A pyrazole nucleus is an easy-to-prepare scaffold with large therapeutic potential. Consequently, the search for new pyrazole-based compounds is of great interest to the academic community as well as industry. In the last ten years, a large number of papers and reviews on the design, synthesis, and biological evaluation of different classes of pyrazoles and many pyrazole-containing compounds have been published. However, an overview of pyrazole derivatives bearing a free amino group at the 3, 4, or 5 position (namely, 3-aminopyrazoles, 4-aminopyrazoles, and 5-aminopyrazoles, respectively) and their biological properties is still missing, despite the fact that aminopyrazoles are advantageous frameworks able to provide useful ligands for receptors or enzymes, such as p38MAPK, and different kinases, COX and others, as well as targets important for bacterial and virus infections. With the aim to fill this gap, the present review focuses on aminopyrazole-based compounds studied as active agents in different therapeutic areas, with particular attention on the design and structure-activity relationships defined by each class of compounds. In particular, the most relevant results have been obtained for anticancer/anti-inflammatory compounds, as the recent approval of Pirtobrutinib demonstrates. The data reported here are collected from different databases (Scifinder, Web of Science, Scopus, Google Scholar, and Pubmed) using \"aminopyrazole\" as the keyword.

Vanadium, a transition metal, ubiquitous in nature is known to have therapeutic effect as well as toxic effect. It is known to possess antidiabetic, antitumor and antiparasitic activity. However, on long term exposure, it produces neurotoxicity which may result in memory impairment. The possible mechanism known to cause neurotoxicity suggested is oxidative stress and inflammation of neuronal cells. The present review has focused on discussing the role of protein P38 mitogen-activated protein kinase and oxidative stress as possible targets to treat vanadium-induced neurotoxicity.

A review of the published literature on the history, pathogenesis, and treatment of pemphigus vulgaris (PV) and its ocular involvement.
Literature searches were conducted in MEDLINE (Ovid), and google scholar for pemphigus vulgaris and ocular PV. Inclusion criteria were given to meta-analysis, case-controlled studies, and documented case reports. The data were examined and independently analyzed by more than two of the authors.
PV is a humoral autoimmune disease with a preponderance of IgG4 anti-desmoglein 3 antibodies. Upon antibody binding, there is an intracellular signaling mechanism that leads to blister formation. Ocular findings are seen in up to 16% of PV patients with conjunctivitis being the most common clinical presentation. New steroid-sparing agents have helped with the control of this deadly disease, and with better understanding of the pathogenesis of PV, other cytokine blockers currently available are promising steroid-sparing agents.
Ocular pemphigus can occasionally present prior to mucocutaneous findings. Recalcitrant conjunctivitis with conjunctival blisters should warrant a workup for systemic PV.

Introduction: Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen synthase kinase (GSK) 3a/β. Several reports on GSK3\'s functional role exist; however, the specific role of GSK3 in reproductive tissues and its contribution to normal or abnormal parturition are still unclear. To fill this knowledge gap, a systematic review of literature was conducted to better understand the functional role of GSK3 in various intrauterine tissues during implantation, pregnancy, and parturition.Methods: We conducted a systematic review of literature on GSK3\'s expression and function reported between 1980 and 2017 in reproductive tissues during pregnancy using three electronic databases (Web of Science, Medline, and ClinicalTrials.gov). Study selection, data extraction, quality assessment and analyses were performed in duplicate by two independent reviewers.Results: A total of 738 citations were identified; 80 were selected for full text evaluation and 25 were included for final review. GSK3\'s regulation and function were mostly studied in tissues and cells from placentas (12), fetuses (8), uteruses (6), and ovaries (2). GSK3 is primarily reported as a downstream responder of protein kinase B (AKT)-, Wnt-, and reactive oxygen species (ROS)-related pathways where it plays a critical role in cell survival and growth in reproductive tissues.Conclusions: Though GSK3 has been functionally linked to a number of biological processes in reproductive tissues, it has primarily been studied as a secondary signaler of various conserved cell signaling pathways. Lack of scientific rigor in studying GSK3\'s role in reproductive tissues makes this molecule\'s function still obscure. No studies have reported GSK3 in the cervix, and very few reports exist in myometrium and decidua. This systematic review suggests more functional and mechanistic studies focusing on GSK3 need to be conducted in reproductive biology.

Toll like receptors (TLRs) are one of the major families of pattern recognition receptors (PRRs). MicroRNAs (MiRs) are small noncoding RNAs with regulatory effects on biological process, and it has been recently shown that they can control inflammatory process and the response to an infection by modulating the function of TLRs. In this study, we designed a systematic review to clarify the reciprocal interaction between TLRs and MiRs, in order to identify possible future therapeutic targets and strategies. On the one hand, TLRs stimulation can change expression level of miRs in various ways, which can lead to modulating their effects. On the other hand, MiRs also influence the expression of TLRs and the intensity of the inflammatory reaction. We therefore conclude that the interaction between MiRs and TLRs is a key regulator of innate immune system. Investigations discovering therapeutic approaches by manipulation of miRs expression level may open a new approach for the treatment of inflammatory diseases.