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1.
Biochem Biophys Res Commun ; 512(4): 647-652, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30685091

RESUMO

nc886, a long non-coding RNA (ncRNA) of 101 nucleotides in length, is known as a vault RNA or microRNA precursor. Despite the recent discovery that ncRNAs in the nucleus play a crucial role in regulating chromosomal transformation and transcription, only a few studies have focused on the function of ncRNAs in the cytoplasm, such as nc886. Several studies have investigated the function of nc886 as a suppressor of carcinogenesis and inflammation in different cancer cell types; however, its role in the skin has yet to be clearly elucidated. The two RNA binding sites for protein kinase RNA-activated (PKR) are located in the central region of the stable structure of nc886, which competes with other double-stranded RNA species. Successful binding results in decreased PKR activity. Among changes in skin cells induced by ultraviolet B (UVB) radiation, nc886 expression decreases, whereas PKR phosphorylation via mitogen-activated protein kinases (MAPKs) increases. Reduced nc886 expression leads to uncontrolled PKR activity and increases in the expression of inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), type IV collagenase, and cyclooxygenase (COX-2), which ultimately accelerate inflammatory responses and skin aging. The present study investigated the regulatory mechanism associated with PKR activity and nc886-PKR binding in skin cell aging and inflammation. These results suggest a role for nc886 in controlling photoaging and inflammation in skin cells.


Assuntos
Ciclo-Oxigenase 2/genética , Queratinócitos/efeitos da radiação , Metaloproteinase 9 da Matriz/genética , RNA Longo não Codificante/genética , Raios Ultravioleta , Linhagem Celular , Regulação para Baixo/efeitos da radiação , Humanos , Queratinócitos/metabolismo , MicroRNAs/genética , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Regulação para Cima/efeitos da radiação
2.
BMC Complement Altern Med ; 18(1): 218, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021579

RESUMO

BACKGROUND: The polysaccharide component of Angelica gigas induces immuno-stimulatory effects on innate immune cells. However, it is unclear whether A. gigas' adjuvant activity on the immune system can elicit anti-cancer responses. METHODS: A water-soluble immuno-stimulatory component of A. gigas was prepared. How this ISAg modulated the activation of innate immune cells such as dendritic cells (DCs) was examined. ISAg-induced cytotoxic activity via natural killer (NK) and NKT cells was also tested using a tumor-bearing mouse model. RESULTS: ISAg treatment induced nitric oxide (NO) production and cytokine gene expression involved in innate immune responses. ISAg activated macrophages and DCs to secrete cytokine IL-12, through the TLR4 signaling pathway. IL-12 plays a crucial role in ISAg-mediated NK and NKT cell activation. Thus, the anti-cancer activity of NK and NKT cells induced ISAg-mediated cytotoxicity of B16 melanoma cells in mice. CONCLUSIONS: These results indicated that the natural ingredient, ISAg, has adjuvant activity to induce strong anti-cancer activity of NK and NKT cells in vivo.


Assuntos
Angelica/química , Antineoplásicos/farmacologia , Imunidade Inata/efeitos dos fármacos , Células Matadoras Naturais , Células T Matadoras Naturais , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/imunologia , Polissacarídeos/farmacologia , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Med Food ; 19(2): 120-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26741654

RESUMO

Although it has been previously reported that Rhus verniciflua Stokes (RVS) possesses in vitro anti-inflammatory activity, the precise in vivo mechanisms of RVS extracts and a main active component called fisetin have not been well elucidated. In this study, using newly developed protocols, we prepared urushiol-free but fisetin-enriched RVS extracts and investigated their effects on the vascular immune system. We found that the water-soluble fractions of detoxified RVS with the flavonoid fisetin can inhibit lipopolysaccharide-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Furthermore, RVS can reduce inducible nitric oxide synthase and COX2 gene expression levels, which are responsible for NO and PGE2 production, respectively, in RAW264.7 macrophage cells. Because inflammation is linked to the activation of the coagulation system, we hypothesized that RVS and its active component fisetin possess anticoagulatory activities. As expected, we found that both RVS and fisetin could inhibit the coagulation of human peripheral blood cells. Moreover, in vivo RVS treatment could return the retarded blood flow elicited by a high-fat diet (HFD) back to the normal level in mice. In addition, RVS treatment has significantly reduced body weight gained by HFD in mice. Taken together, the fisetin-rich RVS extracts have potential antiplatelet and antiobesity activities and could be used as a functional food ingredient to improve blood circulation.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Dieta Hiperlipídica , Flavonoides/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Rhus/química , Animais , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Flavonóis , Ácido Gálico/farmacologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
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