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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/29129644/role-of-kinase-coupled-trp-channels-in-mineral-homeostasis
#1
REVIEW
Vladimir Chubanov, Lorenz Mittermeier, Thomas Gudermann
Transient receptor potential (TRP) proteins TRPM6 and TRPM7 are α-kinase-coupled divalent cation-selective channels activated upon a reduction of cytosolic levels of Mg(2+) and Mg·ATP. Emerging evidence indicate that one of the main physiological functions of TRPM6 and TRPM7 is maintaining of cellular metabolism of Mg(2+) and likely other essential metals such as Ca(2+) and Zn(2+). Recent experiments with genetic animal models have shown that TRPM6 and TRPM7 are essential for epithelial Mg(2+) transport in the placenta and intestine...
November 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129643/tgf%C3%AE-pathway-inhibition-in-the-treatment-of-non-small-cell-lung-cancer
#2
REVIEW
Pınar Ö Eser, Pasi A Jänne
Advanced non-small cell lung cancer (NSCLC) continues to be an incurable family of thoracic malignancies that is chronically managed with chemotherapy, targeted therapy, and immunotherapy. While the discovery of driver oncogenes and the advent of targeted and immunotherapies in the last decade have vastly improved clinical disease management for patients harboring druggable mutations, the mainstay treatment for the majority of NSCLC patients remains cytotoxic chemotherapy. The clinical efficacy of targeted, immune, and cytotoxic therapies is limited by the development of drug resistance...
November 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29128343/post-stroke-depression-mechanisms-and-pharmacological-treatment
#3
REVIEW
Roberto Federico Villa, Federica Ferrari, Antonio Moretti
Depression, the most frequent psychiatric disorder following ischaemic stroke, negatively affects survivals' functional outcome, response to rehabilitation and quality of life. Approximately, one-third of them are affected by post-stroke depression (PSD), making it a serious social and public health problem and anti-depressant preventive and curative therapies worth investigating. However, a two-way association between depression and stroke has been also established: stroke increases the risk of PSD, but depression is an independent risk factor for stroke...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29128342/readers-of-dna-methylation-the-mbd-family-as-potential-therapeutic-targets
#4
REVIEW
Gordon D Ginder, David C Williams
DNA methylation represents a fundamental epigenetic modification that regulates chromatin architecture and gene transcription. Many diseases, including cancer, show aberrant methylation patterns that contribute to the disease phenotype. DNA methylation inhibitors have been used to block methylation dependent gene silencing to treat hematopoietic neoplasms and to restore expression of developmentally silenced genes. However, these inhibitors disrupt methylation globally and show significant off-target toxicities...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29080702/glioblastoma-and-chemoresistance-to-alkylating-agents-involvement-of-apoptosis-autophagy-and-unfolded-protein-response
#5
REVIEW
Sabine Hombach-Klonisch, Maryam Mehrpour, Shahla Shojaei, Craig Harlos, Marshall Pitz, Ahmed Hamai, Krzysztof Siemianowicz, Wirginia Likus, Emilia Wiechec, Brian D Toyota, Reyhane Hoshyar, Amir Seyfoori, Zahra Sepehri, Sudharsana R Ande, Forough Khadem, Mohsen Akbari, Adrienne M Gorman, Afshin Samali, Thomas Klonisch, Saeid Ghavami
Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29127024/the-sphingosine-1-phosphate-receptor-modulator-fingolimod-as-a-therapeutic-agent-recent-findings-and-new-perspectives
#6
REVIEW
Andrea Huwiler, Uwe Zangemeister-Wittke
The immunomodulatory drug fingolimod (FTY720, Gilenya(R)) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P1 subtype by induction of receptor downregulation. Since S1P1 is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression...
November 7, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29097309/emerging-tumor-spheroids-technologies-for-3d-in-vitro-cancer-modeling
#7
REVIEW
Tânia Rodrigues, Banani Kundu, Joana Silva-Correia, S C Kundu, Joaquim M Oliveira, Rui L Reis, Vitor M Correlo
Cancer is a leading cause of mortality and morbidity worldwide. Around 90% of deaths are caused by metastasis and just 10% by primary tumor. The advancement of treatment approaches is not at the same rhythm of the disease; making cancer a focal target of biomedical research. To enhance the understanding and promts the therapeutic delivery; concepts of tissue engineering are applied in the development of in vitro models that can bridge between 2D cell culture and animal models, mimicking tissue microenvironment...
