Background/purpose: Increasing evidence suggests that single-nucleotide polymor-phisms (SNPs) in Th1/Th2-related cytokine genes correlated with oral lichen planus (OLP) sus-ceptibility. However, these results were inconsistent and inconclusive. Hence, the aim of this study is to draw a more precise estimation of the genetic associations between SNPs in 6 cy-tokines (IFN-g, IL-18, TGF131, IL-113, IL-2, IL-4) and OLP.Materials and methods: A systematic literature search was conducted to identify all eligible case-control studies on the association between SNPs in 6 cytokines and OLP susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association.Results: A significant association of IFN-g (874A/T) polymorphism with OLP was found (OR, 1.49; 95%CI, 1.22-1.81; P < 0.001) based on 6 eligible studies. A significant association of IL-18 (137G/C) polymorphism with OLP was found (OR, 1.64; 95%CI, 1.24-2.18; P < 0.001) based on 3 studies. A marginally significant association of TGFb1 (509C/T) polymorphism in allele model with OLP was found (OR, 1.31; 95%CI, 1.01-1.71; P Z 0.05) based on 4 studies. Nevertheless, lack of significant association of IL-1b (3954C/T), IL-2 (330T/G), IL-4 (590C/T), and IL-18 (607C/A) polymorphisms with OLP was found (P > 0.05) based on 3 studies, respec-tively.Conclusion: This is the first meta-analysis to investigate the associations of 6 cytokines poly-morphisms with OLP, suggesting that SNPs in IFN-g, IL-18, and TGFb1 may act as genetic factors for OLP risk. Further well-designed studies with larger sample size and multiple ethnicities are needed to validate these associations.(c) 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

BACKGROUND:Cervical cancer the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020 for high rates of recurrence and metastasis. Identification of novel targets could aid in the prediction and treatment of cervical cancer. NADPH oxidase 1 (NOX1) gene-mediated production of reactive oxygen species (ROS) could induce migration and invasion of cervical cancer cells. Tumor-associated macrophages (TAMs) play important roles in cervical cancer. Tumor cell-derived exosomes mediate signal transduction between the tumor and tumor microenvironment. Elucidation of the mechanisms of NOX1-carrying exosomes involved in the regulation of TAMs may provide valuable insights into the progression of cervical cancer.METHODS:Uniformly standardized mRNA data of pan-carcinoma from the UCSC database were downloaded. Expression of NOX1 in tumor and adjacent normal tissues for each tumor type was calculated using R language software and significant differences were analyzed. SNP data set were downloaded for all TCGA samples processed using MuTect2 software from GDC. Cell experiment and animal tumor formation experiment were used to evaluate whether exosomal NOX1 stimulating ROS production to promote M2 polarization of TAM in cervical cancer.RESULTS:NOX1 is highly expressed with a low mutational frequency in pan-carcinoma. Upregulation of NOX1 may be associated with infiltration of M2-type macrophages in cervical cancer tissues, and NOX1 promotes malignant features of cervical cancer cells by stimulating ROS production. Exosomal NOX1 promotes M2 polarization of by stimulating ROS production. Exosomal NOX1 enhances progression of cervical cancer and M2 polarization in vivo by stimulating ROS production.CONCLUSION:Exosomal NOX1 promotes TAM M2 polarization-mediated cancer progression through stimulating ROS production in cervical cancer.

Periosteum is indispensable in bone repair and is an important source of skeletal stem cells (SSCs) for endogenous bone regeneration. However, there are only a few studies about SSCs in periosteum. The craniomaxillofacial bone regeneration is done under the hypoxia microenvironment, in which HIF-1α plays an important role. The effect of HIF-1α on periosteum-derived stem cells (PDSCs) and the mechanisms of PDSCs activation under hypoxia conditions are unknown. In this study, the calvarial bone defect was established, with the periosteum removed or retained. Results show that the bone regeneration was severely impaired in the periosteum removed group. Moreover, pluripotent PDSCs isolated from the periosteum were positive for mesenchymal stem cell (MSC) markers. To determine the role of HIF-1α, the expression of HIF-1α was knocked down in vivo and in vitro, impairing the bone regeneration or osteogenesis of PDSCs. Furthermore, the knockdown of HIF-1α expression also reduced periostin (POSTN) expression, and recombinant POSTN addition partly rescued the osteogenic inhibition. Finally, to explore the mechanism under POSTN activation, the phosphorylation level of the PI3K/AKT pathway was assessed in transfected PDSCs. The phosphorylation level of PI3K and AKT was enhanced with HIF-1α overexpression and inhibited with HIF-1α knockdown, and the addition of PI3K activator or AKT activator could partly rescue POSTN expression. In conclusion, as a potential target to promote bone repair under the hypoxia microenvironment, HIF-1α can regulate the osteogenic differentiation of PDSCs via the PI3K/AKT/POSTN pathway, which lay a solid foundation for periosteum-based craniomaxillofacial bone regeneration.