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https://www.readbyqxmd.com/read/29351497/screen-targeting-lung-and-prostate-cancer-oncogene-identifies-novel-inhibitors-of-rgs17-and-problematic-chemical-substructures
#1
Christopher R Bodle, Josephine H Schamp, Joseph B O'Brien, Michael P Hayes, Meng Wu, Jonathan A Doorn, David L Roman
Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein-coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29351464/vitamin-d-and-regulation-of-vascular-cell-function
#2
Nasim Jamali, Christine M Sorenson, Nader Sheibani
Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for treatment of various types of cancer and chronic diseases. We previously showed that the active form of vitamin D (1, 25(OH)2D3) is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351455/thrombosis-systemic-and-cardiac-oxidative-stress-and-dna-damage-induced-by-pulmonary-exposure-to-diesel-exhaust-particles-and-the-effect-of-nootkatone-thereon
#3
Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Badreldin H Ali
Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particles-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEP) has not been studied before...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#4
Shannon H Lacy, Amali P Epa, Stephen J Pollock, Collynn F Woeller, Thomas H Thatcher, Richard P Phipps, Patricia J Sime
In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and deposit excessive extracellular matrix in the interstitium, impairing normal lung function. As most forms of PF have a poor prognosis and limited treatment options, PF represents an urgent unmet need for novel, effective therapeutics. While the role of immune cells in lung fibrosis is unclear, recent studies suggest that T lymphocyte (T cell) activation may be impaired in PF patients. Further, we have previously shown that activated T cells can produce prostaglandins with anti-scarring potential...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#5
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351416/acute-and-chronic-resistance-training-downregulates-select-line-1-retrotransposon-activity-markers-in-human-skeletal-muscle
#6
Matthew A Romero, C Brooks Mobley, Petey W Mumford, Paul A Roberson, Cody T Haun, Wesley C Kephart, James C Healy, Darren T Beck, Kaelin C Young, Jeffrey S Martin, Christopher M Lockwood, Michael D Roberts
Herein, we examined if acute or chronic resistance exercise affected markers of skeletal muscle LINE-1 retrotransposon activity. In study 1, 10 resistance-trained college-aged males performed three consecutive daily back squat sessions, and vastus lateralis biopsies were taken prior to (Pre), 2 h following session 1 (Post1), and 3 days following session 3 (Post2). In study 2, 13 untrained college-aged males performed a full-body resistance training program (3 d/wk), and vastus lateralis biopsies were taken prior to (week 0) and ~72 h following training cessation (week 12)...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351409/pharmacological-activation-of-ppar%C3%AE-inhibits-hypoxia-induced-proliferation-through-a-caveolin-1-targeted-and-dependent-mechanism-in-pasmcs
#7
Kai Yang, Mingming Zhao, Junyi Huang, Chenting Zhang, Qiu Yu Zheng, Yuqin Chen, Haiyang Jiang, Wenju Lu, Jian Wang
Previously, we and others have demonstrated that activation of peroxisome proliferator- activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351389/proliferation-of-hepatic-stellate-cells-mediated-by-yap-and-taz-contributes-to-liver-repair-and-regeneration-after-liver-ischemia-reperfusion-injury
#8
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key regulators of cell proliferation and organ size, however, their physiological contribution after liver injury has not been fully understood. In this study, we sought to determine the role of YAP and TAZ during liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. After liver injury, there was marked activation and proliferation of hepatic stellate cells...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#9
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29351283/decreased-mir-17-in-glioma-cells-increased-cell-viability-and-migration-by-increasing-the-expression-of-cyclin-d1-p-akt-and-akt
#10
Guangwei Sun, Guozhong SiMa, Chunhui Wu, Yongzhong Fan, Yong Tan, Zhong Wang, Gang Cheng, Jie Li
BACKGROUND: The activating mutations of micro RNA (miR)-17 have been revealed in tumors such as human non-Hodgkin's lymphoma and T cell leukemia. However, it is unclear about the role of miR-17 in glioma cells. The current study aimed to investigate effects of miR-17 mimics or inhibitor on the viability and migration of rat glioma C6 cells, and explore possible mechanisms. METHODS: The expression of miR-17 in rat glioma C6 cells and normal brain tissue was detected by quantitative PCR...
