Pharmacological research : the official journal of the Italian Pharmacological Society
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Diabetic nephropathy (DN) is still one of the leading causes of end-stage renal disease despite the emergence of different therapies to counter the metabolic, hemodynamic and fibrotic pathways, implicating a prominent role of genetic and epigenetic factors in its progression. Epigenetics is the study of changes in the expression of genes which may be inheritable and does not involve a change in the genome sequence. Thrust areas of epigenetic research are DNA methylation and histone modifications. ⋯ Conversely, miRNAs (miR-301, miR-449 etc.) themselves modulated levels of DNA methyltranferases (DNMTs) and Histone deacetylases (HDACs), enzymes vital to epigenetic modifications. With already few FDA approved epigenetic -modulating drugs (Vorinostat, Decitabine) in the market and miRNA therapeutic drugs under clinical trial it becomes imperative to analyze the possible interaction between the two classes of drugs in the modulation of a disease process. The purpose of this review is to articulate the interplay between miRNA expression and epigenetic modifications with a particular focus on its impact on the development and progression of DN.
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The zebrafish (Danio rerio) is increasingly utilized as a powerful new model organism in neurobehavioral research. Aggression is a common symptom of many CNS disorders, has some genetic determinants and can be modulated pharmacologically in humans and animal model species. ⋯ Here, we discuss mechanisms of zebrafish aggression and their pharmacological, pharmacogenetic and pharmacogenomic models, as well as recent developments and existing challenges in this field. We also emphasize the growing utility of zebrafish models in translational neuropharmacological research of aggression, fostering future discoveries of potential therapeutic agents for aggressive behavior.
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Meta Analysis
Effects of statin exposure and lung cancer survival: A meta-analysis of observational studies.
Statin exposure has been reported to improve survival in several cancers. However, studies evaluating the association between statins and prognostic outcomes in patients with lung cancer are conflicting and heterogeneous. Pubmed, EMBASE and reference lists of included studies were searched to identify studies investigating the association between statin exposure and lung cancer prognosis. ⋯ Besides, statin users were likely to have more survival benefits in stage IV lung cancer patients (HR 0.77, 95% CI 0.74-0.79) than in mixed stage (I-IV or I-III) patients (P for interaction = 0.004). Statin exposure is associated with significantly improved survival in patients with lung cancer. Future studies are warranted to further demonstrate the therapeutic role of statins in specific lung cancer patients.
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During critical period, the heightened plasticity in neocortex opens a time window when, with proper external environmental stimuli, experience dependent refinement processes help to optimize the function of neuronal networks. With the closure of critical periods, the gradually decreased plasticity leaves a mature system which is stable to perform its function but with limited plasticity for changes in the adult. ⋯ Among them, the abundance of AMPA receptor silent synapses, as substrates for Hebbian plasticity, is shown to be closely related to not only critical period plasticity, but also the network refinement at glutamatergic synapses of principal neurons. Here, I discuss the role of silent synapses and how they interact with other known mechanisms involved in critical period plasticity.
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Meta Analysis Comparative Study
Etrolizumab versus infliximab in the treatment of induction phase of ulcerative colitis: A systematic review and indirect comparison.
There is still a need to develop new effective medications for the treatment of ulcerative colitis, particularly for patients who are intolerant or resistant to first line therapies. This article compared the efficacy and safety of etrolizumab and infliximab in moderate to severe ulcerative colitis. ⋯ Seven trials were sufficiently homogeneous to be used for indirect comparison of the induction phase of the treatment. There were no significant differences in clinical remission and serious adverse events between etrolizumab and infliximab. Moreover, adverse events of etrolizumab were significantly less than those of infliximab. However, further trials are required to compare other parameters of efficacy such as the clinical response and mucosal healing of etrolizumab with infliximab in anti-TNF alpha naïve patients.