Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine

AIM:To determine the molecular mechanisms involved in experimental hepatic fibrosis prevention by caffeine(CFA).METHODS:Liver fibrosis was induced in Wistar rats by intraperitoneal thioacetamide or bile duct ligation and they were concomitantly treated with CFA(15 mg/kg per day).Fibrosis and inflammatory cell infiltrate were evaluated and classified by Knodell index.Inflammatory infiltrate was quantified by immunohistochemistry(anti-CD11b).Gene expression was analyzed by quantitative reverse transcription-polymerase chain reaction for collagenⅠ?(Col-1),connective tissue growth factor(CTGF),transforming growth factorβ1(TGF-β1),tumor necrosis factor alpha(TNF-α),interleukin-1(IL-1),IL-6,superoxide dismutase(SOD)and catalase(CAT).Activation of Nrf2 and Snail-1 was analyzed by Westernblot.TNF-αexpression was proved by enzyme-linked immunosorbant assay,CAT activity was performed by zymography.RESULTS:CFA treatment diminished fibrosis index in treated animals.The Knodell index showed both lower fibrosis and necroinflammation.Expression of profibrogenic genes CTGF,Col-1 and TGF-β1 and proinflammatory genes TNF-α,IL-6 and IL-1 was substantially diminished with CFA treatment with less CD11b positive areas.Significantly lower values of transcriptional factor Snail-1 were detected in CFA treated rats compared with cirrhotic rats without treatment;in contrast Nrf2was increased in the presence of CFA.Expression of SOD and CAT was greater in animals treated with CFA showing a strong correlation between mRNA expression and enzyme activity.CONCLUSION:Our results suggest that CFA inhibits the transcriptional factor Snail-1,down-regulating profibrogenic genes,and activates Nrf2 inducing antioxidant enzymes system,preventing inflammation and fibrosis.

Mexican Guidelines for the Diagnosis and Treatment of Chronic Myeloid Leukaemia

Background: This document includes recommendations and guidelines issued by a group of Mexican researchers and specialists gathered in the First National Colloquium for the Diagnosis and Management of Chronic Myeloid Leukaemia (CML) by initiative of Instituto Nacional de Cancerología and with the support of the Leukaemia Department of the MD Anderson Cancer Center. Mexico lacks of updated information taken from its own reality on the diagnosis and treatment of CML and other haematological disorders;besides, there are no national guidelines. Aim: To publish a consensus document with guidelines for the management of CML adjusted to the national environment and overall characteristics. Method: The participants answered a DELPHI questionnaire about the overall aspects of the disease, aiming to target controversial topics, discuss them in the colloquium, and to agree on the best ones. After those meetings, a final document was drawn up. Results: The group presents recommendations for definition, diagnosis, prognosis, monitoring, and treatment of CML in Mexico. Conclusions: Having consensus guidelines for the clinical management of CML in our country will enable the consensual practice of Mexican specialists regarding the clinical approach to CML, as well as optimize the resources which allow the rational planning of the medical care strategies.