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Ganaxolone: A Review in Epileptic Seizures Associated with Cyclin-Dependent Kinase-Like 5 Deficiency Disorder.

Paediatr Drugs

January 2025

Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.

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Purpose: Fuchs endothelial corneal dystrophy (FECD) displays a higher incidence in females than in males, yet the underlying mechanism remains unclear. This study aimed to elucidate sex-dependent differential gene expressions in corneal endothelial cells (CECs) from healthy non-FECD individuals and from patients with FECD.

Methods: RNA-Seq data from CECs of non-FECD subjects (3 males, 4 females) and FECD subjects (5 males, 5 females) were analyzed to identify differentially expressed genes (DEGs) between the sexes.

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Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in , loss of or activation of receptor tyrosine kinases. In HPV‑negative tumors, (encoding p16 protein) inactivation or (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines.

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Our study focused on the potential mechanism of microRNA-490-3p (miR-490-3p) on learning/memory disability of rats resulting from sevoflurane (Sev). The rat model of cognitive dysfunction was established by infection with miR-490-3p mimic and Sev-exposure. Morris water maze and open field test assay were used for the assessment of cognitive deficits.

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High glucose induces renal tubular epithelial cell senescence by inhibiting autophagic flux.

Hum Cell

January 2025

Department of Nephrology, Zhong Da Hospital, Gulou District, No. 87, Dingjiaqiao, Zhongyangmen Street, Nanjing, 210009, Jiangsu, China.

Autophagy, a cellular degradation process involving the formation and clearance of autophagosomes, is mediated by autophagic proteins, such as microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), and modulated by 3-methyladenine (3-MA) as well as chloroquine (CQ). Senescence, characterised by permanent cell cycle arrest, is marked by proteins such as cyclin-dependent kinase inhibitor 1 (p21) and tumour protein 53 (p53). This study aims to investigate the relationship between cell senescence and renal function in diabetic kidney disease (DKD) and the effect of autophagy on high-glucose-induced cell senescence.

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