RESUMEN
ß-Glucans have been studied in animal species, from earthworms to humans. They form a heterogenous group of glucose polymers found in fungi, plants, bacteria, and seaweed. ß-Glucans have slowly emerged as an important target for the recognition of pathogens. In the current review, we highlight the major roles of mushroom-derived ß-glucans on cancer progression.
RESUMEN
Tert-butylhydroquinone (tBHQ) is a highly effective phenolic antioxidant used in edible oils and fats in foods as well as in medicines and cosmetics. TBHQ has been shown to have both chemoprotective and carcinogenic effects. Furthermore, it has potential anti-inflammatory, antiatherogenic, and neuroprotective activities. TBHQ induces phase II detoxification enzymes via the Keap1/Nrf2/ARE mechanism, which contributes to its chemopreventive functions. Nonetheless, there is growing evidence that biological effects of tBHQ may be mediated by Nrf2-independent mechanisms related to various signaling cascades. Here, we studied changes in gene expression of phase I, II, and III drug metabolizing enzymes/transporters as well as protein levels and activities of cytochromes P450 (CYPs) elicited by tBHQ and its structural homolog TS-13 in the mouse liver. Next, we carried out gene expression analysis to identify signal transduction pathways modulated by the antioxidants. Mice received 100 mg/kg tBHQ or TS-13 per day or only vehicle. The liver was collected at 12 hours and after 7 days of the treatment. Protein and total RNA were extracted. Gene expression was analyzed using Mouse Drug Metabolism and Signal Transduction PathwayFinder RT2Profiler™PCR Arrays. A western blot analysis was used to measure protein levels and a fluorometric assay was employed to study activities of CYPs. Genes that were affected more than 1.5-fold by tBHQ or TS-13 treatment compared with vehicle were identified. Analysis of the gene expression data revealed changes in various genes that are important for drug metabolism, cellular defense mechanisms, inflammation, apoptosis, and cell cycle regulation. Novel target genes were identified, including xenobiotic metabolism genes encoding CYPs, phase II/III drug metabolizing enzymes/transporters. For Cyp1a2 and Cyp2b, we observed an increase in protein levels and activities during tBHQ or TS-13 treatment. Changes were found in the gene expression regulated by NFκB, androgen, retinoic acid, PI3K/AKT, Wnt, Hedgehog and other pathways.
Asunto(s)
Hidroquinonas/farmacología , Hígado/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ácidos Tiosulfónicos/farmacología , Transcriptoma/efectos de los fármacos , Animales , Western Blotting , Sistema Enzimático del Citocromo P-450/metabolismo , Inactivación Metabólica/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVES: We evaluated the hypolipidaemic effect of mannan Candida albicans serotype A, relative to atorvastatin, in a mouse model of hyperlipidaemia. METHODS: Mannan serotype A was investigated in vitro and in vivo to determine its effects on macrophage proliferation, nitric oxide (NO) production by cultured macrophages, serum and liver lipids, changes in liver morphology and serum chitotriosidase activity and its expression in the liver. KEY FINDINGS: Mannan serotype A stimulates the macrophage proliferation and NO production in murine peritoneal macrophages in vitro. The activity of serum chitotriosidase (an enzyme released from the activated macrophages) was found to be significantly increased in P-407-induced hyperlipidaemic mice pretreated with low-dose mannan compared with mice administered P-407 only. Mannan treatment in mice was shown to significantly increase the chitotriosidase expression in the liver of both non-hyperlipidaemic and P-407-induced hyperlipidaemic mice. Lastly, mice pretreated with mannan before the induction of hyperlipidaemia with P-407 showed a significant reduction in the serum concentration of atherogenic LDL cholesterol, total cholesterol, triglycerides and liver triglycerides. CONCLUSIONS: It is suggested that mannan serotype A, like ß-glucan, may represent another hypolipidaemic agent, which could potentially be used as an adjunctive therapy with conventional antihyperlipidaemic drugs (statins and fibrates) in humans.
Asunto(s)
Atorvastatina/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hiperlipidemias/tratamiento farmacológico , Lípidos/sangre , Hígado/efectos de los fármacos , Mananos/farmacología , Poloxámero , Animales , Biomarcadores/sangre , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hexosaminidasas/metabolismo , Hiperlipidemias/sangre , Hiperlipidemias/inducido químicamente , Hiperlipidemias/patología , Gotas Lipídicas/efectos de los fármacos , Gotas Lipídicas/metabolismo , Gotas Lipídicas/ultraestructura , Hígado/metabolismo , Hígado/ultraestructura , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/patología , Masculino , Ratones Endogámicos CBA , Microscopía Electrónica , Óxido Nítrico/metabolismoRESUMEN
We determined the frequencies of null mutations of the FLG gene--2282del4, R501X, R2447X, 3702delG, S3247X, and the 12-repeat allele (rs12730241)--among 460 Caucasians of the city of Novosibirsk, Russia. The frequency was 17.7% for rs12730241, 2.73% for 2282del4, 0.22% for R501X, 0.33% for R2447X, and 0% for 3702delG and S3247X in a western Siberian population. A case-control study showed that the deletion 2282del4 was associated with atopic dermatitis in children (odds ratio 7.01; p<0.001). The other mutations were not.