Increase In Calcium Research Articles

Pharmacological activation of PIEZO1 in human red blood cells prevents Plasmodium falciparum invasion

An inherited gain-of-function variant (E756del) in the mechanosensitive cationic channel PIEZO1 was shown to confer a significant protection against severe malaria. Here, we demonstrate in vitro that human red blood cell (RBC) infection by Plasmodium falciparum is prevented by the pharmacological activation of PIEZO1. Yoda1 causes an increase in intracellular calcium associated with rapid echinocytosis that inhibits RBC invasion, without affecting parasite intraerythrocytic growth, division or egress. Notably, Yoda1 treatment significantly decreases merozoite attachment and subsequent RBC deformation. Intracellular Na+/K+ imbalance is unrelated to the mechanism of protection, although delayed RBC dehydration observed in the standard parasite culture medium RPMI/albumax further enhances the resistance to malaria conferred by Yoda1. The chemically unrelated Jedi2 PIEZO1 activator similarly causes echinocytosis and RBC dehydration associated with resistance to malaria invasion. Spiky outward membrane projections are anticipated to reduce the effective surface area required for both merozoite attachment and internalization upon pharmacological activation of PIEZO1. Globally, our findings indicate that the loss of the typical biconcave discoid shape of RBCs, together with an altered optimal surface to volume ratio, induced by PIEZO1 pharmacological activation prevent efficient P. falciparum invasion.

Roflumilast alleviates adenine-induced chronic kidney disease by regulating inflammatory biomarkers

The present investigation was carried out to explore the role of roflumilast, a PDE4 inhibitor, as a potential treatment option for chronic kidney disease. Forty-six male Wistar rats were divided into five groups: Control, Disease control (50 mg/kg Adenine p.o.), Adenine + Roflumilast (0.5, 1 and 1.5 mg/kg, p.o.). Various urinary and serum biomarkers, antioxidant status, histopathology, and protein expression of inflammatory markers were measured to investigate the effects of roflumilast on kidney functions. Adenine was found to elevate the levels of serum creatinine, urea, uric acid, sodium, potassium, chloride, magnesium, and phosphorus and reduce the level of serum calcium. Further, adenine significantly increased the serum TGF-β levels and reduced the anti-oxidant indices. Significant elevation was observed in protein expression of IL-1β, TNF-α, MCP-1, ICAM-1, and Fibronectin. Histopathologically, adenine caused thickening of the glomerular basement membrane, inflammatory cells infiltration, atrophy, and glomeruli deterioration. However, Roflumilast administration (1 mg/kg) remarkably decrease serum creatinine, urea, uric acid, sodium, potassium, chloride, magnesium, phosphorus by 61%, 40%, 44%, 41%, 49%, 58%, 59% and 42% respectively, and increase in calcium by 158%. Moreover, Roflumilast (1 mg/kg) significantly reduced serum TGF-β levels by 50% and elevated anti-oxidant indices by 257%, 112%, and 60%, respectively. The protein expression was significantly reduced by 5.5-fold, 7-fold, 5.7-fold, 6.2-fold, and 5.1-fold individually. Roflumilast noticeably improved the structure of glomeruli, tubules, and cellular functioning. The study confirmed that Roflumilast has the potential to ameliorate renal injury by reducing and regulating inflammatory responses.

Changes in K+ Concentration as a Signaling Mechanism in the Apicomplexa Parasites Plasmodium and Toxoplasma.

During their life cycle, apicomplexan parasites pass through different microenvironments and encounter a range of ion concentrations. The discovery that the GPCR-like SR25 in Plasmodium falciparum is activated by a shift in potassium concentration indicates that the parasite can take advantage of its development by sensing different ionic concentrations in the external milieu. This pathway involves the activation of phospholipase C and an increase in cytosolic calcium. In the present report, we summarize the information available in the literature regarding the role of potassium ions during parasite development. A deeper understanding of the mechanisms that allow the parasite to cope with ionic potassium changes contributes to our knowledge about the cell cycle of Plasmodium spp.

Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.

The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E2 (PGE2), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE2 and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE2 whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair.

Possible pathogenetic features of the development and progression of osteoarthritis in the metabolic syndrome (diabetes mellitus, obesity, arterial hypertension)


 The paper emphasizes the pathogenetic features of osteoarthritis in the metabolic syndrome (type 2 diabetes, obesity, and arterial hypertension), such as the violation of the structure of the bone and cartilage tissue of the joints. Attention is paid to such mechanisms as oxidative stress, low-grade chronic systemic inflammation, and participation of the cartilage extracellular matrix, where matriline-3 protein plays an important role. It is involved in cartilage development and possible pathological mechanisms contributing to the onset and progression of osteoarthritis/osteoarthritis.
 The significance of abnormal levels of reactogenic forms of oxygen, superoxide anion, and nitrogen monoxide, which provide an increase in the level of peroxynitrite, hydrogen peroxide, myeloperoxidase, and hypochlorous acid, is discussed in detail. It is indicated that in the presence of iron and hydrogen peroxide, chondrocytes release hydroxyl radicals that react with unsaturated fatty acids of membranes and start a chain reaction, producing radicals with a long lifetime. This causes degradation of both the cellular and intercellular components of the cartilage. In addition, intra-articular connections are formed, and the vascular wall is restructured, leading to impaired microcirculation in bone and cartilage tissue due to damage to the vascular endothelium, vasospasm, increased blood clotting, the formation of microemboli, and venous occlusion. As a result, ischemia of the subchondral bone develops, along with damage to the cartilage tissue and a local disturbance of microcirculation. The thickness of the subchondral bone decreases due to angiogenesis at the junction of the articular hyaline cartilage and adjacent subchondral bone in patients with osteoarthritis. This process enhances degenerative-inflammatory changes in the structure of the cartilage due to a violation of metabolic processes in it.
 The importance of lipid and protein peroxidation in the regulation of intracellular calcium homeostasis and the ability of smooth muscles to undergo persistent contractions, which cause muscle pain, are emphasized. Pathogenetically, an important role in this process is played by the inhibition of calcium-ATPase in the sarcoplasmic reticulum, the activation of calcium flow through calcium channels, and an increase in intracellular calcium. Hypocalcemia and hypercalciuria in patients with metabolic syndrome contribute to the progression of not only osteoarthritis but other components of the syndrome.
 Attention is drawn to the significance of the cytokine link as an important mechanism for the onset and progression of osteoarthritis/osteoarthritis. The features of the reaction of chronic systemic inflammation with the participation of IL-18 and IL-10 in the structure of the extracellular matrix of cartilage, where matrilin-3 protein plays an important role since it is involved both in the development of cartilage and in the progression of osteoarthrosis, depending on multimorbidity with other components of metabolic syndrome, are highlighted.

Effect of engineered water and scale inhibitor concentration on the adsorption performance of gypsum inhibitors on multi‐walled carbon nanotubes and crushed sandstone

AbstractEngineered waterflooding is an effective process for enhanced oil recovery, but it can lead to mineral scale deposition due to the incompatibility of brines. Previous studies on scale mitigation have mainly focused on high‐temperature baryte and anhydrite scales, neglecting gypsum precipitation and inhibitors adsorption at low temperatures. Additionally, earlier research has used simple brines that do not reflect the actual injection and formation water in reservoirs. In this study, the impact of temperature, various brine mixtures, and thermodynamic databases on saturation ratio and scale precipitation is explored using PHREEQC (pH‐REdox‐EQuilibrium‐C program). The study reveals that the copresence of calcium and magnesium ions improves the gypsum inhibition efficiency of scale inhibitors (SIs) at low concentrations to a maximum of 79%. However, this effect is reversed or neutral at higher SI concentrations. The study also shows that the presence of monovalent ions reduces the adsorption of SIs by multi‐walled carbon nanotubes (MWCNTs). Removing sodium ions from seawater while leaving calcium and magnesium ions intact increases MWCNTs' adsorption capability to 93%. This is because monovalent cations attach to the adsorbent surface and block the active sites, whereas divalent cations act as a bridge between MWCNT and SIs. The study establishes that the behaviour of SIs regarding adsorption on MWCNT and crushed sandstone depends on various factors, including molecule size, calcium toleration of the SIs, point of zero charge, and solution pH. Understanding these factors can improve the effectiveness of SIs, reduce chemical costs, and prolong the life of oil wells.

