Modulation of epithelial-mesenchymal transition by gemcitabine: Targeting ionizing radiation-induced cellular senescence in lung cancer cell
This study investigates the effects of ionizing radiation and gemcitabine on lung cancer cells, with a focus on induced senescence, EMT, and apoptosis. Human-derived A549, PC-9, and mouse-derived Lewis lung carcinoma cells exposed to 10 Gy X-ray irradiation exhibited senescence, as indicated by morphological changes, β-galactosidase staining, and cell cycle arrest through the p53-p21 pathway. Ionizing radiation also promoted EMT via TGFβ/SMAD signaling, evidenced by increased TGFβ1 levels, altered EMT marker expressions, and enhanced cell migration. Gemcitabine, a first-line lung cancer treatment, was shown to enhance a...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Heng Zhou Chenghao Li Yanxian Ren Wen-An Wang Jiayuan Zhuang Yue Ren Lin Shen Yong Chen Source Type: research
Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms
Biochem Pharmacol. 2024 Apr 24:116236. doi: 10.1016/j.bcp.2024.116236. Online ahead of print.ABSTRACTTrace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, incl...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Linlin Peng Jing Zhang Jialu Feng Jing Ge Yu Zou Yun Chen Lang Xu Yan Zeng Jun-Xu Li Jianfeng Liu Source Type: research
Variable CGRP family peptide signaling durations and the structural determinants thereof
Biochem Pharmacol. 2024 Apr 24;224:116235. doi: 10.1016/j.bcp.2024.116235. Online ahead of print.ABSTRACTCalcitonin gene-related peptides alpha and beta (αCGRP, βCGRP), adrenomedullin (AM), and adrenomedullin 2/intermedin (AM2/IMD) function in pain signaling, neuroimmune communication, and regulation of the cardiovascular and lymphatic systems by activating either of two class B GPCRs, CLR and CTR, in complex with a RAMP1, -2, or -3 modulatory subunit. Inspired by our recent discovery that AM2/IMD(1-47) activation of CLR-RAMP3 elicits long duration cAMP signaling, here we used a live-cell cAMP biosensor assay to characte...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Katie M Babin Sandra E Gostynska Jordan A Karim Augen A Pioszak Source Type: research
Modulation of epithelial-mesenchymal transition by gemcitabine: Targeting ionizing radiation-induced cellular senescence in lung cancer cell
This study investigates the effects of ionizing radiation and gemcitabine on lung cancer cells, with a focus on induced senescence, EMT, and apoptosis. Human-derived A549, PC-9, and mouse-derived Lewis lung carcinoma cells exposed to 10 Gy X-ray irradiation exhibited senescence, as indicated by morphological changes, β-galactosidase staining, and cell cycle arrest through the p53-p21 pathway. Ionizing radiation also promoted EMT via TGFβ/SMAD signaling, evidenced by increased TGFβ1 levels, altered EMT marker expressions, and enhanced cell migration. Gemcitabine, a first-line lung cancer treatment, was shown to enhance a...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Heng Zhou Chenghao Li Yanxian Ren Wen-An Wang Jiayuan Zhuang Yue Ren Lin Shen Yong Chen Source Type: research
Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms
Biochem Pharmacol. 2024 Apr 24:116236. doi: 10.1016/j.bcp.2024.116236. Online ahead of print.ABSTRACTTrace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, incl...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Linlin Peng Jing Zhang Jialu Feng Jing Ge Yu Zhou Yun Chen Lang Xu Yan Zeng Jun-Xu Li Jianfeng Liu Source Type: research
Variable CGRP family peptide signaling durations and the structural determinants thereof
Biochem Pharmacol. 2024 Apr 24:116235. doi: 10.1016/j.bcp.2024.116235. Online ahead of print.ABSTRACTCalcitonin gene-related peptides alpha and beta (αCGRP, βCGRP), adrenomedullin (AM), and adrenomedullin 2/intermedin (AM2/IMD) function in pain signaling, neuroimmune communication, and regulation of the cardiovascular and lymphatic systems by activating either of two class B GPCRs, CLR and CTR, in complex with a RAMP1, -2, or -3 modulatory subunit. Inspired by our recent discovery that AM2/IMD(1-47) activation of CLR-RAMP3 elicits long duration cAMP signaling, here we used a live-cell cAMP biosensor assay to characterize...
