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Trends in Pharmacological Sciences

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https://www.readbyqxmd.com/read/28899620/the-action-radius-of-oxytocin-release-in-the-mammalian-cns-from-single-vesicles-to-behavior
#1
REVIEW
Bice Chini, Matthijs Verhage, Valery Grinevich
The hypothalamic neuropeptide oxytocin (OT) has attracted the attention both of the scientific community and a general audience because of its prosocial effects in mammals, and OT is now seen as a facilitator of mammalian species propagation. Furthermore, OT is a candidate for the treatment of social deficits in several neuropsychiatric and neurodevelopmental conditions. Despite such possibilities and a long history of studies on OT behavioral effects, the mechanisms of OT actions in the brain remain poorly understood...
September 9, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28886953/activating-or-inhibiting-nrf2
#2
Xin-Yi Chu, Ye-Mao Liu, Hong-Yu Zhang
Activating nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) is a widely recognized strategy for combating oxidative-stress-induced diseases. However, Nrf2 activation does not always bring advantageous effects. Therefore, before performing Nrf2-targeted therapy, we must pinpoint whether Nrf2 should be activated or inhibited.
September 5, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28867259/early-and-late-cns-inflammation-in-alzheimer-s-disease-two-extremes-of-a-continuum
#3
REVIEW
A Claudio Cuello
In 1990 it was reported that individuals receiving NSAIDs (non-steroidal anti-inflammatory drugs) showed a markedly reduced prevalence of Alzheimer's disease (AD) compared to the overall population. Large epidemiological studies corroborated this assertion and provoked numerous prospective AD clinical trials with a variety of NSAIDs, all of which demonstrated lack of efficacy. It is postulated that the explanation for the success of NSAIDS in preventing AD onset when given at preclinical stages, and for their failure when administered after AD clinical presentation, lies in the changing nature of central nervous system (CNS) inflammation in the decades-long continuum of AD pathology...
August 31, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28863985/targeting-12-lipoxygenase-as-a-potential-novel-antiplatelet-therapy
#4
REVIEW
Benjamin E Tourdot, Michael Holinstat
Platelets are key contributors to the formation of occlusive thrombi; the major underlying cause of ischemic heart disease and stroke. Antiplatelet therapy has reduced the morbidity and mortality associated with thrombotic events; however, the utility of current antiplatelet therapies is limited by the concomitant risk of an adverse bleeding event. Novel antiplatelet therapies that are more efficacious at inhibiting thrombosis while minimally affecting hemostasis are required. Platelet-type 12-(S)-lipoxygenase (12-LOX), an oxygenase shown to potentiate platelet activation, represents a novel antiplatelet target...
August 29, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28863984/immunomodulatory-properties-of-plants-and-mushrooms
#5
REVIEW
Jan Martel, Yun-Fei Ko, David M Ojcius, Chia-Chen Lu, Chih-Jung Chang, Chuan-Sheng Lin, Hsin-Chih Lai, John D Young
Plants and mushrooms are used for medicinal purposes and the screening of molecules possessing biological activities. A single plant or mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on experimental conditions, but the reason behind this dichotomy remains obscure. We present here a large body of experimental data showing that water extracts of plants and mushrooms usually activate immune cells, whereas ethanol extracts inhibit immune cells. The mode of extraction of plants and mushrooms may thus determine the effects produced on immune cells, possibly due to differential solubility and potency of stimulatory and inhibitory compounds...
August 29, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28826585/amyloid-in-alzheimer-s-disease-guilty-beyond-reasonable-doubt
#6
Christian Behl
Recently failed antiamyloidogenic trials call for an objective reassessment of the dominating amyloid cascade hypothesis of Alzheimer's disease (AD). Ongoing efforts focusing on amyloid β protein (Aβ), its deposition, and its removal need to be complemented by more intensive research in new directions. Those may either integrate amyloid pathology or will propose pathogenetic routes independent of Aβ in the search for the causes of AD.
August 18, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#7
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28807369/an-interview-with-ruth-nussinov
#8
(no author information available yet)
No abstract text is available yet for this article.
August 11, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28784329/targeting-mechanisms-linking-copd-to-type-2-diabetes-mellitus
#9
REVIEW
Mario Cazzola, Paola Rogliani, Luigino Calzetta, Davide Lauro, Clive Page, Maria Gabriella Matera
Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) often coexist. The mechanistic links between these two diseases are complex, multifactorial, and not entirely understood, but they can influence the approach to treatment. Understanding whether COPD comes first followed by T2DM or vice versa, or whether the two diseases develop simultaneously due to common underlying mechanisms, is important for the development of novel therapeutic approaches to these two important diseases. In this review, we discuss the potential links between COPD and T2DM and pharmacological approaches that might target these links...
August 4, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28760488/genetically-engineered-bacteria-for-treating-human-disease
#10
Buyun Ma, Qiuwei Pan, Maikel P Peppelenbosch
Bacteria have now been harnessed to combat human diseases, especially to meet the challenge of antimicrobial resistance. Modulating the microbiome, particularly by genetically engineering the bacteria, has provided proof-of-concept as potential pharmacotherapy, but those involved in this field should engage in discussion as how to move forward.
