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https://www.readbyqxmd.com/read/28100301/high-throughput-screening-of-a-glaxosmithkline-protein-kinase-inhibitor-set-identifies-an-inhibitor-of-human-cytomegalovirus-replication-that-prevents-creb-and-histone-h3-post-translational-modification
#1
Amina S Khan, Matthew J Murray, Catherine M K Ho, William J Zuercher, Matthew B Reeves, Blair L Strang
To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high throughput strategy to screen a GlaxoSmithKline (GSK) Published Kinase Inhibitor Set (PKIS). This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen we identified compounds within chemotypes that impede HCMV replication and identified kinase proteins associated with inhibition of HCMV replication that are potential novel anti-HCMV targets...
January 18, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28098905/cripto-1-promotes-epithelial-mesenchymal-transition-in-prostate-cancer-via-wnt-%C3%AE-catenin-signaling
#2
Yan Liu, Zhenbang Qin, Kuo Yang, Ranlu Liu, Yong Xu
The Cripto-1 (CR-1) derived EGF-CFC family was overexpressed in tumor development enhancing proliferation, epithelial-mesenchymal transition (EMT) and migration of tumor cells. However, correlation between CR-1 and prostate cancer (PCa) remains still unclear. In the present study, we proved that CR-1 was expressed in PCa and its function was in the progression of PCa. Compared with benign prostatic hyperplasia (BPH) tissues, we confirmed that PCa tissues had high expression of CR-1 by immunohistochemistry and statistical data showed that CR-1 promoted properties of EMT in PCa tissues, including the downregulation of the cell adhesion molecules β-catenin (membrane) and E-cadherin while upregulating transcription factors β-catenin...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098243/vanillic-acid-attenuates-a%C3%AE-1-42-induced-oxidative-stress-and-cognitive-impairment-in-mice
#3
Faiz Ul Amin, Shahid Ali Shah, Myeong Ok Kim
Increasing evidence demonstrates that β-amyloid (Aβ) elicits oxidative stress, which contributes to the pathogenesis and disease progression of Alzheimer's disease (AD). The aims of the present study were to determine and explore the antioxidant nature and potential mechanism of vanillic acid (VA) in Aβ1-42-induced oxidative stress and neuroinflammation mediated cognitive impairment in mice. An intracerebroventricular (i.c.v.) injection of Aβ1-42 into the mouse brain triggered increased reactive oxygen species (ROS) levels, neuroinflammation, synaptic deficits, memory impairment, and neurodegeneration...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093982/pde7-selective-and-dual-inhibitors-advances-in-chemical-and-biological-research
#4
Agnieszka Jankowska, Artur Świerczek, Grażyna Chłoń-Rzepa, Maciej Pawłowski, Elżbieta Wyska
Phosphodiesterase 7 (PDE7) is an intracellular enzyme that specifically hydrolyses the second messenger, cyclic-3',5'-adenosine monophosphate (cAMP), into inactive non-cyclic nucleotide, 5'-AMP. To date, many structurally diverse compounds with PDE7 inhibitory properties have been described, including selective PDE7 inhibitors, dual PDE4/PDE7, PDE7/PDE8, and PDE7/GSK-3 inhibitors, and non-selective PDE inhibitors with high affinity for PDE7. Inhibitors of PDE7 provided beneficial effects in animal models of inflammatory and neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and many others...
16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28093241/new-isatin-derivative-inhibits-neurodegeneration-by-restoring-insulin-signaling-in-brain
#5
Meha Fatima Aftab, Shabbir Khan Afridi, Uzma Rasool Mughal, Aneela Karim, Darakhshan Jabeen Haleem, Nurul Kabir, Khalid M Khan, Rahman M Hafizur, Rizwana S Waraich
Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration...
January 13, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28093238/a-model-of-the-mitochondrial-basis-of-bipolar-disorder
#6
REVIEW
Gerwyn Morris, Ken Walder, Sean L McGee, Olivia M Dean, Susannah J Tye, Michael Maes, Michael Berk
BACKGROUND: Bipolar disorder phenomenologically is a biphasic disorder of energy availability; increased in mania and decreased in depression. In consort, there is accumulating evidence indicating increased mitochondrial respiration and ATP production in bipolar mania which contrasts with decreased mitochondrial function in patients in the euthymic or depressive phase of the illness. Consequently, the central thesis of this paper is that bipolar disorder is due to a phasic dysregulation of mitochondrial biogenergetics...
