Effects of maternal diabetes on male offspring: high cell proliferation and increased activity of MMP-2 in the ventral prostate

This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor beta 1 (TGF beta-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in alpha-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGF beta-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGF beta-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.

Effects of low-level laser therapy on the proliferation and apoptosis of gingival fibroblasts treated with zoledronic acid

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

Reduced levels of intracellular reactive oxygen species and apoptotic status are not correlated with increases in cryotolerance of bovine embryos produced in vitro in the presence of antioxidants

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

GPC3 reduces cell proliferation in renal carcinoma cell lines

Background: Glypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma.Methods: Five clear cell renal cell carcinoma cell lines and carcinoma samples were used to analyze GPC3 mRNA expression (qRT-PCR). Then, representative cell lines, one primary renal carcinoma (786-O) and one metastatic renal carcinoma (ACHN), were chosen to carry out functional studies. We constructed a GPC3 expression vector and transfected the renal carcinoma cell lines, 786-O and ACHN. GPC3 overexpression was analyzed using qRT-PCR and immunocytochemistry. We evaluated cell proliferation using MTT and colony formation assays. Flow cytometry was used to evaluate apoptosis and perform cell cycle analyses.Results: We observed that GPC3 is downregulated in clear cell renal cell carcinoma samples and cell lines compared with normal renal samples. GPC3 mRNA expression and protein levels in 786-O and ACHN cell lines increased after transfection with the GPC3 expression construct, and the cell proliferation rate decreased in both cell lines following overexpression of GPC3. Further, apoptosis was not induced in the renal cell carcinoma cell lines overexpressing GPC3, and there was an increase in the cell population during the G1 phase in the cell cycle.Conclusion: We suggest that the GPC3 gene reduces the rate of cell proliferation through cell cycle arrest during the G1 phase in renal cell carcinoma.

Células T reguladoras em sangue periférico de cães portadores de mastocitoma cutâneo

Pós-graduação em Medicina Veterinária - FCAV

Expressão proteica da via PI3K/AKT/mTOR em mastocitomas cutâneos caninos

Pós-graduação em Medicina Veterinária - FCAV

Inflammation and cancer: role of Annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma

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

Effects of lithium on the proliferation and migration of neuroblasts in the rostral migratory stream in adult mice

The discovery of neurogenesis in adult brains opened the possibility of cellular therapy strategies for the treatment of neurodegenerative diseases, such as Alzheimer’s disease. Neurogenesis in the adult brain occurs in two areas: subgranular zone of the hippocampus and subventricular zone (SVZ) of the lateral ventricles. Neurons that originate from the SVZ migrate to the olfactory bulb (OB) through the rostral migratory stream (RMS). In Alzheimer’s disease, there is a progressive neuronal dysfunction and degeneration, resulting in brain atrophy and cognitive impairments including olfactory dysfunction. Several studies have demonstrated that pharmacological treatment with lithium exerts positive effects on adult neurogenesis, and one pathway seems to be the modulation of factors that regulate the migration of neuroblasts. The objective of this study was to investigate whether treatment with lithium promotes the increase of migratory neuroblasts using as parameter the RMS. Adult male C57BL/6 mice were divided into control and lithium-treated groups. The animals were treated for 6 weeks and, at four different time points, i.e., 10 days, 7 days, 3 days and 1 day before the end of treatments, they received an injection of BrdU (cell proliferation marker). The animals were sacrificed by perfusion fixation and the brains were immunohistochemically labeled for BrdU for analysis of migrating neuroblasts in the RMS. The results showed that the number of BrdU+ cells in the RMS was not significantly different between the two groups, suggesting that lithium, alone, is not capable of increasing the number of neuroblasts migrating from the SVZ to the OB

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Investigação da ação da proteína anexina A1 sobre o processo de angiogênese induzido pelo fator de crescimento do endotélio vascular: modelos experimentais in vivo e in vitro

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

Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil)

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

Interleukin-18 increases TLR4 and mannose receptor expression and modulates cytokine production in human monocytes

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