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Rationale: Alcohol dependence is associated with impaired response inhibition and heightened cue reactivity towards alcohol-related stimuli. Several brain areas, but mainly prefrontal structures, have been linked to response inhibition in addiction. This study aimed at combining both aspects: salience of drug-associated cues and response inhibition using a go/no-go task with alcohol-associated stimuli during functional magnetic resonance imaging (fMRI).
Objectives: Nineteen abstinent alcohol-dependent patients (ADP) and 21 healthy control subjects (HC) were compared on blood oxygen level-dependent (BOLD) responses during successful inhibition of no-go stimuli and successful reactions to go stimuli.
Results: ADP and HC did not significantly differ in their behavioural performance in the task. However, both groups performed worse during the inhibition of alcoholic-associated stimuli compared to neutral stimuli. On the neural level, ADP displayed enhanced BOLD activity relative to HC during successful response inhibition in several areas involved in visual processing, cognitive and impulse control, including occipital structures, anterior cingulate gyrus, medial frontal gyrus and medial orbitofrontal cortex.
Conclusions: We interpret these findings as a possible compensation strategy for impaired cognitive processing. Furthermore, the results underline the impact of salience of alcohol-related stimuli on response inhibition, which seems to affect both ADP and HC.
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http://dx.doi.org/10.1007/s00213-017-4541-9 | DOI Listing |
Chembiochem
September 2025
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China.
The ATPase caseinolytic protease X (ClpX), forming the ClpXP complex with caseinolytic protease P (ClpP), is essential for mitochondrial protein homeostasis. While ClpP targeting is a recognized anticancer strategy, the role of ClpX in cancer remains underexplored. In pancreatic ductal adenocarcinoma (PDAC), elevated CLPX expression correlates with poor prognosis, suggesting its oncogenic function.
View Article and Find Full Text PDFJ Med Chem
September 2025
Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
Nitric oxide (NO) is a multifunctional signaling molecule in oncology, influencing tumor progression, apoptosis, and immune responses. In contrast, chlorambucil (Cbl), a DNA-alkylating chemotherapeutic, induces cytotoxicity through DNA damage. Here, we report a photoresponsive nanoparticle platform for sequential codelivery of NO and Cbl, where NO is released within 10 min of irradiation, followed by Cbl release within 30 min.
View Article and Find Full Text PDFJ Neurochem
September 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Microglia, the resident immune cells of the central nervous system (CNS), are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and Parkinson's disease (PD). 14-3-3 proteins act as molecular hubs to regulate protein-protein interactions, which are involved in numerous cellular functions, including cellular signaling, protein folding, and apoptosis. We previously revealed decreased 14-3-3 levels in the brains of human subjects with neurodegenerative diseases.
View Article and Find Full Text PDFArch Pharm (Weinheim)
September 2025
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Through applying the hybridization technique, new coumarin derivatives (2-17) were prepared with substitution at coumarin C-3 utilizing various heterocyclic derivatives, aiming to afford multi-target carbonic anhydrases (CAs) IX/XII and topoisomerase II (Topo II) inhibitors with potent antiproliferative activity. Eight different cell lines were used to evaluate the growth inhibition percentages (GI%) of cancer cells determined by coumarin analogues 1-17. Analogues 16 and 17 had the most substantial cytotoxic effects, achieving mean GI% of 86.
View Article and Find Full Text PDFMol Ther
September 2025
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. We explored the therapeutic potential of inducing cuproptosis, a copper-dependent regulated cell death, in CSC-enriched PDAC models. Using human and murine PDAC models, we evaluated elesclomol, a copper transport enhancer.
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