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Background/Aims: Although microRNA-301a has been reported to function as an oncogene in many human cancers, the roles of miR-301a in malignant melanoma (MM) is unclear. The present study aims to investigate the functional roles of miR-301a in MM and its possible molecular mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-301a in MM tissues, and analyze its correlation with metastasis and prognosis of MM patients. In vitro, miR-301a was ectopically expressed using overexpression and knock-down strategies, and the effects of miR-301a expression on growth, apoptosis, migration, invasion and chemosensitivity of MM cells were further investigated. Furthermore, the potential and functional target gene was identified by luciferase reporter, qRT-PCR, Western blot assays. Results: We showed that the expression of miR-301a was significantly upregulated in MM tissues, and upregulation of miR-301a correlated with metastasis and poor prognosis of MM patients. Transfection of miR-301a/inhibitor significantly inhibited growth, colony formation, migration, invasion and enhanced apoptosis and chemosensitivity in MM cells, while transfection of miR-301a/mimic could induce the inverse effects on phenotypes of MM cells. Luciferase reporter, qRT-PCR and Western blot assays showed that phosphatase and tensin homolog (PTEN) was a direct and functional target of miR-301a. It was also observed that the Akt and FAK signaling pathways were involved in miR-301/PTEN-promoting MM progression. Conclusion: Taken together, our study suggests that miR-301a may be used as a potential therapeutic target in the treatment of human MM. [ABSTRACT FROM AUTHOR]

Sodium Hypochlorite (NaOCl) and Ethylene Diamine Tetraacetic Acid (EDTA) can change the biochemical and biophysical properties of dentin. However, the response of human dental pulp stem cells (hDPSCs) to NaOCl and EDTA-treated dentin remains unknown. This study was conducted to investigate the effect of NaOCl and EDTA on cell proliferation, osteogenic/odontogenic differentiation, and the response to mechanosensitive gene expression in hDPSCs. Dentin slices were treated with 5.25% NaOCl, 17% EDTA, and saline (0.9% NaCl) separately. The cell viability and osteogenic/odontogenic differentiation of hDPSCs were analyzed using scanning electron microscopy, cell counting assay, alkaline phosphatase (ALP) staining, and quantitative polymerase chain reaction (qPCR). Besides, the hardness was measured by a Vickers microhardness tester. The expression of mechanosensitive genes was detected by the qPCR assay. All the irrigant-treated dentin allowed cell attachment. The EDTA-treated dentin significantly boosted the ALP and osteogenic/odontogenic differentiation, followed by NaCl and NaOCl groups. Remarkably, these trends were similar to the expression of mechanosensitive genes but were different from the trends of hardness values. The effect of irrigant-treated dentin on regulating hDPSCs differentiation might correlate with mechanosensitive signals. Whereas, the hardness changes between groups might not produce significant roles in regulating osteogenic/odontogenic differentiation of stem cells on dentin surfaces. • Irrigants used in clinical endodontics affected cell behaviors. • 17% EDTA-treated dentin enhanced ALP activity of hDPSCs during osteogenic/odontogenic differentiation. • 17% EDTA-treated dentin significantly improved osteogenic/odontogenic differentiation of hDPSCs compared to 5.25% NaOCl. • Biophysical property of irrigant-treated dentin might affect cellular mineralization. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine formula Lizhong Pill (LZP) and its herbal constituents are frequently utilized in Asian (China, Saudi Arabia, India, Japan, etc.) and some European (Russia, Sweden, UK, etc.) nations to treat various gastrointestinal ailments. This study aimed to investigate the protective impact and potential mechanism of LZP against indomethacin (IND)-induced gastric mucosal injury in rats. Using a biochemical kit, we investigated the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in rat serum, as well as pepsin in rat stomach tissue, using an IND-induced rat model of gastric mucosal injury. Various imaging tools, including HE staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to examine the gastric mucosa's surface morphology and ultrastructure. Furthermore, molecular docking was employed to predict the binding capacity of the primary bioactive components of LZP to the critical molecular protein targets in the IL-17 and TNF signaling pathways. At the same time, immunofluorescence was used to determine the protein expressions of CASP3, VCAM1, MAPK15, MMP3, IL-17RA, and TNFR1. The present study demonstrates that LZP (3.75 and 7.50 g/kg) significantly reduces the gastric mucosal injury index induced by IND. This effect is evidenced by the improved morphology, surface, and structure of the gastric mucosa, as determined by HE, SEM, and TEM findings. Additionally, 3.75 and 7.50 g/kg LZP intervention significantly increased SOD and CAT contents and inhibited pepsin and GST activities. Molecular docking analysis revealed that the small molecular components of LZP can bind spontaneously to crucial proteins involved in the IL-17 and TNF signaling pathways, including MAPK15, MMP3, VCAM1, and CASP3. The immunofluorescence findings proved that LZP (3.75 and 7.50 g/kg) can inhibit the protein expressions of MAPK15, MMP3, VCAM1, CASP3, IL-17RA, and TNFR1. Our investigation findings demonstrate that LZP can potentially ameliorate IND-induced damage to the gastric mucosa by inhibiting IL-17 and TNF signaling pathways. These results offer encouraging support for using alternative medicine to manage drug-induced gastric mucosal injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Dysregulation of microRNA-21 plays critical roles in tumor initiation and progression. The purpose of this study was to investigate the status of microRNA-21 expression in human cutaneous malignant melanoma and determine its clinical significance. TaqMan® real-time RT-PCR assay was performed to examine the expression of microRNA-21 in 10 cases of dysplastic nevi, 86 cases of primary cutaneous melanomas, 10 cases of melanoma metastases. The correlation of microRNA-21 expression with clinicopathological factors or prognosis of patients with cutaneous melanoma was statistically analyzed. Additionally, the effects of microRNA-21 expression on growth, apoptosis and chemo- or radiosensitivity of melanoma cells were also investigated by transfection of microRNA-21 inhibitor. We firstly showed that increased levels of microRNA-21 expression were shown from dysplastic nevi to primary cutaneous melanomas to melanoma metastases. Moreover, high miR-21 expression was found to be correlated with Breslow thickness and advanced clinical stage. Patients with high microRNA-21 expression showed shorter 5-year disease-free or overall survival than those with low microRNA-21 expression. Furthermore, multivariate regression analysis showed that the status of microRNA-21 expression was an independent prognostic factor for overall survival of patients. Antisense-mediated microRNA-21 inhibition could significantly suppress growth, increase apoptosis and enhance chemo- or radiosensitivity of human cutaneous melanoma cells by inducing the increased Bax/Bcl-2 ratio. Thus, the status of microRNA-21 might be an independent prognostic factor for patients with cutaneous melanoma, and microRNA-21 has the potential of being a novel molecular target for the treatment of human cutaneous melanoma. [Copyright &y& Elsevier]