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https://www.readbyqxmd.com/read/28645087/ep2-receptor-agonist-ono-ae1-259-01-attenuates-pentylenetetrazole-and-pilocarpine-induced-seizures-but-causes-hippocampal-neurotoxicity
#1
Aline Carré Santos, Fernanda Rossatto Temp, Joseane Righes Marafiga, Micheli Mainardi Pillat, Amanda Titzel Hessel, Leandro Rodrigo Ribeiro, Lígia Gomes Miyazato, Mauro Schneider Oliveira, Carlos Fernando Mello
Epilepsy is a common and devastating neurological disease affecting more than 50 million people worldwide. Accumulating experimental and clinical evidence suggests that inflammatory pathways contribute to the development of seizures in various forms of epilepsy. In this context, while the activation of the PGE2 EP2 receptor causes early neuroprotective and late neurotoxic effects, the role of EP2 receptor in seizures remains unclear. We investigated whether the systemic administration of the highly selective EP2 agonist ONO-AE1-259-01 prevented acute pentylenetetrazole (PTZ)- and pilocarpine-induced seizures...
June 20, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28645006/study-of-intestinal-anti-inflammatory-activity-of-phoenix-loureiroi-kunth-arecaceae-fruit
#2
Rajan Murugan, Shanmugam Saravanan, Thangaraj Parimelazhagan
Phoenix loureiroi Kunth belongs to the family Arecaceae, the fruits are widely consumed by Kurumba and Irula tribes of Tamil Nadu (India) and also used to cure intestinal related diseases in folklore medicine. Therefore, in vivo animal studies were evaluated to confirm the prevention of inflammatory bowel disease (IBD) with the treatment of this plant fruits. The IBD was studied in Wistar albino rats by indomethacin (s.c.), acetic acid (i.c.) and dextran sulfate sodium (DSS) induced models. The diseases parameters such as macroscopic, microscopic features, serum biomarkers levels, haematological profile, biochemical and antioxidant levels were determined...
June 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28644734/high-throughput-phenotypic-screening-of-kinase-inhibitors-to-identify-drug-targets-for-polycystic-kidney-disease
#3
Tijmen H Booij, Hester Bange, Wouter N Leonhard, Kuan Yan, Michiel Fokkelman, Steven J Kunnen, Johannes G Dauwerse, Yu Qin, Bob van de Water, Gerard J P van Westen, Dorien J M Peters, Leo S Price
Polycystic kidney disease (PKD) is a prevalent disorder characterized by renal cysts that lead to kidney failure. Various signaling pathways have been targeted to stop disease progression, but most interventions still focus on alleviating PKD-associated symptoms. The mechanistic complexity of the disease, as well as the lack of functional in vitro assays for compound testing, has made drug discovery for PKD challenging. To identify modulators of PKD, Pkd1(-/-) kidney tubule epithelial cells were applied to a scalable and automated 3D cyst culture model for compound screening, followed by phenotypic profiling to determine compound efficacy...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28644630/expanding-the-therapeutic-potential-of-the-iron-chelator-deferasirox-in-the-development-of-aqueous-stable-ti-iv-anticancer-complexes
#4
Sergio A Loza-Rosas, Alexandra M Vázquez-Salgado, Kennett I Rivero, Lenny J Negrón, Yamixa Delgado, Josué A Benjamín-Rivera, Angel L Vázquez-Maldonado, Timothy B Parks, Charlene Munet-Colón, Arthur D Tinoco
The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV)...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28643892/calcitriol-exerts-an-anti-tumor-effect-in-osteosarcoma-by-inducing-the-endoplasmic-reticulum-er-stress-response
#5
Takatsune Shimizu, Walied A Kamel, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Akihiro Muto, Hideyuki Saya
Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of FDA-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS)...
June 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28643552/drug-induced-physeal-abnormalities-in-preclinical-toxicity-studies
#6
Kendall S Frazier
Most toxic physeal changes are characterized microscopically by altered chondrocyte development, proliferation, or maturation in the growth plate and eventually result in disordered appositional bone growth. Many therapeutic drugs directly or indirectly target proteins involved in chondrocytic differentiation and maturation pathways, so toxic physeal injury has become increasingly common in preclinical toxicologic pathology. While physeal dysplasia has been associated with several different drug classes including bisphosphonates, vascular endothelial growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, transforming growth factor beta receptor inhibitors, and vascular targeting agents, physeal changes often share similar morphologic features including thickening and disorganization of the hypertrophic layer, increased numbers of hypertrophic chondrocytes, altered mineralization of endochondral ossification, and/or increased thickness of subphyseal bone...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28643372/fine-tuning-perk-signaling-for-neuroprotection
#7
REVIEW
Mark Halliday, Daniel Hughes, Giovanna Mallucci
Protein translation and folding are tightly controlled processes in all cells, by proteostasis, an important component of which is the unfolded protein response (UPR). During periods of endoplasmic reticulum stress due to protein misfolding, the UPR activates a coordinated response in which the PERK branch activation restricts translation, while a variety of genes involved with protein folding, degradation, chaperone expression and stress responses are induced through signaling of the other branches. Chronic overactivation of the UPR, particularly the PERK branch is observed in the brains of patients in a number of protein misfolding neurodegenerative diseases, including Alzheimer's, and Parkinson's diseases and the taopathies...
