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Inflammatory cytokines are able to induce vascular smooth muscle cells (VSMCs) to undergo apoptosis, causing atherosclerotic plaque rupture. Changes in the e×pression levels of conne×ins (C×s) have been demonstrated in VSMCs to be involved in the pathogenesis of atherosclerotic progression. The present study e×amined the effect of tumor necrosis factor-ɑ (TNF-ɑ) on C×43 e×pression levels and apoptosis in human VSMCs. Overe×pression of C×43 plasmids notably stimulated VSMC proliferation. TNF-ɑ directly inhibited C×43 e×pression levels in a dose- and time-dependent manner in VSMCs, however this was blocked by c-Jun N-terminal kinase inhibitor. TNF-ɑ also increased caspase-3 activity and apoptosis of VSMCs through the inhibition of C×43. These data suggested that TNF-ɑ induced the apoptosis of VMSCs and prompted the destabilization of atherosclerotic plaques by downregulating C×43. [ABSTRACT FROM AUTHOR]

Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V‑fluorescein isothiocyanate/propidium iodide, 2',7'‑dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase‑3 activity analysis were performed. The results demonstrated that the anti‑proliferative action of the mixture of kaempferol 3‑O‑β‑(2"‑acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti‑proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti‑proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common aggressive sarcoma of the bone in children and adolescents. It is characterized by a high level of genetic instability and recurrent DNA deletions and amplifications. microRNAs (miRNAs) play a key role in cancer initiation, progression and metastasis; however, the potential role of miRNAs in osteosarcoma remains largely unknown. In the present study, miR-433 was shown to be overexpressed in osteosarcoma tissues compared with normal human osteoblasts. Transfection of miR-433 mimics into osteosarcoma cell lines significantly decreased apoptosis by targeting programmed cell death 4, a tumor suppressor that is involved in apoptosis. In contrast, inhibition of miR-433 enhanced apoptosis. Furthermore, in vivo miR-433 overexpression inhibited the apoptosis of tumor cells and increased tumor growth. The results of the present study suggested that miR-433 is a potential molecular target for osteosarcoma therapy. [ABSTRACT FROM AUTHOR]