Diabetic cardiomyopathy (DCM) represents one of the typical complications associated with diabetes. It has been described as anomalies in heart function and structure, with consequent high morbidity and mortality. DCM development can be described by two stages; the first is characterized by left ventricular hypertrophy and diastolic dysfunction, and the second by heart failure (HF) with systolic dysfunction.
View Article and Find Full Text PDFDiabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated.
View Article and Find Full Text PDFBone health is the result of a tightly regulated balance between bone modeling and bone remodeling, and alterations of these processes have been observed in several diseases both in adult and pediatric populations. The imbalance in bone remodeling can ultimately lead to osteoporosis, which is most often associated with aging, but contributing factors can already act during the developmental age, when over a third of bone mass is accumulated. The maintenance of an adequate bone mass is influenced by genetic and environmental factors, such as physical activity and diet, and particularly by an adequate intake of calcium and vitamin D.
View Article and Find Full Text PDFIn the adult brain, the water channel aquaporin-4 (AQP4) is expressed in astrocyte endfoot, in supramolecular assemblies, called "Orthogonal Arrays of Particles" (OAPs) together with the transient receptor potential vanilloid 4 (TRPV4), finely regulating the cell volume. The present study aimed at investigating the contribution of AQP4 and TRPV4 to CNS early postnatal development using WT and AQP4 KO brain and retina and neuronal stem cells (NSCs), as an in vitro model of astrocyte differentiation. Western blot analysis showed that, differently from AQP4 and the glial cell markers, TRPV4 was downregulated during CNS development and NSC differentiation.
View Article and Find Full Text PDFAquaporin-4 (AQP4) is a water channel protein found primarily in the central nervous system (CNS) that helps to regulate water-ion homeostasis. AQP4 exists in two major isoforms: M1 and M23. While both isoforms have a homotetrameric quaternary structure and are functionally identical when transporting water, the M23 isoform forms large protein aggregates known as orthogonal arrays of particles (OAPs).
View Article and Find Full Text PDFLeft ventricular assist devices (LVADs) represent the final treatment for patients with end-stage heart failure (HF) not eligible for transplantation. Although LVAD design has been further improved in the last decade, their use is associated with different complications. Specifically, inflammation, fibrosis, bleeding events, right ventricular failure, and aortic valve regurgitation may occur.
View Article and Find Full Text PDFDespite of the major role of aquaporin (AQP) water channels in controlling transmembrane water fluxes, alternative ways for modulating water permeation have been proposed. In the Central Nervous System (CNS), Aquaporin-4 (AQP4) is reported to be functionally coupled with the calcium-channel Transient-Receptor Potential Vanilloid member-4 (TRPV4), which is controversially involved in cell volume regulation mechanisms and water transport dynamics. The present work aims to investigate the selective role of TRPV4 in regulating plasma membrane water permeability in an AQP4-independent way.
View Article and Find Full Text PDFST2 is a member of interleukin 1 receptor family with soluble sST2 and transmembrane ST2L isoforms. The ligand of ST2 is IL-33, which determines the activation of numerous intracytoplasmic mediators following the binding with ST2L and IL-1RAcP, leading to nuclear signal and cardiovascular effect. Differently, sST2 is released in the blood and works as a decoy receptor, binding IL-33 and blocking IL-33/ST2L interaction.
View Article and Find Full Text PDFAstrocytes are key regulators of brain homeostasis, equilibrating ion, water, and neurotransmitter concentrations and maintaining essential conditions for proper cognitive function. Recently, it has been shown that the excitability of the actin cytoskeleton manifests in second-scale dynamic fluctuations and acts as a sensor of chemophysical environmental cues. However, it is not known whether the cytoskeleton is excitable in astrocytes and how the homeostatic function of astrocytes is linked to the dynamics of the cytoskeleton.
View Article and Find Full Text PDFBackground/aims: The ability of astrocytes to control extracellular volume homeostasis is critical for brain function and pathology. Uncovering the mechanisms of cell volume regulation by astrocytes will be important for identifying novel therapeutic targets for neurological conditions, such as those characterized by imbalances to hydro saline challenges (as in edema) or by altered cell volume regulation (as in glioma). One major challenge in studying the astroglial membrane channels involved in volume homeostasis in cell culture model systems is that the expression patterns of these membrane channels do not resemble those observed in vivo.
View Article and Find Full Text PDFAstrocyte endfeet are endowed with aquaporin-4 (AQP4)-based assemblies called orthogonal arrays of particles (OAPs) whose function is still unclear. To investigate the function of OAPs and of AQP4 tetramers, we have generated a novel "OAP-null" mouse model selectively lacking the OAP forming M23-AQP4 isoform. We demonstrated that AQP4 transcript levels were not reduced by using qPCR.
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