Performance in Behavioral Testing in an Animal Model of Post-Surgical Hypoparathyroidism.

Background: Hypoparathyroidism (HypoPT) is characterized by hypocalcemia and undetectable/inappropriately low PTH. Post-surgical HypoPT (PS-HypoPT) is the most common cause. Patients with PS-HypoPT present neuropsychological symptoms, probably due to the PTH deprivation in the central nervous system (CNS).

Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System.

Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such as the Central Nervous System (CNS). In humans, PTH-related peptides are Parathyroid Hormone (PTH), PTH-like hormones (PTHrP and PTHLH), and tuberoinfundibular peptide of 39 (TIP39 or PTH2).

Role of the interaction between troponin T and AMP deaminase by zinc bridge in modulating muscle contraction and ammonia production.

The N-terminal region of troponin T (TnT) does not bind any protein of the contractile machinery and the role of its hypervariability remains uncertain. In this review we report the evidence of the interaction between TnT and AMP deaminase (AMPD), a regulated zinc enzyme localized on the myofibril. In periods of intense muscular activity, a decrease in the ATP/ADP ratio, together with a decrease in the tissue pH, is the stimulus for the activation of the enzyme that deaminating AMP to IMP and NH displaces the myokinase reaction towards the formation of ATP.

Regulation of skeletal muscle AMP deaminase. Carbethoxylation of His-51 belonging to the zinc coordination sphere of the rabbit enzyme promotes its desensitization towards the inhibition by ATP.

Background: Skeletal muscle AMP deaminase (AMPD1) regulates the concentration of adenine nucleotides during muscle contraction. We previously provided evidence that rabbit AMPD1 is composed by two HPRG 73 kDa subunits and two 85 kDa catalytic subunits with a dinuclear zinc site with an average of two histidine residues at each metal site. AMPD1 is mainly expressed in fast twitching fibers and is inhibited by ATP.

Role of the HPRG Component of Striated Muscle AMP Deaminase in the Stability and Cellular Behaviour of the Enzyme.

Multiple muscle-specific isoforms of the Zn metalloenzyme AMP deaminase (AMPD) have been identified based on their biochemical and genetic differences. Our previous observations suggested that the metal binding protein histidine-proline-rich glycoprotein (HPRG) participates in the assembly and maintenance of skeletal muscle AMP deaminase (AMPD1) by acting as a zinc chaperone. The evidence of a role of millimolar-strength phosphate in stabilizing the AMPD-HPRG complex of both AMPD1 and cardiac AMP deaminase (AMPD3) is suggestive of a physiological mutual dependence between the two subunit components with regard to the stability of the two isoforms of striated muscle AMPD.

Human adult mesangiogenic progenitor cells reveal an early angiogenic potential, which is lost after mesengenic differentiation.

Background: Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential. MPCs have so far been described in detail as progenitors of the mesodermal lineage and appear to be of great significance in tissue regeneration and in hemopoietic niche regulation. On the contrary, information regarding the MPC angiogenic process is still incomplete and requires further clarification.

Structure-function relationships in mammalian histidine-proline-rich glycoprotein.

Histidine-proline-rich glycoprotein (HPRG), or histidine-rich glycoprotein (HRG), is a serum protein that is synthesized in the liver and is actively internalised by different cells, including skeletal muscle. The multidomain arrangement of HPRG comprises two modules at the N-terminus that are homologous to cystatin but void of cysteine proteinase inhibitor function, and a second half consisting of a histidine-proline-rich region (HPRR) located between two proline-rich regions (PRR1 and PRR2), and a C-terminus domain. HPRG has been reported to bind various ligands and to modulate angiogenesis via the histidine residues of the HPRR.

Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles.

Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues.

Pilot in vivo investigation of cerium oxide nanoparticles as a novel anti-obesity pharmaceutical formulation.

Unlabelled: Obesity is a worldwide pathological condition that strongly impairs human health, and, to date, no effective therapy against excessive fat accumulation has been found yet. Since overweight correlates with an increased oxidative stress, our aim is to investigate the antioxidant effects of cerium oxide nanoparticles (nanoceria) as a potential pharmaceutical approach for the treatment of obesity. Nanoceria were tested both in vitro and in vivo; they were proven to interfere with the adipogenic pathway by reducing the mRNA transcription of genes involved in adipogenesis, and by hindering the triglycerides accumulation in 3T3-L1 pre-adipocytes.

Poly(vinyl alcohol)/gelatin Hydrogels Cultured with HepG2 Cells as a 3D Model of Hepatocellular Carcinoma: A Morphological Study.

It has been demonstrated that three-dimensional (3D) cell culture models represent fundamental tools for the comprehension of cellular phenomena both for normal and cancerous tissues. Indeed, the microenvironment affects the cellular behavior as well as the response to drugs. In this study, we performed a morphological analysis on a hepatocarcinoma cell line, HepG2, grown for 24 days inside a bioartificial hydrogel composed of poly(vinyl alcohol) (PVA) and gelatin (G) to model a hepatocellular carcinoma (HCC) in 3D.

Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion.

3-iodothyronamine (T(1)AM) is an endogenous compound which shares structural and functional features with biogenic amines and is able to interact with a specific class of receptors, designed as trace amine associated receptors. T(1)AM has significant physiological effects in mammals and produces a reversible, dose-dependent negative inotropic and chronotropic effect in heart. The aim of the present study was to investigate if T(1)AM is able to reduce irreversible tissue injury in isolated rat hearts subjected to ischemia and reperfusion, as evaluated by triphenyltetrazolium chloride staining.

Effects of zofenopril on cardiac sarcoplasmic reticulum calcium handling.

Isolated rat hearts were perfused for 120 minutes in the presence or in the absence of 10 microM zofenoprilat, the active metabolite of zofenopril. At the end of perfusion, cardiac tissue was used to assay sarcoplasmic reticulum (SR) (45)Ca uptake and SR calcium release, which was determined by automatized quick filtration technique after SR vesicle loading with (45)Ca. The expression of genes involved in the control of calcium homeostasis was evaluated by polymerase chain reaction after reverse transcription.

Structural determinants of heparan sulfate interactions with Slit proteins.

We have previously demonstrated that the Slit proteins, which are involved in axonal guidance and related processes, are high-affinity ligands of the heparan sulfate proteoglycan glypican-1. Glypican-Slit protein interactions have now been characterized in greater detail using two approaches. The ability of heparin oligosaccharides of defined structure (ranging in size from disaccharide to tetradeccasaccharide) to inhibit binding of a glypican-Fc fusion protein to recombinant human Slit-2 was determined using an ELISA.

De novo identification of tumor-specific internalizing human antibody-receptor pairs by phage-display methods.

Three tumor-specific, internalizing human single-chain Fvs (scFvs) were obtained by direct selection against tumor cells from a large, nonimmune scFv-phage library pre-subtracted with various normal human cells. After scFv selection and characterization for cell binding and internalization, the scFvs were also employed in immunoprecipitations to identify putative receptors. In the case of a prostate tumor-cell specific scFv PR5, the receptor that mediated endocytosis was shown to be the transferrin receptor.

Ca2+ channel remodeling in perfused heart: Effects of mechanical work and interventions affecting Ca2+ cycling on sarcolemmal and sarcoplasmic reticulum Ca2+ channels.

We investigated whether changes in cardiac work or in Ca2+ fluxes may affect the expression of sarcolemmal or sarcoplasmic reticulum Ca2+ channels (DHPRs and RyRs, respectively). Isolated rat hearts were perfused at low Ca2+ concentration (0.8 mM instead of 1.