Zhejiang Cancer Hospital

Peri-implantitis represents a prevalent and significant biological challenge in oral implantology, and its etiology remains incompletely understood. The critical role of titanium particles in the progression of peri-implantitis has been largely overlooked, and a deeper understanding of their pathogenic mechanisms is essential for advancing biomaterial-based interventions. In this study, clinical samples were collected and cellular assays performed, along with the modified establishment of a titanium particle-induced animal model of peri-implantitis, to investigate the inflammatory mechanisms triggered by titanium particles. Results showed significantly elevated levels of titanium particles at diseased sites. Transcriptomic analysis revealed upregulation of inflammatory and osteoclast-related pathways and downregulation of osteogenic signaling. Further in vitro validation demonstrated that titanium particles under stimulatory conditions exacerbate inflammatory responses via hyperactivated autophagy. This study elucidates how titanium particles promote inflammation by modulating macrophage autophagy, highlighting their critical role in peri-implantitis and underscore the importance of targeting biomaterial-derived particles in future implant design and therapeutic strategies.

Asthma is a chronic inflammatory airway disease characterized by airway remodeling and hyperresponsiveness, driven in part by TGF-β1-induced epithelial-mesenchymal transition (EMT). The natural compound 1,8-cineol, derived from Eucalyptus globulus, has shown anti-inflammatory potential. This study aimed to investigate its protective effects against EMT and airway inflammation via the NF-κB/COX-2 pathway. In vivo, ovalbumin-sensitized BALB/c mice were treated with 1,8-cineol (50 mg/kg) to evaluate airway resistance, lung compliance, and inflammatory markers (IgE, IL-4, IL-13, IL-17). Histopathological changes were assessed via H&E and PAS staining. In vitro, TGF-β1-stimulated BEAS-2B cells were treated with 1,8-cineol to analyze EMT markers (α-SMA, E-cadherin, N-cadherin), migration capacity, and NF-κB/COX-2 signaling using RT-qPCR, Western blotting, and transwell assays. 1,8-cineol significantly attenuated airway hyperresponsiveness and reduced EMT markers (α-SMA, N-cadherin) in OVA-sensitized mice, while improving lung compliance. In BEAS-2B cells, it suppressed TGF-β1-induced EMT and migration without cytotoxicity. Mechanistically, 1,8-cineol downregulated NF-κB phosphorylation and COX-2 expression. OVA challenge elevated serum IgE and BALF cytokines (IL-4, IL-13, IL-17), which were mitigated by 1,8-cineol. 1,8-cineol inhibits TGF-β1-driven EMT and airway inflammation by modulating the NF-κB/COX-2 pathway, highlighting its therapeutic potential for asthma.

BackgroundPapillary thyroid carcinoma (PTC), the most common thyroid malignancy, shows marked clinical heterogeneity despite generally favorable outcomes. Lysosome-dependent cell death (LDCD), a form of programmed death triggered by lysosomal membrane permeabilization, has emerged as a potential cancer therapy target, but its role in PTC remains unclear.MethodsTranscriptomic data from public cohorts were analyzed to identify LDCD-related genes (LDCDRG) associated with PTC prognosis. Cox analysis and LASSO regression analyses were performed to construct a prognostic model. Immune landscape, drug sensitivity, and single-cell expression profiles were examined. Functional experiments were conducted in vitro to verify the biological effects of the key gene LMTK3 on PTC cell proliferation, viability, and invasion.ResultsNineteen LDCDRG were differentially expressed between normal and tumor tissues, defining three molecular subtypes with distinct immune and prognostic profiles. A six-LDCDRG signature (LMTK3, MCM5, NXF1, TUBB4B, LIMCH1 and APH1B) effectively stratified patients into high- and low-risk groups with significantly different survival outcomes and acceptable predictive performance. High-risk patients showed reduced immune infiltration and lower predicted immunotherapy-related immune activity. LMTK3, the highest-risk gene, was highly expressed in PTC cells, and its knockdown suppressed proliferation and invasion in vitro.ConclusionsThe established six-LDCDRG signature provides an exploratory tool for risk stratification and survival prediction, while LMTK3 emerges as potential target worthy of further investigation. These findings deepen our understanding of lysosome-dependent cell death in thyroid carcinogenesis and may provide insights into the development of personalized management strategies and novel treatment approaches for high-risk PTC patients.

