Medulloblastoma (MB) is the most common malignant tumor of the cerebellum in children. The Sonic Hedgehog (SHH) subgroup of MB (SHH-MB) is driven by aberrant activation of the SHH pathway; however, mutations in genes related to this pathway are relatively rare, posing challenges for therapeutic development. Glypican-6 (GPC6), a heparan sulfate proteoglycan, is highly expressed in SHH-MB. In this study, we demonstrate the synchronous expression of GPC6 with GLI family zinc finger 1 (GLI1) in both the developing cerebellum and medulloblastoma. GPC6 promotes cell proliferation, migration, and invasion in SHH-MB cell lines (DAOY and ONS-76). Consistently, GPC6 enhances the SHH pathway activity by upregulating GLI1 expression, supports ciliogenesis essential for signal transduction, and facilitates SHH ligand expression via extracellular vesicles. These findings suggest that GPC6 acts as a key regulator of SHH signaling and represents a potential therapeutic target in SHH-MB.

Lung cancer in smokers (LCIS) and lung cancer in never-smokers (LCINS) are different entities with distinct molecular features. However, their cellular heterogeneity still requires further investigation. Through an integrated analysis of single-cell RNA sequencing and bulk sequencing data, we identified cell subpopulations associated with smoking and non-smoking patients. Subsequent transcriptomic analyses were performed to elucidate differences in cellular functions and the tumor microenvironment. We observed that smoking-associated cancer cells exhibited a higher degree of aggressiveness, which may correlate with an adverse prognosis in smoking patients. Additionally, immunosuppressive CXCL10⁺ macrophages may contribute to tumorigenesis in smokers, and the immunoregulatory LGALS9-HAVCR2 axis could be a potential immunotherapeutic target. In non-smokers, the inflammatory microenvironment may be involved in tumor development. Moreover, the reduced anti-tumor cytotoxicity may be associated with their suboptimal immunotherapeutic response. Our study uncovered differences in oncogenic and immune escape mechanisms between LCIS and LCINS patients and suggests potential immunotherapeutic strategies.

PIWI-interacting RNAs (piRNAs) are a class of noncoding RNAs primarily found in germ cells. While piRNAs are known to be involved in various cancers, their specific roles in colorectal cancer (CRC) remain unclear. To elucidate the role of piRNAs in CRC, we first analyzed their expression characteristics by sequencing 10 pairs of tumor and adjacent normal tissues. Subsequently, differentially expressed piRNAs were identified through a two-stage reverse transcription-quantitative PCR (RT-qPCR) validation using 20 and 114 pairs of samples. Subcellular localization was assessed through nucleoplasmic separation and immunofluorescence staining assays. RNA pull-down mass spectrometry was employed to identify piRNA-interacting proteins. We identified piR-61298 as a piRNA significantly upregulated in CRC. Functional assays showed that piR-61298 promoted cell proliferation and migration, inhibited apoptosis, and promoted tumor growth. Mechanistically, piR-61298 bound to ubiquitin-specific peptidase 10 (USP10) in the cytoplasm, impairing its deubiquitinating activity toward p53, thereby leading to p53 ubiquitination and degradation. These findings suggest that piR-61298 plays a critical role in CRC progression by disrupting the USP10-p53 axis. Collectively, the current study highlights piR-61298 as a potential therapeutic target, offering a novel approach for CRC treatment by targeting piRNA-mediated regulation.

Cervical cancer represents a considerable global health challenge, mainly because of ineffective screening programs in low-income countries. The current study aimed to forecast cervical cancer incidence by analyzing behavioral risk factors through logistic regression, employing feature engineering techniques such as principal component analysis (PCA). PCA successfully condensed the dataset into ten principal components, capturing 89% of the variance, while stratified K-fold cross-validation ensured a balanced representation of classes. With the application of L1 regularization, the logistic regression model achieved an accuracy of 97.2%, an area under the curve (AUC) of 98.1%, an F1 score of 97.2%, a specificity of 96.1%, and a log loss of 0.17. The performance of the models was comparatively evaluated, and the results revealed that the logistic regression model achieved the highest accuracy of 97.2% compared with decision trees at 93.33%, random forest at 93.33%, XGBoost at 93.33%, naive Bayes at 91.67%, and non-regularized logistic regression at 87.55%. This research underscores the importance of early prediction of cervical cancer based on behavioral risk factors and suggests a robust, easily implementable workflow to improve classification accuracy. Future research should concentrate on refining these predictive tools to overcome social and behavioral barriers to prevention, particularly within underserved populations.

Ocular diseases, including corneal disease, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity, can significantly impair vision and reduce quality of life. Because degenerated cells in these diseases are unable to regenerate, treatments for these conditions have limited efficacy. Stem cell therapies are revolutionizing the treatment of degenerative eye conditions, enabling structural and functional restoration through mechanisms such as cell replacement and paracrine signaling. This review examines advances in stem cell therapy for ocular diseases, from preclinical studies to early clinical trials, focusing on various types of stem cells, including embryonic stem cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells. Significant progress has been made with iPSC-derived retinal pigment epithelial cell transplantation in AMD treatment, showing cell survival in trials, and with mesenchymal stem cells for corneal repair through anti-inflammatory effects. Challenges remain, such as controlling differentiation to prevent tumorigenesis, managing immune rejection, and ensuring manufacturing processes that comply with Good Manufacturing Practice standards. By integrating mechanistic insights with translational strategies, this review outlines pathways to optimize stem cell therapies for previously intractable ocular diseases.

As the most prevalent cause of death worldwide, ischemic stroke urgently requires innovative therapeutic strategies. The present study demonstrated the therapeutic potential of human umbilical cord-derived mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ameliorating hypoxia-induced cerebrovascular endothelial dysfunction through modulation of the AMPK/NLRP3 signaling pathway. Bioinformatics analysis of DisGeNET and exosomal cargo databases revealed 283 overlapping cerebral ischemia-related genes, implicating hUMSC-Exos in inflammatory regulation. In vitro experiments showed that hUMSC-Exos rescued oxygen-glucose deprivation (OGD)-induced endothelial dysfunction in bEnd.3 mouse brain endothelial cells, restoring viability, migration, and mitochondrial integrity. Mechanistically, hUMSC-Exos reversed OGD-induced AMPK inactivation while suppressing NLRP3 inflammasome activation, caspase-1 cleavage, and gasdermin D (GSDMD)-mediated pyroptosis. Molecular docking revealed that DL-3-n-butylphthalide acts as a dual-target ligand for AMPK/NLRP3, synergizing with hUMSC-Exos to enhance endothelial protection. In vivo, combined therapy in the transient middle cerebral artery occlusion mouse model reduced cerebral infarction and improved neurological outcomes, accompanied by NLRP3/GSDMD downregulation and hippocampal neuron preservation. These findings establish hUMSC-Exos as regulators of AMPK/NLRP3-mediated pyroptosis and propose a translatable combinatorial regimen for ischemic stroke therapy.