Cyanidin inhibits adipogenesis in 3T3-L1 preadipocytes by activating the PLC-IP3 pathway

Cyanidin is the most abundant anthocyanin found in red-purple plants and possesses anti-obesity properties. However, its mechanism of action in adipocytes remains unknown. The objective of this study was to elucidate how cyanidin inhibits adipocyte formation in 3T3-L1 preadipocytes. Cells were cultured in adipogenic differentiation medium supplemented with cyanidin and examined for adipogenesis, cell viability, and adipocyte gene expression using Oil Red O staining, MTT assay, and RT-qPCR. Real-time Ca2+ imaging analysis was performed in living cells to elucidate cyanidin’s mechanism of action. The results demonstrated that cyanidin (1–50 μM) supplementation to the adipogenic medium inhibited adipogenesis by downregulating adipogenic marker gene expression (PPARγ, C/EBPα, adiponectin, and aP2) without affecting cell viability after 4 days of treatment. Stimulation of cells with cyanidin (30–100 μM) increased intracellular Ca2+ in a concentration dependent manner with peak calcium increases at 50 μM. Pretreatment of cells with the phospholipase C (PLC) inhibitor U73122, inositol triphosphate (IP3) receptor blocker 2-APB, and depletion of endoplasmic reticulum Ca2+ stores by thapsigargin abolished the Ca2+ increases by cyanidin. These findings suggested that cyanidin inhibits adipocyte formation by activating the PLC-IP3 pathway and intracellular Ca2+ signaling. Our study is the first report describing the mechanism underlying the anti-obesity effect of cyanidin.

Determination of the roles of cADPR and NAADP as intracellular calcium mobilizing messengers in S1P-induced contractions in rat bladders having IC/PBS

AimsInterstitial cystitis/painful bladder syndrome (IC/PBS) is characterized by lower abdominal pain and increased frequency and urgency of urine. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that plays role in calcium homeostasis in smooth muscle. The intracellular calcium mobilizing secondary messengers are also involved in smooth muscle contraction. The role of intracellular calcium storing depots in S1P-induced contraction was investigated in permeabilized detrusor smooth muscle having cystitis. Main methodsIC/PBS was induced by cyclophosphamide injection. The detrusor smooth muscle strips isolated from rats were permeabilized with β-escin. Key findingsS1P-induced contraction was increased in cystitis. S1P-induced enhanced contraction was inhibited by cyclopiazonic acid, ryanodine and heparin showing involvement of sarcoplasmic reticulum (SR) calcium stores. Inhibition of S1P-induced contraction by bafilomycin and NAADP suggested the participation of lysosome-related organelles. SignificanceIC/PBS triggers S1P-induced increase in intracellular calcium from SR and lysosome-related organelles in permeabilized detrusor smooth muscle.

Glittering Christmas tree cataract – The role of Scheimpflug, anterior segment optical coherence tomography, and biochemical analysis

Christmas tree cataract has rarely been described. It is characterized by a polychromatic luster, the exact etiology of which is unclear. Postulated causes for this include the possible role of cholesterol or calcium deposition. We describe a case of a unilateral Christmas tree cataract in a patient who underwent cataract surgery and highlight the role of Scheimpflug and anterior segment optical coherence tomography (ASOCT) in complementing the clinical diagnosis. Further, biochemical analysis of the lens matter revealed an increase in calcium and cholesterol.

The pair ceramide 1-phosphate/ceramide kinase regulates intracellular calcium and progesterone-induced human sperm acrosomal exocytosis.

