix remodeling, human keratoconus fibroblasts (HKCFBs) were subjected to cyclic stretch in vitro and the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and inflammatory cytokines were evaluated. HKCFBs were seeded into a flexible membrane base and subjected to a cyclic stretch regimen of 10% equibiaxial stretch at a stretching frequency of 1 Hz for 6 h using a Flexcell tension unit...
April 4, 2017: Molecular Medicine Reports
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