The exception was one study that used a nonidentified bpV compound at 20C30?M [26]. muscle mass and nervous system. is usually a known unfavorable regulator of the PI3K/AKT/mTOR signaling pathway, which, by its change, regulates cell proliferation [5]. Studies around the PTEN molecular function revealed that it is essential for embryogenesis and organ development, and that disrupted PTEN resulted in decreased apoptosis and enlarged organs in mouse models [6]. PTEN pharmacological inhibition prospects to PI3K/AKT/mTOR upregulation, Psoralen hence improving cell proliferation and migration, which are crucial factors to the tissue repair [7]. Therefore, a transient downregulation of PTEN has been regarded as a encouraging strategy to aid tissue repair [3,4]. In fact, conditions such as neurodegeneration, ischemia, tissue injuries and insulin-resistant metabolic disorders benefit from increased signaling through the PI3K/AKT/mTOR pathway, which makes inhibition of PTEN a potential pharmacological approach [8,9]. Bisperoxovanadium (bpV) compounds, such as bpV(phen) (bisperoxovanadium 1,10-phenantroline), bpV(pic) (bisperoxovanadium 5-hydroxipyridine) and bpV(HOpic) (bisperoxovanadium 5-hydroxipyridine-2-carboxylic acid), have been proposed as reversible and relatively specific PTEN inhibitors [10C13], which points Psoralen to their potential and beneficial effects around the tissue repair process. Considering such information, our systematic review (SR) aims to investigate the potential evidence for the effects PTEN inhibitors exert on tissue regeneration and injury repair. The motivational question to our evaluate is: does pharmacological inhibition of PTEN enhance the healing after an injury? Methods Study design & review question This SR was reported in accordance with the Preferred Reporting Items for Systematic Reviews Checklist [14]. This review aimed to systematically search and statement the currently available data around the biological effects of PTEN pharmacological inhibition on tissue repair or regeneration. Eligibility criteria Inclusion criteria Articles that evaluated the efficacy of PTEN pharmacological inhibition around the tissue repair using and studies were selected for our SR. Exclusion criteria Studies were excluded for the following reasons: studies with PTEN inhibitors that analyze effects not associated with wound healing, tissue repair or regeneration; studies that do not use PTEN inhibitors; studies that use methods for PTEN inhibition other than MAPK3 pharmacological or that assess RNA-based brokers; studies that administer the PTEN inhibitor before injury (injury prevention or protection); studies written in languages other than English. Reviews, letters, personal opinions, book chapters, conference abstracts or nonpeer review literature were also excluded. Information sources & search strategy The studies considered for inclusion in the SR were identified using individual search strategies on the following electronic databases: Cochrane, Embase, PubMed, Scopus and Web of Science. The gray literature search was performed using Google Scholar. The search included all articles published up to 8 February 2018, with no initial time restriction. Duplicated entries were removed by reference manager software (EndNote?, Thomson Reuters, NY, USA). The reference lists of articles were screened to identify any additional studies. The search strategies for PubMed were: (#1 bpV[phen]?or bpVphen or bpV-phen or bpV phen or bpV[hopic]? or bpVhopic or bpVhopic or bpV hopic or bpV[pic]? or bpVpic or bpV-pic or bpV pic or bpV[bipv]? or bpVbipv or bpV-bipv or bpV bipv or vo-ohpic or voohpic or vo[ohpic]?or vo-oh[pic]?or vo-oh pic or vo oh pic or sf1670 or sf-1670 or sf 1670 or vanadium or bisperoxovanadium or bisperoxovanadate; #2 pten inhibitor or pten inhibitors or pten antagonist or pten antagonists; #3 (#1 or #2); #4 wound or cicatrization or healing or regeneration or cicatrize or heal or regenerate or migration or proliferation or migrate or proliferate or induction or induct or Psoralen recovery or recover or acceleration or accelerate or decrease or repair; #5 (#3 and #4). All search strategies used on the databases can be found in Supplementary Table 1. Study selection The study selection was completed in two phases. In Phase I, three authors (AEM Marques, GA Borges &?LP Webber) independently reviewed the titles and abstracts, and excluded the studies that were clearly not related to the topic. In Phase II, two authors (AEM Marques & GA Borges) independently read the full text of all selected articles and excluded studies according to the selection criteria (Supplementary Table 2). Disagreements between the evaluators were Psoralen solved by consensus; normally, another reviewer (CH Squarize) was involved in making a final decision. Data collection process & analysis One author (GA Borges) collected key information from your articles. A second reviewer (LP Webber) cross-checked the information and accuracy. Any disagreements were resolved by conversation and consensus among the authors (GA Borges, LP Webber &?CH Squarize). The following information was Psoralen collected: 12 months of publication, author(s), country, experimental model (e.g.,.