Spinal muscular atrophy (SMA) is a progressive neuromuscular degenerative disorder caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to insufficient production of the survival motor neuron (SMN) protein. The nearly identical SMN2 gene modifies disease severity but generates only limited amounts of functional SMN protein due to a C-to-T transition in exon 7 that disrupts proper splicing. This review summarizes advances in understanding SMN2 splicing regulation and post-transcriptional modification in SMA pathogenesis. It discusses the roles of cis- and trans-acting elements in exon 7 inclusion, as well as the impact of epigenetic mechanisms such as histone acetylation and DNA methylation on SMN2 expression. This review also examines available therapeutic strategies, including antisense oligonucleotides (Nusinersen), small-molecule splicing modulators (Risdiplam and Branaplam), and gene therapy (Onasemnogene abeparvovec). Emerging approaches such as CRISPR/Cas9 genome editing and nanotechnology-based delivery systems are also highlighted. In addition, this review explores translational research using animal models, iPSC-derived neurons, and multi-omics approaches. Finally, it emphasizes the need for integrated therapeutic strategies that address both SMN-dependent and -independent pathways to improve treatment outcomes.

Primary lung adenocarcinoma is the most common histological subtype of lung cancer. It disproportionately affects female sex, especially never-smokers. The rising incidence among females without a smoking history suggests roles for hormonal, genetic, and environmental factors. We conducted a comprehensive literature review using several databases. We examined global epidemiology data, molecular mechanisms, hormone-related pathways, and new diagnostic and therapeutic approaches. The findings show that estrogen signaling, especially via estrogen receptor beta (ERβ), contributes to oncogenesis. The mechanism involves cross-talk with EGFR and downstream MAPK/PI3K pathways. EGFR mutations appear more frequently in females. The association between KRAS and other cell cycle drivers is mixed across studies. Non-tobacco exposures, including air pollution and secondhand smoke, further increase risk among females. Diagnostic disparities persist because current screening guidelines focus on smoking. This approach excludes many high-risk never-smoking females. This review aims to narrate and synthesize growing evidence highlighting how female sex is associated with a distinct epidemiological footprint, unique molecular and biological profiles, and tailored therapeutic strategies in lung adenocarcinoma, driven by mechanisms beyond traditional tobacco exposure. Incorporating sex-specific risk assessment, hormonal level modification, and targeted gene therapies into clinical practice may improve screening and outcomes for females with lung adenocarcinoma.

Background: Conduction system pacing (CSP) has emerged as an alternative to right ventricular pacing (RVP) for atrioventricular block (AVB) aiming to avoid ventricular dyssynchrony and adverse heart failure outcomes yet clinical adoption remains limited due to insufficient randomised evidence. Objectives: This study aimed to assess the clinical outcomes of CSP versus RVP in patients with AVB based exclusively on randomised controlled trials (RCTs). Methods: MEDLINE, Embase and Cochrane were searched from inception to October 2025. Clinical outcomes comparing CSP and RVP were analysed using HR, risk ratio (RR) and mean difference with 95% CIs. Heterogeneity was assessed with I ² and robustness tested by sensitivity analyses. Outcomes included heart failure hospitalisation (HFH), all-cause mortality (ACM), composite endpoint and key cardiac parameters. Results: Data from five RCTs involving 985 patients with AVB were analysed. In the pooled analysis, the composite endpoint is significantly improved in the intervention pacing (HR=0.54; 95% CI 0.31 to 0.95; p=0.03), similarly with markedly reduced risk for HFH (RR=0.30; 95% CI 0.17 to 0.54; p<0.0001). However, no significant difference was observed between CSP and RVP in ACM (RR=0.69; 95% CI 0.36 to 1.30; p=0.25). Secondary outcomes significantly favoured the CSP group, as the change in left ventricular ejection fraction (LVEF) was significantly increased (p=0.008) and the QRS duration was significantly shorter (p=0.002) compared with RVP. Conclusion: In patients with AVB, CSP provides enhanced cardiac and clinical benefit compared with RVP driven by reduced HFH, improved LVEF and shorter QRS, while evidence regarding its influence on overall mortality remains uncertain.

Familial gliomas are rare primary brain tumors, accounting for around 5% of all glioma cases, and carry a strong familial predisposition, although their genetic basis remains incompletely understood. A recent 2023 Stanford study discovered that genome-wide sequencing has identified deleterious variants in HECT and RCC1-like domain-containing protein 2 (HERC2), the most significantly enriched gene in familial glioma cohorts. HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2), a large (~528 kDa) multifunctional E3 ubiquitin ligase, modulates DNA damage responses by catalyzing ubiquitin signaling cascades, facilitating the recruitment of repair proteins (breast cancer 1, p53-binding protein 1) through the ring finger protein 8/ubiquitin conjugating enzyme E2 13 complex, regulating p53 tetramerization through neuralized E3 ubiquitin protein ligase 4/E6-associated protein complexes, and controlling intra-S-phase checkpoint activation through the ubiquitin-specific peptidase 20-Claspin-checkpoint kinase 1 axis. Structurally, HERC2 comprises RCC1‐like domains for chromatin engagement, a mind bomb/HERC2 domain for E2 interactions, a CPH domain implicated in p53 stabilization, a ZZ‐type zinc finger, a DOC scaffold region, and a catalytic C-terminal HECT domain. Familial glioma-associated HERC2 mutations include missense variants and truncating loss-of-function alleles that impair ubiquitin-mediated coordination of normal protein degradation, induce TP53 dysfunction, and promote genomic instability. These findings highlight HERC2’s potential as a diagnostic biomarker and therapeutic target. Future studies are needed to determine the penetrance of HERC2 variants and assess their prognostic and predictive value in clinical practice.