June 23, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28643358/maximizing-functional-axon-repair-in-the-injured-cns-lessons-from-neuronal-development
#8
Andrew Kaplan, Mardja Bueno, Luyang Hua, Alyson E Fournier
The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors, however it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviours. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system...
June 23, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28643328/drug-repurposing-by-simulating-flow-through-protein-protein-interaction-networks
#9
M Manczinger, V Bodnár, B T Papp, B Sz Bolla, K Szabó, B Balázs, E Csányi, E Szél, G Erős, L Kemény
As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28642806/the-efficacy-of-epigallocatechin-3-gallate-green-tea-in-the-treatment-of-alzheimer-s-disease-an-overview-of-pre-clinical-studies-and-translational-perspectives-in-clinical-practice
#10
REVIEW
Marco Cascella, Sabrina Bimonte, Maria Rosaria Muzio, Vincenzo Schiavone, Arturo Cuomo
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia characterized by cognitive and memory impairment. One of the mechanism involved in the pathogenesis of AD, is the oxidative stress being involved in AD's development and progression. In addition, several studies proved that chronic viral infections, mainly induced by Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), Human herpesvirus 2 (HHV-2), and Hepatitis C virus (HCV) could be responsible for AD's neuropathology...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28642210/rationale-and-design-for-a-randomized-comparison-of-efficacy-and-safety-between-aspirin-and-clopidogrel-in-atrial-fibrillation-patients-with-low-stroke-risk-cesac-af-trial
#11
Sang Min Park, Haemin Jeong, Mi-Hyang Jung, Kyung Soon Hong, Myeong-Ki Hong, Chang Seok Bang, Christopher Y Kim
BACKGROUND: Atrial fibrillation (AF) increases the risk of thromboembolic stroke. An oral anticoagulant should be administrated to prevent stroke in patients with moderate stroke risk (ie, CHA2DS2-VASc score>2). If the stroke risk is low (i.e. the score=1), however, antiplatelet agent such as aspirin is widely used. Aspirin can cause peptic ulcer disease (PUD) while its alternative, clopidogrel, theoretically does not. OBJECTIVE: To elucidate the efficacy and safety between aspirin and clopidogrel, a multicenter randomized controlled trial was designed in AF patients with low stroke risk...
June 19, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28642042/changes-in-biophysical-membrane-properties-induced-by-the-budesonide-hydroxy-%C3%AE-cyclodextrin-complex
#12
Andreia G Dos Santos, Jules Bayiha, Gilles Dufour, Didier Cataldo, Brigitte Evrard, Liana C Silva, Magali Deleu, Marie-Paule Mingeot-Leclercq
Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a biocompatible cyclodextrin known to interact with cholesterol, is used as a drug-solubilizing agent in pharmaceutical formulations. Budesonide administered as an inclusion complex within HPβCD (BUD:HPβCD) required a quarter of the nominal dose of the suspension formulation and significantly reduced neutrophil induced inflammation in a COPD mouse model exceeding the effect of each molecule administered individually...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#13
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28640507/a-liver-specific-gene-expression-panel-predicts-the-differentiation-status-of-in-vitro-hepatocyte-models
#14
Dae-Soo Kim, Jea-Woon Ryu, Mi-Young Son, Jung-Hwa Oh, Kyung-Sook Chung, Sugi Lee, Jeong-Ju Lee, Jun-Ho Ahn, Ju-Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho-Rok Jung, Nam-Soon Kim, Hyun-Soo Cho
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies...
