Qianming Chen

Chronic exposure to severe social and environmental stressors is a major risk factor for tumor initiation and progression, yet the central nervous system (CNS)-driven mechanisms linking stress to cancer immunity remain poorly defined. Here, we identify activation of the hypothalamic-pituitary-bone marrow (HPB) axis as a critical driver of oral squamous cell carcinoma (OSCC). Chronic stress activates hypothalamic paraventricular nucleus (PVN) neurons, inducing pituitary overexpression of POMC and aberrant secretion of α‑MSH. This neuroendocrine activation increases the frequency of PMN-MDSCs in the bone marrow and upregulates the chemokine CXCL13 in the tumor microenvironment. Mechanistic studies show that this stress-responsive neuroendocrine circuit remodels the tumor immune microenvironment by promoting PMN-MDSC recruitment, suppressing CD8⁺ T cell infiltration, and skewing macrophages toward an M2 phenotype, collectively establishing profound immunosuppression. Chronic stress further amplifies this axis, accelerating OSCC progression and recurrence. Therapeutic blockade of MC5R restores antitumor immune surveillance and markedly potentiates PD-1 checkpoint inhibition. These findings delineate a previously underappreciated neuro-immune regulatory pathway governing malignant progression and highlight a tractable target for improving immunotherapy efficacy in stress-associated cancers.

Cementum shares similar characteristics with bone in terms of biochemical composition. Recent studies have reported that glycolysis is the main energy source driving osteoblast differentiation, but the role of glycolysis in cementoblast differentiation remains elusive. Previously, we found Sirtuin 6 (SIRT6) suppressed cementoblast differentiation and mineralization via inhibiting glucose transporter 1 (GLUT1), indicating that glycolysis may also be required for cementogenesis. However, the underlying mechanisms remain largely unknown. In this study, we observed that the expression of glycolytic enzymes increased progressively during cementoblast differentiation. Measurements of extracellular acidification rate, glucose uptake, lactate release, and gain‐and‐loss of function demonstrated that overexpressing SIRT6 in immortalized mouse cementoblasts (OCCM‐30) suppressed cementoblast glycolysis. Mechanistically, chromatin immunoprecipitation assay results revealed that SIRT6 inhibits insulin receptor substrate 2 (IRS2) transcription by deacetylating histone H3 at lysine K9 (H3K9). Overexpression of IRS2 promoted OCCM‐30 glycolysis and mineralization through phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway, whereas SIRT6 significantly inhibited PI3K/AKT pathway activity. Overall, our results demonstrate that SIRT6 inhibits IRS2 transcription by deacetylating histone H3K9, thereby reducing PI3K/AKT signaling‐induced glycolysis and suppressing cementoblast mineralization.

Objective: Sleep regulates immune and inflammatory processes and may influence periodontal health, though evidence remains inconsistent. This meta‐analysis evaluated the association between sleep characteristics, including sleep quality and sleep duration, and periodontal disease (PD). Methods: Systematic searches up tos May 2025 identified eligible studies. Sleep‐related exposures were assessed using validated questionnaires or sleep duration (< 7 h); periodontal outcomes were defined by clinical examination or self‐report. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed or random effects model, depending on heterogeneity. Results: Fourteen studies ( n = 126,425) met inclusion criteria, of which nine ( n = 55,524) provided adjusted odds ratios for meta‐analysis. Six assessed questionnaire‐based sleep quality and three assessed sleep duration alone. Across these heterogeneous exposure definitions, adverse sleep characteristics were associated with greater odds of PD (OR = 1.25; 95% CI: 1.11–1.41; p < 0.001, I ² = 53.8%). Sensitivity analyses showed no substantial change in the pooled estimate, and no statistically significant evidence of publication bias was detected. Conclusions: Adverse sleep characteristics were associated with greater odds of PD, with a stronger association observed for severe periodontitis in subgroup analysis. However, the certainty of evidence was very low, and prospective studies are warranted to clarify causality

Background: Aurora Kinase A (AURKA), a highly conserved and potent kinase, is frequently overexpressed in diverse cancers. However, its role in the malignant transformation (MT) of oral mucosa remains poorly understood. This study investigated the expression pattern of AURKA and evaluated the therapeutic potential of its inhibitor in oral leukoplakia (OLK), the most representative oral potentially malignant disorder. Methods: Immunohistochemistry was performed on clinical samples (21 normal controls, 27 OLK, 23 MT of OLK) to examine AURKA expression and its correlation with clinicopathological characteristics. The inhibitory effect of targeting AURKA on tumor proliferation was verified in vitro using two oral squamous cell carcinoma (OSCC) cell lines. Additionally, the chemopreventive effect of the AURKA inhibitor Alisertib on MT was assessed using a 4‐nitroquinoline oxide (4NQO)–induced mouse OLK model. Results: AURKA expression levels positively correlated with the malignant progression of OLK. Significantly higher AURKA expression percentages were observed in non‐homogeneous lesions (10.39% ± 4.28% vs. 3.53% ± 4.22% homogeneous, p < 0.001), lesions ≥ 2 cm ² (11.19% ± 4.55% vs. 4.69% ± 4.36% < 2 cm ² , p < 0.01), and lesions with high‐risk dysplasia (12.10% ± 4.04% vs. 4.59% ± 4.12% low‐risk dysplasia, p < 0.001). Targeting AURKA significantly inhibited the proliferation of OSCC cells in vitro. Furthermore, Alisertib treatment effectively suppressed oral mucosa carcinogenesis in the 4NQO model. Conclusion: Increased AURKA expression may represent an early molecular event in OLK carcinogenesis, and targeting AURKA with alisertib is a candidate for potential applications in the management of OLK.

