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JOURNAL ARTICLE
Yizhen Zhu, Xue Zhao, Ruojing Liu, Dan Yang, Guo Ge
Stroke is a cerebrovascular disease that threatens human health. Developing safe and effective drugs and finding therapeutic targets has become an urgent scientific problem. The aim of this study was to investigate the effect of oxygen-glucose deprivation of the microglia-derived exosome on hippocampal neurons and its relationship to miR-124 in the exosome. We incubated hippocampal neurons with exosomes secreted by oxygen-glucose deprivation/ reoxygenation (OGD/R) microglia. The levels of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) in the culture supernatant were detected by ELISA...
April 10, 2024: Journal of Molecular Histology
#2
JOURNAL ARTICLE
Gerasimos Anagnostopoulos, Ester Saavedra, Flavia Lambertucci, Omar Motiño, Jordan Dimitrov, David Roiz-Valle, Victor Quesada, Karla Alvarez-Valadez, Hui Chen, Allan Sauvat, Yan Rong, Uxía Nogueira-Recalde, Sijing Li, Léa Montégut, Mojgan Djavaheri-Mergny, Maria Castedo, Carlos Lopez-Otin, Maria Chiara Maiuri, Isabelle Martins, Guido Kroemer
Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAA R) γ2 subunit (GABAA Rγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAA Rγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists...
April 6, 2024: Cell Death & Disease
#3
JOURNAL ARTICLE
Josquin Moraly, Julien Rossignol, Claire Rouzaud, Thomas Gabas, Hassiba Bouktit, Ludovic Lhermitte, Danielle Canioni, Sylvie Fraitag, Julie Bruneau, Stéphane Barete, Felipe Suarez, Thomas Ballul, Cécile Meni, Laura Polivka, Louis Terriou, David Launay, Laurence Bouillet, Caroline Gaudy-Marqueste, Marie Gousseff, Edwige Le Mouel, Antoine Neel, Dana Ranta, Roland Jaussaud, Philippe Guilpain, Laurent Frenzel, Julie Agopian, Patrice Dubreuil, Céline Greco, Sophie Dimicoli-Salazar, Mael Heiblig, Clément Gourguechon, Olivier Tournilhac, Rose-Marie Javier, Florence Castelain, Quentin Cabrera, Marie Pierre Gourin, Ewa Wierzbicka-Hainaut, Jose Miguel Torregrosa-Diaz, Cristina Bulai, Christian Lavigne, Cyrille Hoarau, Michel Arock, Gandhi Damaj, Olivier Lortholary, Olivier Hermine
Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM...
April 6, 2024: American Journal of Hematology
#4
JOURNAL ARTICLE
Lorena Melo, Marie C Beaupain, Elham Ghanavati, Min-Fang Kuo, Michael A Nitsche
BACKGROUND: Studies in animals and humans have shown that cortical neuroplasticity can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. OBJECTIVE: We aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans...
April 2, 2024: Brain Stimulation
#5
JOURNAL ARTICLE
Abdul Rashid Issahaku, Anke Wilhelm, Marietjie Schutte-Smith, Elizabeth Erasmus, Hendrik Visser
Gamma-aminobutyric acid (GABA) signaling is the principal inhibitory pathway in the central nervous system. It is critical in neuronal cell proliferation and fate determination. Any aberration in GABA inhibition results in psychiatric and neurological diseases. Thus, modulating GABAergic neurotransmission has become the basis of drug therapy for psychiatric and several neurological diseases. Though GABA and muscimol are classical inhibitors of GABA receptors, the search for novel inhibitors continues unabated...
March 23, 2024: Journal of Biomolecular Structure & Dynamics
#6
JOURNAL ARTICLE
Smitha Mohanlal, Diprupa Saha, Shubhant Pandey, Rudresh Acharya, Nagendra K Sharma
GABA (γ-amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well-known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl-protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd-catalyzed C(sp3)-H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee...
March 18, 2024: Chemistry, An Asian Journal
#7
JOURNAL ARTICLE
Shiv Verma, Vaibhav Singh, VijayKrishna Nagampalli, Lee E Ponsky, Chiang-Shan R Li, Herta Chao, Sanjay Gupta
Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations...