October 30, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29097308/analysis-of-natural-product-regulation-of-opioid-receptors-in-the-treatment-of-human-disease
#8
REVIEW
S Badal, S Turfus, R Rajnarayanan, C Wilson-Clarke, S L Sandiford
Opioid receptors (ORs), μOR, δOR, κOR and ORL1 mediate numerous signaling cascades, most importantly, through the modulation of ion channels. Research demonstrates the role of OR mediated signal transduction in treating pain, cancer, neurodegenerative disorders and cardiac insults. Yet, the primary application of drugs that modulate ORs is analgesia. Current opioids like morphine that are mainly μOR orthosteric agonists attract many undesirable side-effects (constipation, urinary retention, respiratory depression and hypotension) and the existing modus operandi against these is the inclusion of a μOR antagonist (for example...
October 30, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29097307/effect-fingerprinting-of-new-psychoactive-substances-nps-what-can-we-learn-from-in-vitro-data
#9
REVIEW
Laura Hondebrink, Anne Zwartsen, Remco H S Westerink
The use of new psychoactive substances (NPS) is increasing and currently >600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCCP, TFMPP, BZP)...
October 30, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29097306/conserved-structural-and-functional-aspects-of-the-tripartite-motif-gene-family-point-towards-therapeutic-applications-in-multiple-diseases
#10
REVIEW
Liubov V Gushchina, Thomas A Bodnar, Sayak Bhattacharya, Noah L Weisleder
The tripartite motif (TRIM) gene family is a highly conserved group of E3 ubiquitin ligase proteins that can establish substrate specificity for the ubiquitin-proteasome complex and also have proteasome-independent functions. While several family members were studied previously, it is relatively recent that over 80 genes, based on sequence homology, were grouped to establish the TRIM gene family. Functional studies of various TRIM genes linked these proteins to modulation of inflammatory responses showing that they can contribute to a wide variety of disease states including cardiovascular, neurological and musculoskeletal diseases, as well as various forms of cancer...
October 30, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29092775/cytokines-as-therapeutic-targets-in-primary-sj%C3%A3-gren-syndrome
#11
REVIEW
Soledad Retamozo, Alejandra Flores-Chavez, Marta Consuegra-Fernández, Francisco Lozano, Manuel Ramos-Casals, Pilar Brito-Zerón
Primary Sjögren syndrome (SjS) is a systemic autoimmune disease that may affect 1 in 1000 people (overwhelmingly women) and that can be a serious disease with excess mortality due to severe organ-specific involvements and the development of B cell lymphoma; systemic involvement clearly marks the disease prognosis, and strongly suggests the need for closer follow-up and more robust therapeutic management. Therapy is established according to the organ involved and severity. As a rule, the management of systemic SjS should be organ-specific, with glucocorticoids and immunosuppressive agents limited to potentially-severe involvements; unfortunately, the limited evidence available for these drugs, together with the potential development of serious adverse events, makes solid therapeutic recommendations difficult...
October 29, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29080703/hormesis-as-a-mechanistic-approach-to-understanding-herbal-treatments-in-traditional-chinese-medicine
#12
REVIEW
Dali Wang, Edward J Calabrese, Baoling Lian, Zhifen Lin, Vittorio Calabrese
Traditional Chinese medicine (TCM) has been long practiced and is becoming ever more widely recognized as providing curative and/or healing treatments for a number of diseases and physiological conditions. This paper posits that herbal medicines used in TCM treatments may act through hormetic dose-response mechanisms. It is proposed that the stimulatory (i.e., low dose) and inhibitory (i.e., high dose) components of the hormetic dose response correspond to respective "regulating" and "curing" aspects of TCM herbal treatments...
October 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29080701/g-protein-coupled-receptors-as-anabolic-drug-targets-in-osteoporosis
#13
REVIEW
Natalie Diepenhorst, Patricia Rueda, Anna E Cook, Philippe Pastoureau, Massimo Sabatini, Christopher J Langmead
Osteoporosis is a progressive bone disorder characterised by imbalance between bone building (anabolism) and resorption (catabolism). Most therapeutics target inhibition of osteoclast-mediated bone resorption, but more recent attention in early drug discovery has focussed on anabolic targets in osteoblasts or their precursors. Two marketed agents that display anabolic properties, strontium ranelate and teriparatide, mediate their actions via the G protein-coupled calcium-sensing and parathyroid hormone-1 receptors, respectively...
