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Prunella vulgaris, a traditional Chinese medicine, has been used to treat various benign and malignant tumours for centuries in China. In our previous studies, Prunella vulgaris extract (PVE) was shown to promote apoptosis in differentiated thyroid cancer (DTC) cells. However, whether other mechanisms are involved in the antitumour effect of PVE in thyroid cancer (TC) cells remains unclear. The present study aimed to investigate the antiproliferative and antimigratory effects of PVE on TC cell lines both in vitro and in vivo. First, the TPC-1 and SW579 human TC cell lines were screened by MTT assay for their high level of sensitivity to PVE. Then, the results of cell growth curve and colony formation assay and cell cycle analyses, wound healing, and migration assays demonstrated that PVE inhibited the proliferation and migration of TPC-1 and SW579 cells. Moreover, the antitumour effect of PVE was verified in a subcutaneous xenotransplanted tumour model. Next, MKI67, PCNA, CTNNB1, and CDH1 were screened by qRT-PCR for their significantly differential expression levels in xenograft tissue with and without PVE treatment, and expression of MKI67, PCNA, and CDH1 was verified by Western blot. Finally, an integrated bioinformatics analysis containing protein-protein interaction network, KEGG pathway, and GO analysis was conducted to explore more potential antitumour mechanisms of PVE. In summary, PVE could inhibit the proliferation and migration of TC cells both in vitro and in vivo, which may have been achieved by modulation of the expression of MKI67, PCNA, and CDH1. These data suggest that PVE has the potential to be developed into a new anticancer drug for the treatment of TC. [ABSTRACT FROM AUTHOR]

This study aims to investigate the levels of SLIT3 in gingival crevicular fluid (GCF) of healthy and periodontal disease subjects, and their correlations to periodontal disease. A total of 45 periodontal patients and 45 periodontally healthy volunteers were enrolled. The clinical parameters, radiographic bone loss and the levels of SLIT3, receptor activator of NF‐κB ligand (RANKL) and osteoprotegerin (OPG) in GCF were measured. The prevalences of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in subgingival plaque were also analyzed. The expression of SLIT3 and RANKL was detected in the periodontium of experimental periodontitis in rats and lipopolysaccharide (LPS)‐induced mouse macrophage. The total amounts and concentrations of SLIT3 and RANKL were significantly higher in periodontitis than those in healthy, while the level of OPG was significantly lower (p <.05). Significant positive correlations were observed between the level of GCF SLIT3 and clinical attachment level and radiographic bone loss (p <.05). There existed a significant positive correlation between SLIT3 and RANKL (p <.05). Increased expression of SLIT3 and RANKL was observed in the periodontium of periodontal rats. SLIT3 expression was induced by LPS stimulation in macrophages. These results suggest that SLIT3 may act as a diagnostic indicator of periodontal disease and should be further investigated. [ABSTRACT FROM AUTHOR]

FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, that has shown strong antiproliferative activity in human lymphoma, lung adenocarcinoma and acute myeloid leukemia. In this study, we investigated the effects of FNC on mantle cell (MCL) and the underlying mechanisms. In in vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle progression and apoptosis were assessed by flow cytometry, and the expression of relative apoptosis proteins were detected by Western Blot. The in vivo antitumor effect of FNC was investigated in a SCID xenograft model. Finally, the mechanisms of action of FNC were assessed using a whole human genome expression profile chip. The data showed that FNC inhibited cell growth in a dose- and time-dependent manner, and FNC could induce apoptosis by the death recepter pathways in JeKo-1 cells and arrest the cell cycle in the G1/S or G2/M phase. Notably, FNC showed in vivo efficacy in mice bearing JeKo-1 xenograft tumors. Gene expression profile analysis revealed that the differentially expressed genes were mainly focused on the immune system process, cellular process and death. These findings implied that FNC may be a valuable therapeutic in mantle cell and provided an experimental basis for the early clinical application of FNC. [ABSTRACT FROM AUTHOR]

This work describes the synthesis of new 2′-fluoro-2′- C -methyl 8-azanebularine nucleoside derivatives with moderate to good in vitro anti-HBV activity. 2g can efficiently inhibit the wild-type and lamivudine-resistant HBV DNA replication. Hepatitis B virus (HBV) is a global health problem requiring more efficient and better tolerated anti-HBV agent. In this paper, a series of novel 2′-deoxy-2′-fluoro-2′- C -methyl-β- d -arabinofuranosyl 8-azanebularine analogues (1 and 2a) and N4 -substituted 8-azaadenosine derivatives (2b-g) were designed, synthesized and screened for in vitro anti-HBV activity. Two concise and practical synthetic routes were developed toward the structural motif construction of 2′-deoxy-2′-fluoro-2′- C -methyl-β- d -arabinofuranosyl 8-azainosine from the ribonolactone 3 under mild conditions. The in vitro anti-HBV screening results showed that these 8-azanebularine analogues had a significant inhibitory effect on the expression of HBV antigens and HBV DNA at a concentration of 20 μM. Among them, halogen-substituted 8-azaadenosine derivative 2g displayed activities comparable to that of 3TC. In particular, 2g retained excellent activity against lamivudine-resistant HBV mutants. [ABSTRACT FROM AUTHOR]