June 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28640255/aqp9-induced-cell-cycle-arrest-is-associated-with-ras-activation-and-improves-chemotherapy-treatment-efficacy-in-colorectal-cancer
#15
Dandan Huang, Xingzhi Feng, Yiting Liu, Yanhong Deng, Hao Chen, Daici Chen, Lekun Fang, Yue Cai, Huanliang Liu, Lei Wang, Jianping Wang, Zihuan Yang
Aquaporin-9 (AQP9) expression is associated with arsenic sensitivity in leukemia cells. However, the role of AQP9 in regulating tumor sensitivity to adjuvant chemotherapy in colorectal cancer (CRC) has not been elucidated. In this study, we demonstrated that AQP9 can serve as an independent predictive marker for adjuvant chemotherapy in CRC. Patients with high AQP9 expression had higher rate of disease-free survival (DFS) than those with low AQP9 expression. Upregulation of AQP9 was associated with enhanced chemosensitivity to 5-fluorouracil (5-FU) both in vitro and in vivo...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28638862/raw-rehmannia-radix-polysaccharide-can-effectively-release-peroxidative-injury-induced-by-duck-hepatitis-a-virus
#16
Meiyun Song, Yun Chen, Hongxu Du, Shuaibing Zhang, Yixuan Wang, Ling Zeng, Jingjing Yang, Jintong Shi, Yi Wu, Deyun Wang, Yuanliang Hu, Jiaguo Liu
BACKGROUND: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH. MATERIALS AND METHODS: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28638678/detailed-features-of-hematological-involvement-and-medication-induced-cytopenia-in-systemic-lupus-erythematosus-patients-single-center-results-of-221-patients
#17
Hava Üsküdar Teke, Döndü Üsküdar Cansu, Cengiz Korkmaz
OBJECTIVE: Systemic lupus erythematosus (SLE) may affect a number of systems, with the hematological system being one of the most common. Our aim is to determine the existence of cytopenia at diagnosis or during follow-up of our SLE patients as well as the associated factors. MATERIAL AND METHODS: A cohort of SLE patients that had been followed-up in the Department of Rheumotology from 1998 to 2015 was retrospectively assessed. Clinical and laboratory findings about the patients were recorded...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28638267/synergistic-antitumor-effect-of-sorafenib-in-combination-with-atm-inhibitor-in-hepatocellular-carcinoma-cells
#18
Jianhua Liu, Yahui Liu, Lingyu Meng, Bai Ji, Daqing Yang
Background: Currently, sorafenib is the only systemic chemotherapy drug for advanced stage Hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicate that sorafenib alone has only moderate antitumor efficacy, and could not inhibit disease metastasis and progression. KU-55933 is a specific ATM inhibitor, which has pro-apoptotic effect on tumor cells. In this study, we analyzed the synergistic effect of sorafenib and KU-55933 on the proliferation of HCC cell lines. Methods: Three HCC cell lines were treated with sorafenib and KU-55933 alone or combination in vitro to investigate inhibitory effect by MTT and wound healing assay...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28638234/ischemic-or-toxic-injury-a-challenging-diagnosis-and-treatment-of-drug-induced-stenosis-of-the-sigmoid-colon
#19
Zong-Ming Zhang, Xiang-Chun Lin, Li Ma, An-Qin Jin, Fang-Cai Lin, Zhuo Liu, Li-Min Liu, Chong Zhang, Na Zhang, Li-Juan Huo, Xue-Liang Jiang, Feng Kang, Hong-Jun Qin, Qiu-Yang Li, Hong-Wei Yu, Hai Deng, Ming-Wen Zhu, Zi-Xu Liu, Bai-Jiang Wan, Hai-Yan Yang, Jia-Hong Liao, Xu Luo, You-Wei Li, Wen-Ping Wei, Meng-Meng Song, Yue Zhao, Xue-Ying Shi, Zhao-Hui Lu
A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28636787/a-co-drug-conjugate-of-naringenin-and-lipoic-acid-mediates-neuroprotection-in-a-rat-model-of-oxidative-stress
#20
Tarek M Saleh, Monique C Saleh, Barry J Connell, Yang-Heon Song
Using our in vitro and in vivo models of oxidative stress, the current study was designed to determine the neuroprotective potential of naringenin, alone or in combination with lipoic acid. In our mixed neuronal culture exposed to hypoxia and subsequent reoxygenation, naringenin was shown to provide significant neuroprotection against cell death at a concentration of 2.5 μM. Lipoic acid (LA) did not produce neuroprotection at any concentration tested (0.25 to 100 μM). In contrast, when naringenin was covalently combined with LA, producing a novel compound named "VANL-100", significant neuroprotection was observed at a concentration as low as 2 x 10(-2) μM (100-fold more potent)...
June 21, 2017: Clinical and Experimental Pharmacology & Physiology
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