Before fertilization, spermatozoa must undergo calcium-regulated acrosome exocytosis in response to physiological stimuli such as progesterone and zona pellucida. Our laboratory has elucidated the signaling cascades accomplished by different sphingolipids during human sperm acrosomal exocytosis. Recently, we established that ceramide increases intracellular calcium by activating various channels and stimulating the acrosome reaction. However, whether ceramide induces exocytosis on its own, activation of the ceramide kinase/ceramide 1-phosphate (CERK/C1P) pathway or both is still an unsolved issue. Here, we demonstrate that C1P addition induces exocytosis in intact, capacitated human sperm. Real-time imaging in single-cell and calcium measurements in sperm population showed that C1P needs extracellular calcium to induce [Ca2+]i increase. The sphingolipid triggered the cation influx through voltage-operated calcium (VOC) and store-operated calcium (SOC) channels. However, it requires calcium efflux from internal stores through inositol 3-phosphate receptors (IP3R) and ryanodine receptors (RyR) to achieve calcium rise and the acrosome reaction. We report the presence of the CERK in human spermatozoa, the enzyme that catalyzes C1P synthesis. Furthermore, CERK exhibited calcium-stimulated enzymatic activity during the acrosome reaction. Exocytosis assays using a CERK inhibitor demonstrated that ceramide induces acrosomal exocytosis, mainly due to C1P synthesis. Strikingly, progesterone required CERK activity to induce intracellular calcium increase and acrosome exocytosis. This is the first report, implicating the bioactive sphingolipid C1P in the physiological progesterone pathway leading to the sperm acrosome reaction.

Multi-Parametric Birefringence Control in Ultrashort-Pulse Laser-Inscribed Nanolattices in Fluorite

An ultrashort-pulse laser inscription of embedded birefringent microelements was performed inside bulk fluorite in pre-filamentation (geometrical focusing) and filamentation regimes as a function of laser wavelength, pulsewidth and energy. The resulting elements composed of anisotropic nanolattices were characterized by retardance (Ret) and thickness (T) quantities, using polarimetric and 3D-scanning confocal photoluminescence microscopy, respectively. Both parameters exhibit a monotonous increase versus pulse energy, going over a maximum at 1-ps pulsewidth at 515 nm, but decrease versus laser pulsewidth at 1030 nm. The resulting refractive-index difference (RID) Δn = Ret/T ~ 1 × 10-3 remains almost constant versus pulse energy and slightly decreases at a higher pulsewidth, generally being higher at 515 nm. The birefringent microelements were visualized using scanning electron microscopy and chemically characterized using energy-dispersion X-ray spectroscopy, indicating the increase of calcium and the contrary decrease of fluorine inside them due to the non-ablative inscription character. Dynamic far-field optical diffraction of the inscribing ultrashort laser pulses also demonstrated the accumulative inscription character, depending on the pulse energy and the laser exposure. Our findings revealed the underlying optical and material inscription processes and demonstrated the robust longitudinal homogeneity of the inscribed birefringent microstructures and the facile scalability of their thickness-dependent retardance.

Iatrogenic endocrine complications of lithium therapy

Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine complications of lithium treatment affect thyroid and parathyroid glands, in association with renal complications. Thyroid adverse effects, which are more frequent in women, comprise hypothyroidism, goiter, or sometimes hyperthyroidism, through interference with the iodine symporter. The increase in thyroid volume is early. Prevalence of goiter is 4 times higher than in the general population and hypothyroidism (8–20%) more frequent in case of pre-existing thyroid autoimmunity. Hyperthyroidism likely to worsen mood is reported in 5% of cases but the causal link to lithium is unproven. An increase in serum calcium and PTH occurs in 30% of cases, as lithium stimulates parathyroid cell proliferation by activating the Wnt pathway. The risk of hyperparathyroidism, by adenoma and especially by hyperplasia, is 5 times higher than in the general population, with the particularity of frequent low urine calcium by action on the calcium-sensing receptor (CaSR). Renal complications include risk of acute or chronic renal failure and nephrogenic diabetes insipidus, which is a factor for hypernatremia and hypercalcemia through dehydration. Nephrogenic diabetes insipidus is not always reversible after lithium therapy discontinuation. Metabolically, weight gain can be observed, but rather less than with other psychotropic drugs, and lithium does not in itself induce diabetes. At pituitary level, corticotropic activation is frequent, but implicating the disease rather than lithium. Lithium treatment induces little or no hyperprolactinemia. Regular monitoring of serum calcium, the ionogram, creatinine and TSH is recommended in lithium treatment.

