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https://www.readbyqxmd.com/read/28110213/cannabidiol-attenuates-ogd-r-induced-damage-by-enhancing-mitochondrial-bioenergetics-and-modulating-glucose-metabolism-via-pentose-phosphate-pathway-in-hippocampal-neurons
#1
Shanshan Sun, Fangyuan Hu, Jihong Wu, Shenghai Zhang
Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers...
December 31, 2016: Redox Biology
https://www.readbyqxmd.com/read/28108651/roflumilast-and-aquaporin-2-regulation-in-rat-renal-inner-medullary-collecting-duct
#2
Ezigbobiara N Umejiego, Yanhua Wang, Mark A Knepper, Chung-Lin Chou
Roflumilast is a cyclic nucleotide phosphodiesterase inhibitor that is FDA-approved for treatment of chronic obstructive pulmonary disease. With a view toward possible use for treatment of patients with X-linked nephrogenic diabetes insipidus (NDI) due to hemizygous mutations in the V2 vasopressin receptor, this study sought to determine the effect of roflumilast on aquaporin-2 (AQP2) phosphorylation, AQP2 trafficking, and water permeability in the rat inner medullary collecting duct (IMCD). In the presence of the vasopressin analog dDAVP (0...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28108623/tumor-induced-stromal-stat1-accelerates-breast-cancer-via-deregulating-tissue-homeostasis
#3
Victoria R Zellmer, Patricia M Schnepp, Sarah L Fracci, Xuejuan Tan, Erin N Howe, Siyuan Zhang
: The tumor microenvironment (TME) is a dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphological and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAGs) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108250/synthesis-of-vorinostat-and-cholesterol-conjugate-to-enhance-the-cancer-cell-uptake-selectivity
#4
Nethrie D Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su
Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28107783/lorcaserin-suppresses-oxycodone-self-administration-and-relapse-vulnerability-in-rats
#5
Harshini Neelakantan, Erica D Holliday, Robert G Fox, Sonja J Stutz, Sandra D Comer, Margaret Haney, Noelle C Anastasio, Frederick Gerard Moeller, Kathryn A Cunningham
Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses ("cue reactivity") that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is FDA-approved for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28107775/beta-caryophyllene-protects-against-alcoholic-steatohepatitis-by-attenuating-inflammation-and-metabolic-dysregulation-in-mice
#6
Zoltan V Varga, Csaba Matyas, Katalin Erdelyi, Resat Cinar, Daniela Nieri, Andrea Chicca, Balazs Tamas Nemeth, Janos Paloczi, Tamas Lajtos, Lukas Corey, Gyorgy Hasko, Bin Gao, George Kunos, Jürg Gertsch, Pal Pacher
BACKGROUND AND AIMS: Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. METHODS: In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses...
January 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28107310/the-renin-inhibitor-aliskiren-protects-rat-lungs-from-the-histopathologic-effects-of-fat-embolism
#7
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
February 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28106876/inhibition-of-innate-immune-cytosolic-surveillance-by-an-m-tuberculosis-phosphodiesterase
#8
Ruchi Jain Dey, Bappaditya Dey, Yue Zheng, Laurene S Cheung, Jie Zhou, David Sayre, Pankaj Kumar, Haidan Guo, Gyanu Lamichhane, Herman O Sintim, William R Bishai
Mycobacterium tuberculosis infection leads to cytosolic release of the bacterial cyclic dinucleotide (CDN) c-di-AMP and a host-generated CDN, cGAMP, both of which trigger type I interferon (IFN) expression in a STING-dependent manner. Here we report that M. tuberculosis has developed a mechanism to inhibit STING activation and the type I IFN response via the bacterial phosphodiesterase (PDE) CdnP, which mediates hydrolysis of both bacterial-derived c-di-AMP and host-derived cGAMP. Mutation of cdnP attenuates M...
February 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#9
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106111/broad-range-antiviral-activity-of-hydrogen-sulfide-against-highly-pathogenic-rna-viruses
#10
Nikolay Bazhanov, Olivier Escaffre, Alexander N Freiberg, Roberto P Garofalo, Antonella Casola
Hydrogen sulfide is an important endogenous mediator that has been the focus of intense investigation in the past few years, leading to the discovery of its role in vasoactive, cytoprotective and anti-inflammatory responses. Recently, we made a critical observation that H2S also has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study we tested the antiviral and anti-inflammatory activity of the H2S slow-releasing donor GYY4137 on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104468/composite-material-consisting-of-microporous-%C3%AE-tcp-ceramic-and-alginate-for-delayed-release-of-antibiotics
#11
Michael Seidenstuecker, Juergen Ruehe, Norbert P Suedkamp, Annerose Serr, Annette Wittmer, Marc Bohner, Anke Bernstein, Hermann O Mayr
OBJECTIVE: The aim of this study was to produce a novel composite of microporous β-TCP filled with alginate and Vancomycin (VAN) to prolong the release behavior of the antibiotic for up to 28 days. MATERIAL AND METHODS: Using the flow chamber developed by the group, porous ceramics in a directional flow were filled with alginates of different composition containing 50 mg/mL of antibiotics. After cross-linking the alginate with calcium ions, incubation took place in 10 mL double-distilled water for 4 weeks at 37 °C...