2018: PloS One
https://www.readbyqxmd.com/read/29351188/proangiogenic-effect-of-metformin-in-endothelial-cells-is-via-upregulation-of-vegfr1-2-and-their-signaling-under-hyperglycemia-hypoxia
#11
Sherin Bakhashab, Farid Ahmed, Hans-Juergen Schulten, Fahad W Ahmed, Michael Glanville, Mohammed H Al-Qahtani, Jolanta U Weaver
Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34⁺ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350876/mechanism-of-mer-receptor-tyrosine-kinase-inhibition-of-glomerular-endothelial-cell-inflammation
#12
Yuxuan Zhen, Fred D Finkelman, Wen-Hai Shao
Endotoxin induces a variety of proinflammatory mediators and plays a crucial role in kidney inflammation. The receptor tyrosine kinase, Mer, diminishes renal inflammation by attenuating inflammatory responses. We previously reported that Mer is predominantly expressed on glomerular endothelial cells (GECs) and that Mer deficiency is associated with increased renal inflammation when mice are challenged with nephrotoxic serum. We consequently hypothesized that Mer signaling down-regulates LPS-driven inflammatory responses in GECs...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350834/proton-pump-inhibitors-elevate-infection-rate-in-cardiothoracic-surgery-patients-by-influencing-pmn-function-in-vitro-and-in-vivo
#13
Carolin Maria Haas, Martina Maywald, Andreas Goetzenich, Christian Stoppe, Lothar Rink
Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350683/ccat1-stimulation-of-the-symmetric-division-of-nsclc-stem-cells-through-activation-of-the-wnt-signalling-cascade
#14
Chongwen Xu, Guodong Xiao, Boxiang Zhang, Meng Wang, Jichang Wang, Dapeng Liu, Jing Zhang, Hong Ren, Xin Sun
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortalities worldwide, yet this condition remains a poorly understood malignancy, and the subgroup of cancer stem cells (CSCs) leading to therapeutic resistance and adverse prognosis have not been well studied. CSCs frequently undergo symmetric division, which facilitates expansion of the stem cell pool, contributing to long-term relapse and therapy failure. CCAT1 could act as a miRNA sponge to influence downstream genes; however, its roles in NSCLC stem cell are unclear...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29350680/effects-of-microrna-135a-on-the-epithelial-mesenchymal-transition-migration-and-invasion-of-bladder-cancer-cells-by-targeting-gsk3%C3%AE-through-the-wnt-%C3%AE-catenin-signaling-pathway
#15
Xia-Wa Mao, Jia-Quan Xiao, Zhong-Yi Li, Yi-Chun Zheng, Nan Zhang
This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350566/abp-501-for-the-treatment-of-rheumatoid-arthritis
#16
Eleftherios Pelechas, Paraskevi V Voulgari, Alexandros A Drosos
Rheumatoid arthritis (RA) is an autoimmune disease, which has a negative impact on the ability to perform activities daily. Tumour necrosis factor α (TNF) is a cytokine with diverse cellular effects, and a key regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a TNF inhibitor. Areas covered: In this review, we examined ABP 501, as a biosimilar candidate to adalimumab in the treatment of RA focusing on the available data. Current data indicate that ABP 501 is a highly similar alternative to adalimumab in terms of safety, efficacy, tolerability and immunogenicity...
January 19, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29350484/paraptosis-inducing-nanomedicine-overcomes-cancer-drug-resistance-for-a-potent-cancer-therapy
#17
Yongcun Zhou, Feiteng Huang, Ying Yang, Pingli Wang, Zhen Zhang, Yining Tang, Youqing Shen, Kai Wang
Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer activity by inducing cancer cell apoptosis. However, cancer cells inherently have and acquire many antiapoptosis mechanisms, causing cancer drug resistance and poor prognoses in patients. Herein, a potent paraptosis-inducing nanomedicine is reported that causes quick nonapoptotic death of cancer cells, overcoming apoptosis-based resistance and effectively inhibiting drug-resistant tumor growth. The nanomedicine is composed of micelles made from an amphiphilic 8-hydroxyquinoline (HQ)-conjugate block copolymer with polyethylene glycol...
January 19, 2018: Small
https://www.readbyqxmd.com/read/29350470/specific-expression-of-pd-l1-in-rela-fusion-supratentorial-ependymoma-implications-for-pd-1-targeted-therapy
#18
Davis A Witt, Andrew M Donson, Vladimir Amani, Daniel C Moreira, Bridget Sanford, Lindsey M Hoffman, Michael H Handler, Jean M Mulcahy Levy, Kenneth L Jones, Anandani Nellan, Nicholas K Foreman, Andrea M Griesinger
BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN) exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN have significant infiltration of immune cells, which correlates with outcome. Immune checkpoint inhibitors provide an avenue for new treatments. This study characterizes tumor-infiltrating immune cells in EPN and aims at predicting candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1 (programmed death ligand 1/programmed death 1)...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29350433/amino-group-of-salicylic-acid-exhibits-enhanced-inhibitory-potential-against-insulin-amyloid-fibrillation-with-protective-aptitude-toward-amyloid-induced-cytotoxicity
#19
Masihuz Zaman, Mohsin Vahid Khan, Syed Mohammad Zakariya, Saima Nusrat, Syed Mustapha Meeran, Parvez Alam, Mohammad Rehan Ajmal, Wahiduzzaman Wahiduzzaman, Yasser E Shahein, Amira M Abouelella, Rizwan Hasan Khan
Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5-amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T...
December 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29350427/role-of-microglia-in-the-spinal-cord-in-colon-to-bladder-neural-crosstalk-in-a-rat-model-of-colitis
#20
Tsuyoshi Majima, Yasuhito Funahashi, Naoki Kawamorita, Shun Takai, Yoshihisa Matsukawa, Tokunori Yamamoto, Naoki Yoshimura, Momokazu Gotoh
AIMS: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group...
January 19, 2018: Neurourology and Urodynamics
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