The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression.

Dysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues. The conditioned medium co-culture model validated that Fn and macrophages exhibited tumor-promoting properties by facilitating OSCC cell proliferation, migration, and invasion. Besides, Fn and OSCC cells can recruit macrophages and facilitate their M2 polarization. This crosstalk between OSCC cells and macrophages was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL2 in response to Fn stimulation was a significant mediator. Suppression of CXCL2 in OSCC cells weakened Fn's promoting effects on OSCC cell proliferation, migration, macrophage recruitment, and M2 polarization. Conversely, knocking down CXCL2 in macrophages reversed the Fn-induced feedback effect of macrophages on the highly invasive phenotype of OSCC cells. Mechanistically, Fn activated the NF-κB pathway in both OSCC cells and macrophages, leading to the upregulation of CXCL2 expression. In addition, the SCC7 subcutaneous tumor-bearing model in C3H mice also substantiated Fn's ability to enhance tumor progression by facilitating cell proliferation, activating NF-κB signaling, up-regulating CXCL2 expression, and inducing M2 macrophage infiltration. However, these effects were reversed by the CXCL2-CXCR2 inhibitor SB225002. In summary, this study suggests that Fn contributes to OSCC progression by promoting tumor cell proliferation, macrophage recruitment, and M2 polarization. Simultaneously, the enhanced CXCL2-mediated crosstalk between OSCC cells and macrophages plays a vital role in the pro-cancer effect of Fn.

System-level biological effects of extremely low-frequency electromagnetic fields: an in vivo experimental review.

During the past decades, the potential effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health have gained great interest all around the world. Though the International Commission on Non-Ionizing Radiation Protection recommended a 100 µT, and then a 200 µT magnetic field limit, the long-term effects of ELF-EMFs on organisms and systems need to be further investigated. It was reported that both electrotherapy and possible effects on human health could be induced under ELF-EM radiation with varied EM frequencies and fields. This present article intends to systematically review the in vivo experimental outcome and the corresponding mechanisms to shed some light on the safety considerations of ELF-EMFs. This will further advance the subsequent application of electrotherapy in human health.

Carbon Monoxide-Releasing Molecule-3 Suppresses Tumor Necrosis Factor-α- and Interleukin-1ß-Induced Expression of Junctional Molecules on Human Gingival Fibroblasts via the Heme Oxygenase-1 Pathway.

Human gingival fibroblast barrier dysfunction caused by inflammation contributes to gingivitis and can lead to inflammatory periodontal disease. The disease features include upregulated epithelial permeability, increased inflammatory mediators, and downregulated junctional complex molecules. Carbon monoxide- (CO-) releasing molecule-3 (CORM-3) is a water-soluble compound that has demonstrated anti-inflammatory effects in in vitro and in vivo studies. In this study, we aimed to investigate the effects of CORM-3 on the expression of tight and adherens junction molecules on human gingival fibroblasts (HGFs) stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). HGFs were cultured from the explants of normal human gingival tissues, which were stimulated in the presence or absence of CORM-3. Epithelial barrier function was evaluated by paracellular permeability and junctional complex molecule expression analyses. The protein and mRNA expression levels of adherens junction molecules (VE-cadherin and ß-catenin) and tight junction molecules (zona occludens-1, ZO-1) were studied using western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-PCR). The mRNA and protein expression levels of these cytokines were also analyzed in HGFs transiently transfected with HO-1 small interfering RNA (siRNA) in response to TNF-α and IL-1ß stimulation. CORM-3 reduced permeability and enhanced the expression of junctional complex molecules (ZO-1, VE-cadherin, and ß-catenin) in TNF-α- and IL-1ß-induced HGFs. However, these effects of CORM-3 were attenuated when HO-1 siRNA was transiently transfected in HGFs. These findings indicate that CORM-3 exerts anti-inflammatory effects on TNF-α- and IL-1ß-stimulated HGFs via the HO-1 pathway, which suggests the promising potential of CORM-3 in the treatment of inflammatory periodontal disease.