Epilepsy is a chronic neurological disorder with significant treatment challenges, necessitating the search for alternative therapies. This study evaluates the anticonvulsant activity and toxicological profile of Verbesina persicifolia leaf extracts. Methanolic and sequential fractions (hexane, dichloromethane, ethyl acetate, and methanol) were tested using a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio), measuring seizure latency, severity, and survival rates. Phytochemical screening confirmed the presence of flavonoids, alkaloids, and steroids, suggesting potential neuroactive properties. The hexane extracts significantly increased seizure latency and survival rates, with co-administration of hexane extract (5 µg/mL) and diazepam (35.5 µM) further enhancing these effects. Toxicity assessment in Artemia salina indicated low to moderate toxicity in methanolic extracts, while sequential fractions exhibited higher toxicity, particularly in hexane and ethyl acetate extracts. These findings suggest that V. persicifolia extracts exert anticonvulsant effects, likely through GABAergic modulation, and exhibit a favorable safety profile at therapeutic doses. The results support further investigations to isolate active constituents, confirm their mechanisms of action, and explore their potential as plant-derived anticonvulsant agents.

Epilepsy remains a widespread neurological disorder, with approximately 30% of patients showing resistance to current antiepileptic therapies. To address this unmet need, a series of 2-(isoindolin-2-yl) esters derived from natural amino acids were designed and evaluated for their potential interaction with the GABA_A receptor. Sixteen derivatives were subjected to in silico assessments, including physicochemical and ADMET profiling, virtual screening–ensemble docking, and enhanced sampling molecular dynamics simulations (metadynamics calculations). Among these, compounds derived from the aromatic amino acids, phenylalanine, tyrosine, tryptophan, and histidine, exhibited superior predicted affinity, attributed to π–π stacking interactions at the benzodiazepine binding site of the GABA_A receptor. Based on computational performance, the tyrosine and tryptophan derivatives were synthesized and further assessed in vivo using the pentylenetetrazole-induced seizure model in zebrafish (Danio rerio). The tryptophan derivative produced comparable behavioral seizure reduction to the reference drug diazepam at the tested concentrations. The results implies that aromatic amino acid-derived isoindoline esters are promising anticonvulsant candidates and support the hypothesis that π–π interactions may play a critical role in modulating GABA_A receptor binding affinity.

Epilepsy is a chronic neurological disorder with significant treatment challenges, necessitating the search for alternative therapies. This study evaluates the anticonvulsant activity and toxicological profile of Verbesina persicifolia leaf extracts. Methanolic and sequential fractions (hexane, dichloromethane, ethyl acetate, and methanol) were tested using a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio), measuring seizure latency, severity, and survival rates. Phytochemical analysis identified flavonoids, alkaloids, and steroids, suggesting neuroactive potential. Ethyl acetate and hexane fractions significantly increased seizure latency and survival rates, with co-administration of hexane extract and diazepam enhancing these effects. Toxicity assessment in Artemia salina indicated low to moderate toxicity in methanolic extracts, whereas sequential fractions exhibited higher toxicity, particularly in hexane and ethyl acetate extracts. Cell viability assays in chicken embryo fibroblasts confirmed a concentration-dependent safety profile. The findings suggest that V. persicifolia extracts exert anticonvulsant effects, likely through GABAergic modulation, and have a favorable safety profile at therapeutic doses. These results support further investigations to isolate active constituents and explore their potential as plant-derived anticonvulsant agents.

Epilepsy remains a widespread neurological disorder, with approximately 30% of patients showing resistance to current antiepileptic therapies. To address this unmet need, a series of 2-(isoindolin-2-yl) esters derived from natural amino acids were designed and evaluated for their potential interaction with the GABAA receptor. Sixteen derivatives were subjected to in silico assessments, including physicochemical and ADMET profiling, virtual screening - ensemble docking, and enhanced sampling molecular dynamics simulations (metadynamics calculations). Among these, compounds derived from the aromatic amino acids, phenylalanine, tyrosine, tryptophan, and histidine exhibited superior predicted affinity, attributed to π–π stacking interactions at the benzodiazepine binding site of the GABAA receptor. Based on computational performance, the tyrosine and tryptophan derivatives were synthesized and further assessed in vivo using the pentylenetetrazole-induced seizure model in zebrafish (Danio rerio). Both compounds significantly reduced seizure severity, with the tryptophan derivative demonstrating equal efficacy to the reference drug diazepam. The results suggest that aromatic amino acid-derived isoindoline esters are promising anticonvulsant candidates and suggest that π–π interactions play a critical role in modulating GABAA receptor binding affinity.

La pandemia por SARS-CoV-2 y la enfermedad derivada, la COVID-19, representan un reto que pone a prueba la capacidad de respuesta de las instituciones de salud, pero que afecta todos los ámbitos de la práctica clínica, incluida la investigación. El alto riesgo de contagio en las interacciones ha dificultado todos los aspectos de la socialización. Los médicos que se dedican a la investigación han encontrado una barrera, ya que deben considerar la posibilidad de infección. Este artículo propone modificaciones al consentimiento informado, considerando este riesgo latente, procurando que sea entendible y expresado de forma clara y sencilla para los participantes. Asimismo, se considera importante identificar las medidas extrapoladas de la atención clínica que deben utilizarse en la interacción entre investigadores y sujetos de estudio, buscando la identificación de casos y prevención de la enfermedad, priorizando las consideraciones bioéticas de la investigación, en momentos de incertidumbre..

Background: Following the end of the COVID-19 pandemic, attention shifted towards patients who developed sequelae, persistent symptoms, or relapsing or remitting symptoms of new conditions after a prior history of acute SARS-CoV-2 infection. The objective of the present study was to identify the prevalence, clinical characteristics, and potential associated factors of long COVID in children treated during the pandemic in a primary care unit. Methods: A cross-sectional analytical study was conducted from January to December 2022. Children under 18 years of age and their parents were included in the study if they had been treated at the Mexican Social Security Institute. Two distinct manifestations of long COVID were considered: (a) “persistence”, defined as continuous symptoms beginning in the acute phase and lasting for more than 3 months; and (b) “post-COVID conditions”, defined as new or recurrent symptoms lasting for more than 3 months, appearing after the acute episode, and not associated with any active disease or infectious condition. An exploratory binary logistic regression analysis was performed to identify associated factors, using an odds ratio (OR) as the measure of association. Results: The study included 349 children and adolescents. The prevalence of long COVID was 11.8% ( _95% CI 7.8%–17.5%). For “persistence”, the most frequent symptoms were cough (50%) and rhinorrhea (15.4%); for “post-COVID conditions”, the most common symptoms were myalgia (33.3%), asthenia and irritability (26.7% each), and constipation (20%). Multivariate analysis revealed that the associated factors for individuals aged over 8 years were a history of reinfection (OR 9.7, _95% CI 1.6–58) and BMI at the time of the survey (OR 1.1, _95% CI 1.0–1.2), while for those aged under 8 years, the associated factor was male sex (OR 4.7, _95% CI 1.3–17.3). It is important to emphasize that these results are the product of an exploratory analysis and aim to create and test new hypotheses. Conclusions: For healthcare professionals, it is crucial to consider the possibility of long COVID, as this study indicated that approximately 12% of children and adolescents may be affected. Further research is necessary to better understand and manage long COVID in pediatric populations and to investigate the association between reinfections and their increased prevalence.