Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34⁺-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

Anaphylaxis is a severe allergic reaction, rapid in onset, and can lead to fatal consequences if not promptly treated. The incidence of anaphylaxis has risen at an alarming rate in past decades and continues to rise. Therefore, there is a general interest in understanding the molecular mechanism that leads to an exacerbated response. The main effector cells are mast cells, commonly triggered by stimuli that involve the IgE-dependent or IgE-independent pathway. These signaling pathways converge in the release of proinflammatory mediators, such as histamine, tryptases, prostaglandins, etc., in minutes. The action and cell targets of these proinflammatory mediators are linked to the pathophysiologic consequences observed in this severe allergic reaction. While many molecules are involved in cellular regulation, the expression and regulation of transcription factors involved in the synthesis of proinflammatory mediators and secretory granule homeostasis are of special interest, due to their ability to control gene expression and change phenotype, and they may be key in the severity of the entire reaction. In this review, we will describe our current understanding of the pathophysiology of human anaphylaxis, focusing on the transcription factors’ contributions to this systemic hypersensitivity reaction. Host mutation in transcription factor expression, or deregulation of their activity in an anaphylaxis context, will be updated. So far, the risk of anaphylaxis is unpredictable thus, increasing our knowledge of the molecular mechanism that leads and regulates mast cell activity will enable us to improve our understanding of how anaphylaxis can be prevented or treated.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.

IntroductionEssential oils (EOs) have been the subject of extensive investigation due to their diverse biological properties, including antimicrobial, antioxidant, fungicidal, and anti-inflammatory activities. Synthesized by over 17 500 plant species, EOs are intricate mixtures of terpenes, terpenoids, and phenylpropanoids, among other bioactive compounds. These attributes render EOs as promising candidates for addressing microbial infections, particularly those associated with biofilms, which account for a substantial proportion of nosocomial infections and microbial infections at large. MethodsA systematic literature search was performed using the PubMed and SciELO databases. Articles were selected based on predefined inclusion criteria, emphasizing studies that explored the chemical composition and antimicrobial mechanisms of EOs, the processes of biofilm formation, their structural characteristics, resistance mechanisms, and the application of microencapsulation techniques to enhance EO stability and antimicrobial efficacy. ResultsA total of 30 articles met the inclusion criteria and were subjected to detailed review. These studies provide a comprehensive analysis of the antimicrobial potential of EOs and demonstrate the significant enhancement of their efficacy through microencapsulation. The compiled data enable the assessment of both the inherent antimicrobial activity of EOs and the mechanisms by which microencapsulation amplifies this activity. ConclusionsThis review underscores the chemical composition and antimicrobial mechanisms of EOs, as well as the dynamics of biofilm formation and resistance. Furthermore, it highlights the role of microencapsulation as a strategy to preserve and enhance the antimicrobial properties of EOs.

Introduction: GISTs are sarcomas arising from interstitial cells of Cajal that account for about 1 % of all gastrointestinal tumors. The diagnosis of GIST involves imaging tests and invasive determinations such as endoscopy and biopsy. KIT and PDGFRA immunohistochemistry staining can detect 95 % of GISTs in biopsy samples. MicroRNAs (miRNAs) play a crucial role in angiogenesis physiology, immunology, and neural origins of GIST biology, and may be able to provide a valuable prognostic clue. Objective: this research aims to establish tumor markers (miRNAs) for the early diagnosis of GIST patients. Methods: a qualitative approach was used, of a bibliographic-documentary type, and through consultation in various databases found in indexed scientific journals. Results: miR-221, miR-222 play a functional, diagnostic, therapeutic, and prognostic role in GIST. The miR221/222 ratio is considered a genetic biomarker to detect the risk of developing GIST and hsa-miR-218-5p was the best predictor in the development of GIST as well as hsa-miR-146a-5p, hsa-miR- 222-3p, hsa-miR-126-3p and hsamiR-218-5p. Conclusions: new non-invasive diagnostic techniques for GIST could become a valuable strategy for early diagnosis and monitoring of patient treatment