Targeting the Ca signaling toolkit as an alternative strategy to mitigate SARS-CoV-2-induced cardiovascular adverse events.

Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiovascular complications. SARS-CoV-2 binds to the ACE2 receptor on endothelial and cardiomyocyte surfaces, triggering abnormal increases in intracellular Ca levels that promote endothelial dysfunction, inflammation, and hypercoagulation.

The Roles of Transient Receptor Potential (TRP) Channels Underlying Aberrant Calcium Signaling in Blood-Retinal Barrier Dysfunction.

The inner blood-retinal barrier (iBRB) protects the retinal vasculature from the peripheral circulation. Endothelial cells (ECs) are the core component of the iBRB; their close apposition and linkage via tight junctions limit the passage of fluids, proteins, and cells from the bloodstream to the parenchyma. Dysfunction of the iBRB is a hallmark of many retinal disorders.

The Role of Newborn Pulse Oximetry Screening for Detecting Critical Congenital Heart Defects: A Narrative Review.

Critical congenital heart diseases are life-threatening, with a high morbidity rate and mortality among newborns; in fact, a newborn discharged from the hospital with undiagnosed heart disease may experience severe complications during the initial days or weeks of their life, necessitating emergency care and even death. Among all kinds of critical congenital heart disease, coarctation of the aorta is one of the most difficult to diagnose because it only becomes noticeable a few days after birth, when patients have already been discharged from the hospital. This underlines the importance of having a reliable diagnostic tool to discover these diseases.

Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis.

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart-brain axis could be severely compromised by both neurological and cardiovascular disorders.

Design of a hybrid nanoscaled skin photoprotector by boosting the antioxidant properties of food waste-derived lignin through molecular combination with TiO nanoparticles.

TiO nanoparticles loaded with pistachio shell lignin (8 % and 29 % w/w) were prepared by a hydrothermal wet chemistry approach. The efficient interaction at the molecular level of the biomacromolecule and inorganic component was demonstrated by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-Visible (UV-Vis), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), and electron paramagnetic resonance (EPR) analysis. The synergistic combination of lignin and TiO nanoparticles played a key role in the functional properties of the hybrid material, which exhibited boosted features compared to the separate organic and inorganic phase.

The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow.

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma.

An automated planar patch-clamp approach to measure the membrane potential and resting membrane currents in a human cerebrovascular endothelial cell line.

Background: The conventional "whole-cell patch-clamp" recording technique is widely used to measure the resting membrane potential (V) and to dissect the underlying membrane ionic conductances in isolated vascular endothelial cells.

New Method: Herein, we assessed whether the automated patch-clamp (APC) technology, which replaces the traditional patch-pipette with a planar substrate to permit researchers lacking formal training in electrophysiology to generate large amounts of data in a relatively short time, can be used to characterize the bioelectrical activity of vascular endothelial cells. We assessed whether the Port-a-Patch planar patch-clamp system, which is regarded as the smallest electrophysiological rig available on the market, can be used to measure the V and resting membrane currents in the human cerebrovascular endothelial cell line, hCMEC/D3.

Lysosomal TRPML1 triggers global Ca signals and nitric oxide release in human cerebrovascular endothelial cells.

Lysosomal Ca signaling is emerging as a crucial regulator of endothelial Ca dynamics. Ca release from the acidic vesicles in response to extracellular stimulation is usually promoted Two Pore Channels (TPCs) and is amplified by endoplasmic reticulum (ER)-embedded inositol-1,3,4-trisphosphate (InsP) receptors and ryanodine receptors. Emerging evidence suggests that sub-cellular Ca signals in vascular endothelial cells can also be generated by the Transient Receptor Potential Mucolipin 1 channel (TRPML1) channel, which controls vesicle trafficking, autophagy and gene expression.

β-Cyclodextrin-NHC-Au(I)-Catalyzed Enantioconvergent 1,5-Enyne Cycloisomerizations.

Enantioconvergent transformations from racemic mixtures are attractive since they allow the generation of optically active products with full conversion despite the possibly adverse kinetic resolution process. When dealing with gold(I)-catalyzed cycloisomerizations, chirality transfer from the precursor is another possible diverting pathway, which renders enantioconvergence challenging. Not surprisingly, enantioconvergent Au(I)-catalyzed processes have remained extremely rare.

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.

Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca entry and activity-dependent change in the strength of synaptic transmission, as well as by metabotropic glutamate receptors (mGluRs), which mediate slower postsynaptic responses through the recruitment of second messenger systems. A wealth of evidence reported over the last three decades has shown that this dogmatic subdivision between iGluRs and mGluRs may not reflect the actual physiological signaling mode of the iGluRs, i.

Tamoxifen Activates Transcription Factor EB and Triggers Protective Autophagy in Breast Cancer Cells by Inducing Lysosomal Calcium Release: A Gateway to the Onset of Endocrine Resistance.

