The Ca2+-MdCRF4-MdWRKY9 module negatively affects apple fruit watercore formation by suppressing the transcription of MdSOT2.

Watercore is a common physiological disease of Rosaceae plants, such as apples (Malus domestica), usually occurring during fruit ripening. Apple fruit with watercore symptoms is prone to browning and rotting, thus losing commercial viability. Sorbitol and calcium ions are considered key factors affecting watercore occurrence in apples. However, the mechanism by which they affect the occurrence of watercore remains unclear. Here, we identified that the transcription factor MdWRKY9 directly binds to the promoter of MdSOT2, positively regulates the transcription of MdSOT2, increases sorbitol content in fruit, and promotes watercore occurrence. Additionally, MdCRF4 can directly bind to MdWRKY9 and MdSOT2 promoters, positively regulating their expression. Since calcium ions can induce the ubiquitination and degradation of the transcription factor MdCRF4, they can inhibit the transcription of MdWRKY9 and MdSOT2 by degrading MdCRF4, thereby reducing the sorbitol content in fruit and inhibiting the occurrence of fruit watercore disease. Our data sheds light on how calcium ions mitigate watercore in fruit, providing molecular-level insights to enhance fruit quality artificially.

Analyzing fuzzy boundary value problems: a study on the influence of mitochondria and ER fluxes on calcium ions in neuron cells.

Cytosolic-free calcium ions play an important role in various physical and physiological processes. A vital component of neural signaling is the free calcium ion concentration often known as the second messenger. There are many parameters that effect the cytosolic free calcium concentration like buffer, voltage-gated ion channels, Endoplasmic reticulum, Mitochondria, etc. Mitochondria are small organelles located within the nervous system that are involved in processes within cells such as calcium homeostasis management, energy generation, response to stress, and cell demise pathways. In this work, a mathematical model with fuzzy boundary values has been developed to study the effect of Mitochondria and ER fluxes on free Calcium ions. The intended findings are displayed utilizing the physiological understanding that amyloid beta plaques and tangles of neurofibrillary fibers have been identified as the two main causes of AD. The key conclusion of the work is the investigation of [Formula: see text] for healthy cells and cells affected by Alzheimer's disease, which may aid in the study of such processes for computational scientists and medical practitioners. Also, it has been shown that when a unique solution is found for a specific precise problem, it also successfully deals with any underlying ambiguity within the problem by utilizing a technique based on the principles of linear transformation. Furthermore, the comparison between the analytical approach and the generalized hukuhara derivative approach is shown here, which illustrates the benefits of the analytical approach. The simulation is carried out in MATLAB.

Insufficient and excessive Ca2+ intake negatively impact the life history performance and disrupt the hemolymph metabolism of Spodoptera litura.

Calcium ions (Ca2+), essential as second messengers in all cells, play a pivotal role as micronutrients in insects. However, few studies have explored the effects of both insufficient and excessive Ca2+ intake on life history performance and population parameters. This study examines the impact of varying Ca2+ intake levels-insufficient (0 mg/kg), appropriate (100 mg/kg), and excessive (250 mg/kg)-on the life history performance and population parameters of Spodoptera litura using two-sex life tables. Insufficient and excessive Ca2+ intakes significantly extended the preadult development period and decreased the preadult survival rates of S. litura, compared to those on an appropriate Ca2+ intake. The population parameters (Intrinsic rate of increase (r), Finite rate of increase (λ), and Net reproductive rate (R0)) of S. litura on a 100 mg/kg diet (r = 0.1364, λ = 1.1462, R0 = 390) were significantly higher than those on a 0 mg/kg diet (r = 0.1091, λ = 1.1153, R0 = 130.52). Additionally, untargeted metabolomics analysis revealed that inappropriate Ca2+ levels (either insufficient or excessive) triggered significant up-regulation of 71.1 % and 92.8 % of the metabolites in the hemolymph, respectively, compared to the appropriate Ca2+ intake. Notably, disruptions in metabolite balance affected critical components such as melatonin and melanin within the tryptophan and tyrosine metabolism pathways. These findings underscore that both insufficient and excessive Ca2+ intakes adversely affect the life history performance and disrupt hemolymph metabolic balance in S. litura.

The effect of apple pomace powder and calcium ions on selected physicochemical properties of freeze-dried carrot-orange-ginger snacks.