January 14, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28091556/vegf-b-promotes-recovery-of-corneal-innervations-and-trophic-functions-in-diabetic-mice
#7
Guohu Di, Xiaowen Zhao, Xia Qi, Songmei Zhang, Lu Feng, Weiyun Shi, Qingjun Zhou
Vascular endothelial growth factor (VEGF)-B possesses the capacity of promoting injured peripheral nerve regeneration and restore their sensory and trophic functions. However, the contribution and mechanism of VEGF-B in diabetic peripheral neuropathy remains unclear. In the present study, we investigated the expression and role of VEGF-B in diabetic corneal neuropathy by using type 1 diabetic mice and cultured trigeminal ganglion (TG) neurons. Hyperglycemia attenuated the endogenous expression of VEGF-B in regenerated diabetic corneal epithelium, but not that of VEGF receptors in diabetic TG neurons and axons...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088881/an-industry-update-the-latest-developments-in-therapeutic-delivery
#8
Iain Simpson
This Industry Update covers the period from 1 October through to 31 October 2016, and is based on information sourced from company press releases, scientific literature, patents and various news websites. The month saw several news items covering drug-delivery devices, including a new sensor to monitor and support the use of inhalers; launch in the UK of a new autoinjector for Cimzia(®), UCB's rheumatoid arthritis drug; and approval of Roche's Lucentis(®) in a prefilled syringe. Research was also published to show the value of continuous blood pressure monitoring in dementia management...
February 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#9
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28078079/looking-forward-to-new-targeted-treatments-for-chronic-spontaneous-urticaria
#10
REVIEW
Emek Kocatürk, Marcus Maurer, Martin Metz, Clive Grattan
The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28069177/increased-expression-of-integrin-linked-kinase-during-decidualization-regulates-the-morphological-transformation-of-endometrial-stromal-cells
#11
Chih-Feng Yen, Sung Hoon Kim, Shuen-Kuei Liao, Cem Atabekoglu, Serpil Uckac, Aydin Arici, Sefa Arlier, Chyi-Long Lee, Hsin-Shih Wang, Umit A Kayisli
OBJECTIVE: To study the impact of integrin-linked kinase (ILK) in endometrial stromal cells (ESCs) during decidualization. DESIGN: Laboratory study with the use of human endometrium. SETTING: University hospital. PATIENT(S): Fertile reproductive-age women who had not received hormonal treatment for 3 months before tissue collection. INTERVENTION(S): Endometrium tissue collection, in vitro decidualization of isolated ESCs, and small interfering (si) RNA transfection...
January 6, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28068632/hydroxysafflor-yellow-a-cardioprotection-in-ischemia-reperfusion-i-r-injury-mainly-via-akt-hexokinase-ii-independent-of-erk-gsk-3%C3%AE-pathway
#12
Jia Min, Cui Wei
Hydroxysafflor yellow A (HSYA) is the main active component of Carthamus tinctorius L which has been used for hundreds of years in Chinese folk medicine in the treatment cardiovascular disease. This study was designed to investigate whether HSYA exerts cardioprotection in ischemia-reperfusion (I/R) injury heart and the mechanisms involved. The protective effect and mechanisms in myocardial ischemia reperfusion injury of HSYA was evaluated by hypoxia-recover (H/R) injury cell model which induced by hypoxia and recovered with oxygen in H9c2 cells...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28067250/promotion-of-natural-tooth-repair-by-small-molecule-gsk3-antagonists
#13
Vitor C M Neves, Rebecca Babb, Dhivya Chandrasekaran, Paul T Sharpe
The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp. Biodegradable, clinically-approved collagen sponges are used to deliver low doses of small molecule glycogen synthase kinase (GSK-3) antagonists that promote the natural processes of reparative dentine formation to completely restore dentine...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064424/gender-related-hippocampal-proteomics-study-from-young-rats-after-chronic-unpredicted-mild-stress-exposure
#14
Lin-Na Ning, Teng Zhang, Jiang Chu, Na Qu, Li Lin, Ying-Yan Fang, Yan Shi, Peng Zeng, Er-Li Cai, Xiao-Ming Wang, Qun Wang, You-Ming Lu, Xin-Wen Zhou, Qi Zhang, Qing Tian
Clinical data have shown women are more susceptible to depression. This study was performed to identify differentially regulated proteins from hippocampus in chronic unpredicted mild stress (CUMS)-exposed male and female young rats. After 7 weeks of CUMS, depressed male (M-D) and female rats (F-D) and unstressed male (M-C) and female controls (F-C) were studied. By proteomics analysis, 74 differential proteins in F-C/M-C, 79 in F-D/M-D, 77 in F-D/F-C, and 32 in M-D/M-C were found. Further, the synapse-related proteins, cytoskeleton protein tau, and stress-related kinases in hippocampus were assayed by Western blotting...
January 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28061901/rbm5-inhibits-tumorigenesis-of-gliomas-through-inhibition-of-wnt-%C3%AE-catenin-signaling-and-induction-of-apoptosis
#15
Yuanpei Jiang, Hongling Sheng, Lei Meng, Hongsheng Yue, Bo Li, Aijun Zhang, Yanan Dong, Yuguang Liu
BACKGROUND: Gliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown. METHODS: The mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test...
January 6, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28060847/enhanced-chondrogenic-differentiation-of-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stem-cells-by-gsk-3-inhibitors
#16
Prapot Tanthaisong, Sumeth Imsoonthornruksa, Apichart Ngernsoungnern, Piyada Ngernsoungnern, Mariena Ketudat-Cairns, Rangsun Parnpai
Articular cartilage is an avascular, alymphatic, and aneural system with very low regeneration potential because of its limited capacity for self-repair. Mesenchymal stem cells (MSCs) are the preferred choice for cell-based therapies. Glycogen synthase kinase 3 (GSK-3) inhibitors are compounds that can induce the Wnt signaling pathway, which is involved in chondrogenesis and cartilage development. Here, we investigated the influence of lithium chloride (LiCl) and SB216763 synergistically with TGF-β3 on chondrogenic differentiation in human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28060833/wnt-signaling-prevents-the-a%C3%AE-oligomer-induced-mitochondrial-permeability-transition-pore-opening-preserving-mitochondrial-structure-in-hippocampal-neurons
#17
Macarena S Arrázola, Eva Ramos-Fernández, Pedro Cisternas, Daniela Ordenes, Nibaldo C Inestrosa
Alzheimer's disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through the induction of the mitochondrial permeability transition pore (mPTP). The mPTP is a non-selective pore that is formed under apoptotic conditions, disturbing mitochondrial structure and thus, neuronal viability. In AD, Aβ oligomers (Aβos) favor the opening of the pore, activating mitochondria-dependent neuronal cell death cascades...
2017: PloS One
https://www.readbyqxmd.com/read/28059970/artesunate-protects-against-the-organ-injury-and-dysfunction-induced-by-severe-hemorrhage-and-resuscitation
#18
Regina Sordi, Kiran K Nandra, Fausto Chiazza, Florence L Johnson, Claudia P Cabrera, Hew D Torrance, Noriaki Yamada, Nimesh S A Patel, Michael R Barnes, Karim Brohi, Massimo Collino, Christoph Thiemermann
OBJECTIVE: To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. BACKGROUND: HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects...
February 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28057765/insulin-signaling-regulates-a-functional-interaction-between-adenomatous-polyposis-coli-apc-and-cytoplasmic-dynein
#19
Feng J Gao, Liang Shi, Timothy Hines, Sachin Hebbar, Kristi L Neufeld, Deanna S Smith
Diabetes is linked to an increased risk for colorectal cancer, but the mechanistic underpinnings of this clinically important effect are unclear. Here we describe an interaction between the microtubule motor cytoplasmic dynein, the adenomatous polyposis coli tumor suppressor protein (APC), and glycogen synthase kinase-3β (GSK-3β) that could shed light on this issue. GSK-3β is perhaps best known for glycogen regulation, being inhibited downstream in an insulin-signaling pathway. However, the kinase is also important in many other processes...
January 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28054586/hepatic-mir-291b-3p-mediated-glucose-metabolism-by-directly-targeting-p65-to-upregulate-pten-expression
#20
Jun Guo, Lin Dou, Xiangyu Meng, Zhenzhen Chen, Weili Yang, Weiwei Fang, Chunxiao Yang, Xiuqing Huang, Weiqing Tang, Jichun Yang, Jian Li
Several studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice...
January 5, 2017: Scientific Reports
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