Background: The value of radical prostatectomy (RP) in large volume and unresectable locally advanced prostate cancer (LAPC) or oligometastatic prostate cancer (OMPC) is largely unknown. This retrospective study aims to evaluate the conversion efficacy and safety profile of preoperative androgen deprivation therapy combined with docetaxel (A + D) in patients with large-volume (≥60 mL) and initially unresectable LAPC or OMPC. Methods: Patients with LAPC or OMPC from three large tertiary medical centers (between April 2017 and October 2024) were included. Eligibility criteria included prostate volume ≥60 mL, unresectability, and an expected survival of more than 5 years, as confirmed by two senior urologists and one radiologist. All patients received preoperative A + D therapy (≥3 cycles), followed by reassessment for RP feasibility with multimodal therapy discussion. The primary endpoint was surgical conversion rate. Secondary endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), overall survival (OS), PSA response rate, adverse events, pathological response, perioperative complications, urinary continence, and sexual function. Results: Among 31 enrolled patients, the mean age was 67.71 ± 6.69 years, and 29 (93.55%) successfully underwent RP. The mean follow-up duration was 42.83 ± 23.58 months (up to October 2024). Median PSA-PFS was 49 months (95% CI: 24.20–73.79 months), and median OS was not reached. Hematologic toxicity was the most common adverse event during chemotherapy. After A + D therapy, median prostate tumor volume decreased from 67.50 mL to 25.81 mL, and median PSA declined from 168 to 0.49 ng/mL. After RP, 11 patients (37.93%) experienced a downgrade in Gleason score, and 14 patients (48.28%) experienced a downgrade in T-stage. Positive surgical margins were found in 11 patients (37.93%). Perioperative complications included blood transfusion (11.11%), rectal injury (3.70%), lymphorrhea (7.41%), and fever >38.5°C (3.70%). The 1-year urinary continence rate was 89.66%, while 100% of patients experienced sexual dysfunction. Conclusion: Preliminary data suggest that preoperative A + D therapy followed by RP may be integrated into multimodal management for large-volume, initially unresectable LAPC and OMPC, demonstrating promising conversion efficacy and clinical outcomes.

Bone regeneration of oral and maxillofacial defects in situ remains a significant clinical challenge. This study investigates the synergistic effects of phosphorus (P) and zinc (Zn) co-doping in wollastonite bioceramics to enhance osteogenic activity and antibacterial potential for bone repair. Cylindrical bioceramic granules with varying P/Zn ratios (CSi-P8: CSi-Zn6 = 3:0, 2:1, 1:2 and 0:3) were fabricated via co-precipitation and evaluated for in-vitro bioactivity, cell proliferation, osteogenic differentiation, and antibacterial performance. The experimental results demonstrated that the co-doped groups (8P/6Zn-2:1 and 8P/6Zn-1:2) exhibited superior hydroxyapatite formation in simulated body fluid (SBF), sustained Ca²⁺/Si⁴⁺ ion release, and synergistic osteogenic effects, as evidenced by elevated RUNX2/β-catenin expression and BMSC proliferation. Zn doping conferred dose-dependent antibacterial activity against Staphylococcus aureus (93% inhibition for 8P/6Zn-0:3). In vivo cranial defect experiments in rabbits revealed that the 8P/6Zn-2:1 granules significantly promoted new bone trabeculae formation and defect closure within 16 weeks, outperforming single-doped and control groups. Histological and micro-CT analyses confirmed enhanced bone volume fraction (BV/TV%) and trabecular density (Tb.N) in the co-doped groups. These findings highlight the dual functionality of P/Zn co-doped wollastonite (e.g. 8P/6Zn-2:1), where P enhances osteogenesis via increasing the expression of RUNX2/β-catenin and apatite deposition, while Zn provides antibacterial protection, offering more promising implants for infected oral bone defects.