Sensorineural hearing loss (SNHL) is the most common sensory deficit globally. Acquired SNHL results from ototoxic damage to cochlear hair cells (HCs) and is typically irreversible due to their limited regenerative capacity. While no cure currently exists, targeting the underlying pathology offers potential. Preclinical studies have investigated transcription factors like ATOH1, which can induce non-sensory cells to transdifferentiate into HCs. Gene therapy using viral vectors to deliver ATOH1 is emerging as a promising regenerative approach. PubMed, Web of Science, and Embase were systematically searched. The review was conducted following the Systematic Review Center for Laboratory Animal Experimentation guidelines. Random-effects meta-analysis was conducted using R’s “meta” and “metafor” packages. To corroborate our findings, differential gene expression (DEG) analysis was performed on the GEO dataset GSE127683 using DESeq2. K-means clustering and gene set enrichment analysis (GSEA) were conducted using iDEP 2.0 and Enrichr, respectively. Four studies including 52 rodents were included. ATOH1 gene therapy significantly reduced Auditory Brainstem Response thresholds ( MD = −21.37 dB SPL, CI: [−40.19; −2.54], p = 0.027), indicating improved hearing. DEG analysis showed upregulation of genes crucial for hair cell differentiation and functioning, including GFI1, PTPRQ, OTOF, USH2A, and POU4F3. GSEA highlighted key upregulated pathways related to inner ear development, auditory receptor cell differentiation and sensory perception of sound. ATOH1 gene therapy shows promise for treating acquired SNHL. However, further clinical trials are essential to confirm these preclinical findings and advance towards a potential cure.

Background: Pancreatic adenocarcinoma (PAAD) is an aggressive subtype of pancreatic cancer that is estimated to have a 5-year overall survival rate of only 13%. Most patients present with advanced disease with unpredictable outcomes. The identification of prognostic biomarkers is important to accurately stratify these patients. Methods: We investigated the molecular and survival-related role of ENHO in PAAD by analyzing TGCA mRNA and miRNA data. Survival analysis was conducted using TIMER2.0, “survival”, and “survminer”. Gene set enrichment analysis was conducted using enrichr, while miRNA-mRNA interactions were identified using “multiMiR”. Immune infiltration was assessed using CIBERSORT ABS and ImmuCellAI. Results: We observed that ENHO was strikingly downregulated in PAAD tissues (p = 3.68 × 10⁻⁶⁸), and patients with higher ENHO levels enjoyed significantly better overall survival (HR = 0.597; 95% CI: 0.419–0.852; p < 0.01). Pathway analysis showed that genes co-upregulated with ENHO were enriched for insulin secretion and ion channel activity, whereas those co-downregulated were related to epithelial–mesenchymal transition and extracellular matrix remodeling. Higher ENHO also tracked with increased CD8⁺ T-cell infiltration and correlated positively with PDCD1 and LAG3 but negatively with B7-H3, CD70, and NT5E. Conclusions: Our results point to a protective role for ENHO in pancreatic adenocarcinoma.

1. Intraosseous (IO) access is a technique for obtaining vascular access by infusing fluids and medications directly into the bone marrow cavity, thereby achieving access to the venous circulation ...