Oral submucous fibrosis (OSF) is a chronic, progressive, premalignant disorder with expanding epidemiology, rising annual incidence, and increasing malignant transformation rates. Therefore, elucidating its pathogenesis and establishing early intervention strategies remain urgent priorities. In this study, we evaluated the interplay between USP10 and IL‐6 and its potential influence on the development of oral submucous fibrosis. Immunohistochemistry and immunofluorescence were used to examine the correlation among IL‐6, USP10, and pathological angiogenesis in OSF clinical samples and mouse models, revealing high IL‐6 expression in the inflammatory microvasculature alongside downregulated USP10. Functional experiments on human umbilical vein endothelial cells (HUVECs) in vitro, including administration of recombinant human IL‐6, demonstrated that USP10 inhibited angiogenesis, cell migration, and cell proliferation, and that targeting USP10 reversed IL‐6‐mediated pathological angiogenesis. RNA sequencing further identified differentially expressed genes in HUVECs, while mass spectrometry, western blotting, and co‐immunoprecipitation uncovered that USP10 interacts with vascular endothelial growth factor receptor 1 (VEGFR1) and inhibits its ubiquitination, thereby suppressing angiogenesis. Collectively, these findings indicate that IL‐6 promotes pathological angiogenesis by suppressing USP10 and its interaction with VEGFR1, thus accelerating OSF progression, and suggest that targeting USP10 may represent a promising mechanism for further investigation in OSF therapy.

Background: Head and neck squamous cell carcinoma (HNSCC) faces challenges with limited immune checkpoint inhibitors (ICIs) efficacy. This study identifies NLRX1, highly expressed in HNSCC tumor cells, as a key driver of immune evasion and ICIs’ resistance. Methods: This study investigated the role of NLRX1 in HNSCC immune evasion and ICIs resistance. We performed retrospective analyses on patient cohorts to correlate NLRX1 expression with clinical outcomes. Bioinformatic analyses and immunofluorescence staining of human HNSCC tissues were employed to assess associations between immune cell infiltration, gene expression correlations and PD-L1 levels on antigen-presenting cells (APCs). In vitro experiments were conducted to investigate the regulatory role of NLRX1 on cell proliferation and gene expression profiling by overexpressing or knocking down NLRX1. In vivo studies of subcutaneous tumor models in both immunodeficient and immunocompetent mice were utilized to assess the function of NLRX1 on tumor progression. Results: The expression NLRX1 is correlated with unfavorable patient outcomes. NLRX1 promotes tumor progression by modulating the immune microenvironment, not directly affecting tumor cell proliferation. Mechanistically, NLRX1 suppresses the type I interferon (IFN-I) pathway by inhibiting STING expression in HNSCC. Notably, tumor cell-intrinsic NLRX1 negatively correlates with PD-L1 expression on APCs in HNSCC. In vivo , NLRX1 knockdown activated STING-IFN-I signaling, upregulated APC PD-L1, suppressed tumor growth, and significantly boosted anti-PD-L1 therapy in murine tumor models. Conclusions: NLRX1 mediates immune evasion in HNSCC by downregulating STING protein abundance, suppressing the IFN-I pathway, and decreasing PD-L1 expression of APCs. Targeting NLRX1 offers a promising strategy to overcome ICI resistance and improve immunotherapeutic efficacy in HNSCC.

The aging of mesenchymal stromal cells (MSCs) is characterized by impaired osteogenic differentiation and enhanced adipogenic differentiation. Studies have identified stanniocalcin‑1 (STC1) as a core component of the senescence‑associated secretory phenotype and a regulator of osteoblast maturation; however, its role in MSC biology remains poorly understood. In the present study, bone marrow‑derived MSCs were used and in vitro functional assays together with molecular and omics‑based analyses were performed to investigate the role of STC1. It was observed that STC1 expression was upregulated in aged MSCs and during both osteogenic and adipogenic differentiation. Small interfering RNA‑mediated depletion of STC1 reduced cellular senescence and notably impaired osteogenic differentiation, whereas adipogenic and chondrogenic differentiation were not significantly affected. RNA sequencing revealed that STC1 knockdown led to the downregulation of osteogenesis‑related genes and the concomitant upregulation of inflammatory factors. Genes associated with closing differentially accessible regions (DARs) were enriched in osteogenic pathways, whereas those associated with opening DARs were predominantly involved in inflammatory responses. Mechanistically, STC1 knockdown led to the activation of NF‑κB signaling. Pharmacological inhibition assays using NF‑κB inhibitors were performed to validate pathway involvement. Pharmacological inhibition of NF‑κB signaling significantly mitigated the impairment in osteogenic differentiation and attenuated the inflammatory response induced by STC1 depletion. Collectively, these findings suggest that STC1 is involved in the regulation of osteogenic differentiation and inflammatory signaling through the modulation of NF‑κB activity in MSCs. Furthermore, targeting STC1 while inhibiting NF‑κB signaling may represent a promising therapeutic strategy for alleviating MSC dysfunction and age‑related bone loss.