Valproate is highly effective for genetic generalized epilepsies but carries substantial dose-dependent risks of major congenital malformations and adverse neurodevelopment after in utero exposure. Guidelines therefore recommend avoiding it in individuals with pregnancy potential when effective alternatives are available. This dilemma is concentrated in generalized epilepsies; focal epilepsies should generally be treated with other appropriate antiseizure medicines irrespective of reproductive potential. In many low- and middle-income countries, however, inconsistent access to lamotrigine, levetiracetam, and ethosuximide, limited specialist and reproductive-health services, and weak procurement and pharmacovigilance constrain substitution. This narrative review integrates comparative efficacy, pregnancy-safety, health-economic, and implementation evidence. We distinguish cost-effectiveness from short-term budget impact and argue that restriction without reliable alternative supply may worsen seizure control and inequity. We propose syndrome-specific prescribing: prioritise safer alternatives, reserve valproate for documented cases in which they are ineffective, contraindicated, unavailable, or unaffordable, and pair its use with counselling, effective contraception, folic acid, lowest-effective-dose monotherapy, and regular review. National policies should combine reproductive safeguards with essentialmedicines inclusion, pooled procurement, quality assurance, and monitoring.

Maternal diet may influence fetal neurodevelopment through nutrient availability, placental function, and maternal-fetal metabolite signaling. This critical narrative review used a structured, purposive search to organize human evidence on prenatal dietary patterns, choline, and polyphenol-related exposures according to outcome directness: diagnosed autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD), related dimensional traits, and general neurodevelopment. Whole-diet studies provide the most direct human evidence, but diagnostic findings are cohort-dependent and vulnerable to residual familial and genetic confounding. Choline trials and cohorts mainly address attention-related traits or general cognition; they do not establish prevention of diagnosed ASD or ADHD. Polyphenol evidence is limited to food proxies and one trimester-specific cohort of estimated intake, without diagnostic or biomarker-based studies. Preclinical data support biological plausibility-particularly for choline in BTBR, maternal immune-activation/CHRNA7, and Ts65Dn models and for resveratrol in valproate-exposed rodents-but remain model-specific. The evidence is therefore best treated as an organizing framework rather than a confirmed causal hypothesis. Clinical translation should prioritize achieving recommended dietary adequacy and balanced dietary patterns; evidence does not support high-dose single-nutrient or concentrated-polyphenol supplementation for ASD/ADHD prevention.

Inducing differentiation of glioma cells, including glioma stem cells (GSCs), into neuron-like cells represents a promising therapeutic strategy. Our previous drug repositioning study revealed that histone deacetylase (HDAC) inhibitors are potential inducers of glioma cell differentiation. In this study, the antiepileptic drug valproic acid (VPA), a known HDAC inhibitor with blood-brain barrier permeability, was investigated for its ability to induce neuronal differentiation in glioma. The results showed that VPA treatment induced pronounced neuronal-like morphological changes and upregulated expression of neuronal markers in glioma cell lines U87 and LN229 and their derived GSCs, while concurrently inhibiting proliferation and attenuating stemness. Proteomic sequencing and bioinformatics analyses confirmed the enrichment of neuronal differentiation-associated proteins and downregulation of cell cycle-related proteins following VPA exposure. Mechanistically, VPA reduced the thermal stability of HDAC1 and RE-1 silencing transcription factor (REST) and downregulated their protein levels. Pharmacological inhibition of HDAC1 or REST phenocopied VPA-induced differentiation, whereas REST overexpression attenuated this effect. In vivo, VPA administration significantly delayed subcutaneous U87 xenograft tumor growth, prolonged survival in an orthotopic GSC xenograft model, and reduced HDAC1/REST expression while inducing neuronal marker expression in tumor tissues. Furthermore, Connectivity Map analysis identified mTOR inhibitors as potential synergistic agents, and the combination of VPA with rapamycin exhibited synergistic anti-proliferative effects. Collectively, these findings demonstrate that VPA suppresses glioma growth by inducing neuronal-like differentiation partly through HDAC1/REST inhibition, which uncovers a distinct differentiation-based anti-glioma mechanism of VPA, supporting its potential clinical utility and providing a rationale for combination strategies in glioma differentiation therapy.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by neuronal dysfunction and impaired autophagy. Salidroside (SAL), a bioactive component derived from Rhodiola, exhibits neuroprotective activity; however, its effects and mechanisms in ASD remain largely unknown. Here, we examined the effects of SAL on valproic acid (VPA)-induced neuronal injury and ASD-related behaviors and assessed the role of the sirtuin 2 (SIRT2)/forkhead box O1 (FoxO1) pathway. VPA-induced HT22 cell injury models and ASD mouse models were used in this study. HT22 cells were exposed to 2mM VPA and treated with 20μM SAL, with AGK2 applied for SIRT2 inhibition. ASD mice received SAL administration from postnatal day 21 for 14 days, and AK-7 was used to further evaluate SIRT2 involvement. VPA exposure decreased HT22 cell viability, caused neuronal damage, increased autophagosome accumulation, and induced ASD-like behaviors in mice, including impaired social interaction, enhanced repetitive grooming, and reduced exploratory activity. SAL treatment improved cell viability, alleviated neuronal damage, attenuated autophagy-related changes, and improved behavioral abnormalities, whereas these effects were partially blocked by AGK2 or AK-7. Furthermore, SAL reversed VPA-induced alterations in autophagy-related proteins, including decreased Beclin-1 and LC3 expression and increased p62 expression, while restoring SIRT2, FoxO1, NeuN, and MAP2 levels and reducing the Ac-FoxO1/FoxO1 ratio in HT22 cells and hippocampal tissues. These findings indicate that SAL protects against VPA-induced neuronal injury and ASD-related behavioral deficits, which are associated with changes in the SIRT2/FoxO1 pathway and autophagy-related processes.

Polyethylenimine (PEI)-mediated transient transfection represents a pivotal methodology for recombinant protein production in HEK293 and derived cell lines. Despite extensive application, substantial potential for enhancement in transfection efficiency and exogenous protein expression persists, with the role of metal ions remaining inadequately characterized. We hypothesized that iron ions exert a concentration-dependent, biphasic regulation on PEI-mediated transfection, affecting both extracellular complex formation and intracellular gene expression. To test this hypothesis, we systematically investigated the impact of ferric ammonium citrate (FAC) on transient transfection efficiency and anti-PD-1 antibody production in Expi293F cells. Supplementation of iron-depleted basal medium with 10 μM FAC was identified as optimal, achieving 63.7% transfection efficiency for enhanced green fluorescent protein (eGFP) and an anti-PD-1 antibody yield of 55.0 mg/L. Transmission electron microscopy analysis revealed that FAC modulates transfection efficiency by altering PEI/DNA complex morphology. Quantitative real-time PCR demonstrated significant enhancement of intracellular DNA transcription by both FAC and calcium ions. The histone deacetylase inhibitor valproic acid further augmented transcription efficiency by 2.8-fold. Ultimately, anti-PD-1 monoclonal antibody production reached 171.0 mg/L in a 3-L bioreactor, representing a 10.6-fold improvement over initial conditions. This study provides preliminary evidence for establishing an efficient transient expression platform while offering initial mechanistic insights into how iron ions influence PEI-mediated transfection via complex morphology and transcriptional regulation.