Delving into the Latest Updates on Faculdade de Medicina de São José do Rio Preto with Synapse

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Congenital Disorders

Immune System Diseases

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TGF-β(Transforming growth factor beta)	1

BACKGROUNDWe evaluated the performance of TargetScan, miRDB, and miRWalk for predicting miRNA-mRNA interactions in HNSCC. Based on clinical tumor and cancer-free tissue data, miRWalk emerged as the most comprehensive tool. Validation using NanoString technology and MiRTarBase confirmed key predictions, highlighting the important roles of the PI3K-Akt and Wnt pathways. This study underscores the importance of integrating bioinformatics and experimental data to better understand HNSCC.BACKGROUND■ miRWalk had the highest predicted interactions and validated miRNA networks in HNSCC.BACKGROUND■ Around 3.3% of interactions overlapped across tools, emphasizing the need for multitool approaches.BACKGROUND■ Dysregulated genes and miRNAs were tied to cancerdriving PI3K-Akt and Wnt pathways.BACKGROUND■ The validated approach highlights the importance of integrating computational and molecular data.OBJECTIVEHead and neck squamous cell carcinoma (HNSCC) has a poor prognosis largely due to late diagnosis and a lack of reliable biomarkers. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are promising biomarkers for HNSCC. This study evaluated miRNA-mRNA interactions in HNSCC using conventional computational tools and validated the results using molecular data.METHODSWe compared three miRNA-mRNA interaction prediction tools, TargetScan, miRDB, and miRWalk, using differentially expressed miRNAs and mRNAs from HNSCC and cancer-free tissues. NanoString nCounter was used to measure miRNA and mRNA expression and the miRTarBase database was used to validate the predicted miRNA-mRNA interactions.RESULTSTargetScan and miRWalk provide a comprehensive overview of potential interactions, whereas miRDB provides functional insights. Our results identified 77 and 154 differentially expressed miRNAs and mRNAs in HNSCC, respectively. miRWalk predicted the highest number of miRNA-mRNA interactions, followed by miRDB and TargetScan. Only 3.3% of interactions were common among the tools. The MiRTarBase analysis confirmed a small subset of the predictions. Biological pathway analysis highlighted the dysregulation of PI3K-Akt and Wnt signaling; miRWalk was the best for elucidating how miRNAs modulate target mRNAs in these key pathways during HNSCC progression.CONCLUSIONmiRWalk emerged as the most robust tool for predicting miRNA-mRNA interactions. Our findings highlight the importance of integrating bioinformatics predictions with experimental data to better understand the regulatory networks in HNSCC and identify potential biomarkers for diagnosis and therapy.

01 Apr 2025·Journal of Molecular Medicine

Regulatory role of annexin A1 in NLRP3 inflammasome activation in atopic dermatitis: insights from keratinocytes in human and murine studies

Article

Author: Gil, Cristiane D ; D'Ávila, Solange C G P ; Corrêa, Mab P ; Oliani, Sonia M ; Greco, Karin V ; Correia-Silva, Rebeca D ; Almeida, Joaquim S ; de Castro, Maria Eduarda

Despite the well-documented regulatory role of annexin A1 (ANXA1) in numerous stages of the inflammatory response, its involvement in regulating the NLRP3 inflammasome in the context of allergic responses has not been extensively investigated to date. This study evaluated the expression patterns of the ANXA1 and NLRP3 proteins in human skin samples obtained from patients with atopic dermatitis (AD) and in mice with ovalbumin (OVA)-induced experimental AD. Furthermore, the in vitro effect of the ANXA1 mimetic peptide Ac2-26 on IL-4-stimulated human keratinocytes was evaluated. IL-4-stimulated keratinocytes were treated with Ac2-26 (a mimetic peptide of ANXA1) in two different concentrations: 5 and 25 ng/mL. Additionally, some cells were treated with the pan-formyl peptide receptor antagonist Boc2 at a concentration of 10 µM, administered 15 min before Ac2-26. The NLRP3 protein demonstrated intense immunoreactivity in both murine and human AD skin samples, with NLRP3 and ANXA1 exhibiting particularly high coexpression in keratinocytes. A significant increase in ANXA1 and NLRP3 transcripts was observed in AD skins (GSE16161 study). ANXA1 transcript levels were elevated in the AD epidermis relative to the non-lesional epidermis, while NLRP3 transcript levels were reduced in the AD epidermis (GSE120721 study). The Ac2-26 treatment reduced the proliferation rate of IL-4-stimulated keratinocytes, an effect abolished by Boc2 and IL-1β and ROS production. In conclusion, our findings indicate that ANXA1 plays a role in regulating NLRP3 activation in keratinocytes, contributing to the pathogenesis of AD. KEY MESSAGES: ANXA1 and NLRP3 levels are upregulated and exhibit coexpression in murine and human AD skins. ANXA1-FPR axis regulates the proliferation of human keratinocytes under IL-4 stimulation. ANXA1-derived peptide Ac_2-26 regulates oxidative stress and NLRP3 activation in human keratinocytes.

100 Deals associated with Faculdade de Medicina de São José do Rio Preto

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100 Translational Medicine associated with Faculdade de Medicina de São José do Rio Preto

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Pipeline

Pipeline Snapshot as of 31 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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