BACKGROUND: This study aimed to determine the effect of various amounts of dried apple pomace (AP) powder and calcium ions on selected physicochemical properties of restructured freeze-dried snacks in comparison with products obtained with low-methoxyl pectin (LMP). The material was prepared using frozen carrot, orange concentrate, ginger, water, and various concentrations of AP (1, 3, 5%) and calcium lactate (0, 0.01, 0.05%). The reference samples were without additives, and with 0.5 or 1.5% of LMP combined with 0.01% of calcium lactate. RESULTS: The material was studied in terms of water content and activity, hygroscopic properties, structure, texture, color, and polyphenol content (TPC), and antioxidant activity. The addition of AP resulted in reducing water activity and porosity. As a consequence of the increasing density of the structure, the reduction of hygroscopic properties by up to 16% followed the increasing amount of AP. Apple pomace and calcium ions strengthened the structure. The addition of 3% and 5% of AP gave a hardening effect close to or better than 0.5% LMP. Because of the pigment dilution, LMP caused significantly greater total color change than AP. The incorporation of AP also increased TPC and enhanced antioxidant activity in comparison with the reference materials by up to 18%. CONCLUSION: The results showed that dried AP powder can be applied successfully as an additive enhancing stability, texture and bioactive compound content, thus fortifying the physicochemical properties of restructured freeze-dried fruit and vegetable snacks. © 2023 Society of Chemical Industry.

Analysis of the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis.

PURPOSE: To investigate the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis and to analyse the possible mechanism. METHODS: Forty rabbits were divided into five groups randomly: 0.1% riboflavin-balanced salt solution (BSS) by iontophoresis group, 0.1% riboflavin-saline solution by iontophoresis group, 0.1% riboflavin-zinc gluconate solution by iontophoresis group, 0.1% riboflavin-calcium gluconate solution by iontophoresis group and classical riboflavin instillation after corneal de-epithelialization as the control group. The riboflavin concentrations in corneal stroma were determined and compared by high-performance liquid chromatography (HPLC) after removing epithelium and endothelium. RESULTS: Iontophoretic delivery of a 0.1% riboflavin-calcium gluconate solution was the closest to the effect of classical de-epithelialization. The other solvents were unsufficient at enhancing the permeability of the riboflavin. CONCLUSION: Calcium ions can promote the penetrability of riboflavin into the corneal stroma by iontophoresis.

Development and physicochemical characteristics of multicomponent freeze-dried snacks obtained with blackcurrant pomace powder and calcium ions as structuring agents.

Consumers seek healthy and sustainable products, whereas the food industry faces the challenge of processing by-products management. The application of fruit pomace as an additive could be a solution addressing the needs of both consumers and producers. The research objective has been to assess the effect of dried blackcurrant pomace powder (BP) and calcium ions in varied concentration on the physicochemical properties of multicomponent freeze-dried snacks as compared to the influence of low-methoxyl pectin (LMP). The snacks were prepared using varied content of BP (1, 3, 5%) and calcium lactate (0, 0.01, 0.05%). Water content and activity, hygroscopic properties, structure, texture, colour, polyphenols content (TPC), and antioxidant activity were analysed. The addition of BP resulted in lowering water activity and porosity. The microstructure of the snacks consisted of a large number of small and unevenly distributed pores. Consequently, the reduction of hygroscopic properties with the growing amount of BP was observed. Applied additives strengthened the structure and caused changes in compression curves indicating enhanced hardness and crispiness. The effect given by 5% of BP was comparable to that obtained with 0.5% of LMP. Additionally, blackcurrant pomace infusion increased TPC and enhanced antioxidant activity but it also caused significant changes in the colour of the snacks. Overall, obtained results have shown that dried blackcurrant pomace powder (BP) can be successfully applied as a food additive supporting stability, texture, and bioactive compounds content, thus fortifying the physicochemical properties of freeze-dried fruit and vegetable snacks.

Sustainable, Insoluble, and Photonic Cellulose Nanocrystal Patches for Calcium Ion Sensing in Sweat.

