河北医科大学

Periodontal ligament stem cells (PDLSCs) are regarded as among the most promising seed cells for periodontal tissue regeneration because of their strong self-renewal ability, multipotent differentiation potential, and accessibility. However, their biological behaviors vary significantly under different microenvironments and stimuli, and the underlying regulatory mechanisms remain unclear. Recent advances have identified mitochondria as central signaling hubs that regulate cell fate. This review summarizes current progress in understanding the role of mitochondria in modulating the biological behaviors of PDLSCs, focusing on mitochondrial reactive oxygen species and oxidative stress, mitochondrial dynamics, mitophagy, glucose metabolic reprogramming, and tricarboxylic acid cycle metabolites. We integrate evidence linking mitochondrial function with key biological processes in PDLSCs, including osteogenic differentiation, senescence, inflammation, apoptosis, and regenerative capacity. Furthermore, we highlight major unresolved issues and challenges in current research and emphasize the significant "dual effects" of mitochondria-related signaling in diverse physiological and pathological conditions. A deeper understanding of mitochondrial regulatory networks in PDLSCs may provide a theoretical foundation for mitochondria-targeted precision therapies and reveal novel therapeutic strategies for periodontal tissue regeneration and related diseases.

With the acceleration of industrialization, mercury pollution in water bodies has become a severe threat to both the ecological environment and human health.The development of efficient and cost-effective technologies for mercury ion removal has become crucial. This study designed and synthesized a novel triazine-based porous organic polymer, TTIA, using cyanuric chloride and 2-aminoimidazole as monomers via a nucleophilic substitution reaction, with the aim of creating a high-performance Hg(II) adsorption material. Systematic characterization of the material’s structure and morphology confirmed that TTIA features a stable cross-linked network, a surface enriched with nitrogen-based active sites, and a mesoporous-dominated porosity (BET surface area: 34.82 ± 0.15 m2/g), which provides abundant binding sites and efficient mass transfer pathways for Hg(II) adsorption. Adsorption performance testing demonstrated that TTIA exhibits exceptional adsorption efficiency toward Hg(II) in aqueous solutions. Langmuir model fitting revealed a maximum adsorption capacity of 1545.2 mg/g (R2 = 0.989), significantly surpassing most reported adsorbents. Mechanistic analysis indicates that TTIA forms coordination bonds with Hg(II) through the lone pair electrons of nitrogen atoms in both the triazine ring and imidazole unit. The nitrogen-enriched region serves as the key active center.

OBJECTIVE:Endoscopic submucosal dissection (ESD) has become a first-line treatment for early esophageal cancer and precancerous lesions; however, non-curative resection (N-CR) occurs in a significant proportion of cases, necessitating additional surgical or chemoradiotherapy treatment. This study aimed to analyze the risk factors associated with N-CR following ESD and compare the efficacy of different secondary treatment strategies. METHODS:We conducted a retrospective analysis of 306 patients who underwent ESD for early esophageal lesions at The Fourth Hospital of Hebei Medical University between January 2017 and December 2021. Patients were divided into curative resection (CR) and non-curative resection (N-CR) groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for N-CR. A predictive nomogram model was constructed using R software. For the 49 patients with N-CR, we compared recurrence rates at 3 months, 1 year, and 2 years among three treatment strategies: no additional treatment (n = 22), surgical resection (n = 17), and chemoradiotherapy (n = 10). RESULTS:The overall N-CR rate was 16.0% (49/306). Multivariate analysis identified four independent risk factors for N-CR: gastroscopic pathology (OR = 0.186, 95% CI: 0.037-0.948, P = 0.043), depth of infiltration (OR = 0.012, 95% CI: 0.002-0.077, P < 0.001), lesion location (OR = 0.185, 95% CI: 0.038-0.890, P = 0.035), and gross morphological type (OR = 0.018, 95% CI: 0.002-0.209, P = 0.001). The nomogram demonstrated good predictive accuracy. The 2-year recurrence rates were 18.18% for the no-treatment group, 11.79% for the surgical group, and 10.00% for the chemoradiotherapy group. No significant differences in overall survival or disease-free survival were observed among the three groups (P > 0.05). CONCLUSIONS:ESD is a safe and effective treatment for early esophageal lesions. Gastroscopic pathology, depth of infiltration, lesion location, and gross type are independent predictors of N-CR. The predictive nomogram can assist clinical decision-making. Both surgical resection and chemoradiotherapy provide effective secondary treatment options for N-CR cases, with comparable oncological outcomes.

