The Kaohsiung journal of medical sciences最新文献

Rheumatoid arthritis (RA) is a common autoimmune disease, and early diagnosis is critical for effective treatment. This study aims to identify potential biomarkers related to pyroptosis through serum proteomics analysis, offering new insights for the early diagnosis of RA. We enrolled 100 participants, including 50 patients with RA and 50 healthy controls. Serum samples were collected and analyzed using high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomics profiling. Differential protein expression analysis and functional annotation revealed significant upregulation of pyroptosis-related proteins in the serum of patients with RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, along with protein-protein interaction (PPI) network analysis, showed that these proteins are involved in inflammation and immune pathways, particularly the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Enzyme-linked immunosorbent assay (ELISA) validation confirmed a significant increase in PCSK9 levels in patients with RA, suggesting that PCSK9 may play a key role in the pathogenesis of RA. This study provides new directions for biomarker research in RA, particularly regarding the potential involvement of the pyroptosis pathway, with significant clinical application prospects.

The prevalence of postmenopausal osteoporosis (PMOP) has been steadily increasing. Ferroptosis has been recognized as a critical factor influencing the bone-forming ability of bone marrow mesenchymal stem cells (BMSCs). Valproic acid (VPA), an HDAC inhibitor, has been suggested to play a role in regulating osteoporosis development; however, its underlying mechanism remains unclear. This study aims to explore the impact of VPA on ferroptosis, a process that is triggered by Erastin, and to assess its implications for postmenopausal osteoporosis (PMOP). We evaluated the effects of valproate sodium on Erastin-induced ferroptosis in BMSCs through in vitro experiments, including CCK-8 assays, Western blot analysis, mitochondrial function assessments (MDA, GSH, ROS, and MMP), and osteogenic evaluations (ALP and ARS staining). The impact of VPA on bone integration in ovariectomized (OVX) rats was assessed using micro-CT, hematoxylin-eosin (HE) staining, Masson's trichrome staining, and RT-PCR analysis. RNA sequencing was employed to investigate the underlying mechanisms of VPA action. Our findings demonstrate that VPA treatment prevents the Erastin-induced decline in the osteogenic capacity of BMSCs. In addition, VPA treatment suppresses ferroptosis, as indicated by decreased malondialdehyde levels, reduced mitochondrial ROS, and increased glutathione concentrations. Moreover, VPA treatment promotes trabecular bone growth and enhances bone integration. Mechanistic studies reveal that SIRT1-siRNA counteracts the beneficial effects of VPA in Erastin-treated BMSCs. VPA improves bone integration in OVX rats by activating the AMPK/SIRT1 pathway and inhibiting ferroptosis.

This study evaluated the effects of puerarin and adipose-derived stem cells (ADSCs), alone or combined, on p38MAPK activity, alveolar bone preservation, and inflammatory responses in a rat periodontitis (PD) model and in vitro. ADSCs were exposed to various puerarin concentrations to assess cell proliferation, osteogenic differentiation, and p38MAPK-related protein expression. Additional experiments employed anisomycin (a p38 MAPK activator) and Porphyromonas gingivalis LPS (Pg-LPS) to determine whether puerarin attenuates p38MAPK overactivation and reduces pro-inflammatory cytokine production. In vivo, ligature- and Porphyromonas gingivalis-induced periodontitis rats were randomized to Normal, PD, PD + ADSCs, PD + puerarin, or PD + puerarin + ADSCs groups, and alveolar bone microarchitecture (micro-CT) and periodontal p38MAPK activation and osteogenic/inflammatory proteins (Western blot, ELISA) were assessed. At 10^-6 M, puerarin significantly increased ADSC proliferation and osteogenic differentiation, whereas anisomycin activation diminished these benefits, which were restored by co-treatment with puerarin. Puerarin also reduced Pg-LPS induced secretion of pro-inflammatory cytokines by suppressing p38MAPK. In vivo, the periodontitis group showed substantial alveolar bone loss and marked inflammatory cell infiltration. Both ADSCs and puerarin partially alleviated these changes but did not fully reverse them. Notably, their combination provided the greatest benefit, nearly normalizing alveolar bone parameters, strongly inhibiting p38MAPK, and further reducing inflammatory cytokine levels in periodontal tissues. Collectively, puerarin and ADSCs exert complementary anti-inflammatory and pro-osteogenic effects associated with attenuation of p38MAPK signaling. Co-administration produced superior therapeutic outcomes, supporting this dual approach as a potential strategy for periodontitis-associated bone loss.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent chronic liver condition that can progress to severe complications such as metabolic dysfunction-associated steatohepatitis (MASH). Despite its growing burden, there are no reliable non-invasive biomarkers for tracking disease progression. In this study, we established a murine MASLD/MASH model using a high-fat diet and chemical (CCl₄) induction. We analyzed serum-derived extracellular vesicles (EVs) at 14 and 28 weeks to identify stage-specific proteomic signatures. Proteomic profiling of circulating EVs revealed key proteins associated with disease progression, including cathepsin B (Ctsb) and prosaposin (Psap) in early MASLD, and coagulation factor XIII A chain (F13a1) and polymeric immunoglobulin receptor (Pigr) in early MASH. The significant and severe MASH stages notably enriched Psma2, Psmb3, and Psmb5. These findings suggest EV-associated proteins may be promising non-invasive biomarkers for differentiating MASLD/MASH stages and guiding clinical monitoring.

