(Stef.) Extract Induces Lung Cancer Apoptosis via Mitochondrial-Dependent Apoptosis Pathway.

Non-small-cell lung carcinoma remains a significant health concern due to its high incidence and mortality rates. Traditional medicines play a central role in cancer therapy, with plant-derived bioactive compounds being studied for their potential to offer fewer side effects than conventional treatments. In traditional Kurdish medicine, different species are used to treat burns, inflammation, and other conditions.

New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment.

Schizophrenia (SZ) is a complex neuropsychiatric disorder associated with severe cognitive dysfunction. Although research has mainly focused on forebrain abnormalities, emerging results support the involvement of the cerebellum in SZ physiopathology, particularly in Cognitive Impairment Associated with SZ (CIAS). Besides its role in motor learning and control, the cerebellum is implicated in cognition and emotion.

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.

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.

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.

Cytological, molecular, cytogenetic, and physiological characterization of a novel immortalized human enteric glial cell line.

Enteric glial cells (EGCs), the major components of the enteric nervous system (ENS), are implicated in the maintenance of gut homeostasis, thereby leading to severe pathological conditions when impaired. However, due to technical difficulties associated with EGCs isolation and cell culture maintenance that results in a lack of valuable models, their roles in physiological and pathological contexts have been poorly investigated so far. To this aim, we developed for the first time, a human immortalized EGC line (referred as ClK clone) through a validated lentiviral transgene protocol.

Hydrogen Sulfide (HS): As a Potent Modulator and Therapeutic Prodrug in Cancer.

Hydrogen sulfide (HS) is an endogenous gaseous molecule present in all living organisms that has been traditionally studied for its toxicity. Interestingly, increased understanding of HS effects in organ physiology has recently shown its relevance as a signalling molecule, with potentially important implications in variety of clinical disorders, including cancer. HS is primarily produced in mammalian cells under various enzymatic pathways are target of intense research biological mechanisms, and therapeutic effects of HS.

GABA and GABA Receptors Mediate GABA-Induced Intracellular Ca Signals in Human Brain Microvascular Endothelial Cells.

Numerous studies recently showed that the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), can stimulate cerebral angiogenesis and promote neurovascular coupling by activating the ionotropic GABA receptors on cerebrovascular endothelial cells, whereas the endothelial role of the metabotropic GABA receptors is still unknown. Preliminary evidence showed that GABA receptor stimulation can induce an increase in endothelial Ca levels, but the underlying signaling pathway remains to be fully unraveled. In the present investigation, we found that GABA evoked a biphasic elevation in [Ca] that was initiated by inositol-1,4,5-trisphosphate- and nicotinic acid adenine dinucleotide phosphate-dependent Ca release from neutral and acidic Ca stores, respectively, and sustained by store-operated Ca entry.

Ca dysregulation in cardiac stromal cells sustains fibro-adipose remodeling in Arrhythmogenic Cardiomyopathy and can be modulated by flecainide.

Background: Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown.

Platelet-Derived Extracellular Vesicles Stimulate Migration through Partial Remodelling of the Ca Handling Machinery in MDA-MB-231 Breast Cancer Cells.

Background: Platelets can support cancer progression via the release of microparticles and microvesicles that enhance the migratory behaviour of recipient cancer cells. We recently showed that platelet-derived extracellular vesicles (PEVs) stimulate migration and invasiveness in highly metastatic MDA-MB-231 cells by stimulating the phosphorylation of p38 MAPK and the myosin light chain 2 (MLC2). Herein, we assessed whether the pro-migratory effect of PEVs involves the remodelling of the Ca handling machinery, which drives MDA-MB-231 cell motility.

Store-Operated Ca Entry Is Up-Regulated in Tumour-Infiltrating Lymphocytes from Metastatic Colorectal Cancer Patients.

(1) Background: Store-operated Ca entry (SOCE) drives the cytotoxic activity of cytotoxic T lymphocytes (CTLs) against cancer cells. However, SOCE can be enhanced in cancer cells due to an increase in the expression and/or function of its underlying molecular components, i.e.

Optical excitation of organic semiconductors as a highly selective strategy to induce vascular regeneration and tissue repair.

Therapeutic neovascularization represents a promising strategy to rescue the vascular network and restore organ function in cardiovascular disorders (CVDs), including acute myocardial infarction, heart failure, peripheral artery disease, and brain stroke. Endothelial colony forming cells (ECFCs), which are mobilized in circulation upon an ischemic insult, are commonly regarded as the most suitable cellular tool to achieve therapeutic neovascularization. ECFCs can be genetically or pharmacologically manipulated to enhance their vasoreparative potential by boosting specific pro-angiogenic signalling pathways.

Targeting endothelial ion signalling to rescue cerebral blood flow in cerebral disorders.

The mechanism whereby an increase in neuronal activity (NA) leads to a local elevation in cerebral blood flow to supply the active neurons with oxygen and nutrients and remove the catabolic waste has been termed neurovascular coupling (NVC). Although it has long been thought that the vasoactive mediators involved in NVC are generated by neurons and astrocytes, recent evidence unveiled the crucial role of cerebrovascular endothelial cells in NVC. Brain capillary endothelial cells express a complement of ion channels, including inward-rectifier K (K2.

Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells.

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca release. NAADP-induced lysosomal Ca release may be amplified by the endoplasmic reticulum (ER) through the Ca-induced Ca release (CICR) mechanism. NAADP-induced intracellular Ca signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown.

Conjugated polymers mediate intracellular Ca signals in circulating endothelial colony forming cells through the reactive oxygen species-dependent activation of Transient Receptor Potential Vanilloid 1 (TRPV1).

