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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/30240635/roles-of-dna-repair-enzyme-ogg1-in-innate-immunity-and-its-significance-for-lung-cancer
#1
REVIEW
Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan Boldogh
Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway...
September 18, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30240634/roles-of-dna-repair-enzyme-ogg1-in-innate-immunity-and-its-significance-for-lung-cancer
#2
REVIEW
Spiros Vlahopoulos, Maria Adamaki, Nikolas Khoury, Vassilis Zoumpourlis, Istvan Boldogh
Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway...
September 18, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30189292/druggable-targets-in-the-rho-pathway-and-their-promise-for-therapeutic-control-of-blood-pressure
#3
REVIEW
Rachel A Dee, Kevin D Mangum, Xue Bai, Christopher P Mack, Joan M Taylor
The prevalence of high blood pressure (also known as hypertension) has steadily increased over the last few decades. Known as a silent killer, hypertension increases the risk for cardiovascular disease and can lead to stroke, heart attack, kidney failure and associated sequela. While numerous hypertensive therapies are currently available, it is estimated that only half of medicated patients exhibit blood pressure control. This signifies the need for a better understanding of the underlying cause of disease and for more effective therapies...
September 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30189291/genetic-variants-in-major-depressive-disorder-from-pathophysiology-to-therapy
#4
REVIEW
Xenia Gonda, Peter Petschner, Nora Eszlari, Daniel Baksa, Andrea Edes, Peter Antal, Gabriella Juhasz, Gyorgy Bagdy
In spite of promising preclinical results there is a decreasing number of new registered medications in major depression. The main reason behind this fact is the lack of confirmation in clinical studies for the assumed, and in animals confirmed, therapeutic results. This suggests low predictive value of animal studies for central nervous system disorders. One solution for identifying new possible targets is the application of genetics and genomics, which may pinpoint new targets based on the effect of genetic variants in humans...
September 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30189290/tspo-in-diverse-cns-pathologies-and-psychiatric-disease-a-critical-review-and-a-way-forward
#5
REVIEW
Tomás R Guilarte
The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging biomarker of brain injury and neuroinflammation has increased exponentially in the last decade. There has been a furious pace in the development of new radiotracers for TSPO positron emission tomography (PET) imaging and its use has now been extensively described in many neurological and mental disorders. This fast pace of research and the ever-increasing number of new laboratories entering the field often times lack an appreciation of the historical perspective of the field and introduce dogmatic, but unproven facts, related to the underlying neurobiology of the TSPO response to brain injury and neuroinflammation...
September 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149105/neurobiology-and-therapeutic-applications-of-neurotoxins-targeting-transmitter-release
#6
REVIEW
Saak V Ovsepian, Valerie B O'Leary, Naira M Ayvazyan, Ahmed Al-Sabi, Vasilis Ntziachristos, James O Dolly
Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomolecules and neuroactive peptides have co-evolved, which selectively target the transmitter release machinery, with the aim of subduing natural rivals or neutralizing prey...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149104/myocardial-metbolism-in-heart-failure-purinergic-signalling-and-other-metabolic-concepts
#7
REVIEW
Andreas L Birkenfeld, Jens Jordan, Markus Dworak, Tobias Merkel, Geoffrey Burnstock
Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of cardiac metabolism has therefore become an attractive clinical target. Cardiac metabolism is based on the integration of adenosine triphosphate (ATP) production and utilization pathways...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149103/extracellular-matrix-roles-in-cardiorenal-fibrosis-potential-therapeutic-targets-for-cvd-and-ckd-in-the-elderly
#8
REVIEW
Hiroe Toba, Merry L Lindsey
