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https://www.readbyqxmd.com/read/28102934/crosstalk-between-angiotensin-and-the-non-amyloidogenic-pathway-of-alzheimer-s-amyloid-precursor-protein
#1
Anna Maria Kanarek, Annika Wagner, Jim Küppers, Michael Gütschow, Rolf Postina, Elzbieta Kojro
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is activation of G protein-coupled receptors (GPCRs)...
January 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28102849/berberine-sonodynamic-therapy-induces-autophagy-and-lipid-unloading-in-macrophage
#2
Jiayuan Y Kou, Ying Li, Zhaoyu Y Zhong, Yueqing Q Jiang, Xuesong S Li, Xiaobo B Han, Zhongni N Liu, Ye Tian, Liming M Yang
Impaired autophagy in macrophages accompanies the progression of atherosclerosis and contributes to lipid loading in plaques and ineffective lipid degradation. Therefore, evoking autophagy and its associated cholesterol efflux may provide a therapeutic treatment for atherosclerosis. In the present study, berberine-mediated sonodynamic therapy (BBR-SDT) was used to induce autophagy and cholesterol efflux in THP-1 macrophages and derived foam cells. Following BBR-SDT, autophagy was increased in the macrophages, autophagy resistance in the foam cells was prevented, and cholesterol efflux was induced...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#3
REVIEW
Christian Henninger, Gerhard Fritz
Cancer patients receiving anthracycline-based chemotherapy are at risk to develop life-threatening chronic cardiotoxicity with the pathophysiological mechanism of action not fully understood. Besides the most common hypothesis that anthracycline-induced congestive heart failure (CHF) is mainly caused by generation of reactive oxygen species, recent data point to a critical role of topoisomerase II beta (TOP2B), which is a primary target of anthracycline poisoning, in the pathophysiology of CHF. As the use of the only clinically approved cardioprotectant dexrazoxane has been limited by the FDA in 2011, there is an urgent need for alternative cardioprotective measures...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102743/expression-and-alteration-of-bkca-channels-in-the-sphincter-of-oddi-s-from-rabbits-with-hypercholesterolemia
#4
Dan Feng, Haiyan Nan, Wen Wang, Linfeng Yan, Pang Du, Lin Zuo, Kun Zhang, Minggao Zhao, Guangbin Cui
This study aimed to investigate the expression and function of BKCa channels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into two groups: the control group was fed standard chow (n = 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n = 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups...
January 19, 2017: Channels
https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#5
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28102733/plk1-polo-like-kinase-1-inhibits-mtor-complex-1-and-promotes-autophagy
#6
Stefanie Ruf, Alexander Martin Heberle, Miriam Langelaar-Makkinje, Sara Gelino, Deepti Wilkinson, Carolin Gerbeth, Jennifer Jasmin Schwarz, Birgit Holzwarth, Bettina Warscheid, Chris Meisinger, Marcel A T M van Vugt, Ralf Baumeister, Malene Hansen, Kathrin Thedieck
Mechanistic target of rapamycin complex 1 (MTORC1) and PLK1 (polo like kinase 1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 interactor in human cancer cells. PLK1 inhibition enhances MTORC1 activity under nutrient sufficiency and in starved cells, and PLK1 directly phosphorylates the MTORC1 component RPTOR/RAPTOR in vitro...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102435/effects-of-tryptophan-containing-peptides-on-angiotensin-converting-enzyme-activity-and-vessel-tone-ex-vivo-and-in-vivo
#7
Sherif Khedr, Andreas Deussen, Irakli Kopaliani, Birgit Zatschler, Melanie Martin
PURPOSE: Over-activation of the renin-angiotensin axis and worsening of vascular function are critical contributors to the development of hypertension. Therefore, inhibition of angiotensin-converting enzyme (ACE), a key factor of the renin-angiotensin axis, is a first line treatment of hypertension. Besides pharmaceutical ACE inhibitors, some natural peptides have been shown to exert ACE-inhibiting properties with antihypertensive effects and potentially beneficial effects on vascular function...
January 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28102363/smarca4-inactivating-mutations-increase-sensitivity-to-aurora-kinase-a-inhibitor-vx-680-in-non-small-cell-lung-cancers
#8
Vural Tagal, Shuguang Wei, Wei Zhang, Rolf A Brekken, Bruce A Posner, Michael Peyton, Luc Girard, TaeHyun Hwang, David A Wheeler, John D Minna, Michael A White, Adi F Gazdar, Michael G Roth
Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102325/viral-micrornas-target-a-gene-network-inhibit-stat-activation-and-suppress-interferon-responses
#9
Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs during latency that are processed to yield ~25 mature microRNAs (miRNAs). We were interested in identifying cellular networks that were targeted by KSHV-miRNAs and employed network building strategies using validated KSHV miRNA targets. Here, we report the identification of a gene network centering on the transcription factor- signal transducer and activator of transcription 3 (STAT3) that is targeted by KSHV miRNAs. KSHV miRNAs suppressed STAT3 and STAT5 activation and inhibited STAT3-dependent reporter activation upon IL6-treatment...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102324/antiproliferative-and-apoptosis-inducing-effect-of-exo-protoporphyrin-ix-based-sonodynamic-therapy-on-human-oral-squamous-cell-carcinoma
#10
Yanhong Lv, Jinhua Zheng, Qi Zhou, Limin Jia, Chunying Wang, Nian Liu, Hong Zhao, Hang Ji, Baoxin Li, Wenwu Cao
Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3-4 times more cell apoptosis compared to sonocation alone...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102288/acetylcholine-acts-through-m3-muscarinic-receptor-to-activate-the-egfr-signaling-and-promotes-gastric-cancer-cell-proliferation
#11
Huangfei Yu, Hongwei Xia, Qiulin Tang, Huanji Xu, Guoqing Wei, Ying Chen, Xinyu Dai, Qiyong Gong, Feng Bi
Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102226/chronic-lymphocytic-leukaemia
#12
Thomas J Kipps, Freda K Stevenson, Catherine J Wu, Carlo M Croce, Graham Packham, William G Wierda, Susan O'Brien, John Gribben, Kanti Rai
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all...
