A5022385349- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- Blood Coagulation and Thrombosis Mechanisms
- Cancer-related molecular mechanisms research
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- Caveolin-1 and cellular processes
- Drug Transport and Resistance Mechanisms
- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Child Nutrition and Water Access
- Renal and related cancers
- Kruppel-like factors research
- Lipid metabolism and disorders
- Chemotherapy-induced cardiotoxicity and mitigation
- Blood groups and transfusion
- Microtubule and mitosis dynamics
- Blood properties and coagulation
- Histone Deacetylase Inhibitors Research
- Biomarkers in Disease Mechanisms
- Venous Thromboembolism Diagnosis and Management
Brescia University
2022-2024
University of Brescia
2015-2024
New York Blood Center
2024
University of California System
2020
Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate (CRPC). Ferroptosis recently described form cell requires abundant cytosolic labile iron to promote membrane lipid peroxidation which can be induced by agents inhibit glutathione peroxidase-4 activity such RSL3. Exploiting vitro vivo human murine PCa models multistage transgenic...
Mitochondrial ferritin is a functional that localizes in the mitochondria. It expressed testis, heart, brain, and cells with active respiratory activity. Its overexpression cultured protected against oxidative damage reduced cytosolic iron availability. However, no overt phenotype was described mice inactivation of FtMt gene. Here, we used doxorubicin model cardiac injury novel strain FtMt-null to investigate antioxidant role FtMt. These did not show any evident phenotype, but after acute...
Sucrosomial® Iron is a recently developed formulation to treat iron deficiency based on ferric pyrophosphate covered by matrix of phospholipids plus sucrose esters fatty acids. Previous data indicated that efficiently absorbed iron-deficient subjects, even at low dosage, and without side effects. Its structural properties may suggest it an intestinal pathway which different the one used ionic iron. Although, studies in vitro showed readily absorbed, no animal models have been established...
Identifying the molecular mechanisms underlying radioresistance is a priority for treatment of RMS, myogenic tumor accounting approximately 50% all pediatric soft tissue sarcomas. We found that irradiation (IR) transiently increased phosphorylation Akt1, Src, and Cav1 in human RD RH30 lines. Synthetic inhibition Akt1 Src ROS levels RMS lines, promoting cellular radiosensitization. Accordingly, elevated activation Akt1/Src/Cav1 pathway, as detected two lines characterized by overexpression...
In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation the mammalian target rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting loss both MyoD and myogenic capacity, an increase Ki67 due high cell mitosis. MyrAkt1 migratory invasive traits, as detected by wound healing, zymography,...
Hepcidin is a liver-derived peptide hormone that controls systemic iron homeostasis. Its expression regulated by the bone morphogenetic protein 6 (BMP6)/SMAD1/5/8 pathway and proinflammatory cytokine interleukin (IL6). Proteoglycans function as receptors of these signaling proteins in liver are commonly decorated heparan sulfate, but potential role hepatic sulfate hepcidin homeostasis unclear. Here, we show modulation significantly alters metabolism both vitro vivo. Specifically, enzymatic...
Hepcidin is the key regulator of systemic iron availability that acts by controlling degradation exporter ferroportin. It expressed mainly in liver and regulated iron, inflammation, erythropoiesis hypoxia. The various agents control its expression act via BMP6/SMAD signaling pathway. Among them are exogenous heparins, which strong hepcidin repressors with a mechanism action not fully understood but may involve competition structurally similar endogenous Heparan Sulfates (HS). To verify this...
Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase systemic iron availability. seem to act by interfering with BMP6 signaling pathways that control the liver hepcidin, causing suppression SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when heparin anticoagulant property is abolished or reduced chemical reactions oxidation/reduction (glycol-split, Gs-Heparins) high sulfation (SS-Heparins), but structural characteristics...
Hepcidin is a liver-synthesized hormone that plays central role in the regulation of systemic iron homeostasis. To produce new tool for its functional properties cDNA coding camel hepcidin-25 was cloned at 5'end human FTH sequence into pASK-IBA43plus vector expression Escherichia coli The recombinant fusion hepcidin-ferritin-H subunit isolated as an insoluble iron-containing protein. When alone it did not refold 24-mer ferritin molecule, but when renatured together with H- or L-ferritin...
Abstract Iron‐refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary absorption, leading to a form resistant oral supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared asymptomatic heterozygous (msk/wt)...
Rhabdomyosarcoma (RMS) is an aggressive rare neoplasm that derives from mesenchymal cells, which frequently develops resistance to the current therapies and formation of metastases. Thus, new are needed. The alteration iron metabolism in cancer cells was effective reducing progression many tumors but not yet investigated RMS. Here we effect modulation RMS both vitro vivo. We first characterized most used cell lines representing common subtypes, embryonal (ERMS, RD cells) alveolar (ARMS, RH30...
Abstract The simultaneous measurement of the decrease available Fe II ions and increase III allowed analysis ferroxidase activity two distinct apoferritins. Although recombinant human apoferritin (HuFtH) rapidly oxidizes to , this iron is not properly stored in ferritin cavity, as otherwise occurs horse‐spleen H/L‐apoferritin (HsFt; H=heavy subunit, L=light subunit). Iron storage these apoferritins was also studied presence copper‐loaded mammalian metallothioneins (MT2 MT3), a scenario that...