Lina Yu

Activation of the cGAS-STING pathway is a potential strategy to potentiate anti-tumor immunity. However, clinical translation of STING agonists such as cGAMP is hampered by poor targeting, enzymatic degradation, and systemic off-target toxicity. Nanocarrier-based drug delivery systems (nano-DDS) overcome these limitations by improving stability, bioavailability, and tumor-specific delivery. This review summarizes recent advances in lipid-based, polymeric, metallic, mesoporous silica, and exosomal for STING agonist delivery. These nanoplatforms enable precise drug delivery and controlled release, thereby significantly augmenting anti-tumor immune responses. We further discuss combination strategies of STING nanoagonists with radiotherapy, chemotherapy, phototherapy, and immune checkpoint inhibitors. Finally, we outline current challenges and future directions, including protein corona effects, scalable manufacturing, and personalized therapy.

Periodontitis is the most prevalent oral disease worldwide, leading to inflammation, alveolar bone loss, and tooth loss. Mesenchymal stem cells (MSCs) transplantation has the potential to alleviate periodontitis and restore alveolar bone, but numerous studies have found that transplanted MSCs undergo apoptosis, releasing apoptotic extracellular vesicles (ApoEVs). Human periodontal ligament stem cells (hPDLSCs) ApoEVs have immunomodulatory and tissue regenerative potential. Still, their role in periodontitis treatment and alveolar bone restoration has not been investigated yet. The study isolated hPDLSCs-ApoEVs and investigated the modulatory effect on macrophaghe. We explored the specific molecular mechanisms of hPDLSC-ApoEVs in regulating macrophage polarization in vitro through mRNA-seq and inhibitors. Co-culture experiment demonstrated that hPDLSC-ApoEVs promoted hPDLSC osteogenic differentiation by regulating macrophage polarization. Finally, we verified that hPDLSC-ApoEVs inhibited periodontitis-induced periodontal tissue defects and promoted periodontal bone tissue regeneration in vivo. This study found that hPDLSCs-ApoEVs regulate M0 to anti-inflammatory M2 macrophage polarization, as indicated by the upregulation of CD163, IL-10, and ARG1. hPDLSCs-ApoEVs activated NF-κB signaling that upregulated S100A9 in macrophages. hPDLSCs-ApoEVs failed M2 macrophage polarization during inhibition of NF-κB or S100A9. Furthermore, hPDLSCs-ApoEVs-treated macrophage-conditioned medium robustly promoted osteogenic differentiation of hPDLSCs in vitro. Finally, we verified these results in the periodontitis model of male C57BL/6 mice. Local injection of hPDLSCs-ApoEVs facilitated macrophage M2 polarization, alleviated periodontitis, and restored alveolar bone. In conclusion, these findings provide new evidence for the clinical application of hPDLSCs-ApoEVs in periodontitis treatment via macrophage immune modulation-mediated alveolar bone restoration.

Apoptotic extracellular vesicles (ApoEVs) derived from human dental pulp stem cells (hDPSCs) are subcellular structures released during programmed cell death. These vesicles carry rich biological information and regulatory potential, and have demonstrated significance in regulating cell behavior and tissue repair. Human periodontal ligament stem cells (hPDLSCs) are key to regenerating periodontal tissue, and their osteogenic differentiation ability directly influences the repair and reconstruction of periodontal bone tissue. However, the potential of ApoEVs derived from human dental pulp stem cells (hDPSCs-ApoEVs) to regulate the osteogenic differentiation of hPDLSCs remains unexplored. This study aims to investigate the effects of hDPSCs-ApoEVs on the osteogenic differentiation of hPDLSCs, offering new insights and methods for treating periodontal bone tissue injuries, with important scientific and clinical implications. hDPSCs-ApoEVs were isolated via ultracentrifugation and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and Western blot. In vitro, hPDLSCs were treated with hDPSCs-ApoEVs to determine whether the vesicles could enter hPDLSCs and to assess the proliferation, migration, and osteogenic potential of hPDLSCs. In vivo, a rat periodontal bone defect model was established, with local injections of hDPSCs-ApoEVs or PBS administered every other day. After 6 weeks, the maxillae were collected and analyzed using micro-CT and histological staining. In vitro, hDPSCs-ApoEVs promoted the migration and osteogenic differentiation of hPDLSCs. In vivo, treatment with hDPSCs-ApoEVs can enhance the recovery of periodontal bone defects in rats. hDPSCs-ApoEVs play a significant role in promoting bone regeneration, suggesting their potential as a promising cell-free therapeutic strategy for periodontal bone tissue regeneration.

Insulin-like growth factor-binding protein 5 (IGFBP5) is associated with nonalcoholic fatty liver disease (NAFLD). IGFBP5 has a higher binding affinity to IGF1 and modulates its effects in serum. However, the effect of exercise on its expression remains unclear. Hence, this study investigated whether exercise regulated hepatic and circulating IGFBP5 levels to ameliorate NAFLD. The NAFLD mice were regularly trained for 12 weeks on a treadmill at a 0% grade. Serum levels of IGFBP5, total IGF1, and free IGF1 were detected using proteome analyses and ELISA. Critical cytokines, such as IRS1, Akt, and AMPKα, and their phosphorylation levels mediated by IGFBP5/IGF1 were confirmed via Western blotting. The results indicated that exercise remarkably alleviated HFD-induced NAFLD and insulin resistance. Although exercise lowered serum IGFBP5 levels and the IGFBP5/total IGF1 ratio in NAFLD mice, it had no effect on the hepatic expression of IGFBP5, IGF1, and IGF1R. Moreover, exercise increased serum levels of free IGF1 in NAFLD mice, which, when bound to IGF1R, accelerated the phosphorylation levels of hepatic IRS1, Akt, and AMPKα to ameliorate NAFLD. The present study confirmed that exercise activated the effects of IGF1 by reducing the serum IGFBP5/IGF1 ratio, consequently triggering the IRS1/Akt/AMPK pathway to ameliorate HFD-induced NAFLD.

