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1.
Tissue Cell ; 63: 101329, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223956

RESUMO

To investigate the protective function of low-level laser irradiation (LLLI) against ionizing irradiation and explore the molecular mechanism of photomodulation of Nrf2 protein, the impact of LLLI (635 nm, 5.7 J/cm2) before 2 Gy gamma ray radiation of radio-sensitive tissue hematopoietic stem cells was evaluated. As a result, reduced levels of reactive oxygen species and increased expression of antioxidant enzymes were detected. Moreover, increased expression of Nrf2 was observed after LLLI, whereas brusatol pretreatment before LLLI abolished this effect. In vivo, transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was employed for therapy of hematopoietic function in an acute radiation sickness (H-ARS) mouse model, which was induced by 6-Gy ionizing irradiation; different hUC-MSC pretreatments including LLLI and Nrf2 RNAi were accounted for during experimental grouping. LLLI treatment of cells significantly increased the erythrocyte count and number of myelopoiesis clones (P < 0.05), but such improvements were reduced by Nrf2 RNAi pretreatment compared with cells transplanted without intervention. Therefore, LLLI may improve the radiation protection effect through molecular mechanisms related to the Nrf2 antioxidant pathway.


Assuntos
Proliferação de Células/efeitos da radiação , Células-Tronco Mesenquimais/efeitos da radiação , Fator 2 Relacionado a NF-E2/genética , Animais , Antioxidantes/metabolismo , Diferenciação Celular/efeitos da radiação , Linhagem Celular , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Lasers/efeitos adversos , Transplante de Células-Tronco Mesenquimais , Camundongos , Proteção Radiológica , Cordão Umbilical/efeitos da radiação
2.
J Ethnopharmacol ; 200: 107-116, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28088493

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies reported that the active component tanshinones displayed a variety of biological activities: anti-thrombous, anti-allergic, anti-inflammatory, antioxidant and anti-tumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated. The aim of this study was to investigate the effects of CTN on the growth inhibition, apoptosis and molecular targets of human non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: CTN-induced cytotoxicity was determined by MTT assay. The cell survival was evaluated using clonogenic survival assay. The morphology of Glc-82 cells after treatment with CTN was determined by fluorescence microscopy. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and TUNEL assays. The expression levels of proteins were analyzed using western blot. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. RESULTS: CTN inhibited the proliferation of NSCLC in a dose-dependent manner and induced both early and late apoptosis. Treatment of Glc-82 cells with CTN (5-80µg/ml) significantly (p<0.05) suppressed the cell proliferation in a concentration and time-dependent manner. CTN induced significant (p<0.05) and dose-dependent apoptosis of Glc-82 cells. Cell cycle assay showed that CTN induced a G2/M phase arrest, and significantly (p<0.05) increased expression of p53 and p21, actived caspase-3/9 and PARP1, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, CTN decreased expression of the anti-apoptotic protein Bcl-2, Bcl-xl and increased expression of the pro-apoptotic protein Bax. Result also showed that CTN could increase expression levels of PTEN, and reduce the phosphorylated levels of Akt (protein kinase B) on Thr 308 and Ser 473 domain. In vivo assay showed that the antitumor effect of CTN was significantly augmented without increasing toxicity in nude mice bearing Glc-82 xenograft. CONCLUSION: The PTEN/Akt signaling axis is defined as a critical pathway regulated by PTEN in NSCLC. CTN, the methanol extract of Salvia miltiorrhiza Bunge, are the active compounds as shown by their ability to induce apoptosis through the mitochondrial pathway of apoptosis and PTEN-mediated inhibition of PI3K/Akt pathway. CTN could inhibit tumor growth more efficiently, which supports the ethno-medicinal use of this herb as an alternative or complementary therapy for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteína Oncogênica v-akt/antagonistas & inibidores , PTEN Fosfo-Hidrolase/biossíntese , Inibidores de Fosfoinositídeo-3 Quinase , Extratos Vegetais/uso terapêutico , Salvia miltiorrhiza , Células A549 , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Metanol/farmacologia , Metanol/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
3.
JIMD Rep ; 6: 79-83, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23430943

RESUMO

The history of the Newborn Screening Program in Mainland China begins in 1981, when a pilot plan was developed that demonstrated the feasibility of its implementation. It has so far focused on the detection of congenital hypothyroidism (CH) and phenylketonuria (PKU) to prevent or reduce mental and physical developmental retardation in children. Throughout this period, a total of 35,795,550 dried blood samples (DBS) of newborns (NB) have been analyzed for PKU, and 35,715,988 for CH. During this period, 3,082 cases with PKU have been diagnosed, resulting in an incidence of 1 case per 11,614 (95% confidence interval 11,218-12,039) live births. In relation to CH, 17,556 cases have been confirmed, arriving at an incidence of 1 case per 2,034(95% confidence interval 2,005-2,065) live births. The biggest challenge for universal newborn screening is still to increase coverage to mid-western area. In Mainland China, MS/MS newborn screening started in 2004. In a pilot study, 371,942 neonates were screened, and 98 cases were detected with one of the metabolic disorders, and the collective estimated prevalence amounted to 1 in 3795 (95% confidence interval 3,168-4,732) live births, with a sensitivity of 98.99%, a specificity of 99.83%, and a positive predictive value of 13.57%. The most important is to get the government's policy and financial support for expanded screening.

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