Source: Biochemical Pharmacology - April 26, 2024 Category: Drugs & Pharmacology Authors: Katie M Babin Sandra E Gostynska Jordan A Karim Augen A Pioszak Source Type: research
Dual-specificity tyrosine phosphorylation-regulated kinase 1A promotes the inclusion of amyloid precursor protein exon 7
Biochem Pharmacol. 2024 Apr 23:116233. doi: 10.1016/j.bcp.2024.116233. Online ahead of print.ABSTRACTExtracellular amyloid plaques made of Amyloid-β (Aβ) derived from amyloid precursor protein (APP) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). There are three major isoforms of APP, APP770, APP751, and APP695 generated by alternative splicing of exons 7 and 8. Exon 7 encodes the Kunitz protease inhibitor (KPI) domain. Its inclusion generates APP isoforms containing KPI, APPKPI+, which is elevated in AD and Down syndrome (DS) brains and associated with increased Aβ deposition. Dual-specific...
Source: Biochemical Pharmacology - April 25, 2024 Category: Drugs & Pharmacology Authors: Dandan Chu Leyi Lei Shu Gu Fei Liu Feng Wu Source Type: research
Control of articular degeneration by extracellular vesicles from stem/stromal cells as a potential strategy for the treatment of osteoarthritis
Biochem Pharmacol. 2024 Apr 23:116226. doi: 10.1016/j.bcp.2024.116226. Online ahead of print.ABSTRACTOsteoarthritis (OA) is a degenerative joint condition that contributes to years lived with disability. Current therapeutic approaches are limited as there are no disease-modifying interventions able to delay or inhibit the progression of disease. In recent years there has been an increasing interest in the immunomodulatory and regenerative properties of mesenchymal stem/stromal cells (MSCs) to develop new OA therapies. Extracellular vesicles (EVs) mediate many of the biological effects of these cells and may represent an al...
Source: Biochemical Pharmacology - April 25, 2024 Category: Drugs & Pharmacology Authors: Mar ía José Alcaraz Source Type: research
Dual-specificity tyrosine phosphorylation-regulated kinase 1A promotes the inclusion of amyloid precursor protein exon 7
Biochem Pharmacol. 2024 Apr 23:116233. doi: 10.1016/j.bcp.2024.116233. Online ahead of print.ABSTRACTExtracellular amyloid plaques made of Amyloid-β (Aβ) derived from amyloid precursor protein (APP) is one of the major neuropathological hallmarks of Alzheimer's disease (AD). There are three major isoforms of APP, APP770, APP751, and APP695 generated by alternative splicing of exons 7 and 8. Exon 7 encodes the Kunitz protease inhibitor (KPI) domain. Its inclusion generates APP isoforms containing KPI, APPKPI+, which is elevated in AD and Down syndrome (DS) brains and associated with increased Aβ deposition. Dual-specific...
Source: Biochemical Pharmacology - April 25, 2024 Category: Drugs & Pharmacology Authors: Dandan Chu Leyi Lei Shu Gu Fei Liu Feng Wu Source Type: research
Control of articular degeneration by extracellular vesicles from stem/stromal cells as a potential strategy for the treatment of osteoarthritis
Biochem Pharmacol. 2024 Apr 23:116226. doi: 10.1016/j.bcp.2024.116226. Online ahead of print.ABSTRACTOsteoarthritis (OA) is a degenerative joint condition that contributes to years lived with disability. Current therapeutic approaches are limited as there are no disease-modifying interventions able to delay or inhibit the progression of disease. In recent years there has been an increasing interest in the immunomodulatory and regenerative properties of mesenchymal stem/stromal cells (MSCs) to develop new OA therapies. Extracellular vesicles (EVs) mediate many of the biological effects of these cells and may represent an al...
Source: Biochemical Pharmacology - April 25, 2024 Category: Drugs & Pharmacology Authors: Mar ía José Alcaraz Source Type: research
Generation and characterization of cytochrome P450 3A74 CRISPR/Cas9 knockout bovine foetal hepatocyte cell line (BFH12)
Biochem Pharmacol. 2024 Apr 20:116231. doi: 10.1016/j.bcp.2024.116231. Online ahead of print.ABSTRACTIn human, the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes (DMEs) is responsible for a significant number of phase I reactions, with the CYP3A4 isoform superintending the hepatic and intestinal metabolism of diverse endobiotic and xenobiotic compounds. The CYP3A4-dependent bioactivation of chemicals may result in hepatotoxicity and trigger carcinogenesis. In cattle, four CYP3A genes (CYP3A74, CYP3A76, CYP3A28 and CYP3A24) have been identified. Despite cattle being daily exposed to xenobiotics (e.g., myc...