Endoplasmic Reticulum Calcium MediatesDrosophilaWing Development

Background: The temporal dynamics of morphogen presentation impacts transcriptional responses and tissue patterning. However, the mechanisms controlling morphogen release are far from clear. We found that inwardly rectifying potassium (Irk) channels regulate endogenous transient increases in intracellular calcium and bone morphogenetic protein (BMP/Dpp) release for Drosophila wing development. Inhibition of Irk channels reduces BMP/Dpp signaling, and ultimately disrupts wing morphology. Ion channels impact development of several tissues and organisms in which BMP signaling is essential. In neurons and pancreatic beta cells, Irk channels modulate membrane potential to affect intracellular Ca++ to control secretion of neurotransmitters and insulin. Based on Irk activity in neurons, we hypothesized that electrical activity controls endoplasmic reticulum (ER) Ca++ release into the cytoplasm to regulate the release of BMP. Materials and Methods: To test this hypothesis, we reduced expression of four proteins that control ER calcium, Stromal interaction molecule 1 (Stim), Calcium release-activated calcium channel protein 1 (Orai), SarcoEndoplasmic Reticulum Calcium ATPase (SERCA), small conductance calcium-activated potassium channel (SK), and Bestrophin 2 (Best2) using RNAi and documented wing phenotypes. We use live imaging to study calcium and Dpp release within pupal wings and larval wing discs. Additionally, we employed immunohistochemistry to characterize Small Mothers Against Decapentaplegic (SMAD) phosphorylation downstream of the BMP/Dpp pathway following RNAi knockdown. Results: We found that reduced Stim and SERCA function decreases amplitude and frequency of endogenous calcium transients in the wing disc and reduced BMP/Dpp release. Conclusion: Our results suggest control of ER calcium homeostasis is required for BMP/Dpp release, and Drosophila wing development.

P85α regulatory subunit isoform controls PI3-kinase and TRPC6 membrane translocation

Activation of phosphatidylinositol 3-kinase (PI3K) by lipid oxidation products, including lysophosphatidylcholine (lysoPC), increases the externalization of canonical transient receptor potential 6 (TRPC6) channels leading to a subsequent increase in intracellular calcium that contributes to cytoskeletal changes which inhibit endothelial cell (EC) migration in vitro and impair EC healing of arterial injuries in vivo. The PI3K p110α and p110δ catalytic subunit isoforms regulate lysoPC-induced TRPC6 externalization in vitro, but have many other functions. The goal of the current study is to identify the PI3K regulatory subunit isoform involved in TRPC6 externalization to potentially identify a more specific treatment regimen to improve EC migration and arterial healing, while minimizing off-target effects. Decreasing the p85α regulatory subunit isoform protein levels, but not the p85β and p55γ regulatory subunit isoforms, with small interfering RNA inhibits lysoPC-induced translocation of the PI3K catalytic subunit to the plasma membrane, dramatically decreased phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production and TRPC6 externalization, and significantly improves EC migration in the presence of lysoPC. These results identify the important and specific role of p85α in controlling translocation of PI3K from the cytosol to the plasma membrane and PI3K-mediated TRPC externalization by oxidized lipids. Current PI3K inhibitors block the catalytic subunit, but our data suggest that the regulatory subunit is a novel therapeutic target to promote EC migration and healing after arterial injuries that occur with angioplasty.