March 14, 2024: Molecular Carcinogenesis
#8
JOURNAL ARTICLE
Raj Katariya, Kartikey Mishra, Shivkumar Sammeta, Milind Umekar, Nandkishor Kotagale, Brijesh Taksande
Huntington's disease (HD) is a progressive neurodegenerative condition characterized by a severe motor incoordination, cognitive decline, and psychiatric complications. However, a definitive cure for this devastating disorder remains elusive. Agmatine, a biogenic amine, has gain attention for its reported neuromodulatory and neuroprotective properties. The present study was designed to examine the influence of agmatine on the behavioral, biochemical, and molecular aspects of HD in an animal model. A mitochondrial toxin, 3-nitro propionic acid (3-NP), was used to induce HD phenotype and similar symptoms such as motor incoordination, memory impairment, neuro-inflammation, and depressive-like behavior in rats...
March 5, 2024: Neurotoxicology
#9
REVIEW
Alexandre Bacq, Antoine Depaulis, Vincent Castagné, Marie-Emmanuelle Le Guern, Elaine C Wirrell, Marc Verleye
Stiripentol (Diacomit® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits...
March 5, 2024: Advances in Therapy
#10
JOURNAL ARTICLE
Mohammad Amin Manavi, Samaneh Toutounchian, Sahar Afsahi, Zahra Ebrahim Soltani, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Status epilepticus (SE) is a critical medical emergency marked by persistent or rapidly repeating seizures, posing a threat to life. Using the lithium-pilocarpine-induced SE model, we decide to evaluate the anti-seizure effects of ivermectin as a positive allosteric modulator of GABAA receptor and the underlying mechanisms involved. Lithium chloride was injected intraperitoneally at a dose of 127 mg/kg, followed by the administration of pilocarpine at a dose of 60 mg/kg after a 20-h interval in order to induce SE...
February 29, 2024: Molecular Neurobiology
#11
REVIEW
Dora Kolić, Zrinka Kovarik
Acute organophosphorus compound (OP) poisoning induces symptoms of the cholinergic crises with the occurrence of severe epileptic seizures. Seizures are induced by hyperstimulation of the cholinergic system, but are enhanced by hyperactivation of the glutamatergic system. Overstimulation of muscarinic cholinergic receptors by the elevated acetylcholine causes glutamatergic hyperexcitation and an increased influx of Ca2+ into neurons through a type of ionotropic glutamate receptors, N-methyl-d-aspartate (NMDA) receptors (NMDAR)...
February 28, 2024: BioFactors
#12
JOURNAL ARTICLE
Ke Nan, Ziwen Zhong, Ying Yue, Wenchang Zhou, Xingfeng Sun, Yang Shen, Mengdi Qu, Zhaoyuan Chen, Jiahui Gu, Caihong Sun, Xun Sun, Lihong Lu, Jie Zhang, Changhong Miao, Minli Sun
BACKGROUND: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. AIMS: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. METHODS: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals...
February 20, 2024: Digestive Diseases and Sciences
#13
JOURNAL ARTICLE
Junjiao Wu, Jie Ren, Hongfei Cui, Yali Xie, Yu Tang
BACKGROUND: Different neural subtypes are selectively lost in diverse neurodegenerative diseases. Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor abnormalities that primarily affect the striatum. The Huntingtin (HTT) mutation involves an expanded CAG repeat, leading to insoluble polyQ, which renders GABA+ medium spiny neurons (MSN) more venerable to cell death. Human pluripotent stem cells (hPSCs) technology allows for the construction of disease-specific models, providing valuable cellular models for studying pathogenesis, drug screening, and high-throughput analysis...
February 15, 2024: Inflammation and Regeneration
#14
JOURNAL ARTICLE
Bhavana Pothuri, Sileny Han, Dana M Chase, Florian Heitz, Robert A Burger, Lydia Gaba, Linda Van Le, Eva Guerra, David Bender, Jacob Korach, Noelle Cloven, Cristina Churruca, Philippe Follana, Paul DiSilvestro, Jean-François Baurain, Kris Jardon, Carmela Pisano, Ulla Peen, Johanna Mäenpää, Divya Gupta, Emeline Bacqué, Yong Li, Natalie Compton, Jenya Antonova, Bradley J Monk, Antonio González-Martín
OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death...
February 6, 2024: Gynecologic Oncology
#15
REVIEW
Sergey A Menzikov, Danila M Zaichenko, Aleksey A Moskovtsev, Sergey G Morozov, Aslan A Kubatiev
γ-Aminobutyric acid type A receptors (GABAA Rs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which are widespread throughout the invertebrate and vertebrate central nervous system. GABAA Rs are engaged in short-term changes of the neuronal concentrations of chloride (Cl- ) and bicarbonate (HCO3 - ) ions by their passive permeability through the ion channel pore. GABAA Rs are regulated by various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols...