October 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29080700/allosteric-pathways-in-nuclear-receptors-potential-targets-for-drug-design
#14
REVIEW
Elias J Fernandez
The nuclear receptor family of transcription factor proteins mediate endocrine function and play critical roles in development, physiology and pharmacology. Malfunctioning nuclear receptors are associated with several disease states. The functional activity of nuclear receptors is regulated by small molecular hormonal and synthetic molecules. Multiple sources of evidence have identified and distinguished between the different allosteric pathways initiated by ligands, DNA and cofactors such as co-activators and co-repressors...
October 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29080699/therapeutic-potential-of-omega-3-fatty-acid-derived-epoxyeicosanoids-in-cardiovascular-and-inflammatory-diseases
#15
REVIEW
Wolf-Hagen Schunck, Anne Konkel, Robert Fischer, Karsten-Henrich Weylandt
Numerous benefits have been attributed to dietary long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs), including protection against cardiac arrhythmia, triglyceride-lowering, amelioration of inflammatory, and neurodegenerative disorders. This review covers recent findings indicating that a variety of these beneficial effects are mediated by "omega-3 epoxyeicosanoids", a class of novel n-3 LC-PUFA-derived lipid mediators, which are generated via the cytochrome P450 (CYP) epoxygenase pathway. CYP enzymes, previously identified as arachidonic acid (20:4n-6; AA) epoxygenases, accept eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), the major fish oil n-3 LC-PUFAs, as efficient alternative substrates...
October 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29055715/live-or-let-die-neuroprotective-and-anti-cancer-effects-of-nutraceutical-antioxidants
#16
REVIEW
Xiao-Yuan Mao, Ming-Zhu Jin, Jin-Fei Chen, Qin Li, Hong-Hao Zhou, Wei-Lin Jin
Diet sources are closely involved in the pathogenesis of diverse neuropsychiatric disorders and cancers, in addition to inherited factors. Currently, natural products or nutraceuticals (commonly called medical foods) are increasingly employed for adjunctive therapy of these patients. However, the potential molecular mechanisms of the nutrient efficacy remain elusive. In this review, we summarized the neuroprotective and anti-cancer mechanisms of nutraceuticals. It was concluded that the nutraceuticals exerted neuroprotection and suppressed tumor growth possibly through the differential modulations of redox homeostasis...
October 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024739/direct-antiviral-agents-daas-a-new-age-in-the-treatment-of-hepatitis-c-virus-infection
#17
REVIEW
Ulrich Spengler
Hepatitis C virus (HCV) is a global health problem, because infection frequently leads to chronic hepatitis C eventually progressing to liver cirrhosis and liver cancer. Improved insights into the HCV replication cycle and the role of HCV non-structural proteins have recently enabled to identify drugs directly acting on specific HCV target structures. Agents from three drug classes have been developed and approved by the health authorities. Combinations of two or more drugs from different classes achieve high (>90%) HCV clearance rates and are well tolerated...
October 10, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024742/cyp-mediated-drug-metabolism-in-the-brain-impacts-drug-response
#18
REVIEW
Douglas M McMillan, Rachel F Tyndale
The functional role of cytochrome P450 (CYP) enzymes in the brain is an exciting and evolving field of research. CYPs are present and active in the brain, with heterogeneous patterns of expression, activity, and sensitivity to modulation across cell types, regions, and species. Despite total brain CYP expression being a fraction of hepatic CYP expression, the expanding literature of in vitro and in vivo experiments have provided evidence that brain CYPs can impact acute and chronic drug response, susceptibility to damage by neurotoxins, and are associated with altered personality, behaviour, and risk of neurological disease...
October 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024741/in-vivo-potency-revisited-keep-the-target-inl-sight
#19
REVIEW
Johan Gabrielsson, Lambertus A Peletier, Stephan Hjorth
Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure...
October 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29024740/antimicrobial-peptides-nanotechnology-and-natural-metabolites-as-novel-approaches-for-cancer-treatment
#20
REVIEW
Michel L Leite, Nicolau B da Cunha, Fabricio F Costa
Despite the advances in tumor identification and treatment, cancer remains the primary driver of death around the world. Also, regular treatments for the disease are incapable of targeting particular cancer types at different stages since they are not specifically focused on harmful cells since they influence both solid and tumor cells, causing side effects and undesirable symptoms. Therefore, novel strategies should be developed to treat this disease. Several efforts have been made in this direction to find more effective alternatives to cancer treatment, such as the use of antimicrobial peptides (AMPs) with antitumoral activity, nanocarriers and natural compounds from a variety of sources...
October 9, 2017: Pharmacology & Therapeutics
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