Self-assembly of cellulose nanocrystals (CNCs) is invaluable for the development of sustainable optics and photonics. However, the functional failure of CNC-derived materials in humid or liquid environments inevitably impairs their development in biomedicine, membrane separation, environmental monitoring, and wearable devices. Here, a facile and robust method to fabricate insoluble hydrogels in a self-assembled CNC-polyvinyl alcohol (PVA) system is reported. Due to the reconstruction of inter- or intra-molecular hydrogen bond interactions, thermal dehydration makes an optimized CNC/PVA photonic film form a stable hydrogel network in an aqueous solution rather than dissolve. Notably, the resulting hydrogel exhibits superb mechanical performance (stress up to 3.3 Mpa and tough up to 0.73 MJ m-3 ) and reversible conversion between dry and wet states, enabling it convenient for specific functionalization. Sodium alginate (SA) can be adsorbed into the CNC photonic structure by swelling dry CNC/PVA film in a SA solution. The prepared hydrogel showcases the comprehensive properties of freezing resistance (-20°C), strong adhesion, satisfactory biocompatibility, and highly sensitive and selective Ca2+ sensing. The material could act as a portable wearable patch on the skin for the continuous analysis of calcium trends during different physical exercises, facilitating their development in precision nutrition and health monitoring.

An In Situ Assembled Trapping Gel Repairs Spinal Cord Injury by Capturing Glutamate and Free Calcium Ions.

Spinal cord injury (SCI) can lead to devastating autonomic dysfunction. One of the most challenging issues for functional repair in SCI is the secondary damage caused by the increased release of glutamate and free Ca2+ from injured cells. Here, an in situ assembled trapping gel (PF-SA-GAD) is developed to sweep glutamate and Ca2+ , promoting SCI repair. The hydrogel solution is a mixture of recombinant glutamate decarboxylase 67 (rGAD67) protein, sodium alginate (SA), and pluronic F-127 (PF-127). After intrathecal administration, temperature-sensitive PF-127 promoted in situ gelation. Glutamate (Glu) is captured and decarboxylated by rGAD67 into γ-aminobutyric acid (GABA). SA reacted with the free Ca2+ to generate gellable calcium alginate. Thereby, this in situ trapping gel retarded secondary neuron injury caused by Glu and free Ca2+ during SCI. In rat models of SCI, PF-SA-GAD reduces the lesion volume and inflammatory response after SCI, restores the motor function of rats with SCI. Together, the in situ assembled trapping gel is a long-term effective and minimally invasive sweeper for the direct elimination of glutamate and Ca2+ from injury lesions and can be a novel strategy for SCI repair by preventing secondary injury.

Ca2+ Regulates Autophagy Through CaMKKß/AMPK/mTOR Signaling Pathway in Mechanical Spinal cord Injury: An in vitro Study.

Spinal cord injury (SCI), resulting in damage of the normal structure and function of the spinal cord, would do great harm to patients, physically and psychologically. The mechanism of SCI is very complex. At present, lots of studies have reported that autophagy was involved in the secondary injury process of SCI, and several researchers also found that calcium ions (Ca2+) played an important role in SCI by regulating necrosis, autophagy, or apoptosis. However, to our best of knowledge, no studies have linked the spinal cord mechanical injury, intracellular Ca2+, and autophagy in series. In this study, we have established an in vitro model of SCI using neural cells from fetal rats to explore the relationship among them, and found that mechanical injury could promote the intracellular Ca2+ concentration, and the increased Ca2+ level activated autophagy through the CaMKKß/AMPK/mTOR pathway. Additionally, we found that apoptosis was also involved in this pathway. Thus, our study provides new insights into the specific mechanisms of SCI and may open up new avenues for the treatment of SCI.

Gene editing of putative cAMP and Ca2+ -regulated proteins using an efficient cloning-free CRISPR/Cas9 system in Trypanosoma cruzi.

Trypanosoma cruzi, the agent of Chagas disease, must adapt to a diversity of environmental conditions that it faces during its life cycle. The adaptation to these changes is mediated by signaling pathways that coordinate the cellular responses to the new environmental settings. Cyclic AMP (cAMP) and Calcium (Ca2+ ) signaling pathways regulate critical cellular processes in this parasite, such as differentiation, osmoregulation, host cell invasion and cell bioenergetics. Although the use of CRISPR/Cas9 technology prompted reverse genetics approaches for functional analysis in T. cruzi, it is still necessary to expand the toolbox for genome editing in this parasite, as for example to perform multigene analysis. Here we used an efficient T7RNAP/Cas9 strategy to tag and delete three genes predicted to be involved in cAMP and Ca2+ signaling pathways: a putative Ca2+ /calmodulin-dependent protein kinase (CAMK), Flagellar Member 6 (FLAM6) and Cyclic nucleotide-binding domain/C2 domain-containing protein (CC2CP). We endogenously tagged these three genes and determined the subcellular localization of the tagged proteins. Furthermore, the strategy used to knockout these genes allows us to presume that TcCC2CP is an essential gene in T. cruzi epimastigotes. Our results will open new venues for future research on the role of these proteins in T. cruzi.