January 19, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28102109/epigenetic-regulation-of-rgs2-regulator-of-g-protein-signaling-2-in-chemoresistant-ovarian-cancer-cells
#13
Ercan Cacan
Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively...
January 19, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28102076/kinobead-and-single-shot-lc-ms-profiling-identifies-selective-pkd-inhibitors
#14
Martin Golkowski, Rama Subba Rao Vidadala, Chloe K Lombard, Hyong Won Suh, Dustin J Maly, Shao-En Ong
ATP-competitive protein kinase inhibitors are important research tools and therapeutic agents. Because there are >500 human kinases that contain highly conserved active sites, the development of selective inhibitors is extremely challenging. Methods to rapidly and efficiently profile kinase inhibitor targets in cell lysates are urgently needed to discover selective compounds and to elucidate the mechanisms of action for polypharmacological inhibitors. Here, we describe a protocol for microgram-scale chemoproteomic profiling of ATP-competitive kinase inhibitors using kinobeads...
January 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28102059/v%C3%AE-1%C3%A2-%C2%BA-%C3%AE-%C3%AE-t-cells-are-correlated-with-increasing-expression-of-eosinophil-cationic-protein-and-metalloproteinase-7-in-chronic-rhinosinusitis-with-nasal-polyps-inducing-the-formation-of-edema
#15
Luo Ying Yang, Xia Li, Wen Ting Li, Jian Cong Huang, Zhi Yuan Wang, Zi Zhen Huang, Li Hong Chang, Ge Hua Zhang
PURPOSE: We have found that expression of γδT cells is increased in pathological mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP) compared with normal nasal mucosa. This increase is correlated with the infiltration of eosinophils in CRSwNP. Here, we investigated the expression of γδT cells, inflammation and tissue remodeling factors as well as their probable relationships in different types of chronic rhinosinusitis (CRS) in China. METHODS: A total of 76 surgical tissue samples that included 43 CRSwNP samples (15 eosinophilic and 28 non-eosinophilic), 17 CRS samples without nasal polyps (CRSsNP), and 16 controls were obtained...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28102022/the-flavonoid-7-4-dihydroxyflavone-prevents-dexamethasone-paradoxical-adverse-effect-on-eotaxin-production-by-human-fibroblasts
#16
Changda Liu, Nan Yang, Xiaoke Chen, Jody Tversky, Jixun Zhan, Mirna Chehade, Rachel L Miller, Xiu-Min Li
Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition...
January 19, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28101945/epidermal-growth-factor-receptor-egfr-mapk-nuclear-factor-nf-%C3%AE%C2%BAb-il8-a-possible-mechanism-of-particulate-matter-pm-2-5-induced-lung-toxicity
#17
Seung-Chan Jeong, Yoon Cho, Mi-Kyung Song, Eunil Lee, Jae-Chun Ryu
Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2...
January 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28101818/autophagy-is-a-regulator-of-trail-induced-apoptosis-in-nsclc-a549-cells
#18
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
Autophagy, a catabolic process by which cytoplasmic components are degraded in lysosomes, plays an important role in the maintenance of cellular homeostasis. Dysregulation of autophagy is associated with several diseases. However, few studies have addressed the role of autophagy in the lung, and its role in lung diseases remains unclear. In the present study, we examined the effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on autophagy in A549 cells and explored the underlying mechanisms...
January 18, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28101799/antitumor-efficacy-of-slpi-promoter-controlled-expression-of-artificial-microrna-targeting-egfr-in-a-squamous-cell-carcinoma-cell-line
#19
Jia Chen, Shoude Zhang, Yi Lin, Beibei Yang, Jiang Cao
The purpose of this study was to develop a recombinant adenovirus with secretory leukoprotease inhibitor (SLPI) promoter-controlled expression for gene therapy of squamous cell carcinoma (SCC). An artificial microRNA targeting epidermal growth factor receptor (EGFR) was designed, and used to construct a replication-defective recombinant adenovirus with SLPI promoter-controlled expression. The silencing efficiency of this vector (Ad-SLPI-EGFRamiR) was detected in Hep-2 cells. Western blotting showed that the expression of 170 kD EGFR was significantly reduced in Hep-2 cells 72 h after infection with Ad-SLPI-EGFRamiR...
January 18, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28101628/rho-kinase-inhibitor-fasudil-mitigates-high-cholesterol-diet-induced-hypercholesterolemia-and-vascular-damage
#20
Nibrass Taher Abdali, Awny H Yaseen, Eman Said, Tarek M Ibrahim
The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2...
January 18, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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