Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.
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http://dx.doi.org/10.1016/j.tranon.2021.101303 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Cognition relies on transforming sensory inputs into a generalizable understanding of the world. Mirror neurons have been proposed to underlie this process, mapping visual representations of others' actions and sensations onto neurons that mediate our own, providing a conduit for understanding. However, this theory has limitations.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.
View Article and Find Full Text PDFPLoS One
January 2025
Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Preeclampsia is characterized by insufficient invasion of extravillous trophoblasts and is a consequence of failed adaption of extravillous trophoblasts to changes in the intrauterine environment developing embryo. Specific miRNAs are implicated in the development of preeclampsia (PE). miR-455-5p is present at low levels in PE but its role is not known.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Department of Traditional Chinese Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University of Medicine, Shanghai, China.
Based on network pharmacology and molecular docking methods, this study explored its active compounds and confirmed its potential mechanism of action against Hand-foot skin reaction induced by tumor-targeted drugs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and UniProt Database were used to obtain the active ingredients and target proteins of Spatholobi Caulis. All hand-foot skin reaction (HFSR)-related targets were obtained with the help of the Human Gene Database, Online Mendelian Inheritance in Humans (OMIM), DisGeNET and DrugBank databases.
View Article and Find Full Text PDFJ ECT
January 2025
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia.
Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD), even though the molecular mechanisms underlying its efficacy remain largely unclear. This study aimed, for the first time, to analyze plasma levels of miRNAs, key regulators of gene expression, in TRD patients undergoing ECT to investigate potential changes during treatment and their associations with symptom improvement.
Methods: The study involved 27 TRD patients who underwent ECT.
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