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[Mechanisms of action of antidepressive pharmacotherapy: brain and mind-body and environment].
Nervenarzt
January 2025
Abteilung für Molekulares Neuroimaging, Zentralinstitut für Seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg, 68159, Mannheim, Deutschland.
Background: Novel antidepressive substances are challenging the explanations for the mechanisms of action of traditional psychopharmacology.
Objective: What could be the shared effects of various antidepressants and in this context what role do extrapharmacological factors, such as the body and environment, play?
Material And Method: The available literature on clinical and preclinical data for assumed combined active factors of serotonergic psychedelic drugs, (es)ketamine, monoaminergic antidepressants and zuranolone are presented and the influence of context factors on the individual mechanisms of action is discussed.
Results: There are many indications that classical and novel pharmacological approaches could share similar mechanisms of action in the treatment of depression.
Biofabricated 3D Intestinal Models as an Alternative to Animal-Based Approaches for Drug Toxicity Assays.
Tissue Eng Regen Med
January 2025
Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Sao Paulo, 13083-100, Brazil.
Background: The main challenge in new drug development is accurately predicting the human response in preclinical models.
Methods: In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
Mice develop obesity and lose myocardial metabolic flexibility months after exertional heat stroke.
Commun Biol
January 2025
Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL, USA.
As global temperatures rise, heat-related chronic health disorders are predicted to become more prevalent. We tested whether a single exposure to acute heat illness, using a preclinical mouse model of exertional heat stroke (EHS), can induce late-emerging health disorders that progress into chronic disease. Following EHS, mice were followed for 3 months; after two weeks of recovery, half were placed on a Western diet to determine if previous EHS exposure amplifies the negative consequences of an atherogenic diet.
View Article and Find Full Text PDFOptimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2.
Respir Res
January 2025
Department of Pediatrics, David Geffen School of Medicine, UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, UCLA, Los Angeles, CA, 90095, USA.
Background: Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. As a result, most of the drug screening assays for respiratory viruses are performed on commercial cell line-based 2D cultures that provide limited translational ability.
View Article and Find Full Text PDFLow dose DNA methyltransferase inhibitors potentiate PARP inhibitors in homologous recombination repair deficient tumors.
Breast Cancer Res
January 2025
Department of Medicine (Hematology/Oncology), School of Medicine, University of California San Francisco, 1450 Third St, San Francisco, CA, 94158, USA.
Background: Poly (ADP-Ribose) polymerase inhibitors are approved for treatment of tumors with BRCA1/2 and other homologous recombination repair (HRR) mutations. However, clinical responses are often not durable and treatment may be detrimental in advanced cancer due to excessive toxicities. Thus we are seeking alternative therapeutics to enhance PARP-directed outcomes.
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