Source: Biochemical Pharmacology - April 22, 2024 Category: Drugs & Pharmacology Authors: Silvia Iori Caterina D'Onofrio Nihay Laham-Karam Isidore Mushimiyimana Lorena Lucatello Ludovica Montanucci Rosa Maria Lopparelli Federico Bonsembiante Francesca Capolongo Marianna Pauletto Mauro Dacasto Mery Giantin Source Type: research
Challenging and target-based shifting strategies for heart failure treatment: An update from the last decades
Biochem Pharmacol. 2024 Apr 20:116232. doi: 10.1016/j.bcp.2024.116232. Online ahead of print.ABSTRACTHeart failure (HF) is a major global health problem afflicting millions worldwide. Despite the significant advances in therapies and prevention, HF still carries very high morbidity and mortality, requiring enormous healthcare-related expenditure, and the search for new weapons goes on. Following initial treatment strategies targeting inotropism and congestion, attention has focused on offsetting the neurohormonal overactivation and three main therapies, including angiotensin-converting enzyme inhibitors or angiotensin II t...
Source: Biochemical Pharmacology - April 22, 2024 Category: Drugs & Pharmacology Authors: Yuichi Hattori Kohshi Hattori Kuniaki Ishii Masanobu Kobayashi Source Type: research
Generation and characterization of cytochrome P450 3A74 CRISPR/Cas9 knockout bovine foetal hepatocyte cell line (BFH12)
Biochem Pharmacol. 2024 Apr 20:116231. doi: 10.1016/j.bcp.2024.116231. Online ahead of print.ABSTRACTIn human, the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes (DMEs) is responsible for a significant number of phase I reactions, with the CYP3A4 isoform superintending the hepatic and intestinal metabolism of diverse endobiotic and xenobiotic compounds. The CYP3A4-dependent bioactivation of chemicals may result in hepatotoxicity and trigger carcinogenesis. In cattle, four CYP3A genes (CYP3A74, CYP3A76, CYP3A28 and CYP3A24) have been identified. Despite cattle being daily exposed to xenobiotics (e.g., myc...
Source: Biochemical Pharmacology - April 22, 2024 Category: Drugs & Pharmacology Authors: Silvia Iori Caterina D'Onofrio Nihay Laham-Karam Isidore Mushimiyimana Lorena Lucatello Ludovica Montanucci Rosa Maria Lopparelli Federico Bonsembiante Francesca Capolongo Marianna Pauletto Mauro Dacasto Mery Giantin Source Type: research
Challenging and target-based shifting strategies for heart failure treatment: An update from the last decades
Biochem Pharmacol. 2024 Apr 20:116232. doi: 10.1016/j.bcp.2024.116232. Online ahead of print.ABSTRACTHeart failure (HF) is a major global health problem afflicting millions worldwide. Despite the significant advances in therapies and prevention, HF still carries very high morbidity and mortality, requiring enormous healthcare-related expenditure, and the search for new weapons goes on. Following initial treatment strategies targeting inotropism and congestion, attention has focused on offsetting the neurohormonal overactivation and three main therapies, including angiotensin-converting enzyme inhibitors or angiotensin II t...
Source: Biochemical Pharmacology - April 22, 2024 Category: Drugs & Pharmacology Authors: Yuichi Hattori Kohshi Hattori Kuniaki Ishii Masanobu Kobayashi Source Type: research
Generation and characterization of cytochrome P450 3A74 CRISPR/Cas9 knockout bovine foetal hepatocyte cell line (BFH12)
Biochem Pharmacol. 2024 Apr 20:116231. doi: 10.1016/j.bcp.2024.116231. Online ahead of print.ABSTRACTIn human, the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes (DMEs) is responsible for a significant number of phase I reactions, with the CYP3A4 isoform superintending the hepatic and intestinal metabolism of diverse endobiotic and xenobiotic compounds. The CYP3A4-dependent bioactivation of chemicals may result in hepatotoxicity and trigger carcinogenesis. In cattle, four CYP3A genes (CYP3A74, CYP3A76, CYP3A28 and CYP3A24) have been identified. Despite cattle being daily exposed to xenobiotics (e.g., myc...
Source: Biochemical Pharmacology - April 22, 2024 Category: Drugs & Pharmacology Authors: Silvia Iori Caterina D'Onofrio Nihay Laham-Karam Isidore Mushimiyimana Lorena Lucatello Ludovica Montanucci Rosa Maria Lopparelli Federico Bonsembiante Francesca Capolongo Marianna Pauletto Mauro Dacasto Mery Giantin Source Type: research
