The Effects of Sirolimus and Magnesium on Primary Human Coronary Endothelial Cells: An In Vitro Study.

Drug eluting magnesium (Mg) bioresorbable scaffolds represent a novel paradigm in percutaneous coronary intervention because Mg-based alloys are biocompatible, have adequate mechanical properties and can be resorbed without adverse events. Importantly, Mg is fundamental in many biological processes, mitigates the inflammatory response and is beneficial for the endothelium. Sirolimus is widely used as an antiproliferative agent in drug eluting stents to inhibit the proliferation of smooth muscle cells, thus reducing the occurrence of stent restenosis.

Magnesium and the Brain: A Focus on Neuroinflammation and Neurodegeneration.

Magnesium (Mg) is involved in the regulation of metabolism and in the maintenance of the homeostasis of all the tissues, including the brain, where it harmonizes nerve signal transmission and preserves the integrity of the blood-brain barrier. Mg deficiency contributes to systemic low-grade inflammation, the common denominator of most diseases. In particular, neuroinflammation is the hallmark of neurodegenerative disorders.

The presence of BBB hastens neuronal differentiation of cerebral organoids - The potential role of endothelial derived BDNF.

Despite remaining the best in vitro model to resemble the human brain, a weakness of human cerebral organoids is the lack of the endothelial component that in vivo organizes in the blood brain barrier (BBB). Since the BBB is crucial to control the microenvironment of the nervous system, this study proposes a co-culture of BBB and cerebral organoids. We utilized a BBB model consisting of primary human brain microvascular endothelial cells and astrocytes in a transwell system.

A Novel Fluidic Platform for Semi-Automated Cell Culture into Multiwell-like Bioreactors.

In this work, we developed and characterized a novel fluidic platform that enables long-term in vitro cell culture in a semi-automated fashion. The system is constituted by a control unit provided with a piezoelectric pump, miniaturized valves, and a microfluidic network for management and fine control of reagents' flow, connected to a disposable polymeric culture unit resembling the traditional multiwell-like design. As a proof of principle, Human Umbilical Vein Endothelial Cells (HUVEC) and Human Mesenchymal Stem Cells (hMSC) were seeded and cultured into the cell culture unit.

From Cultured Vascular Cells to Vessels: The Cellular and Molecular Basis of Vascular Dysfunction in Space.

Life evolved on this planet under the pull of gravity, shielded from radiation by the magnetosphere and shaped by circadian rhythms due to Earth's rotation on its axis. Once living beings leave such a protective environment, adaptive responses are activated to grant survival. In view of long manned mission out of Earth's orbit, it is relevant to understand how humans adapt to space and if the responses activated might reveal detrimental in the long run.

Human endothelial cells in high glucose: New clues from culture in 3D microfluidic chips.

Several studies have demonstrated the role of high glucose in promoting endothelial dysfunction utilizing traditional two-dimensional (2D) culture systems, which, however, do not replicate the complex organization of the endothelium within a vessel constantly exposed to flow. Here we describe the response to high glucose of micro- and macro-vascular human endothelial cells (EC) cultured in biomimetic microchannels fabricated through soft lithography and perfused to generate shear stress. In 3D macrovascular EC exposed to a shear stress of 0.

Vitamin D Prevents High Glucose-Induced Lipid Droplets Accumulation in Cultured Endothelial Cells: The Role of Thioredoxin Interacting Protein.

Vitamin D (VitD) exerts protective effects on the endothelium, which is fundamental for vascular integrity, partly by inhibiting free radical formation. We found that VitD prevents high glucose-induced Thioredoxin Interacting Protein (TXNIP) upregulation. Increased amounts of TXNIP are responsible for the accumulation of reactive oxygen species and, as a consequence, of lipid droplets.

Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity.

Mechanical cues contribute to the maintenance of a healthy endothelium, which is essential for vascular integrity. Indeed endothelial cells are mechanosensors that integrate the forces in the form of biochemical signals. The cytoskeleton is fundamental in sensing mechanical stimuli and activating specific signaling pathways.

Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation.

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera.

Reactive oxygen species are implicated in altering magnesium homeostasis in endothelial cells exposed to high glucose.

Transient Receptor Potential Melastatin (TRPM)7 is important in maintaining the intracellular homeostasis of magnesium (Mg), which is instrumental for vital cellular functions. Since the upregulation of TRPM7 has been proposed as a marker of endothelial dysfunction, we evaluated the effects of high glucose, which markedly impacts endothelial performance, on TRPM7 and intracellular Mg homeostasis in human macrovascular endothelial cells. We show that glucose-induced free radicals increase the amounts of TRPM7 as well as total intracellular magnesium.

Mitophagy contributes to endothelial adaptation to simulated microgravity.

Exposure to real or simulated microgravity is sensed as a stress by mammalian cells, which activate a complex adaptive response. In human primary endothelial cells, we have recently shown the sequential intervention of various stress proteins which are crucial to prevent apoptosis and maintain cell function. We here demonstrate that mitophagy contributes to endothelial adaptation to gravitational unloading.

Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells.

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA.