Inhibition of NHE1 transport activity and gene transcription in DRG neurons in oxaliplatin-induced painful peripheral neurotoxicity

Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN), one of the major dose-limiting side effects of colorectal cancer treatment, is characterized by both acute and chronic syndromes. Acute exposure to low dose OHP on dorsal root ganglion (DRG) neurons is able to induce an increase in intracellular calcium and proton concentration, thus influencing ion channels activity and neuronal excitability. The Na+/H+ exchanger isoform-1 (NHE1) is a plasma membrane protein that plays a pivotal role in intracellular pH (pHi) homeostasis in many cell types, including nociceptors. Here we show that OHP has early effects on NHE1 activity in cultured mouse DRG neurons: the mean rate of pHi recovery was strongly reduced compared to vehicle-treated controls, reaching levels similar to those obtained in the presence of cariporide (Car), a specific NHE1 antagonist. The effect of OHP on NHE1 activity was sensitive to FK506, a specific calcineurin (CaN) inhibitor. Lastly, molecular analyses revealed transcriptional downregulation of NHE1 both in vitro, in mouse primary DRG neurons, and in vivo, in an OIPN rat model. Altogether, these data suggest that OHP-induced intracellular acidification of DRG neurons largely depends on CaN-mediated NHE1 inhibition, revealing new mechanisms that OHP could exert to alter neuronal excitability, and providing novel druggable targets.

CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles.

Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.

The effect of GdYVO4:Eu3+ nanocrystals on the intercellular adhesion of mesenchymal stem cells in vitro

Adult stem cells, such as MSCs, spontaneously differentiate in vitro. This makes it difficult both to study this important cell type and to grow large numbers of MSCs for clinical use. While conventional cell cultivation methods cannot cope with this problem, nanostructured materials science offers hope. The effect of small-sized spherical nanoparticles based on orthovanadates of rare-earth elements activated by europium (GdYVO4:Eu3+ nanoparticles, diameter 1–2 nm) on cell-cell adhesion of rat bone marrow mesenchymal stem cells (rBM-MSCs) in vitro was studied using electrophoretic separation of proteins, immunofluorescence and confocal laser scanning microscopy. Our study revealed that rBM-MSCs treated with small-sized GdYVO4:Eu3+ nanoparticles had a significant impairment of intercellular adhesion in vitro. The pre-incubation of mesenchymal stem cells of rat bone marrow with GdYVO4:Eu3+ nanocrystals at a non-toxic concentration of 0.5 µg/mL during 1 hour of cultivation did not lead to significant changes in cell monolayer, the number of cells and the area of cell bodies did not change. However, the density of the monolayer and the area of the cell field decreased after the incubation. The incubation of cells with nanoparticles led to an increase in the area of the intercellular gate – a location of disruption of cell adhesion, compared to cells without nanoparticles in culture medium. The pre-incubation of rBM-MSCs with nanocrystals caused no changes in the content of total cadherins in the plasma membrane; a decrease in the content of cytoplasmic calreticulin and an increase in the content of surface calreticulin; a decrease in the content of free calcium in the cytoplasm, and an increase in protein-bound intercellular calcium and calcium in the extracellular space. The colocalization analysis revealed that the colocalization of calreticulins with cadherins on the outer surface of the plasma membrane of cells significantly increased after the incubation with GdYVO4:Eu3+ nanocrystals. The paper proposes a possible mechanism of reducing the degree of adhesion by nanocrystals. This study emphasizes the possibility of modulating MSCs adhesion using GdYVO4:Eu3+ nanoparticles. The development of new technologies capable of mitigating adhesion is crucial for the development of regenerative strategies using stem cells.