This study investigated the impact of pretreatment nutritional status, psychological health, fatigue, and insomnia on outcomes of immune checkpoint inhibitors (ICIs) monotherapy in patients with advanced non-small cell lung cancer (NSCLC). A total of 80 patients with stage IV NSCLC were enrolled. Baseline assessments included the Controlling Nutritional Status (CONUT) score, Herth Hope Index (HHI), Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and Athens Insomnia Scale (AIS). Response to ICImonotherapy, along with progression-free survival (PFS) and overall survival (OS), was evaluated at week eight and through subsequent survival analyses. At week eight, partial response (PR), stable disease (SD), and progressive disease (PD) were observed in 31.8%, 33.0%, and 35.2% of patients, respectively. PD patients had significantly higher pretreatment CONUT scores, greater anxiety and depression, and more severe fatigue and insomnia than PR patients. Low nutritional risk was associated with improved OS and PFS. Higher HHI scores and lower HADS-A/D, BFI, and AIS scores correlated with better survival outcomes. In multivariate analysis, anxiety was independently associated with PFS, and depression and fatigue independently predicted OS. Pretreatment nutritional status, psychological health, fatigue, and insomnia significantly influence immunotherapy response and survival in advanced NSCLC. These findings underscore the clinical importance of comprehensive baseline assessments to identify high-risk patients who may benefit from targeted interventions before initiating immunotherapy. Addressing nutritional deficits, psychological distress, fatigue, and insomnia early could potentially enhance treatment response and improve survival outcomes, offering valuable insights for personalized cancer care strategies.

Hepatocellular carcinoma (HCC) surveillance with semi-annual ultrasound (US) is recommended for high-risk patients. This study investigates the impact of hepatobiliary abbreviated magnetic resonance imaging (AMRI) performed annually on the recommended US surveillance. Patients with compensated liver cirrhosis at regular HCC surveillance using US and alpha-fetoprotein, with adequate renal function and without HCC diagnosis, were enrolled. Patients were randomized into add-on hepatobiliary AMRI and continuous US surveillance groups. For patients in the AMRI group, gadoxetic acid-enhanced AMRI was performed at enrollment and annually. Liver nodule detection, HCC diagnostic tests, and HCC development were compared between the two groups. One hundred and four patients were initially enrolled, with 15 patients excluded for loss of regular follow-up, giving a total of 89 patients (AMRI: 45 and US: 44) that were analyzed in a median follow-up of 33.6 months. There were no significant differences in baseline characteristics nor statistical differences in hepatic nodule detections (AMRI:10 vs. US:18, p = 0.074) and HCC developments (1 vs. 6, p = 0.058) between the groups. While one HCC with a size of 1.2 cm (BCLC stage:0) was diagnosed in the AMRI group, six HCCs with a mean size of 2.4 cm (BCLC stage 0:2, A:3, B:1) were found in the US group. Compared with the AMRI group, there were more patients in the US group (18 vs. 9, p = 0.032) underwent dynamic imaging and/or biopsy. Curative treatments were performed for all patients with HCC. For compensated cirrhosis patients in the recommended US surveillance, hepatobiliary AMRI annually might reduce the frequency of HCC diagnostic tests.

Brain metastases (BM) among elderly patients with cancer are increasing, and decision-making for treatment is complicated by comorbidities. This study aimed to identify prognostic factors that can help make informed decisions regarding surgical resection in elderly patients with BM. We retrospectively included elderly patients (65 years or older) with newly diagnosed BM who underwent surgery. We conducted survival analyses and Cox regression analyses to identify potential independent predictors of poor survival. A total of 124 elderly patients with BM undergoing surgical resection were enrolled. In the multivariate analysis, male sex (HR: 1.96, 95% CI: 1.22-3.13), ECM (HR: 2.97, 95% CI: 1.82-4.85), BM in eloquent locations (HR: 1.64, 95% CI: 1.02-2.64), KPS deterioration (HR: 1.93, 95% CI: 1.20-3.10), and mFI-5 equal to or greater than 2 (HR: 2.10, 95% CI: 1.12-3.95) were associated with poor overall survival. Conversely, receiving systemic treatment after the diagnosis of BM showed a significant overall survival benefit (HR: 0.45, 95% CI: 0.28-0.70). Elevated SII (HR: 1.99, 95% CI: 1.02-3.90) was significantly associated with poor survival, while elevated PNI (HR: 0.56, 95% CI: 0.33-0.94) indicated better survival. Clinicians should adopt a personalized approach when selecting treatment options for elderly patients with BM, considering BM location, the presence of ECM, comorbidities, and suitability for postoperative systemic treatment. Evaluating preoperative nutritional and inflammatory status and monitoring performance status pre- and postoperatively are needed, as these factors may affect prognosis.