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https://www.readbyqxmd.com/read/28927115/wee1-inhibition-by-mk1775-as-a-single-agent-therapy-inhibits-ovarian-cancer-viability
#1
Minghui Zhang, Donye Dominguez, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Xia Li, Yi Zhang, Huirong Shi, Bin Zhang
Wee1-like protein kinase (WEE1) physiologically serves a key function in maintaining the integrity of the cell genome through mediating the activation of cyclin-dependent kinase (CDK)1 and CDK2. Increased expression of WEE1 has been associated with the poor prognosis of patients with ovarian cancer. The present study aimed at examining the in vitro and in vivo antitumor activity of MK1775, a potent pharmacological inhibitor of WEE1, as a single agent against ovarian cancer cells. The cytotoxicity of MK1775 was examined in a panel of tumor cells using MTT in vitro...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927083/expression-of-thymidylate-synthase-predicts-clinical-outcomes-of-s-1-based-chemotherapy-in-squamous-cell-lung-cancer
#2
Yuichiro Honma, Shinsaku Togo, Kazue Shimizu, Miniwan Tulafu, Takuo Hayashi, Toshimasa Uekusa, Shigeru Tominaga, Kenji Kido, Yuichi Fujimoto, Yukiko Nanba, Kazuya Takamochi, Shiaki Oh, Kenji Suzuki, Kazuhisa Takahashi
Non-small cell lung cancer (NSCLC) patients with squamous cell carcinoma (SCC) histology have limited chemotherapeutic options. Treatment with S-1 combined with carboplatin (CBDCA) has been shown to provide a significant survival benefit in SCC patients compared with treatment with combined CBDCA and paclitaxel. The aim of the present study was to investigate the association between the expression of molecular markers related to the pharmacological action of S-1, including thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD), and the clinical efficacy of S-1-based chemotherapy in SCC patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926969/cardiovascular-activity-of-the-chemical-constituents-of-essential-oils
#3
REVIEW
Tadeu Uggere de Andrade, Girlandia Alexandre Brasil, Denise Coutinho Endringer, Flávio Rogério da Nóbrega, Damião Pergentino de Sousa
Cardiovascular diseases are a leading cause of death in developed and developing countries and decrease the quality of life, which has enormous social and economic consequences for the population. Recent studies on essential oils have attracted attention and encouraged continued research of this group of natural products because of their effects on the cardiovascular system. The pharmacological data indicate a therapeutic potential for essential oils for use in the treatment of cardiovascular diseases. Therefore, this review reports the current studies of essential oils chemical constituents with cardiovascular activity, including a description of their mechanisms of action...
September 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28926925/roxatidine-attenuates-degradation-of-extracellular-matrix
#4
Renhao Ze, Shangyu Wang, Mao Xie, Bo Zhang, Xin Tang, Jin Li
Degradation of extracellular matrix such as type II collagen and aggrecan induced by proinflammatory cytokines has been considered as an important hallmark of Osteoarthritis (OA). Roxatidine is a licensed specific competitive H (2) -receptor antagonist used for the treatment of gastric and duodenal ulcers. The pharmacological function of roxatidine on Osteoarthritis (OA) remains unknown. In the current study, we report that roxatidine attenuated TNF-α- induced degradation of type II collagen by suppressing the expression of MMP-3 and MMP-13 in human chondrosarcoma cell line SW1353 cells...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28926619/liver-x-receptor-activation-promotes-differentiation-of-regulatory-t-cells
#5
Martin Herold, Johanna Breuer, Stephanie Hucke, Percy Knolle, Nicholas Schwab, Heinz Wiendl, Luisa Klotz
The nuclear receptor Liver X Receptor (LXR) is a ligand-activated transcription factor that has been implicated in control of chronic inflammation by downregulating pro-inflammatory T cell responses. An impaired function of regulatory T cells, a subset of CD4+ T cells with a crucial role in maintaining lymphocytes homeostasis and immune regulation, is frequently observed in chronic inflammatory diseases. We observed that pharmacological activation of LXR in T cells not only resulted in a thorough suppression of Th1 and Th17 polarization in vitro, but also significantly induced regulatory T cells (Treg) cell differentiation in a receptor-specific fashion...
2017: PloS One
https://www.readbyqxmd.com/read/28926466/barriers-impeding-the-use-of-non-pharmacological-non-surgical-care-in-hip-and-knee-osteoarthritis-the-views-of-general-practitioners-physical-therapists-and-medical-specialists
#6
Ellen M H Selten, Johanna E Vriezekolk, Marc W Nijhof, Henk J Schers, Roelien G van der Meulen-Dilling, Willemijn H van der Laan, Rinie Geenen, Cornelia H M van den Ende
BACKGROUND: Non-pharmacological, non-surgical treatment modalities are underused in the management of knee and hip osteoarthritis (OA). One possible explanation for this could be healthcare providers' opinions about these treatment modalities. The objective of this qualitative study was to identify healthcare providers' views on non-pharmacological, non-surgical care for OA. METHODS: Semi-structured in-depth interviews with 24 healthcare providers (rheumatologists, orthopedic surgeons, physical therapists and general practitioners) were held...
September 19, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28926091/functional-role-of-mesenchymal-stem-cells-in-the-treatment-of-chronic-neurodegenerative-diseases
#7
Debora Lo Furno, Giuliana Mannino, Rosario Giuffrida
Mesenchymal stem cells (MSCs) can differentiate into not only cells of mesodermal lineages, but also into endodermal and ectodermal derived elements, including neurons and glial cells. For this reason, MSCs have been extensively investigated to develop cell-based therapeutic strategies, especially in pathologies whose pharmacological treatments give poor results, if any. As in the case of irreversible neurological disorders characterized by progressive neuronal death, in which behavioral and cognitive functions of patients inexorably decline as the disease progresses...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925885/spreading-depolarization-waves-in-neurological-diseases-a-short-review-about-its-pathophysiology-and-clinical-relevance
#8
Yağmur Çetin Taş, İhsan Solaroğlu, Yasemin Gürsoy-Özdemir
Lesion growth following acutely injured brain tissue after stroke, subarachnoid hemorrhage and traumatic brain injury is an important issue and a new target area for promising therapeutic interventions. Spreading depolarization or peri-lesion depolarization waves were demonstrated as one of the significant contributors of continued lesion growth. In this short review, we discuss the pathophysiology for SD forming events and try to list findings detected in neurological disorders like migraine, stroke, subarachnoid hemorrhage and traumatic brain injury in both human as well as experimental studies...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28925861/perioperative-pulmonary-medication-management
#9
Johnathan Ross Renew, Stephen Aniskevich
BACKGROUND: Pulmonary conditions such as asthma and chronic obstructive pulmonary disease (COPD) are common conditions that warrant special consideration in the perioperative period. When these patients undergo surgical interventions, they have risk of complications such as bronchospasm, hypoxia, and even postoperative respiratory failure that warrants unplanned intensive care unit admission. Thus, clinicians must be familiar with pulmonary medication regimens that are critical for maintaining stable homeostasis of these chronic conditions...
September 18, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28925698/an-ultraviolet-resonance-raman-spectroscopic-study-of-cisplatin-and-transplatin-interactions-with-genomic-dna
#10
Jiafeng Geng, Mena Aioub, Mostafa A El-Sayed, Bridgette A Barry
Ultraviolet resonance Raman (UVRR) spectroscopy is a label-free method to define biomacromolecular interactions with anticancer compounds. Using UVRR, we describe the binding interactions of two Pt(II) compounds, cisplatin (cis-diamminedichloroplatinum(II)) and its isomer, transplatin, with nucleotides and genomic DNA. Cisplatin binds to DNA and other cellular components and triggers apoptosis, whereas transplatin is clinically ineffective. Here, a 244 nm UVRR study shows that purine UVRR bands are altered in frequency and intensity when mononucleotides are treated with cisplatin...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28925334/comparative-patient-satisfaction-and-feasibility-of-a-pilot-parkinson-s-disease-enrichment-program
#11
Tabina K Choudhury, Celeste Harris, Kathleen Crist, Terry K Satterwhite, Michele K York
BACKGROUND: Available treatment options for Parkinson's disease (PD) are primarily aimed at pharmacological and/or neurosurgical management of motor symptoms. However, many patients also experience chronic non-motor symptoms (NMS), including significant cognitive and mood changes. Currently, there is a gap in the neuropsychological literature regarding the efficacy of nonpharmacological treatment options for cognitive and mood changes in PD. OBJECTIVE: We sought to evaluate the efficacy and patient satisfaction of a pilot nonpharmacological intervention for alleviating NMS in patients with PD...
September 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28925162/-effect-of-corydalis-rhizoma-and-l-tetrahydropalmatine-on-dopamine-system-of-hippocampus-and-striatum-in-morphine-induced-conditioned-place-preference-rats
#12
Shou-Yang Yu, Wei-Feng Bai, Ping Tu, Cheng-Kai Qiu, Pei-Run Yang, Su-Yuan Luo
To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹)...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28924942/exploring-the-anti-proliferative-activity-of-pelargonium-sidoides-dc-with-in-silico-target-identification-and-network-pharmacology
#13
A S P Pereira, M J Bester, Z Apostolides
Pelargonium sidoides DC (Geraniaceae) is a medicinal plant indigenous to Southern Africa that has been widely evaluated for its use in the treatment of upper respiratory tract infections. In recent studies, the anti-proliferative potential of P. sidoides was shown, and several phenolic compounds were identified as the bioactive compounds. Little, however, is known regarding their anti-proliferative protein targets. In this study, the anti-proliferative mechanisms of P. sidoides through in silico target identification and network pharmacology methodologies were evaluated...
September 18, 2017: Molecular Diversity
https://www.readbyqxmd.com/read/28924605/pai-1-is-a-critical-regulator-of-fgf23-homeostasis
#14
Mesut Eren, Aaron T Place, Paul M Thomas, Panagiotis Flevaris, Toshio Miyata, Douglas E Vaughan
Elevated levels of fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, are associated with a number of pathologic conditions including chronic kidney disease, cardiac hypertrophy, and congestive heart failure. Currently, there are no specific treatments available to lower plasma FGF23 levels. We have recently reported that genetic plasminogen activator inhibitor-1 (PAI-1) deficiency provided a significant reduction in circulating FGF23 levels while simultaneously prolonging the life span of Klotho-deficient mice...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28924483/thyroidectomy-for-the-treatment-of-graves-thyrotoxicosis-in-thioamide-induced-agranulocytosis-and-sepsis
#15
Colin L Knight, Shamil D Cooray, Jaideep Kulkarni, Michael Borschmann, Mark Kotowicz
A 51 year old man presented with sepsis in the setting of thioamide-induced agranulocytosis. Empiric broad-spectrum antibiotics was followed by directed narrow-spectrum antibiotics, and his neutrophil count recovered with support from granulocyte-colony stimulating factor (G-CSF) analogue transfusions. After a brief period of multi-modal therapy for nine days including potassium iodide (Lugol's iodine), cholestyramine, propanolol and lithium to temper his persisting hyperthyroidism, a total thyroidectomy was performed while thyroid hormone levels remained at thyrotoxic levels...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#16
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923912/exploiting-drug-addiction-mechanisms-to-select-against-mapki-resistant-melanoma
#17
Aayoung Hong, Gatien Moriceau, Lu Sun, Shirley Lomeli, Marco Piva, Robert Damoiseaux, Sheri L Holmen, Norman E Sharpless, Willy Hugo, Roger S Lo
Melanoma resistant to MAPK inhibitor(s) (MAPKi) displays loss-of-fitness upon experimental MAPKi withdrawal and, clinically, may be re-sensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi-addiction in MAPKi-resistant MUTBRAF or MUTNRAS melanoma. MAPKi-addiction phenotypes evident upon drug-withdrawal spanned transient cell-cycle slow-down to cell-death responses, the latter of which required a robust p-ERK rebound. Generally, drug withdrawal-induced p-ERK rebound up-regulated p38-FRA1-JUNB-CDKN1A and down-regulated proliferation, but only a robust p-ERK rebound resulted in DNA damage and parthanatos-related cell death...
September 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28923789/assessing-the-efficacy-and-safety-of-an-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor-azd4017-in-the-idiopathic-intracranial-hypertension-drug-trial-iih-dt-clinical-methods-and-design-for-a-phase-ii-randomized-controlled-trial
#18
Keira Annie Markey, Ryan Ottridge, James L Mitchell, Caroline Rick, Rebecca Woolley, Natalie Ives, Peter Nightingale, Alexandra J Sinclair
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition with few effective management options. So far, there have been no randomized controlled trials evaluating new treatments in IIH. OBJECTIVES: The purpose of this paper is to outline the trial design for the Idiopathic Intracranial Hypertension Drug Trial (IIH:DT), assessing an innovative medical treatment in IIH and the rationale for the chosen trial methodology. METHODS: IIH:DT is a phase II double-blind randomized placebo-controlled trial recruiting 30 female participants with active IIH (intracranial pressure >25cm H2 O and papilledema)...
September 18, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28923571/ophthalmic-administration-of-a-10-fold-lower-dose-of-conventional-nanoliposome-formulations-caused-levels-of-intraocular-pressure-similar-to-those-induced-by-marketed-eye-drops
#19
C M Arroyo, D Quinteros, M J Cózar-Bernal, S D Palma, A M Rabasco, M L González-Rodríguez
The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles...
September 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28923474/beyond-the-inhaled-nitric-oxide-in-persistent-pulmonary-hypertension-of-the-newborn
#20
REVIEW
Mei-Yin Lai, Shih-Ming Chu, Satyan Lakshminrusimha, Hung-Chih Lin
Persistent pulmonary hypertension (PPHN) is a consequence of failed pulmonary vascular transition at birth and leads to pulmonary hypertension with shunting of deoxygenated blood across the ductus arteriosus (DA) and foramen ovale (FO) resulting in severe hypoxemia, and it may eventually lead to life-threatening circulatory failure. PPHN is a serious event affecting both term and preterm infants in the neonatal intensive care unit. It is often associated with diseases such as congenital diaphragmatic hernia, meconium aspiration, sepsis, congenital pneumonia, birth asphyxia and respiratory distress syndrome...
August 10, 2017: Pediatrics and Neonatology
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