Whereas hypertension, diabetes, and dyslipidemia are age-related risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), aging alone is an independent risk factor. With advancing age, the heart and kidney gradually but significantly undergo inflammation and subsequent fibrosis, which eventually results in an irreversible decline in organ physiology. Through cardiorenal network interactions, cardiac dysfunction leads to and responds to renal injury, and both facilitate aging effects. Thus, a comprehensive strategy is needed to evaluate the cardiorenal aging network...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149102/depression-and-schizophrenia-viewed-from-the-perspective-of-amino-acidergic-neurotransmission-antipodes-of-psychiatric-disorders
#9
REVIEW
Joanna M Wierońska, Andrzej Pilc
Depression and schizophrenia are burdensome, costly serious and disabling mental disorders. Moreover the existing treatments are not satisfactory. As amino-acidergic (AA) neurotransmitters built a vast majority of brain neurons, in this article we plan to focus on drugs influencing AA neurotransmission in both diseases: we will discuss several facts concerning glutamatergic and GABA-ergic neurotransmission in these diseases, based mainly on preclinical experiments that used stimulators and/or blockers of both neurotransmitter systems...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149100/interactions-between-dyslipidemia-and-the-immune-system-and-their-relevance-as-putative-therapeutic-targets-in-atherosclerosis
#10
REVIEW
Michael Lacy, Dorothee Atzler, Rongqi Liu, Menno de Winther, Christian Weber, Esther Lutgens
Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated as lipid particles accumulate and become trapped in vessel walls. The subsequent immune response, involving both adaptive and immune cells, progresses plaque development, which may be exacerbated under dyslipidemic conditions...
August 25, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149101/harnessing-cxcl12-signaling-to-protect-and-preserve-functional-%C3%AE-cell-mass-and-for-cell-replacement-in-type-1-diabetes
#11
REVIEW
David A Alagpulinsa, Jenny J L Cao, Don Sobell, Mark C Poznansky
Type 1 diabetes (T1D) is a complex multifactorial disease characterized by autoimmune destruction of insulin-producing pancreatic β cells. Our understanding of the pathogenic mechanisms and natural history of T1D has evolved significantly over the past two decades; we can efficiently predict high-risk individuals, early diagnose the disease and stage progression. Fortuitously, novel in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells have been developed...
August 24, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30149099/zinc-signaling-and-epilepsy
#12
REVIEW
Urszula Doboszewska, Katarzyna Młyniec, Aleksandra Wlaź, Ewa Poleszak, Gabriel Nowak, Piotr Wlaź
Evidence from both preclinical and clinical studies suggest the importance of zinc homeostasis in seizures/epilepsy. Undoubtedly, zinc, via modulation of a variety of targets, is necessary for maintaining the balance between neuronal excitation and inhibition, while an imbalance between excitation and inhibition underlies seizures. However, the relationship between zinc signaling and seizures/epilepsy is complex as both extracellular and intracellular zinc may produce either protective or detrimental effects...
August 24, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30138638/air-pollution-and-resistance-to-inhaled-glucocorticoids-evidence-mechanisms-and-gaps-to-fill
#13
REVIEW
Christopher F Rider, Chris Carlsten
Substantial evidence indicates that cigarette smoke exposure induces resistance to glucocorticoids, the primary maintenance medication in asthma treatment. Modest evidence also suggests that air pollution may reduce the effectiveness of these critical medications. Cigarette smoke, which has clear parallels with air pollution, has been shown to induce glucocorticoid resistance in asthma and it has been speculated that air pollution may have similar effects. However, the literature on an association of air pollution with glucocorticoid resistance is modest to date...
August 20, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30125527/epigenome-modifiers-and-metabolic-rewiring-new-frontiers-in-therapeutics
#14
REVIEW
Alessandra Ferrari, Raffaella Longo, Rui Silva, Nico Mitro, Donatella Caruso, Emma De Fabiani, Maurizio Crestani
In the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possibilities to treat many pathological conditions induced by epigenetic alterations, by manipulating metabolic pathways producing metabolites that work also as epigenetic modifiers...
