ContextThere is growing evidence of the role of epigenetic regulation of growth, and miRNAs poten... more ContextThere is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role.ObjectiveThe aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response.Design and MethodsThe expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t−3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain...
Abstract: Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fi... more Abstract: Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose...
Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system in... more Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity
Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is assoc... more Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is associated with an increased rate of infertility. Its etiology remains largely unknown, although both genetic and environmental factors play a role. PCOS is characterized by insulin resistance, metabolic disorders and low-grade chronic inflammation. To date, the treatment of PCOS is mainly symptomatic and aimed at reducing clinical signs of hyperandrogenism (hirsutism and acne), at improving menstrual cyclicity and at favouring ovulation. Since PCOS pathophysiology is still largely unknown, the therapeutic interventions currently in place are rarely cause-specific. In such cases, the therapy is mainly directed at improving hormonal and metabolic dysregulations typical of this condition. Diet and exercise represent the main environmental factors influencing PCOS. Thus, therapeutic lifestyle changes represent the first-line of intervention, which, in combination with oral contraceptives, repres...
Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronaviru... more Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus, Sars-Cov-2. This infection can cause mild to very severe respiratory and systemic illness mainly related with a cytokine storm. The epidemiology of COVID-19 is under continuous evolution, and studies are ongoing aiming at identifying the possible factors facilitating the diffusion of this infection. (www.actabiomedica.it)
Normal fetal growth and development depend on several endocrine, metabolic, and nutritional facto... more Normal fetal growth and development depend on several endocrine, metabolic, and nutritional factors (1). Among them, an important role is played by thyroid hormones (TH) (T4 thyroxine and T3 triiodothyronine) both of maternal and fetal origin. The supply of maternal TH to the human fetus depends mainly on the mother’s thyroid function and on several placental transport mechanisms. Moreover, during pregnancy, double the normal iodine intake of the mother is required to preserve normal TH concentrations (2). In fetus hypothalamus-pituitary-thyroid–target tissue axis is activated shortly after the thyroid gland has reached his anatomical site in the first gestation weeks. A full maturation of the complex system including TH transport, receptor availability, and normal function of postreceptoral mechanism is however needed to ensure the specific biological action at target tissues.
ContextThere is growing evidence of the role of epigenetic regulation of growth, and miRNAs poten... more ContextThere is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role.ObjectiveThe aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response.Design and MethodsThe expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t−3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain...
Abstract: Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fi... more Abstract: Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose...
Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system in... more Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity
Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is assoc... more Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women and it is associated with an increased rate of infertility. Its etiology remains largely unknown, although both genetic and environmental factors play a role. PCOS is characterized by insulin resistance, metabolic disorders and low-grade chronic inflammation. To date, the treatment of PCOS is mainly symptomatic and aimed at reducing clinical signs of hyperandrogenism (hirsutism and acne), at improving menstrual cyclicity and at favouring ovulation. Since PCOS pathophysiology is still largely unknown, the therapeutic interventions currently in place are rarely cause-specific. In such cases, the therapy is mainly directed at improving hormonal and metabolic dysregulations typical of this condition. Diet and exercise represent the main environmental factors influencing PCOS. Thus, therapeutic lifestyle changes represent the first-line of intervention, which, in combination with oral contraceptives, repres...
Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronaviru... more Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus, Sars-Cov-2. This infection can cause mild to very severe respiratory and systemic illness mainly related with a cytokine storm. The epidemiology of COVID-19 is under continuous evolution, and studies are ongoing aiming at identifying the possible factors facilitating the diffusion of this infection. (www.actabiomedica.it)
Normal fetal growth and development depend on several endocrine, metabolic, and nutritional facto... more Normal fetal growth and development depend on several endocrine, metabolic, and nutritional factors (1). Among them, an important role is played by thyroid hormones (TH) (T4 thyroxine and T3 triiodothyronine) both of maternal and fetal origin. The supply of maternal TH to the human fetus depends mainly on the mother’s thyroid function and on several placental transport mechanisms. Moreover, during pregnancy, double the normal iodine intake of the mother is required to preserve normal TH concentrations (2). In fetus hypothalamus-pituitary-thyroid–target tissue axis is activated shortly after the thyroid gland has reached his anatomical site in the first gestation weeks. A full maturation of the complex system including TH transport, receptor availability, and normal function of postreceptoral mechanism is however needed to ensure the specific biological action at target tissues.
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Papers by Maria Street