Glioblastoma (GBM) represents an extremely aggressive brain malignancy with limited treatment options, poor prognosis and a highly heterogeneous cellular architecture, including a subpopulation of cancer stem-like cells (CSCs). These CSCs frequently rely on developmental signaling pathways such as Sonic Hedgehog (SHH), which are typically dormant in adult tissue but reactivated in tumors. This study aimed to investigate how SHH pathway inhibition affects both bulk GBM cells (GBMCs) and CD133+ GBM cells (GBM CSCs), with particular emphasis on the influence of astrocyte co-culture, which more closely mimics the brain tumor microenvironment. GBMCs and GBM CSCs were cultured in mono- and astrocyte co-culture systems. They were evaluated through RT-qPCR, immunofluorescence staining, ELISA, TUNEL assay, and cell cycle analysis. By comparing treatment and culture context independently, cyclopamine-mediated SHH inhibition and astrocyte-dependent signals use distinct but interacting effects on cell behavior. Cyclopamine treatment changed SHH pathway activity depending on the cell type and culture condition, whereas astrocyte co-culture regulated GLI1, GLI3, and SUFU expression through a mechanism different from cyclopamine’s effect. GBM CSCs exhibited higher SHH secretion in monoculture, which was attenuated under co-culture with cyclopamine. Cell cycle analysis revealed G2/M arrest in GBMCs and G0/G1 arrest in CSCs, with astrocyte co-culture shifting CSCs toward G2/M. Apoptotic gene expression and TUNEL staining indicated enhanced extrinsic apoptosis (via CASP8) in CSCs, further intensified by SHH inhibition and co-culture. Astrocyte co-culture significantly modulates the molecular and phenotypic response of GBM cells to SHH inhibition, reshaping apoptotic and proliferative behaviors in both CSCs and bulk populations. These findings highlight the critical importance of the tumor microenvironment in therapeutic response and suggest that effective targeting of SHH signaling may require models that account for astroglial interactions.

Objective: The clinical relevance of inherited thrombophilia‐related polymorphisms in COVID‐19 remains uncertain. This study investigated the distribution of Factor V Leiden (FVL) G1691A and MTHFR A1298C polymorphisms in patients with COVID‐19 and associations with laboratory findings and short‐term mortality. Methods: This case‐control study included 150 patients with PCR‐confirmed COVID‐19 and 300 controls. Genomic DNA was isolated from peripheral blood, and FVL G1691A and MTHFR A1298C polymorphisms were analyzed. Associations with d‐dimer levels, hospitalization duration, and 30‐ and 90‐day mortality were evaluated using multivariable linear and Cox regression analyses. Results: The FVL GG genotype was less frequent in patients than controls (77.3% vs. 87.0%, p = 0.009), whereas the MTHFR AA genotype was more frequent (76.7% vs. 61.3%, p = 0.001). Heterozygosity in both genes did not differ between groups (8.0% vs. 6.3%, p = 0.552). Patients with heterozygosity in both genes had higher d‐dimer levels (median 435.0 vs. 201.0 ng/mL, p = 0.024) and longer hospitalization (median 7.5 vs. 5.0 days, p = 0.037). After adjustment, heterozygosity in both genes remained associated with higher log‐transformed d‐dimer levels ( β = 0.758, 95% CI: 0.239–1.277; p = 0.005), as did MTHFR A1298C ( β = 0.432, 95% CI: 0.007–0.856; p = 0.046). None of the polymorphisms was associated with 30‐ or 90‐day mortality, while age independently predicted both outcomes. Conclusion: Thrombophilia‐related polymorphisms may influence d‐dimer levels and hospitalization duration in COVID‐19 but do not appear to affect short‐term mortality.

Objective: Electrical injuries present a diagnostic and management challenge due to their diverse clinical manifestations and potential complications. Although the current guidelines recommend cardiac monitoring in selected cases, the criteria for risk stratification remain limited. This study aimed to evaluate the epidemiological and clinical characteristics of patients with electrical injuries admitted to the emergency department over a 10‐year period. Methods: This retrospective study reviewed medical records of patients admitted to the Pamukkale University Hospital between 2014 and 2024 due to electrical injuries. Data collected included age, sex, time of injury, voltage level, current type and source, contact site, transthoracic current pathway, ECG findings, laboratory results (troponin T, CK‐MB, and potassium), work‐related status, and mortality. The primary outcomes were epidemiological characteristics, ECG abnormalities, and laboratory evidence of myocardial injury. Results: A total of 112 patients were identified; 91 (81%) patients were male, with a mean age of 31.8 years. High‐voltage injuries (> 1000 V) occurred in 10 patients, while low‐voltage injuries (< 1000 V) were seen in 80 (60.6%) patients. Work‐related injuries accounted for 14.3% of cases. One patient died due to trauma following high‐voltage exposure. Troponin T was elevated in 57 of 92 tested patients (62.0%), CK‐MB in 25 (22.3%), and hyperkalemia in six (5.3%). ECG abnormalities were detected in 16 patients (14.3%). Conclusion: Biochemical evidence of myocardial injury was observed even in low‐voltage exposures, raising concerns about the safety of early discharge based solely on clinical presentation and ECG findings. Prospective studies are needed to refine risk assessment strategies in electrical injury cases.

Cancer stem cells (CSCs) in malignant melanoma contribute to therapeutic resistance and tumour recurrence. While low‐intensity pulsed ultrasound (LIPUS) has been proposed as a non‐invasive strategy to induce cell death, its effects on CSC‐specific apoptotic and autophagic responses remain unclear. This study aimed to explore the time‐dependent effects of LIPUS on apoptosis and autophagy in CD133+ melanoma CSCs and CD133− non‐stem melanoma cells. Human melanoma cells (CHL‐1) were sorted via FACS into CD133+ and CD133− populations. Cells were exposed to LIPUS (1 MHz, 20% duty cycle, 1 W/cm²) for 1, 5, and 10 min. Protein expression levels of Caspase‐3, Caspase‐8, mTOR, and LC3 were evaluated via immunofluorescence and quantified by image‐based analysis. Both cell populations showed significant increases in Casp3, Casp8, mTOR, and LC3 intensities following LIPUS application. Notably, CD133+ cells exhibited delayed but sustained increases in Casp3 and LC3 expression, while CD133− cells responded more rapidly. mTOR activity demonstrated distinct temporal dynamics between the two groups, suggesting differential modulation of autophagy‐related pathways. LIPUS triggers temporally distinct apoptotic and autophagic responses in melanoma CSCs and non‐stem cancer cells. These findings suggest a potential therapeutic avenue to selectively disrupt CSC survival mechanisms using mechanical stimulation.

Lifestyle factors such as smoking and alcohol may influence colon cancer (CC) survival, but it is unclear whether their effects vary by tumour-infiltrating immune biomarkers. This study examined CC-specific survival by smoking and alcohol status, stratified by immune cell density, in a large population-based cohort. The study included 661 individuals who underwent surgery for stage II or III CC between 2004 and 2008 within two Health and Social Care (HSC) Trusts in Northern Ireland. Representative formalin-fixed, paraffin-embedded (FFPE) tumour blocks were retrieved, and immunohistochemistry (IHC) was performed on tissue microarrays constructed from both the central tumour and the invasive margin. Cox proportional hazards models were used to assess CC-specific survival, adjusting for key clinical and demographic confounders. Ever smoking, compared to never smoking, was associated with poorer CC-specific survival among individuals with lower densities of CD3+, CD4 +, and FOXP3 + tumour-infiltrating immune cells. Among those with higher CD8 + cell density in the central tumour, ever smoking was linked to worse outcomes. Similar patterns were seen in the invasive margin, although these were not all statistically significant. No significant associations were observed between alcohol use and survival across any immune biomarker subgroups. Smoking was associated with poorer survival among patients with CC, and this association appears to be modified by the density of tumour-infiltrating immune cells.