The Kaohsiung journal of medical sciences最新文献

Sepsis-associated liver injury (SALI) plays a major role in aggravating disease progression and worsening prognosis in patients with sepsis. Macrophage polarization is a key factor in the modulation of SALI progression. Recent studies have shown that human breast milk-derived exosomes (HBM-Exos) regulate processes involved in macrophage polarization. Here, we investigated the function and mechanism of action of HBM-Exos in a macrophage polarization model of SALI. The extracted HBM-Exos were identified by morphological analysis and detection of marker proteins using flow cytometry. Human Kupffer cells were treated with lipopolysaccharide (LPS) to simulate macrophage polarization in SALI. Cell viability was measured using a CCK-8 kit. Protein and gene expression levels were evaluated using western blotting and RT-qPCR, respectively. ELISA kits were used to assess the levels of inflammatory cytokines. The interactions between FP671120.4, ELAV Like RNA binding protein 1 (ELAVL1), and nuclear factor erythroid 2-related factor 2 (Nrf2) were verified by RIP analysis. HBM-Exos inhibited M1 macrophage polarization by promoting Nrf2 expression and phosphorylation via activation of the Nrf2/Heme oxygenase-1 (HO-1) signaling pathway in LPS-induced Kupffer cells. Furthermore, FP671120.4 reversed the HBM-Exos-mediated increase in Nrf2 mRNA stability. HBM-Exos-derived FP671120.4 enhanced the interaction between ELAVL1 and Nrf2. As a result, FP671120.4 inhibited M1 polarization by inducing Nrf2 expression via activation of the Nrf2/HO-1 pathway. These findings suggest that HBM-Exos-derived FP671120.4 may inhibit M1 macrophage polarization through the ELVAL1/Nrf2/HO-1 signaling pathway in LPS-induced Kupffer cells.

Oral tongue squamous cell carcinoma (OTSCC) is an aggressive malignancy and the most common subsite of head and neck cancer among Taiwanese males. This study aimed to evaluate the prognostic significance of depth of invasion (DOI) in patients with node-negative OTSCC treated with radical surgery alone. We retrospectively analyzed 243 patients with node-negative OTSCC who had undergone radical surgery with adequate margins between 2005 and 2017. Each millimeter increase in DOI was significantly associated with a higher hazard of all-cause mortality (ACM) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.111; p < 0.001), cancer-specific mortality (CSM) (HR, 1.087; 95% CI, 1.04-1.136; p < 0.001) and local recurrence (LR) (HR, 1.081; 95% CI, 1.021-1.145; p = 0.008), but not regional recurrence (RR) (HR, 1.042; 95% CI, 0.986-1.102; p = 0.144). In multivariate analysis, DOI remained an independent predictor of ACM, CSM, and LR. A DOI-based nomogram demonstrated improved predictive performance, with a concordance index of 0.700 for overall survival. In conclusion, DOI represents a crucial prognostic factor for ACM, CSM, and LR in patients with node-negative OTSCC treated with surgery alone, highlighting its potential clinical utility for early risk stratification and guidance in decision-making regarding adjuvant therapy or intensified surveillance.

This study elucidates the mechanism by which GLIS Family Zinc Finger 2 (GLIS2) promotes epithelial-mesenchymal transition (EMT) in gastric cancer through biglycan (BGN) activation and Wnt/β-catenin stimulation. By analyzing 18 pairs of GC tissues and establishing in vitro models (combining GLIS2 knockdown/BGN overexpression with Wnt pathway modulators), we demonstrated that GLIS2 directly binds to the BGN promoter to enhance its transcription, thereby activating Wnt/β-catenin signaling and significantly promoting GC cell migration, invasion, and EMT. Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β-catenin inhibitor XAV-939 effectively blocks BGN's tumor-promoting effects. These findings establish the crucial role of the GLIS2-BGN-Wnt/β-catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment.

Anomalous pulmonary venous connection (APVC), including total (TAPVC) and partial (PAPVC) forms, is a congenital heart defect with abnormal pulmonary vein drainage; and while surgical repair has improved survival, its long-term impact on cardiopulmonary function remains unclear. This retrospective study evaluated exercise capacity and pulmonary function in 26 pediatric APVC patients (17 TAPVC, 9 PAPVC) using cardiopulmonary exercise testing (CPET) and compared them with 63 age-matched healthy controls. Patients with complex defects or significant comorbidities were excluded. Results showed significantly lower anaerobic threshold VO₂ (p = 0.03), peak VO₂ (p < 0.001) and peak heart rate (p = 0.02) in the APVC group, indicating impaired exercise capacity; though no differences were found between TAPVC and PAPVC subgroups. Despite preserved resting lung function, these findings suggest that children with repaired APVC experience persistent exercise limitations, underscoring the importance of routine functional assessment and potential rehabilitation, with further studies needed to clarify underlying mechanisms and guide long-term care.

Carotid artery stenting (CAS) is an effective treatment for carotid stenosis. Proton-pump inhibitors (PPIs) are commonly prescribed in the general population. However, the impact of PPI use on outcomes following CAS remains unknown. This study investigated the impact of PPI use on CAS using a retrospective, matched-cohort analysis from the TriNetX research network. Propensity score matching (PSM) was employed to create two balanced cohorts consisting of regular PPI users and nonusers who underwent CAS for asymptomatic carotid stenosis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the TriNetX platform to compare cerebrovascular and cardiovascular outcomes. A total of 20,153 patients were included. After PSM, 4691 patients were included in both the PPI and non-PPI cohorts. The mean age at the time of CAS was 70.4 years in both groups. Compared with non-PPI users, patients in the PPI cohort had a higher incidence of 30-day periprocedural stroke (OR: 1.35; 95% CI: 1.08-1.69; p = 0.009). Analyses of 2-year outcomes demonstrated that regular PPI users had a higher incidence of ischemic stroke (OR: 1.16; 95% CI: 1.01-1.32; p = 0.034), transient ischemic attack (TIA) (OR: 1.30; 95% CI: 1.14-1.49; p < 0.001), and myocardial infarction (OR: 1.19; 95% CI: 1.03-1.38; p = 0.018) compared with non-PPI users. In patients undergoing CAS for asymptomatic carotid stenosis, PPI use was associated with an increased risk of periprocedural stroke, as well as a higher incidence of ischemic stroke, TIA, and myocardial infarction over a 2-year follow-up period.

Following anterior cruciate ligament (ACL) reconstruction, enhancing hamstring tenocyte activity and minimizing apoptosis are critical for preventing graft failure and promoting ligamentization. This study investigated the therapeutic potential of extracellular vesicles (EVs) derived from a coculture of ACL remnant cells and bone marrow stromal cells (BMSCs), termed coculture-EV, in comparison with EVs from BMSC monoculture (BMSC-EV). We hypothesized that coculture-EVs could enhance tenocyte activity and reduce apoptosis, with greater effects than BMSC-EVs. ACL remnants, bone marrow, and hamstring tendons were harvested from rabbits 4 weeks post-ACL transection, and the cultured cells were used for coculture and subsequent experiments. EVs were isolated by ultracentrifugation and characterized by nanoparticle size analysis, electron microscopy, and EV-specific markers. Hamstring tenocytes treated with coculture-EVs exhibited significantly improved viability, proliferation (EdU assay), and migration (scratch and transwell assays), along with increased expression of genes related to collagen synthesis, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF). Importantly, coculture-EV treatment more effectively suppressed both intrinsic and extrinsic apoptotic pathways. Coculture-EV treatment reduced early apoptosis in tenocytes by 54.5%, whereas BMSC-EV produced a 21.1% reduction. These findings suggest that EVs from ACL/BMSC coculture possess superior bioactivity compared with BMSC-derived EVs alone. Coculture-EV enhances tenocyte function and survival, indicating its potential as a cell-free therapeutic strategy to promote hamstring graft maturation and improve outcomes after ACL reconstruction.

Autophagy plays either a suppressing or promoting role during tumor development. Clarifying the role of autophagy in bladder tumorigenesis both in vitro and in vivo is crucial for developing novel therapeutic strategies through manipulating autophagy activity. Herein, we noninvasively monitored how autophagy affects bladder tumor formation using a murine model of orthotopic bladder tumor formation by "in vivo imaging system (IVIS) and transabdominal micro-ultrasound imaging (MUI)" and validated the notion in cell lines and bladder cancer patients. Mimic clinical administration, all the drugs were delivered into the urinary bladder of the mice via intravesical instillation. Plasma biochemistry parameters, hemograms, blood pressure, and blood concentration of amiodarone and desethylamiodarone were analyzed in treated mice. Low autophagy activity was detected in the bladder tumors and associated with poor overall survival of bladder cancer patients. Amiodarone-induced autophagy activity suppressed bladder tumor formation, whereas silencing Atg5 expression reversed the suppression. Notably, amiodarone showed equivalent anti-tumor efficacy but with fewer side effects on the treated mice compared to the clinical anti-cancer drug Mitomycin C (MMC). Furthermore, amiodarone delivered by intravesical route showed a negligible influence on the physiologic conditions of the treated mice. Our orthotopic mouse model revealed that increasing autophagy activity alleviated bladder tumor development. Similarly, low autophagy is associated with a poor overall survival rate. Furthermore, repurposing amiodarone-induced autophagy accompanied by trivial side effects shows potential for the treatment of bladder cancer patients.