July 28, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28728963/structural-principles-of-fluorescent-rna-aptamers
#11
REVIEW
Robert J Trachman, Lynda Truong, Adrian R Ferré-D'Amaré
Several aptamer RNAs have been selected in vitro that bind to otherwise weakly fluorescent small molecules and enhance their fluorescence several thousand-fold. By genetically tagging cellular RNAs of interest with these aptamers and soaking cells in their cell-permeable cognate small-molecule fluorophores, it is possible to use them to study RNA localization and trafficking. These aptamers have also been fused to metabolite-binding RNAs to generate fluorescent biosensors. The 3D structures of three unrelated fluorogenic RNAs have been determined, and reveal a shared reliance on base quadruples (tetrads) to constrain the photo-excited chromophore...
July 17, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28711156/towards-a-structural-view-of-drug-binding-to-herg-k-channels
#12
REVIEW
Jamie I Vandenberg, Eduardo Perozo, Toby W Allen
The human ether-a-go-go-related gene (hERG) K(+) channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K(+) channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K(+) channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work...
July 12, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28709554/lessons-learned-from-two-decades-of-anticancer-drugs
#13
REVIEW
Zhichao Liu, Brian Delavan, Ruth Roberts, Weida Tong
Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena...
July 11, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28687272/interstrand-crosslink-repair-as-a-target-for-hdac-inhibition
#14
REVIEW
Teodora Nikolova, Nicole Kiweler, Oliver H Krämer
DNA interstrand crosslinks (ICLs) covalently connect complementary DNA strands. Consequently, DNA replication and transcription are hampered, DNA damage responses (DDR) are initiated, and cell death is triggered. Therefore, drugs inducing ICLs are effective against rapidly growing cancer cells. However, tumors engage a complicated enzymatic machinery to repair and survive ICLs. Several factors, including the post-translational acetylation/deacetylation of lysine residues within proteins, control this network...
July 4, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28668224/the-future-of-cysteine-cathepsins-in-disease-management
#15
REVIEW
Lovro Kramer, Dušan Turk, Boris Turk
Since the discovery of the key role of cathepsin K in bone resorption, cysteine cathepsins have been investigated by pharmaceutical companies as drug targets. The first clinical results from targeting cathepsins by activity-based probes and substrates are paving the way for the next generation of molecular diagnostic imaging, whereas the majority of antibody-drug conjugates currently in clinical trials depend on activation by cathepsins. Finally, cathepsins have emerged as suitable vehicles for targeted drug delivery...
June 28, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28668223/an-overview-of-novel-adjuvants-designed-for-improving-vaccine-efficacy
#16
REVIEW
Srinivasa Reddy Bonam, Charalambos D Partidos, Sampath Kumar M Halmuthur, Sylviane Muller
Adjuvants incorporated in prophylactic and/or therapeutic vaccine formulations impact vaccine efficacy by enhancing, modulating, and/or prolonging the immune response. In addition, they reduce antigen concentration and the number of immunizations required for protective efficacy, therefore contributing to making vaccines more cost effective. Our better understanding of the molecular mechanisms of immune recognition and protection has led research efforts to develop new adjuvants that are currently at various stages of development or clinical evaluation...
June 28, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28734639/ffa4-gpr120-pharmacology-and-therapeutic-opportunities
#17
REVIEW
Graeme Milligan, Elisa Alvarez-Curto, Brian D Hudson, Rudi Prihandoko, Andrew B Tobin
Free Fatty Acid receptor 4 (FFA4), also known as GPR120, is a G-protein-coupled receptor (GPCR) responsive to long-chain fatty acids that is attracting considerable attention as a potential novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Although no clinical studies have yet been initiated to assess efficacy in this indication, a significant number of primary publications and patents have highlighted the ability of agonists with potency at FFA4 to improve glucose disposition and enhance insulin sensitivity in animal models...
September 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28651847/the-cardiovascular-pharmacology-of-nonsteroidal-anti-inflammatory-drugs
#18
REVIEW
Tilo Grosser, Emanuela Ricciotti, Garret A FitzGerald
The principal molecular mechanisms underlying the cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and their relative predisposition to complications. In review article, we discuss how heterogeneity in the pharmacokinetics and pharmacodynamics of distinct NSAIDs may be expected to affect their CV risk profile...
August 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28606479/therapeutic-potential-of-ranibizumab-in-corneal-neovascularization
#19
Marianne L Shahsuvaryan
Ranibizumab is a humanized, affinity-matured vascular endothelial growth factor (VEGF) antibody fragment that neutralizes all isoforms of VEGF and is FDA approved for use in ophthalmology. Recently it was suggested that ranibizumab may be useful in the treatment of corneal neovascularization, but in reality this therapy is not yet evidence based.
August 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28558960/targeting-par1-now-what
#20
REVIEW
Robert Flaumenhaft, Karen De Ceunynck
Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs since the 1990s. Vorapaxar and drotrecogin-alfa are approved PAR1-targeted therapeutics, but safety concerns have limited the clinical use of vorapaxar and questions regarding the efficacy of drotrecogin-alfa led to its withdrawal from the market...
August 2017: Trends in Pharmacological Sciences
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