Severe asthma is characterized by persistent airway inflammation and epithelial injury. Pyroptosis, a Caspase-1–dependent inflammatory cell death pathway, has been implicated in airway inflammation. FBXW7, an E3 ubiquitin ligase involved in inflammatory regulation, may play a role in this process; however, its function in severe asthma remains unclear. Human microarray datasets from the Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes and potential biomarkers using bioinformatics and machine learning approaches. Experimental validation was performed using murine asthma models, including ovalbumin (OVA)-induced and OVA/LPS-induced models. Airway epithelium–specific FBXW7 conditional knockout mice were generated to assess in vivo function. In vitro, murine lung epithelial (MLE12) cells with FBXW7 knockout or overexpression were used to evaluate pyroptosis and inflammatory responses following LPS/ATP stimulation. Cytokine levels, Caspase-1 expression, and signaling pathways were analyzed using ELISA, Western blotting, and immunofluorescence. FBXW7 expression was significantly decreased in severe asthma compared with mild-to-moderate asthma, while Caspase-1 expression was increased. Machine learning analyses identified FBXW7 and Caspase-1 as potential biomarkers in severe asthma. In murine models, FBXW7 downregulation was more pronounced in severe asthma and was associated with increased inflammatory cell infiltration and cytokine production. FBXW7-deficient mice exhibited significantly elevated bronchoalveolar lavage fluid (BALF) inflammatory cell counts and increased IL-1β secretion compared with wild-type controls. In vitro experiments using MLE12 cell lines with FBXW7 overexpression, knockout, and wild-type backgrounds exhibited significant differences in Caspase-1 expression and altered secretion of inflammatory cytokines IL-18 and IL-1β under LPS/ATP-induced pyroptotic conditions, while pharmacological inhibition of Caspase-1 corrected aberrant cytokine secretion. However, mRNA levels of these cytokines remained stable, indicating that FBXW7 controls IL-18/IL-1β maturation/secretion via Caspase-1. Thus, the association among FBXW7, Caspase-1 and cGAS-STING was tested. FBXW7 suppresses airway epithelial pyroptosis and inflammation in severe asthma by regulating Caspase-1, potentially via the cGAS–STING pathway. These findings highlight FBXW7 as a potential biomarker for severe asthma.

Vascular calcification (VC) is highly prevalent and a significant cardiovascular risk factor in patients with chronic kidney disease (CKD). Secreted frizzled-related protein 1 (SFRP1) is a secreted glycoprotein closely associated with the Wnt/β-catenin pathway which plays a crucial role in bone formation, but its function and mechanism in VC remain unknown. Serum and radial artery tissues were collected from CKD patients with or without VC. The cellular model of VSMCs’ calcification was established under high-phosphate conditions in vitro. Western blot, qRT-PCR, and immunofluorescence were used to detect SFRP1 expression. The function of SFRP1 was identified by transfection with sh-SFRP1 and pCMV3-SFRP1 plasmid. Initially, bioinformatics analysis showed that SFRP1 expression was significantly elevated in high-phosphate-stimulated rat VSMCs. Subsequently, we discovered that the expression of SFRP1 was dramatically increased in the calcified arteries of CKD patients. Functionally, when SFRP1 was knocked down, the calcification process and the expression of Runx2 were attenuated. In contrast, SFRP1 overexpression exacerbated the β-GP-induced VSMCs’ calcification. Mechanistically, we confirmed the activation of Wnt/β-catenin signaling in the in vitro calcification model and this activation was inhibited by SFRP1 knockdown. Furthermore, when the Wnt/β-catenin signaling was enhanced with LiCl, the suppressing effect of SFRP1 knockdown on β-GP-induced osteogenic transdifferentiation of VSMCs was reversed, and calcification was promoted. We identified that SFRP1 promoted vascular calcification in CKD partly by regulating the Wnt/β-catenin/Runx2 axis, suggesting that SFRP1 may be a potential biomarker and therapeutic target for VC in CKD.