СОДЕРЖАНИЕ ИОНИЗИРОВАННОГО КАЛЬЦИЯ В РОТОВОЙ ЖИДКОСТИ У ДЕТЕЙ В ГОРОДЕ С ЭКОТОКСИКАНТАМИ

The study of the pathogenesis of enamel demineralization in children living in a city with ecotoxicants is an urgent task of modern dentistry. We examined 183 schoolchildren aged 7 and 12 in Ufa. The children were divided into groups depending on where they live. The first group included 94 children from an area located in an industrial district with an environmentally unfavorable situation. The second group (control) included 89 schoolchildren living in an ecologically good district of the city of Ufa. We studied the content of free calcium in the saliva of schoolchildren in two districts of the city of Ufa. When determining the activity of caries according to Vinogradova T.F. (I, II, III degree) among 7 and 12-year-old children, we did not reveal a high correlation between the district where the children live and the concentration of free calcium in the oral fluid. In the mixed saliva of 7-year-old schoolchildren of the first and second groups, the concentration of free calcium was 0.645 ± 0.018 and 0.638 ± 0.011 mm/l (p > 0.05), in 12-year-olds it was 0.603 ± 0.050 and 0.597 ± 0.040 mm/l (p > 0.05). In the industrial district, we noted the maximum increase in free calcium at the III degree of caries activity. This indicator was 0.851 ± 0.006 mmol/l (p < 0.001) in 7-year-old children, and 0.760 ± 0.005 mmol/l in 12-year-old schoolchildren (p < 0.001). While in the district without ecotoxicants, free calcium in 7-year-old schoolchildren was 0.846 ± 0.026 mmol/l (p < 0.001), and in 12-year-old children it was 0.774 ± 0.010 mmol/l (p < 0.001). Thus, the third degree of caries activity is highly correlated with an increase in the concentration of free calcium in saliva, which is proved by studies of oral fluid in schoolchildren from different districts of Ufa.

Lipid ROS- and Iron-Dependent Ferroptotic Cell Death in Unicellular Algae Chlamydomonas reinhardtii.

The phenomenon of heat stress leading to ferroptosis-like cell death has recently been observed in bacteria as well as plant cells. Despite recent findings, the evidence of ferroptosis, an iron-dependent cell death remains unknown in microalgae. The present study aimed to investigate if heat shock could induce reactive oxygen species (ROS) and iron-dependent ferroptotic cell death in Chlamydomonas reinhardtii in comparison with RSL3-induced ferroptosis. After RSL3 and heat shock (50 °C) treatments with or without inhibitors, Chlamydomonas cells were evaluated for cell viability and the induction of ferroptotic biomarkers. Both the heat shock and RSL3 treatment were found to trigger ferroptotic cell death, with hallmarks of glutathione-ascorbic acid depletion, GPX5 downregulation, mitochondrial dysfunction, an increase in cytosolic calcium, ROS production, lipid peroxidation, and intracellular iron accumulation via heme oxygenase-1 activation (HO-1). Interestingly, the cells preincubated with ferroptosis inhibitors (ferrostatin-1 and ciclopirox) significantly reduced RSL3- and heat-induced cell death by preventing the accumulation of Fe2+ and lipid ROS. These findings reveal that ferroptotic cell death affects the iron homeostasis and lipid peroxidation metabolism of Chlamydomonas, indicating that cell death pathways are evolutionarily conserved among eukaryotes.

The effect of acidification temperature and pH on intermolecular protein bonds and water mobility in heat and acid-induced milk gels

Pre-heated milk was gelled by acidification at 60, 70, 80, and 90 °C, to pH 5.2 or 4.6. The resultant milk gels were characterised in terms of composition, molecular protein bonds, and water mobility. The protein network structure of the gels was mainly governed by calcium bonds (30–63%), independent of the acidification temperature and pH. However, acidification temperature affected the aggregation kinetics and buffer capacity of the milk. Increased temperature led to an increase in total calcium in the gels (187% and 71% for pH 5.2 and 4.6 respectively) since colloidal calcium phosphate dissociated to a lesser degree, increasing the calcium bonds in the protein structure network. The largest water population in the gels was assigned to protons entrapped within the protein network, and the transverse relaxation time decreased with both increase in acidification temperature and decrease of pH, due to the increasing density of the gel aggregates.