January 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28103739/newer-medical-therapies-for-metastatic-soft-tissue-sarcoma
#12
Akash Tiwari, Vineet Govinda Gupta, Sameer Bakhshi
Metastatic/advanced soft tissue sarcoma has a poor prognosis and conventionally, treatment options have been limited. In recent years, this area has been a rich ground for research with many new drugs being approved and several more in the pipeline. With multiple new treatment options available, it is vital to keep up pace with this rapidly changing field. Areas covered: Recent data regarding use of novel agents in advanced soft tissue sarcoma is reviewed with a focus on clinical applicability. The goal is to guide the clinician into choosing appropriate lines of therapy for the individual patient in light of recent availability of multiple new treatment options...
January 20, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28102848/statins-in-anthracycline-induced-cardiotoxicity-rac-and-rho-and-the-heartbreakers
#13
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/28101492/trends-and-predictors-of-chemotherapy-use-among-thyroid-cancer-patients-in-the-national-cancer-database-2004-2013
#14
Stacey A Fedewa, Ahmedin Jemal, Amy Y Chen
BACKGROUND/AIM: Beginning in 2011, the Food and Drug Administration (FDA) approved the use of multikinase inhibitors (MKIs) for medullary thyroid cancers (MTCs), and in 2013 MKIs were approved for metastatic differentiated thyroid cancers (DTCs). However, little is known about the use of chemotherapy in thyroid cancer patients. Thus, the goal of our study was to describe patterns of chemotherapy use, including MKIs, among DTC and MTC patients in the National Cancer Database (NCDB). METHODS: Chemotherapy use, along with other treatment types (surgery and radiation), was assessed between 2004 and 2013...
December 2016: European Thyroid Journal
https://www.readbyqxmd.com/read/28100580/venetoclax-in-patients-with-previously-treated-chronic-lymphocytic-leukemia
#15
Andrew W Roberts, Stephan Stilgenbauer, John F Seymour, David C S Huang
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacological mimic of the proteins that initiate apoptosis (a so-called BH3-mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a Phase 1 study, including complete remissions in 20% of patients...
January 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28100464/six-month-market-exclusivity-extensions-to-promote-research-offer-substantial-returns-for-many-drug-makers
#16
Aaron S Kesselheim, Benjamin N Rome, Ameet Sarpatwari, Jerry Avorn
To incentivize pharmaceutical manufacturers to invest in areas of unmet medical need, policy makers frequently propose extending the market exclusivity period of desired drugs. Some such proposals are modeled after the pediatric exclusivity patent extension program, which since 1997 has provided six additional months of market exclusivity for drugs studied in children. The most recent proposal would encourage rare disease research by providing six months of extended exclusivity for any existing drug that is granted subsequent FDA approval for a new rare disease indication...
January 18, 2017: Health Affairs
https://www.readbyqxmd.com/read/28100254/challenges-in-orphan-drug-development-and-regulatory-policy-in-china
#17
REVIEW
Alice Cheng, Zhi Xie
While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research...
January 18, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28099856/screening-bioactives-reveals-nanchangmycin-as-a-broad-spectrum-antiviral-active-against-zika-virus
#18
Keiko Rausch, Brent A Hackett, Nathan L Weinbren, Sophia M Reeder, Yoel Sadovsky, Christopher A Hunter, David C Schultz, Carolyn B Coyne, Sara Cherry
Zika virus is an emerging arthropod-borne flavivirus for which there are no vaccines or specific therapeutics. We screened a library of 2,000 bioactive compounds for their ability to block Zika virus infection in three distinct cell types with two different strains of Zika virus. Using a microscopy-based assay, we validated 38 drugs that inhibited Zika virus infection, including FDA-approved nucleoside analogs. Cells expressing high levels of the attachment factor AXL can be protected from infection with receptor tyrosine kinase inhibitors, while placental-derived cells that lack AXL expression are insensitive to this inhibition...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099783/ketosis-and-diabetic-ketoacidosis-in-response-to-sglt2-inhibitors-basic-mechanisms-and-therapeutic-perspectives
#19
REVIEW
Hongyu Qiu, Aleksandra Novikov, Volker Vallon
Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of anti-hyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk...
January 18, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28099079/lymphangioleiomyomatosis-a-monogenic-model-of-malignancy
#20
Vera P Krymskaya, Francis X McCormack
Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure...
January 14, 2017: Annual Review of Medicine
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