Interleukin-10 Modulates the Metabolism and Osteogenesis of Human Dental Pulp Stem Cells.

The osteogenic differentiation of mesenchymal stem cells (MSCs) is strongly related with the inflammatory microenvironment. The ability of osteogenic differentiation of MSCs is vital for the bone tissue engineering. Interleukin (IL)-10, a well-known anti-inflammatory factor, plays a key role in tissue repair. Dental pulp stem cells (DPSCs), with the advantage of convenience of extraction, are suitable for the bone tissue engineering. Therefore, it is meaning to explore the effects of IL-10 on the osteogenic differentiation of DPSCs. The proliferation activity of DPSCs were evaluated by MTS assay (CellTiter 96® Aqueous One Solution Cell Proliferation Assay [Promega]) and real-time polymerase chain reaction (RT-PCR). The osteogenic differentiation of DPSCs were determined by Alizarin Red staining, RT-PCR, and alkaline phosphatase activity test. The glucose metabolism was detected by Mito Stress test and glycolysis assay. IL-10 (10 or 20 nM) could enhance the osteogenic differentiation of DPSCs and promoted the metabolic switch from glycolysis to oxidative phosphorylation (OXPHOS), whereas IL-10 (5 and 50 nM) has no obvious effects on the osteogenic differentiation of DPSCs. The OXPHOS inhibitor restrained the promotion of osteogenic differentiation induced by IL-10. These findings show that IL-10 can promote the osteogenesis of DPSCs through the activation of OXPHOS, which provides a potential way for enhancing the osteogenic differentiation of DPSCs in bone tissue engineering.

Molecular mechanism of LKB1 in the invasion and metastasis of colorectal cancer.

The occurrence of colorectal cancer (CRC) is associated with a variety of oncogenes and tumor­suppressor genes. As a tumor­suppressor gene, the liver kinase B1 gene (LKB1, also known as serine/threonine kinase 11, STK11) is closely related to tumor angiogenesis, invasion and metastasis, but its molecular mechanisms remain unclear. The aim of the present study was to investigate the effects of LKB1 on the invasion and metastasis of CRC, and to explore its molecular mechanisms. By detecting the expression of LKB1 in CRC, we can provide a reference index for diagnosing the depth of invasion and lymph node metastasis. Immunohistochemistry results indicated that LKB1 expression was strongly positive in normal colon tissue and that it inhibited the production of CRC. Immunocytochemical staining showed that the expression of LKB1 was significantly decreased in adenocarcinoma and mucinous adenocarcinoma tissues, and this reduced expression induced the invasion and metastasis of CRC. In the present study, LKB1 small interfering RNA (LKB1 siRNA) was transfected into LoVo cells to observe the effect of LKB1 on the invasion and metastasis of CRC. LKB1 silencing decreased the phosphorylation of AMP­activated protein kinase (p­AMPK) in its downstream pathway, which increased the phosphorylation of protein kinase B (p­AKT) and promoted tumor cell proliferation, enhancing the migration and invasion of CRC. The present study also explored the role of metformin in the LKB1 signaling pathway. Metformin inhibits the invasion and metastasis of CRC by activating p­AMPK, thereby inhibiting the activation of p­AKT. These results suggest that LKB1 plays an important role in the invasion and metastasis of CRC by activating AMPK, negatively regulating the AKT signaling pathway and regulating gene expression. Mutation or deletion of LKB1 is expected to be a novel therapeutic target or clinical biomarker for the prevention of the invasion and metastasis of CRC.

Stress analysis of simulated maxillary first molar prepared with three rotary nickel-titanium instruments / 口腔疾病防治

Objective@# To compare the differences in the stress distribution in simulated first molars prepared with three rotary nickel-titanium instruments. @*Methods @#Four simulated first molars were prepared without instruments and with Reciproc, WaveOne and Protaper. Before and after preparation, each simulated molar was scanned by Micro-CT. The data were imported to Mimics 16.0 software to establish three-dimensional models. Finite element analysis was processed with Abaqus 6.14 software under conditions of longitudinal and lateral load. @*Results@# Under vertical load conditions, the maximum von Mises stress of the enamel increased by 1.36%, 21.48% and 20.99% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of the cementum increased by 55.98%, 41.18% and 33.04%, respectively, and the maximum von Mises stress of the alveolar bone increased by 45.55%, 40.37% and 24.09%, respectively. Under 45° lateral load conditions, the maximum von Mises stress of the enamel increased by 1.79%, -4.58% and 3.82% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of cementum increased by 16.33%, 7.58% and 4.32%, respectively, and the maximum von Mises stress of the alveolar bone increased by 46.82%, 36.40% and 8.29%, respectively. Under the same conditions, the von Mises stresses of the cementum and alveolar bones of the simulated molars were higher after preparation than before preparation, especially under lateral load conditions. The stress was focused on the border between the crown and the root. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups under both conditions.@*Conclusion@#The von Mises stress of simulated molars was greater after preparation than before preparation. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups.

Effects of silencing RIP1 with siRNA on the biological behavior of the LoVo human colon cancer cell line.

The present study aimed to investigate the effects of silencing RIP1 by small interfering RNA (siRNA) on the biological behavior of the LoVo human colorectal carcinoma cell line and to provide evidence for the feasibility of colorectal cancer gene therapy. LoVo cells were divided into the RIP1 siRNA group, the blank control group and the negative control group. Chemically synthesized siRNA targeting RIP1 (RIP1 siRNA) was transfected into LoVo cells. Following transfection of the RIP1-targeted siRNA into the LoVo cells, the expression of the RIP1 gene was effectively inhibited. The results demonstrated that RIP1 effectively regulated the malignant biological behavior of the LoVo colon cancer cell line. Furthermore, the proliferation, motility and invasiveness of LoVo cells were inhibited by siRNA knockdown of RIP1. The results revealed that the RIP1 gene has an important role in the regulation of proliferation and apoptosis in colorectal carcinoma cells.

Effects of paeonol on intracellular calcium concentration and expression of RUNX3 in LoVo human colon cancer cells.

Paeonol, a major phenolic component of the root bark of Paeonia moutan, is known to exhibit antitumor effects. However, the underlying mechanisms remain unknown. In the present study, the effects of paeonol on cell viability, intracellular calcium concentration and the expression of runt­related transcription factor 3 (RUNX3) were analyzed in LoVo human colon cancer cells. Results revealed that paeonol markedly reduced LoVo cell viability in a time­ and dose­dependent manner. Flow cytometry assays demonstrated that paeonol blocked the cell cycle at the G1 to S transition and significantly induced apoptosis in LoVo cells. Intracellular calcium accumulation occurred following a 48 h treatment with paeonol. Furthermore, RUNX3 gene expression was increased in paeonol­treated cells. These observations indicate that paeonol possesses antiproliferative properties and apoptosis­inducing activity. One of the antitumor mechanisms of paeonol may be its apoptosis­inducing activity through an increased intracellular calcium concentration and the upregulation of RUNX3 expression. Paeonol may be a promising antitumor agent for colon carcinoma treatment.