9 research outputs found
Proteomic and single-cell analysis shed new light on the anti-inflammatory role of interferonβ in chronic periodontitis
Periodontitis, a condition that results in periodontal attachment loss and alveolar bone resorption, contributes to the global burden of oral disease. The underlying mechanism of periodontitis involves the dysbiosis and dyshomeostasis between host and oral microbes, among which the macrophage is one of the major innate immune cell players, producing interferon β (IFNβ) in response to bacterial infection. The objective of this research was to examine the interaction of macrophages with periodontitis and the role and mechanism of IFNβ on macrophages. IFNβ has been shown to have the potential to induce the differentiation of M1 to M2 macrophages, which are stimulated by low levels of lipopolysaccharide (LPS). Additionally, IFNβ has been demonstrated to promote the production of ISG15 by macrophages, which leads to the inhibition of the innate immune response. Moreover, our investigation revealed that IFNβ has the potential to augment the secretion of ISG15 and its downstream cytokine, IL10, in LPS-stimulated macrophages. Single-cell analysis was conducted on the gingival tissues of patients with periodontitis, which revealed a higher proportion of macrophages in the periodontitis-diseased tissue and increased expression of IFNβ, ISG15, and IL10. Gene Set Enrichment Analysis indicated that bacterial infection was associated with upregulation of IFNβ, ISG15, and IL10. Notably, only IL10 has been linked to immunosuppression, indicating that the IFNβ-ISG15-IL10 axis might promote an anti-inflammatory response in periodontitis through IL10 expression. It is also found that macrophage phenotype transitions in periodontitis involve the release of higher levels of IFNβ, ISG15, and IL10 by the anti-inflammatory M2 macrophage phenotype compared to the pro-inflammatory M1 phenotype and myeloid-derived suppressor cells (MDSCs). This implies that the IFNβ-induced production of IL10 might be linked to the M2 macrophage phenotype. Furthermore, cell communication analysis demonstrated that IL10 can promote fibroblast proliferation in periodontal tissues via STAT3 signaling
Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway
Although substantial progress has been made in cancer biology and treatment, the prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory because of local tumor invasion and frequent lymph node metastasis. The tumor microenvironment (TME) is a potential target in which cancer-associated fibroblasts (CAFs) are of great significance due to their interactions with cancer cells. However, the exact mechanism is still unclear. Therefore, we focus on the crosstalk between cancer cells and CAFs and discover that CAFs are the main source of TGF-β1. Transwell assays and western blot analysis further prove that CAFs activate the TGF-β1/Smad pathway to promote OSCC invasion. Through survival analysis, we confirm that CAF overexpression is correlated with poor overall survival in OSCC. To further elucidate the origin and role of CAFs in OSCC, we analyze single-cell RNA sequencing (scRNA-seq) data from 14 OSCC tumor samples and identify four distinct cell types, including CAFs, in the TME, indicating high intratumoral heterogeneity. Then, two subtypes of CAFs, namely, myofibroblasts (mCAFs) and inflammatory CAFs (iCAFs), are further distinguished. Based on the differentially upregulated genes of mCAFs and iCAFs, GO enrichment analysis reveals their different roles in OSCC progression. Furthermore, the gene expression pattern is dynamically altered across pseudotime, potentially taking part in the transformation from epithelial to mCAFs or iCAFs through the epithelial to mesenchymal transition
Multihierarchically Profiling the Biological Effects of Various Metal-Based Nanoparticles in Macrophages under Low Exposure Doses
Thus
far, tremendous efforts have been made to understand the biosafety
of metal-based nanoparticles (MNPs). Nevertheless, most previous studies
focused on specific adverse outcomes of MNPs at unrealistically high
concentrations with little relevance to the National Institute for
Occupational Safety and Health (NIOSH) exposure thresholds, and failed
to comprehensively evaluate their toxicity profiles. To address these
challenges, we here endeavored to multihierarchically profile the
hazard effects of various popularly used MNPs in macrophages under
low exposure doses. At these doses, no remarkable cell viability drop
and cell death were induced. However, a cellular antioxidant defense
system was seen to be initiated in cells by all MNPs even at these
low concentrations, albeit to a differential extent and through different
pathways, as reflected by differential induction of the antioxidant
enzymes and Nrf2 signaling. Regarding inflammation, rare earth oxide
nanomaterials (REOs) except nCeO<sub>2</sub> greatly increased IL-1β
secretion in a NLRP3 inflammasome-dependent manner. By contrast, six
REOs, AgNP-5nm, nFe<sub>2</sub>O<sub>3</sub>, nFe<sub>3</sub>O<sub>4</sub>, and nZnO were found to elevate TNF-α concentration
through post-transcriptional regulation. Moreover, all MNPs except
nCeO<sub>2</sub> drastically altered cellular membrane/cytoskeleton
meshwork, but leading to different outcomes, with condensed cellular
size and reduced numbers of protrusions by REOs and elongated protrusions
by other MNPs. Consequently, REOs (e.g., nDy<sub>2</sub>O<sub>3</sub> and nSm<sub>2</sub>O<sub>3</sub>) impaired phagocytosis of macrophages,
and other MNPs (such as AgNP-25nm and nZnO) reversely enhanced macrophagic
phagocytosis. Alterations of membrane and cytoskeleton meshwork induced
by these MNPs also caused disordered membrane potential and calcium
ion flux. Collectively, our data profiled the biological effects of
different MNPs in macrophages under low exposure doses, and deciphered
a complex network that links multiparallel pathways and processes
to differential adverse outcomes
Photoluminescence and Electrical Properties of n-Ce-Doped ZnO Nanoleaf/p-Diamond Heterojunction
The n-type Ce:ZnO (NL) grown using a hydrothermal method was deposited on a p-type boron-doped nanoleaf diamond (BDD) film to fabricate an n-Ce:ZnO NL/p-BDD heterojunction. It shows a significant enhancement in photoluminescence (PL) intensity and a more pronounced blue shift of the UV emission peak (from 385 nm to 365 nm) compared with the undoped heterojunction (n-ZnO/p-BDD). The prepared heterojunction devices demonstrate good thermal stability and excellent rectification characteristics at different temperatures. As the temperature increases, the turn-on voltage and ideal factor (n) of the device gradually decrease. The electronic transport behaviors depending on temperature of the heterojunction at different bias voltages are discussed using an equilibrium band diagram and semiconductor theoretical model