Pulmonary complications (PPCs) following mandibular fractures are serious post—surgery problems. This study analyzed risk factors of PPCs following mandibular fractures using the National Inpatient Sample (NIS) database, aiming to help clinicians specify surgical protocols and postoperative care for patients. A retrospective cohort study was conducted to examine patient demographics, hospital characteristics and preoperative comorbidities for identifying risk factors associated with postoperative pulmonary complications (PPCs). The analysis utilized data from the National Inpatient Sample (NIS) database containing patients undergoing mandibular surgery between 2010 and 2019. The cohort was stratified into two groups: those with PPCs and non-PPC cases. Statistical associations were evaluated through univariate and multivariate logistic regression analyses. A threshold of P ≤ 0.001 was set for statistical significance. The study included 41,984 adult patients (33,017 male; 8,967 female; aged ≥ 18 years), with 3,514 cases of postoperative pulmonary complications (PPCs) subclassified as: 1,347 pneumonia, 2,452 acute respiratory failure (ARF), and 212 pulmonary embolism (PE). For patients with PPCs, there was a significant increase in the age by 8 years, length of stay (LOS) by 12 days, the total charge (TOTCHG) by $163,579, and the mortality rate by 8.9%. Following the analysis, the following risk factors and their incidence were identified: number of comorbidities ≥ 3 (OR = 3.72, 40.4%), fluid and electrolyte disorders (OR = 2.66, 46.7%), obesity (OR = 1.38, 5.0%), congestive heart failure (OR = 1.24, 4.4%), coagulopathy (OR = 1.94, 12.4%), peripheral vascular disorders (OR = 1.53, 5.7%), pulmonary circulation disorders (OR = 7 .93, 4.1%), respiratory diseases (OR = 3.93, 5.2%), other neurological disorders (OR = 1.57, 15.2%), and paralysis (OR = 2.43, 5.0%). In this study, statistical methods were employed to identify the risk factors for pulmonary complications following mandibular fractures, which can aid in the establishment of a sound surgical procedure and postoperative care.

Objective To investigate the prevalence of deciduous dental caries in preschool children aged 36–71 months as well as the eruption and caries status of permanent teeth in children aged 60–71 months in Guangzhou city, providing references for oral health work. Design This study was a cross-sectional study design. Setting The study was conducted in 34 kindergartens in the central and non-central urban areas of Guangzhou city. Participants 14 883 preschool children aged 36–71 months in Guangzhou city were included in the ultimate analysis. Main outcome measures The prevalence of dental caries and other indicators of deciduous teeth, eruption and caries status of permanent teeth in children aged 60–71 months. Results The prevalence of dental caries in children aged 36–47 months, 48–59 months and 60–71 months were 41.6% (95% CI: 40.1%, 43.1%), 57.1% (95% CI: 55.8%, 58.5%) and 65.2% (95% CI: 64.0%, 66.4%), respectively. Mean decayed–missing–filled teeth increased with age, with differences between genders and areas. The percentage of permanent first molars and central incisors eruption in children aged 60–71 months differed, and caries conditions varied. Conclusion The problem of early childhood caries in preschool children in Guangzhou city is prominent. Prevention should be strengthened from early life, and oral health education and publicity enhanced to narrow regional oral health gaps.

Background: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare. Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites. Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites. Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.

Apoptosis, a form of programmed cell death, is essential for growth and tissue homeostasis. Apoptotic bodies (ApoBDs) are a form of extracellular vesicles (EVs) released by dying cells in the last stage of apoptosis and were previously regarded as debris of dead cells. Recent studies unraveled that ApoBDs are not cell debris but the bioactive treasure left behind by the dying cells with an important role in intercellular communications related to human health and various diseases. Defective clearance of ApoBDs and infected-cells-derived ApoBDs are possible etiology of some diseases. Therefore, it is necessary to explore the function and mechanism of the action of ApoBDs in different physiological and pathological conditions. Recent advances in ApoBDs have elucidated the immunomodulatory, virus removal, vascular protection, tissue regenerative, and disease diagnostic potential of ApoBDs. Moreover, ApoBDs can be used as drug carriers enhancing drug stability, cellular uptake, and targeted therapy efficacy. These reports from the literature indicate that ApoBDs hold promising potential for diagnosis, prognosis, and treatment of various diseases, including cancer, systemic inflammatory diseases, cardiovascular diseases, and tissue regeneration. This review summarizes the recent advances in ApoBDs-related research and discusses the role of ApoBDs in health and diseases as well as the challenges and prospects of ApoBDs-based diagnostic and therapeutic applications. Graphical Abstract