Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages. Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition, and stability. The heterogenicity and plasticity of atherosclerotic macrophages have been a hotspot in recent years. Studies demonstrated that lipids, cytokines, chemokines, and other molecules in the atherosclerotic plaque microenvironment regulate macrophage phenotype, contributing to the switch of macrophages toward a pro- or anti-atherosclerosis state. Of note, M1/M2 classification is oversimplified and only represent two extreme states of macrophages. Moreover, M2 macrophages in atherosclerosis are not always protective. Understanding the phenotypic diversity and functions of macrophages can disclose their roles in atherosclerotic plaques. Given that lipid-lowering therapy cannot completely retard the progression of atherosclerosis, macrophages with high heterogeneity and plasticity raise the hope for atherosclerosis regression. This review will focus on the macrophage phenotypic diversity, its role in the progression of the dynamic atherosclerotic plaque, and finally discuss the possibility of treating atherosclerosis by targeting macrophage microenvironment.

An early and sustained immune response can lead to chronic inflammation after the implant is placed in the body. The implantable materials with immunomodulatory effects can reduce the body’s immune response and promote the formation of ideal osseointegration between the implants and bone tissue. In this study, zinc-coated titanium micro-arc oxide coating was prepared on titanium surface by micro-arc oxidation. The physical properties, anti-inflammation, and osteogenesis of the material were evaluated. We have physically characterized the surface structure of the coatings by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and atomic force microscopy (AFM) and detected the release of Zn 2+ from the coating surface by inductively coupled optical plasma emission spectrometry (ICP-OES). The BMSCs were inoculated on the surface of the coating, and the biocompatibility of the coating was evaluated by CCK-8 analysis and living and dead cell staining. The osteogenic effect of the layer on BMSCs was evaluated by alkaline phosphatase (ALP) assays, osteocalcin (OCN) immunofluorescence, and quantitative polymerase chain reaction (q-PCR). The survival status of RAW264.7 on the coating surface and the mRNA expression of the associated proinflammatory markers, tumor necrosis factor-α (TNF-α), cluster of differentiation 86 (CD86), and inducible nitric oxide (INOS) were detected by CCK-8 analysis and q-PCR. In parallel, the cell counting kit-8 (CCK-8) analysis and q-PCR screened and evaluated the effective concentration of Zn 2+ anti-inflammatory in vitro. The results show that the coating has good physical characterization, and Zn is uniformly bound to the surface of titanium and shows stable release and good biocompatibility to BMSCs, downregulating the expression of inflammation-related genes promoting the bone formation of BMSCs. We have successfully prepared zinc-coated micro-arc titanium oxide coating on the titanium surface, which has good osteogenesis and great anti-inflammatory potential and provides a new way for osseointegration in the implant.

MicroRNAs (miRNAs) are associated with the initiation and progression of oral squamous cell carcinoma (OSCC) by regulating a variety of cancer-associated behaviors. Fully understanding the regulatory mechanism of miRNAs in the pathogenesis of OSCC may provide novel promising approaches for the identification of prognostic biomarkers and therapeutic targets for this particular malignancy. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was performed to detect miRNA (miR)-495 expression in OSCC tissues and cell lines. The effects of miR-495 on the proliferation and invasion of OSCC cells were determined using Cell Counting Kit-8 and Matrigel invasion assays, respectively. The mechanisms underlying the action of miR-495 in OSCC cells were also investigated. Results from the present study revealed that miR-495 expression was downregulated in OSCC tissues and cell lines compare with in adjacent normal tissues and human oral keratinocytes, respectively. Exogenous expression of miR-495 restricted cell proliferation and invasion of OSCC cells in vitro. Notch1 was identified as a direct functional target of miR-495 in OSCC. Furthermore, Notch1 knockdown exhibited inhibitory effects, similar to those induced by miR-495 overexpression in OSCC cells. Restoration of Notch1 expression rescued the suppressive effects of miR-495 on OSCC cell proliferation and invasion. These findings suggested an important role for miR-495 in the regulation of OSCC cell growth and metastasis, at least partly by directly targeting Notch1. In addition, the findings of the present study revealed the potential of miR-495 as a novel therapeutic target for the treatment of patients with OSCC.

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)‑655‑3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR‑655‑3p associated with OSCC. Data from the present study indicated that miR‑655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR‑655 attenuated cell proliferation and invasion in OSCC in vitro. Metadherin (MTDH) mRNA was predicted as a potential target of miR‑655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR‑655 expression levels. MTDH overexpression reversed the inhibitory effects of miR‑655 mimics in OSCC cells. Notably, the upregulation of miR‑655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC‑α serine/threonine‑protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR‑655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR‑655 expression may be a novel therapeutic strategy for patients with OSCC.

Many observational studies have found that microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 are associated with esophageal cancer risk. However, the results were mixed and inconsistent among these studies. We conducted a meta-analysis to assess the relationship between the polymorphisms of three microRNAs and esophageal cancer susceptibility. We systematically searched the PubMed and EMBASE databases to screen relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to compute the risk of esophageal cancer. Because of the differences in ethnicities, sources of controls, and genotyping methods, the meta-analysis was conducted using a random-effect model regardless of heterogeneity. To further explore potential heterogeneity, we performed subgroup and sensitivity analyses, and publication bias was also evaluated. A total of 6 case-control studies on microRNA-196a2 rs11614913, 4 studies on microRNA-146a rs2910164, and 4 studies on microRNA-423 rs6505162 were considered eligible in the meta-analysis. No statistical association was found between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphisms and esophageal cancer susceptibility in any genetic model. Subgroup and sensitivity analyses showed similar results. In summary, based on the currently limited proof, no association exists between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphism and esophageal cancer risk. However, the result should be cautiously interpreted because of the heterogeneity among studies. Large, high quality clinical trials are required to verify our findings.