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Trends in Pharmacological Sciences

Simona Pisanti, Maurizio Bifulco
No abstract text is available yet for this article.
January 14, 2017: Trends in Pharmacological Sciences
Ethan B Russo
Once a widely ignored phytocannabinoid, cannabidiol now attracts great therapeutic interest, especially in epilepsy and cancer. As with many rising trends, various myths and misconceptions have accompanied this heightened public interest and intrigue. This forum article examines and attempts to clarify some areas of contention.
January 11, 2017: Trends in Pharmacological Sciences
Giuseppe Lippi, Mario Plebani
The US Preventive Services Task Force has recently recommended the use of statins in primary prevention of cardiovascular disease in adults. Doubts remain as to whether this approach is really cost-effective, and additional drawbacks include the increasing burden of potential side effects and incremental costs due to laboratory monitoring.
December 22, 2016: Trends in Pharmacological Sciences
Justin Rustenhoven, Deidre Jansson, Leon C Smyth, Mike Dragunow
Brain pericytes are perivascular cells that regulate capillary function, and this localization puts them in a pivotal position for the regulation of central nervous system (CNS) inflammatory responses at the neurovascular unit. Neuroinflammation, driven by microglia and astrocytes or resulting from peripheral leukocyte infiltration, has both homeostatic and detrimental consequences for brain function and is present in nearly every neurological disorder. More recently, brain pericytes have been shown to have many properties of immune regulating cells, including responding to and expressing a plethora of inflammatory molecules, presenting antigen, and displaying phagocytic ability...
December 22, 2016: Trends in Pharmacological Sciences
Jianming Wu, Tuoen Liu, Zechary Rios, Qibing Mei, Xiukun Lin, Shousong Cao
Heat shock proteins (HSPs) constitute a large family of proteins involved in protein folding and maturation whose expression is induced by heat shock or other stressors. The major groups are classified based on their molecular weights and include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSPs. HSPs play a significant role in cellular proliferation, differentiation, and carcinogenesis. In this article we comprehensively review the roles of major HSPs in cancer biology and pharmacology. HSPs are thought to play significant roles in the molecular mechanisms leading to cancer development and metastasis...
December 21, 2016: Trends in Pharmacological Sciences
Davide Ferrari, Fabio Malavasi, Luca Antonioli
Nucleotides and nucleosides have emerged as important modulators of tumor biology. Recently acquired evidence shows that, when these molecules are released by cancer cells or surrounding tissues, they act as potent prometastatic factors, favoring tumor cell migration and tissue colonization. Therefore, nucleotides and nucleosides should be considered as a new class of prometastatic factors. In this review, we focus on the prometastatic roles of nucleotides and discuss future applications of purinergic signaling modulation in view of antimetastatic therapies...
December 15, 2016: Trends in Pharmacological Sciences
Emelie Perland, Robert Fredriksson
Membrane-bound solute carrier (SLC) transporter proteins are vital to the human body, as they sustain homeostasis by moving soluble molecule as nutrients, drugs, and waste across lipid membranes. Of the 430 identified secondary active transporters in humans, 30% are still orphans, and systematic research has been requested to elaborate on their possible involvement in diseases and their potential as drug targets. To enable this, the various classification systems in use must be understood and used correctly...
December 8, 2016: Trends in Pharmacological Sciences
Mehmet Coskun, Severine Vermeire, Ole Haagen Nielsen
Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e...
December 1, 2016: Trends in Pharmacological Sciences
Matthew L Banks, S Stevens Negus
Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence)...
December 1, 2016: Trends in Pharmacological Sciences
Susanna Molas, Steven R DeGroot, Rubing Zhao-Shea, Andrew R Tapper
While innovative modern neuroscience approaches have aided in discerning brain circuitry underlying negative emotional behaviors including fear and anxiety responses, how these circuits are recruited in normal and pathological conditions remains poorly understood. Recently, genetic tools that selectively manipulate single neuronal populations have uncovered an understudied circuit, the medial habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative emotional responses. Interestingly, the mHb-IPN pathway also represents an essential circuit that signals heightened anxiety induced by nicotine withdrawal...