2024: Frontiers in Pharmacology
#16
JOURNAL ARTICLE
Philippe Damier, Bertrand Degos, Giovanni Castelonovo, Mathieu Anheim, Isabelle Benatru, Nicolas Carrière, Olivier Colin, Luc Defebvre, Marie Deverdal, Alexandre Eusebio, Vanessa Ferrier, Caroline Giordana, Jean-Luc Houeto, Severine Le Dily, Marie Mongin, Claire Thiriez, Christine Tranchant, Denis Ravel, Jean-Christophe Corvol, Olivier Rascol, Yehezkel Ben Ari
BACKGROUND: Acting on the main target of dopaminergic cells, the striatal γ-aminobutyric acid (GABA)-ergic cells, might be a new way to treat persons with Parkinson's disease (PD). OBJECTIVE: The objective of this study was to assess the efficacy of bumetanide, an Na-K-Cl cotransporter (NKCC1) inhibitor, to improve motor symptoms in PD. METHODS: This was a 4-month double-blind, randomized, parallel-group, placebo-controlled trial of 1...
January 30, 2024: Movement Disorders: Official Journal of the Movement Disorder Society
#17
JOURNAL ARTICLE
Kapil Vyas, Kriti Maheshwari, Praveen K Shanmugam Reddy, Rajesh Verma, Iffat Hasan, Asit Mittal
BACKGROUND: Chronic pruritus poses a significant challenge to treating physicians due to multitude of underlying causes and varying treatment strategies. Several topical, systemic, and physical modalities have been tried with variable success. Prescription practices in chronic pruritus are influenced by differential knowledge and experience of physicians, patient-related factors, and resource availability. AIM: The purpose of this survey was to observe the current pattern of practice in Indian dermatologists in the management of chronic pruritus and to identify practice gaps particularly regarding the use of various systemic agents as antipruritics...
2024: Indian Dermatology Online Journal
#18
REVIEW
Mansoor R Mirza, Antonio González-Martín, Whitney S Graybill, David M O'Malley, Lydia Gaba, Oi Wah Stephanie Yap, Eva M Guerra, Peter G Rose, Jean-François Baurain, Sharad A Ghamande, Hannelore Denys, Emily Prendergast, Carmela Pisano, Philippe Follana, Klaus Baumann, Paula M Calvert, Jacob Korach, Yong Li, Izabela A Malinowska, Divya Gupta, Bradley J Monk
WHAT IS THIS SUMMARY ABOUT?: This document provides a summary of results from the article that evaluated the safety and efficacy of the fixed and individualized starting doses of niraparib in the PRIMA study. The original article was published in the journal Cancer in March 2023. The PRIMA study included adult patients with newly diagnosed advanced ovarian cancer who had finished treatment with chemotherapy and surgery. Once patients entered the study, they were treated with an oral (by mouth) medication called niraparib or placebo (substance with no effects that a doctor gives to a patient instead of a drug)...
January 22, 2024: Future Oncology
#19
JOURNAL ARTICLE
Sania Grover, Raj Kumar Narang, Shamsher Singh
Neurological disorders such as epilepsy, autism, Huntington's disease, multiple sclerosis, and Alzheimer's disease alter brain functions like cognition, mood, movements, and language, severely compromising the well-being of persons, suffering from their negative effects. The neurotransmitters (GABA, glutamate, norepinephrine, dopamine) are found to be involved in neuronal signaling and neurotransmission. GABA, a "commanding neurotransmitter" is directly or indirectly associated with various neurological disorders...
January 12, 2024: Central Nervous System Agents in Medicinal Chemistry
#20
JOURNAL ARTICLE
Huan Liu, Zhongda Wu, Yanting Du, Quan Zhou, Lianqing Chen, Shiwei Jin
In the pursuit of novel insecticides with high activity and a unique mode of action on the GABA receptor, a series of phenylpyrazole esterified derivatives ( PEs ) were synthesized using an improved Pinner reaction with high selectivity. Lewis acid catalysis was employed in a one-step solvent-thermal method to convert the cyano group of fipronil into an ester unit. FeCl3 was found to exhibit the highest selectivity for PEs synthesis, yielding PEs at 96.4%, with the byproduct being phenylpyrazole amide ( PE 0 ) at 2...
January 17, 2024: Journal of Agricultural and Food Chemistry
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