Migraine stands as one of the most disabling neurological conditions worldwide. It is a disorder of great challenge to study given its heterogeneous representation, cyclic nature, and complexity of neural networks involved. Despite this, clinical and preclinical research has greatly benefitted from the use of the nitric oxide donor, nitroglycerin (NTG), to model this disorder, dissect underlying mechanisms, and to facilitate the development and screening of effective therapeutics. NTG is capable of triggering a migraine attack, only in migraineurs or patients with a history of migraine and inducing migraine-like phenotypes in rodent models. It is however unclear to what extent NTG and NO, as its breakdown product, is a determinant factor in the underlying pathophysiology of migraine, and importantly, whether it really does facilitate the translation from the bench to the bedside, and vice-versa. This review provides an insight into the evidence supporting the strengths of this model, as well as its limitations, and shines a light into the possible role of NO-related mechanisms in altered molecular signalling pathways.
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http://dx.doi.org/10.1016/j.ynpai.2022.100105 | DOI Listing |
Comput Biol Med
January 2025
Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Centre, Neurology and Cerebrovascular Disease Group, Neuroscience Area La Paz Institute for Health Research (idiPAZ), (La Paz University Hospital- Universidad Autónoma de Madrid), Spain. Electronic address:
The quantitative evaluation of motor function in experimental stroke models is essential for the preclinical assessment of new therapeutic strategies that can be transferred to clinical research; however, conventional assessment tests are hampered by the evaluator's subjectivity. We present an artificial intelligence-based system for the automatic, accurate, and objective analysis of target parameters evaluated by the ledged beam walking test, which offers higher sensitivity than the current methodology based on manual and visual counting. This system employs a residual deep network model, trained with DeepLabCut (DLC) to extract target paretic hindlimb coordinates, which are categorized to provide a ratio measurement of the animal's neurological deficit.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia.
As a promising candidate for tackling drug-resistant cancers, triptolide, a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, has been developed. This review summarizes potential antitumor activities, including the suppression of RNA polymerase II, the suppression of heat shock proteins (HSP70 and HSP90), and the blockade of NF-kB signalling. Triptolide is the first known compound to target cancer cells specifically but spare normal cells, and it has success in treating cancers that are difficult to treat, including pancreatic, breast, and lung cancers.
View Article and Find Full Text PDFExpert Opin Drug Discov
January 2025
Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
Introduction: Kabuki Syndrome (KS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability, and multiple congenital anomalies. It is caused by pathogenic variants in the and genes. Despite its significant disease burden, there are currently no approved therapies for KS, highlighting the need for advanced research and therapeutic development.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFViruses
January 2025
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction.
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