Characterization of the transcriptome of fast and slow muscle myotomal fibres in the pacu (Piaractus mesopotamicus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Curcumin pharmacokinetic and pharmacodynamic evidences in streptozotocin-diabetic rats support the antidiabetic activity to be via metabolite(s)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Biology and oncogenicity of the Kaposi sarcoma herpesvirus K1 protein

The Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, is a gammaherpesvirus etiologically linked to the development of Kaposi sarcoma, primary effusion lymphomas, and multicentric Castleman disease in humans. KSHV is unique among other human herpesviruses because of the elevated number of viral products that mimic human cellular proteins, such as a viral cyclin, a viral G protein-coupled receptor, anti-apoptotic proteins (e.g. v-bcl2 and v-FLIP), viral interferon regulatory factors, and CC chemokine viral homologues. Several KSHV products have oncogenic properties, including the transmembrane K1 glycoprotein. KSHV K1 is encoded in the viral ORFK1, which is the most variable portion of the viral genome, commonly used to discriminate among viral genotypes. The extracellular region of K1 has homology with the light chain of lambda immunoglobulin, and its cytoplasmic region contains an immunoreceptor tyrosine-based activation motif (ITAM). KSHV K1 ITAM activates several intracellular signaling pathways, notably PI3K/AKT. Consequently, K1 expression inhibits proapoptotic proteins and increases the life-span of KSHV-infected cells. Another remarkable effect of K1 activity is the production of inflammatory cytokines and proangiogenic factors, such as vascular endothelial growth factor. KSHV K1 immortalizes primary human endothelial cells and transforms rodent fibroblasts in vitro; moreover, K1 induces tumors in vivo in transgenic mice expressing this viral protein. This review aims to consolidate and discuss the current knowledge on this intriguing KSHV protein, focusing on activities of K1 that can contribute to the pathogenesis of KSHV-associated human cancers. Copyright © 2015 John Wiley & Sons, Ltd.

Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol

In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Downhill running excessive training inhibits hypertrophy in mice skeletal muscles with different fiber type composition

The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. J. Cell. Physiol. 9999: 1-12, 2015. © 2015 Wiley Periodicals, Inc.

Potenciais microRNAs circulantes como biomarcadores de Leucemia Mieloide Crônica - Fase Crônica: recém diagnosticada e tratada com mesilato de imatinibe

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)