Among the several mechanisms accounting for endocrine resistance in breast cancer, autophagy has emerged as an important player. Previous reports have evidenced that tamoxifen (Tam) induces autophagy and activates transcription factor EB (TFEB), which regulates the expression of genes controlling autophagy and lysosomal biogenesis. However, the mechanisms by which this occurs have not been elucidated as yet.

Cracking the Endothelial Calcium (Ca) Code: A Matter of Timing and Spacing.

A monolayer of endothelial cells lines the innermost surface of all blood vessels, thereby coming into close contact with every region of the body and perceiving signals deriving from both the bloodstream and parenchymal tissues. An increase in intracellular Ca concentration ([Ca]) is the main mechanism whereby vascular endothelial cells integrate the information conveyed by local and circulating cues. Herein, we describe the dynamics and spatial distribution of endothelial Ca signals to understand how an array of spatially restricted (at both the subcellular and cellular levels) Ca signals is exploited by the vascular intima to fulfill this complex task.

Bimodal modulation of angiogenesis with photoactive polymer nanoparticles.

Angiogenesis is a fundamental process in biology, given the pivotal role played by blood vessels in providing oxygen and nutrients to tissues, thus ensuring cell survival. Moreover, it is critical in many life-threatening pathologies, like cancer and cardiovascular diseases. In this context, conventional treatments of pathological angiogenesis suffer from several limitations, including low bioavailability, limited spatial and temporal resolution, lack of specificity and possible side effects.

Overcoming barriers to oral contraception in Italy an expert opinion to empower women.

Oral contraceptives are among the most commonly used contraceptive methods. However, Italian women underused reliable hormonal contraceptives as compared with other European women. There is a need to streamline access to oral contraception, with expected benefits on emotional well-being of women and potential savings for health system in Italy.

Store-Operated Ca Entry as a Putative Target of Flecainide for the Treatment of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder that may lead patients to sudden cell death through the occurrence of ventricular arrhythmias. ACM is characterised by the progressive substitution of cardiomyocytes with fibrofatty scar tissue that predisposes the heart to life-threatening arrhythmic events. Cardiac mesenchymal stromal cells (C-MSCs) contribute to the ACM by differentiating into fibroblasts and adipocytes, thereby supporting aberrant remodelling of the cardiac structure.

Injection Treatments for Vulvovaginal Atrophy of Menopause: A Systematic Review.

Background: Injection treatments have been proposed as novel treatment options for Vulvovaginal Atrophy of Menopause (VVA) also known as Genitourinary Syndrome of Menopause (GSM). However, to date data about these treatments are poor.

Objective: To assess all available injection treatments for VVA.

Intracellular Ca signalling: unexpected new roles for the usual suspect.

Cytosolic Ca signals are organized in complex spatial and temporal patterns that underlie their unique ability to regulate multiple cellular functions. Changes in intracellular Ca concentration ([Ca]) are finely tuned by the concerted interaction of membrane receptors and ion channels that introduce Ca into the cytosol, Ca-dependent sensors and effectors that translate the elevation in [Ca] into a biological output, and Ca-clearing mechanisms that return the [Ca] to pre-stimulation levels and prevent cytotoxic Ca overload. The assortment of the Ca handling machinery varies among different cell types to generate intracellular Ca signals that are selectively tailored to subserve specific functions.

Allyl Isothiocianate Induces Ca Signals and Nitric Oxide Release by Inducing Reactive Oxygen Species Production in the Human Cerebrovascular Endothelial Cell Line hCMEC/D3.

Nitric oxide (NO) represents a crucial mediator to regulate cerebral blood flow (CBF) in the human brain both under basal conditions and in response to somatosensory stimulation. An increase in intracellular Ca concentrations ([Ca]) stimulates the endothelial NO synthase to produce NO in human cerebrovascular endothelial cells. Therefore, targeting the endothelial ion channel machinery could represent a promising strategy to rescue endothelial NO signalling in traumatic brain injury and neurodegenerative disorders.

Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca entry, mitochondrial dysfunction, and caspase-3/7 activation in primary cultures of metastatic colorectal carcinoma cells.

Colorectal carcinoma (CRC) represents the fourth most common cancer worldwide and is the third most common cause of malignancy-associated mortality. Distant metastases to the liver and lungs are the main drivers of CRC-dependent death. Pro-oxidant therapies, which halt disease progression by exacerbating oxidative stress, represent an antitumour strategy that is currently exploited by chemotherapy and ionizing radiation.

Alterations of the Ca clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat.

Type 2 Diabetes Mellitus (T2DM) is a rapidly rising disease with cardiovascular complications constituting the most common cause of death among diabetic patients. Chronic hyperglycemia can induce vascular dysfunction through damage of the components of the vascular wall, such as vascular smooth muscle cells (VSMCs), which regulate vascular tone and contribute to vascular repair and remodeling. These functions are dependent on intracellular Ca changes.