August 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30121320/targeting-oncogenic-drivers-in-lung-cancer-recent-progress-current-challenges-and-future-opportunities
#15
REVIEW
Satoshi Yoda, Ibiayi Dagogo-Jack, Aaron N Hata
Targeted therapies have changed the landscape of treatments for non-small cell lung cancer (NSCLC). Specific targeted therapies have been approved for NSCLC patients harboring genetic alterations in four oncogenes, and agents targeting additional oncogenic drivers are under investigation. Standard first-line chemotherapy has been supplanted by these targeted therapies due to superior efficacy and lower toxicity. Despite excellent response rates and durable responses in some cases, most patients experience relapse within a few years due to the development of acquired drug resistance...
August 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30121319/senescence-and-senotherapeutics-a-new-field-in-cancer-therapy
#16
REVIEW
Vassilios Myrianthopoulos, Konstantinos Evangelou, Panagiotis V S Vasileiou, Tomer Cooks, Theodoros P Vassilakopoulos, Gerassimos A Pangalis, Myrsini Kouloukoussa, Christos Kittas, Alexandros G Georgakilas, Vassilis G Gorgoulis
Cellular senescence is a stress response mechanism ensuring homeostasis. Its temporal activation during embryonic development or normal adult life is linked with beneficial properties. In contrast, persistent (chronic) senescence seems to exert detrimental effects fostering aging and age-related disorders, such as cancer. Due to the lack of a reliable marker able to detect senescence in vivo, its precise impact in age-related diseases is to a large extent still undetermined. A novel reagent termed GL13 (SenTraGorTM ) that we developed, allowing senescence recognition in any type of biological material, emerges as a powerful tool to study the phenomenon of senescence in vivo...
August 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30081049/targeting-tlrs-and-the-inflammasome-in-systemic-sclerosis
#17
REVIEW
John Henderson, Swati Bhattacharyya, John Varga, Steven O'Reilly
Systemic sclerosis (SSc) is an idiopathic autoimmune disease characterised by inflammation, vascular problems, cytokine dysregulation and ultimately fibrosis, which accounts for poor prognosis and eventual mortality. At present no curative treatments exist, hence there is an urgent need to better understand the aetiology and develop improved therapies accordingly. Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis...
August 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30081048/anti-platelet-drugs-and-their-necessary-interaction-with-endothelial-mediators-and-platelet-cyclic-nucleotides-for-therapeutic-efficacy
#18
REVIEW
Rebecca B Knowles, Timothy D Warner
For many millions of patients at secondary risk of coronary thrombosis pharmaceutical protection is supplied by dual anti-platelet therapy. Despite substantial therapeutic developments over the last decade recurrent thrombotic events occur, highlighting the need for further optimisation of therapies. Importantly, but often ignored, anti-platelet drugs interact with cyclic nucleotide systems in platelets and these are the same systems that mediate key endogenous pathways of platelet regulation, notably those dependent upon the vascular endothelium...
August 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30081050/extracellular-vesicles-and-their-nucleic-acids-for-biomarker-discovery
#19
REVIEW
Fatemeh Momen-Heravi, Stephen J Getting, Sterghios Athanasios Moschos
Extracellular vesicles (EVs) are a heterogenous population of vesicles originate from cells. EVs are found in different biofluids and carry different macromolecules, including proteins, lipids, and nucleic acids, providing a snap shot of the parental cells at the time of release. EVs have the ability to transfer molecular cargoes to other cells and can initiate different physiological and pathological processes. Mounting lines of evidence demonstrated that EVs' cargo and machinery is affected in disease states, positioning EVs as potential sources for the discovery of novel biomarkers...
August 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30081047/prostaglandins-in-asthma-and-allergic-diseases
#20
REVIEW
R Stokes Peebles
Prostaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD2 , PGE2 , PGF2 , PGI2 , and thromboxane B2 , that all signal through distinct seven transmembrane, G-protein coupled receptors. The receptors through which the prostaglandins signal determines their immunologic or physiologic effects. For instance, the same prostaglandin may have opposing properties, dependent upon the signaling pathways activated. In this article, we will detail how inhibition of cyclooxygenase metabolism and regulation of prostaglandin signaling regulates allergic airway inflammation and asthma physiology...
August 3, 2018: Pharmacology & Therapeutics
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