November 24, 2016: Trends in Pharmacological Sciences
Manuela S Murgueitio, Christin Rakers, Anne Frank, Gerhard Wolber
As essential proteins of the innate immune system, Toll-like receptors (TLRs) are involved in a plethora of physiological pathologies and their modulation is an ongoing quest in the field of drug discovery. Although TLRs recognize an unusually broad range of different molecular patterns, only a few small-molecule TLR modulators have been reported to date. Recent advances in crystallography and in silico techniques provide promising opportunities for TLR investigations and drug design. Here, three application areas for computational approaches are considered: (i) exploration of TLR structure and activation; (ii) understanding TLR modulation; and (iii) TLR drug discovery...
November 15, 2016: Trends in Pharmacological Sciences
István Gyertyán
Despite the abundance of cognitive enhancer mechanisms identified in basic research, drugs approved for cognitive disorders are scarce and of limited efficacy. Although the so-called 'gold-standard' animal assays are well suited to the study of fundamental learning processes, they fail to predict clinical efficacy against complex and robust cognitive defects. Preclinical validation of potential drug targets requires new approaches with higher translational value. Here I propose a rodent cognitive test system that encompasses several learning paradigms each modeling a certain human cognitive domain...
November 14, 2016: Trends in Pharmacological Sciences
Robert A Quinn, Louis-Felix Nothias, Oliver Vining, Michael Meehan, Eduardo Esquenazi, Pieter C Dorrestein
Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment...
November 11, 2016: Trends in Pharmacological Sciences
James R Kintzing, Maria V Filsinger Interrante, Jennifer R Cochran
Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity...
November 8, 2016: Trends in Pharmacological Sciences
Richard M O'Connor, Anand Gururajan, Timothy G Dinan, Paul J Kenny, John F Cryan
Current treatment strategies for psychiatric disorders remain inadequate. Impeding development of novel therapeutics is our incomplete knowledge of the molecular pathophysiology underlying these disorders. Changes to miRNA function and expression are increasingly being associated with pathological behavioral states. Furthermore, the prospect of using of miRNA expression profiles (the miRNome) as objective psychiatric diagnosis tools is gaining traction. In this review, we focus on recent findings surrounding the link between miRNA function and psychiatric disorders, and outline some of the key challenges that will need to be overcome if the therapeutic potential of these molecular effectors is to be fully realized...
November 7, 2016: Trends in Pharmacological Sciences
Boris Cvek
No abstract text is available yet for this article.
November 4, 2016: Trends in Pharmacological Sciences
James A Timmons
As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing...
January 2017: Trends in Pharmacological Sciences
Margaret Warner, Bo Huang, Jan-Ake Gustafsson
A major issue in clinical endocrinology today is how to use hormones to achieve the health benefits that they clearly can provide but avoid the negative side effects, that is, how to develop more precise medicines. This problem of how to use hormones is pervasive in clinical endocrinology. It is true for estrogen, progesterone, androgen, vitamin D, and thyroid hormone, and the problem is amplified in the case of new ligands for the more recently discovered nuclear receptors. Selective targeting of hormone receptor subtypes is one attractive way to harness the beneficial effects of hormones while reducing unwanted side effects...
January 2017: Trends in Pharmacological Sciences
Ana Alfirevic, Munir Pirmohamed
Adverse drug reactions (ADRs) are common, are associated with morbidity and mortality, and are costly to healthcare systems. Genomic factors predispose to ADRs, but these vary depending on the drug, patient, and disease. Genomic testing can not only help to predict and prevent ADRs but can also be used in other ways (diagnosis, closer monitoring of those at risk, pre-emptive genotyping, and understanding of mechanism), all of which will be important in the future to improve the benefit-risk ratio of drugs. In the era of precision medicine, such genomic data will need to be integrated with other forms of data to develop a comprehensive and integrated approach to improve responses to medicines used in patients...
January 2017: Trends in Pharmacological Sciences
Joanna Schaffhausen
No abstract text is available yet for this article.
January 2017: Trends in Pharmacological Sciences
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