Endothelial colony forming cells (ECFCs) represent the most suitable cellular substrate to induce revascularization of ischemic tissues. Recently, optical excitation of the light-sensitive conjugated polymer, regioregular Poly (3-hexyl-thiophene), rr-P3HT, was found to stimulate ECFC proliferation and tube formation by activating the non-selective cation channel, Transient Receptor Potential Vanilloid 1 (TRPV1). Herein, we adopted a multidisciplinary approach, ranging from intracellular Ca imaging to pharmacological manipulation and genetic suppression of TRPV1 expression, to investigate the effects of photoexcitation on intracellular Ca concentration ([Ca]) in circulating ECFCs plated on rr-P3HT thin films.

Reactive Oxygen Species and Endothelial Ca Signaling: Brothers in Arms or Partners in Crime?

An increase in intracellular Ca concentration ([Ca]) controls virtually all endothelial cell functions and is, therefore, crucial to maintain cardiovascular homeostasis. An aberrant elevation in endothelial can indeed lead to severe cardiovascular disorders. Likewise, moderate amounts of reactive oxygen species (ROS) induce intracellular Ca signals to regulate vascular functions, while excessive ROS production may exploit dysregulated Ca dynamics to induce endothelial injury.

NMDA receptors elicit flux-independent intracellular Ca signals via metabotropic glutamate receptors and flux-dependent nitric oxide release in human brain microvascular endothelial cells.

The excitatory neurotransmitter glutamate gates post-synaptic N-methyl-d-aspartate (NMDA) receptors (NMDARs) to mediate extracellular Ca entry and stimulate neuronal nitric oxide (NO) synthase to release NO and trigger neurovascular coupling (NVC). Neuronal and glial NMDARs may also operate in a flux-independent manner, although it is unclear whether their non-ionotropic mode of action is involved in NVC. Recently, endothelial NMDARs were found to trigger Ca-dependent NO production and induce NVC, but the underlying mode of signaling remains elusive.

Endolysosomal Ca signaling in cardiovascular health and disease.

An increase in intracellular Ca concentration ([Ca]) regulates a plethora of functions in the cardiovascular (CV) system, including contraction in cardiomyocytes and vascular smooth muscle cells (VSMCs), and angiogenesis in vascular endothelial cells and endothelial colony forming cells. The sarco/endoplasmic reticulum (SR/ER) represents the largest endogenous Ca store, which releases Ca through ryanodine receptors (RyRs) and/or inositol-1,4,5-trisphosphate receptors (InsPRs) upon extracellular stimulation. The acidic vesicles of the endolysosomal (EL) compartment represent an additional endogenous Ca store, which is targeted by several second messengers, including nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P], and may release intraluminal Ca through multiple Ca permeable channels, including two-pore channels 1 and 2 (TPC1-2) and Transient Receptor Potential Mucolipin 1 (TRPML1).

The human amniotic fluid stem cell secretome triggers intracellular Ca oscillations, NF-κB nuclear translocation and tube formation in human endothelial colony-forming cells.

Second trimester foetal human amniotic fluid-derived stem cells (hAFS) have been shown to possess remarkable cardioprotective paracrine potential in different preclinical models of myocardial injury and drug-induced cardiotoxicity. The hAFS secretome, namely the total soluble factors released by cells in their conditioned medium (hAFS-CM), can also strongly sustain in vivo angiogenesis in a murine model of acute myocardial infarction (MI) and stimulates human endothelial colony-forming cells (ECFCs), the only truly recognized endothelial progenitor, to form capillary-like structures in vitro. Preliminary work demonstrated that the hypoxic hAFS secretome (hAFS-CM ) triggers intracellular Ca oscillations in human ECFCs, but the underlying mechanisms and the downstream Ca -dependent effectors remain elusive.

Corrigendum: Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019.

[This corrects the article DOI: 10.3389/fphys.2021.

Endothelial signaling at the core of neurovascular coupling: The emerging role of endothelial inward-rectifier K (K2.1) channels and N-methyl-d-aspartate receptors in the regulation of cerebral blood flow.

Neurovascular coupling (NVC) represents the mechanisms whereby an increase in neuronal activity (NA) may lead to local vasodilation and increase in regional cerebral blood flow (CBF). It has long been thought that neurons and astrocytes generate the vasoactive mediators regulating local changes in CBF, whereas cerebrovascular endothelial cells are not able to directly sense NA. Unexpectedly, recent evidence demonstrated that brain microvascular endothelial cells may sense NA through inward-rectifier K (K2.

Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019.

Emerging evidence hints in favor of a life-threatening link between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and the cardiovascular system. SARS-CoV-2 may result in dramatic cardiovascular complications, whereas the severity of COronaVIrus Disease 2019 (COVID-19) and the incidence of fatalities tend to increase in patients with pre-existing cardiovascular complications. SARS-CoV-2 is internalized into the host cells by endocytosis and may then escape the endolysosomal system via endosomes.

Hydrogen Sulfide-Evoked Intracellular Ca Signals in Primary Cultures of Metastatic Colorectal Cancer Cells.

Exogenous administration of hydrogen sulfide (HS) is emerging as an alternative anticancer treatment. HS-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and/or inducing apoptosis in several cancer cell types, including colorectal carcinoma (CRC). The mechanism whereby exogenous HS affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca concentration ([Ca]).

A chemometric assessment and profiling of the essential oils from L. from Kurdistan, Iraq.

L. is a tropical plant belonging to the Malvaceae family. In Kurdistan, the Autonomous Region of Iraq, water infusion of calyces is recommended for the treatment of hypotension and the common cold.

Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy.

Cardiovascular disease (CVD) comprises a range of major clinical cardiac and circulatory diseases, which produce immense health and economic burdens worldwide. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization.