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https://www.readbyqxmd.com/read/29148909/inhibition-of-gaba-transporters-fails-to-afford-significant-protection-following-focal-cerebral-ischemia
#1
Maria Ek Lie, Emma K Gowing, Rasmus P Clausen, Petrine Wellendorph, Andrew N Clarkson
Brain ischemia triggers excitotoxicity and cell death, yet no neuroprotective drugs have made it to the clinic. While enhancing GABAergic signaling to counterbalance excitotoxicity has shown promise in animal models, clinical studies have failed. Blockade of GABA transporters (GATs) offers an indirect approach to increase GABA inhibition to lower the excitation threshold of neurons. Among the GATs, GAT1 is known to promote neuroprotection, while the protective role of the extrasynaptic transporters GAT3 and BGT1 is elusive...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#2
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#3
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147570/management-of-an-acute-catecholamine-induced-cardiomyopathy-and-circulatory-collapse-a-multidisciplinary-approach
#4
R T Casey, B G Challis, D Pitfield, R M Mahroof, N Jamieson, C J Bhagra, A Vuylsteke, S J Pettit, K C Chatterjee
A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29146732/mir-539-5p-inhibits-experimental-choroidal-neovascularization-by-targeting-cxcr7
#5
Yifan Feng, Jing Wang, Yuanzhi Yuan, Xi Zhang, Minqian Shen, Fei Yuan
Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146502/protracted-motivational-dopamine-related-deficits-following-adolescence-sugar-overconsumption
#6
Fabien Naneix, Florence Darlot, Véronique De Smedt-Peyrusse, Jean-Rémi Pape, Etienne Coutureau, Martine Cador
Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29146440/clodronate-a-vesicular-atp-release-blocker
#7
REVIEW
Yoshinori Moriyama, Masatoshi Nomura
Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP. Clodronate inhibits vesicular ATP release from neurons and reduces chronic neuropathic and inflammatory pain following blockade of purinergic chemical transmission...
November 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29146186/human-soluble-thrombomodulin-induced-blockade-of-peripheral-hmgb1-dependent-allodynia-in-mice-requires-both-the-lectin-like-and-egf-like-domains
#8
Yusuke Hayashi, Ryuichi Tsujita, Maho Tsubota, Haruka Saeki, Fumiko Sekiguchi, Goichi Honda, Atsufumi Kawabata
Thrombomodulin (TM), an endothelial protein with anti-coagulant activity, is composed of 5 domains, D1-D5. Recombinant human soluble TM (TMα) consisting of D1-D3, which is generated in CHO cells, suppresses inflammatory and nociceptive signals by inactivating high mobility group box 1 (HMGB1), one of damage-associated molecular patterns. TMα sequesters HMGB1 with the lectin-like D1 and promotes its degradation by thrombin binding to the EGF-like D2. We prepared TM's D123, D1 and D2 by the protein expression system of yeast, and evaluated their effects on HMGB1 degradation in vitro and on the allodynia caused by HMGB1 in distinct redox forms in mice in vivo...
November 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29145989/pain-management-strategies-in-shoulder-arthroplasty
#9
REVIEW
Jason L Codding, Charles L Getz
Pain control in total shoulder arthroplasty demands a multidisciplinary approach with collaboration between patients, surgeon, and anesthetist. A multimodal approach with preemptive medication, regional blockade, local anesthetics, and a combination of acetaminophen, nonsteroidal antiinflammatory drugs, tramadol, and gabapentinoids postoperatively leads to pain control and patient satisfaction. Assessment of patients' expectations constitutes a vital aspect of the preoperative patient evaluation. Educating and psychologically preparing patients reduces postoperative pain...
January 2018: Orthopedic Clinics of North America
https://www.readbyqxmd.com/read/29145974/immunotherapy-for-triple-negative-breast-cancer-existing-challenges-and-exciting-prospects
#10
Hongyan Jia, Cristina I Truica, Bin Wang, Yanhong Wang, Xingcong Ren, Harold A Harvey, Jianxun Song, Jin-Ming Yang
Patients with breast tumors that do not express the estrogen receptor, the progesterone receptor, nor Her-2/neu are hence termed "triple negatives", and generally have a poor prognosis, with high rates of systemic recurrence and refractoriness to conventional therapy regardless of the choice of adjuvant treatment. Thus, more effective therapeutic options are sorely needed for triple-negative breast cancer (TNBC), which occurs in approximately 20% of diagnosed breast cancers. In recent years, exploiting intrinsic mechanisms of the host immune system to eradicate cancer cells has achieved impressive success, and the advances in immunotherapy have yielded potential new therapeutic strategies for the treatment of this devastating subtype of breast cancer...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145885/future-perspectives-in-melanoma-research-melanoma-bridge-napoli-november-30th-3rd-december-2016
#11
Paolo A Ascierto, Sanjiv S Agarwala, Gennaro Ciliberto, Sandra Demaria, Reinhard Dummer, Connie P M Duong, Soldano Ferrone, Silvia C Formenti, Claus Garbe, Ruth Halaban, Samir Khleif, Jason J Luke, Lluis M Mir, Willem W Overwijk, Michael Postow, Igor Puzanov, Paul Sondel, Janis M Taube, Per Thor Straten, David F Stroncek, Jennifer A Wargo, Hassane Zarour, Magdalena Thurin
Major advances have been made in the treatment of cancer with targeted therapy and immunotherapy; several FDA-approved agents with associated improvement of 1-year survival rates became available for stage IV melanoma patients. Before 2010, the 1-year survival were quite low, at 30%; in 2011, the rise to nearly 50% in the setting of treatment with Ipilimumab, and rise to 70% with BRAF inhibitor monotherapy in 2013 was observed. Even more impressive are 1-year survival rates considering combination strategies with both targeted therapy and immunotherapy, now exceeding 80%...