Correction to Chemical Fingerprint of Zn-Hydroxyapatite in the Early Stages of Osteogenic Differentiation.

[This corrects the article DOI: 10.1021/acscentsci.9b00509.

Magnesium and the blood-brain barrier in vitro: effects on permeability and magnesium transport.

The blood-brain barrier (BBB) tightly regulates the homeostasis of the central nervous system, and its dysfunction has been described in several neurological disorders. Since magnesium exerts a protective effect in the brain, we assessed whether supraphysiological concentrations of different magnesium salts modulate the permeability and magnesium transport in in vitro models of rat and human BBB. Among various formulations tested, magnesium pidolate was the most efficient in reducing the permeability and in enhancing magnesium transport through the barrier.

Chemical Fingerprint of Zn-Hydroxyapatite in the Early Stages of Osteogenic Differentiation.

The core knowledge about biomineralization is provided by studies on the advanced phases of the process mainly occurring in the extracellular matrix. Here, we investigate the early stages of biomineralization by evaluating the chemical fingerprint of the initial mineral nuclei deposition in the intracellular milieu and their evolution toward hexagonal hydroxyapatite. The study is conducted on human bone mesenchymal stem cells exposed to an osteogenic cocktail for 4 and 10 days, exploiting laboratory X-ray diffraction techniques and cutting-edge developments of synchrotron-based 2D and 3D cryo-X-ray microscopy.

The simultaneous downregulation of TRPM7 and MagT1 in human mesenchymal stem cells in vitro: Effects on growth and osteogenic differentiation.

The magnesium transporters TRPM7 and MagT1 are overexpressed in osteoblastogenesis. We have shown that silencing either TRPM7 or MagT1 accelerates the osteogenic differentiation of human bone mesenchymal stem cells. Here we demonstrate that the simultaneous downregulation of TRPM7 and MagT1 inhibits cell growth and activates autophagy, which is required in the early phases of osteoblastogenesis.

The dynamic adaptation of primary human endothelial cells to simulated microgravity.

Culture of human endothelial cells for 10 d in real microgravity onboard the International Space Station modulated more than 1000 genes, some of which are involved in stress response. On Earth, 24 h after exposure to simulated microgravity, endothelial cells up-regulate heat shock protein (HSP) 70. To capture a broad view of endothelial stress response to gravitational unloading, we cultured primary human endothelial cells for 4 and 10 d in the rotating wall vessel, a U.

Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Differentiation in the Presence of Vitamin D₃.

Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts.

N6-isopentenyladenosine a new potential anti-angiogenic compound that targets human microvascular endothelial cells in vitro.

N6-isopentenyladenosine is an anti-proliferative and pro-apoptotic atypical nucleoside for normal and tumor cells. Considering the role of angiogenesis in various diseases, we investigated the cytotoxic effect of N6-isopentenyladenosine on human microvascular endothelial cells, protagonists in angiogenesis. Our results show that N6-isopentenyladenosine induced a significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis.

TRPM7 and MagT1 in the osteogenic differentiation of human mesenchymal stem cells in vitro.

Mesenchymal stem cells are fundamental for bone formation and repair since they respond to microenvironmental stimuli by undergoing osteogenic differentiation. We show that the kinase and cation channel TRPM7 and the magnesium transporter MagT1 have a role in harmonizing the osteogenic differentiation of human mesenchymal stem cells. TRPM7 and MagT1 are upregulated in osteogenic differentiation and silencing either one accelerates osteogenic differentiation, partly through the activation of autophagy.

Magnesium Deprivation Potentiates Human Mesenchymal Stem Cell Transcriptional Remodeling.

Magnesium plays a pivotal role in energy metabolism and in the control of cell growth. While magnesium deprivation clearly shapes the behavior of normal and neoplastic cells, little is known on the role of this element in cell differentiation. Here we show that magnesium deficiency increases the transcription of multipotency markers and tissue-specific transcription factors in human adipose-derived mesenchymal stem cells exposed to a mixture of natural molecules, i.

Femtograms of Interferon-γ Suffice to Modulate the Behavior of Jurkat Cells: A New Light in Immunomodulation.

Since interferon-γ (IFN-γ) tunes both innate and adaptive immune systems, it was expected to enter clinical practice as an immunomodulatory drug. However, the use of IFN-γ has been limited by its dose-dependent side effects. Low-dose medicine, which is emerging as a novel strategy to treat diseases, might circumvent this restriction.

Silver Nanoparticles in Orthopedic Applications: New Insights on Their Effects on Osteogenic Cells.

Infections of orthopedic implants are associated with high morbidity. The emergence of antibiotic resistant strains and the tendency of microbes to form biofilms on orthopedic devices prompt the individuation of novel antimicrobial agents. Silver nanoparticles represent an interesting alternative, but their effects on bone cells need to be clarified.

The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin.

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells.

Extracellular magnesium and calcium blockers modulate macrophage activity.

Magnesium (Mg) possesses anti-inflammatory properties, partly because it antagonizes calcium (Ca) and inhibits L-type Ca channels. Our aim was to determine the effects of different concentrations of extracellular Mg, with or without Ca-channel blockers, in macrophages. A macrophage-like cell line J774.