November 16, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29145840/blockade-of-nicotine-sensitization-by-methanol-extracts-of-glycyrrhizae-radix-mediated-via-antagonism-of-accumbal-oxidative-stress
#12
Zheng Lin Zhao, Sang Chan Kim, Hong Feng Liu, Yi Yan Wu, Li Bo Li, Yu Hua Wang, Yu Jiao, Yu Fan, Chul Won Lee, Bong Hyeo Lee, Il Je Cho, Chae Ha Yang, Rong Jie Zhao
BACKGROUND: We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. METHODS: Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing...
November 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#13
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#14
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29145244/association-between-renin-angiotensin-aldosterone-system-blockade-and-future-osteoporotic-fracture-risk-in-hypertensive-population-a-population-based-cohort-study-in-taiwan
#15
Chang-I Chen, Jong-Shiuan Yeh, Nai-Wen Tsao, Fen-Yen Lin, Chun-Ming Shih, Kuang-Hsing Chiang, Yung-Ta Kao, Yu-Ann Fang, Lung-Wen Tsai, Wen-Chi Liu, Hironori Nakagami, Ryuichi Morishita, Yi-Jie Kuo, Chun-Yao Huang
Tissue renin-angiotensin-aldosterone system (RAAS) activation in sites of osteoporosis had been demonstrated in animal studies; however, the possibility of RAAS blockade to prevent future osteoporotic fracture had rarely been verified in clinical studies. We Used the Taiwan Longitudinal Health insurance database 2000 to 2008, the cohort study comprised patients age over 40 with a recorded new diagnosis of hypertension between January 1, 2000 to December 31, 2008, in addition, patients who had diagnosis of osteoporosis before the date of cohort enter were excluded...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29145167/contraction-response-to-muscle-percussion-a-reappraisal-of-the-mechanism-of-this-bedside-test
#16
Christoph Czarnetzki, André Truffert, Abdelhafid Mekideche, Antoine Poncet, Christopher Lysakowski, Martin R Tramèr, Michel R Magistris
OBJECTIVE: To study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders. METHODS: In 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide...
October 28, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#17
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have shown that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate anti-tumor immune responses. However, it remains unclear how ICD can be exploited for cancer immunotherapy. Here, we present a new biomaterial-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their immunogenicity in murine models of melanoma and colon carcinoma...
November 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/29144508/ly6g-neutrophil-derived-mir-223-inhibits-the-nlrp3-inflammasome-in-mitochondrial-damp-induced-acute-lung-injury
#18
Zunyong Feng, Shimei Qi, Yue Zhang, Zhilin Qi, Liang Yan, Jing Zhou, Fang He, Qianqian Li, Yanyan Yang, Qun Chen, Shi Xiao, Qiang Li, Yang Chen, Yao Zhang
MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29143869/peripheral-endocannabinoid-concentrations-are-not-associated-with-verbal-memory-impairment-during-mdma-intoxication
#19
E Haijen, M Farre, R de la Torre, A Pastor, E Olesti, N Pizarro, J G Ramaekers, K P C Kuypers
BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory...
November 16, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29143124/the-effect-of-inhibition-on-stimulus-specific-adaptation-in-the-inferior-colliculus
#20
Yaneri A Ayala, Manuel S Malmierca
The inferior colliculus is a center of convergence for inhibitory and excitatory synaptic inputs that may be activated simultaneously by sound stimulation. Stimulus repetition may generate response habituation by changing the efficacy of neuron's synaptic inputs. Specialized IC neurons reduce their response to repetitive tones, but restore their firing when a different and infrequent tone occurs, a phenomenon known as stimulus specific adaptation. Here, using the microiontophoresis technique, we determined the role of GABAA-, GABAB-, and glycinergic receptors in stimulus-specific adaptation (SSA)...
November 15, 2017: Brain Structure & Function
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