Calcium phosphates enhanced with liposomes - the future of bone regeneration and drug delivery.

Effective healing and regeneration of various bone defects is still a major challenge and concern in modern medicine. Calcium phosphates have emerged as extensively studied bone substitute materials due to their structural and chemical resemblance to the mineral phase of bone, along with their versatile properties. Calcium phosphates present promising biological characteristics that make them suitable for bone substitution, but a critical limitation lies in their low osteoinductivity. To supplement these materials with properties that promote bone regeneration, prevent infections, and cure bone diseases locally, calcium phosphates can be biologically and therapeutically modified. A promising approach involves combining calcium phosphates with drug-containing liposomes, renowned for their high biocompatibility and ability to provide controlled and sustained drug delivery. Surprisingly, there is a lack of research focused on liposome-calcium phosphate composites, where liposomes are dispersed within a calcium phosphate matrix. This raises the question of why such studies are limited. In order to provide a comprehensive overview of existing liposome and calcium phosphate composites as bioactive substance delivery systems, the authors review the literature exploring the interactions between calcium phosphates and liposomes. Additionally, it seeks to identify potential interactions between calcium ions and liposomes, which may impact the feasibility of developing liposome-containing calcium phosphate composite materials. Liposome capacity to protect bioactive compounds and facilitate localized treatment can be particularly valuable in scenarios involving bone regeneration, infection prevention, and the management of bone diseases. This review explores the implications of liposomes and calcium phosphate material containing liposomes on drug delivery, bioavailability, and stability, offering insights into their advantages.

Pilot Study of Cytoprotective Mechanisms of Selenium Nanorods (SeNrs) under Ischemia-like Conditions on Cortical Astrocytes.

The cytoprotective properties of the trace element selenium, its nanoparticles, and selenium nanocomplexes with active compounds are shown using a number of models. To date, some molecular mechanisms of the protective effect of spherical selenium nanoparticles under the action of ischemia/reoxygenation on brain cells have been studied. Among other things, the dependence of the effectiveness of the neuroprotective properties of nanoselenium on its diameter, pathways, and efficiency of penetration into astrocytes was established. In general, most research in the field of nanomedicine is focused on the preparation and study of spherical nanoparticles of various origins due to the ease of their preparation; in addition, spherical nanoparticles have a large specific surface area. However, obtaining and studying the mechanisms of action of nanoparticles of a new form are of great interest since nanorods, having all the positive properties of spherical nanoparticles, will also have a number of advantages. Using the laser ablation method, we managed to obtain and characterize selenium nanorods (SeNrs) with a length of 1 µm and a diameter of 100 nm. Using fluorescence microscopy and inhibitory analysis, we were able to show that selenium nanorods cause the generation of Ca2+ signals in cortical astrocytes in an acute experiment through the mobilization of Ca2+ ions from the thapsigargin-sensitive pool of the endoplasmic reticulum. Chronic use of SeNrs leads to a change in the expression pattern of genes encoding proteins that regulate cell fate and protect astrocytes from ischemia-like conditions and reoxygenation through the inhibition of a global increase in the concentration of cytosolic calcium ([Ca2+]i). An important component of the cytoprotective effect of SeNrs during ischemia/reoxygenation is the induction of reactive A2-type astrogliosis in astrocytes, leading to an increase in both baseline and ischemia/reoxygenation-induced phosphoinositide 3-kinase (PI3K) activity and suppression of necrosis and apoptosis. The key components of this cytoprotective action of SeNrs are the actin-dependent process of endocytosis of nanoparticles into cells and activation of the Ca2+ signaling system of astrocytes.

Socrates: A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy.

Epilepsy is one of the common neurological diseases that affects not only adults but also infants and children. Because epilepsy has been studied for a long time, there are several pharmacologically effective anticonvulsants, which, however, are not suitable as therapy for all patients. The genesis of epilepsy has been extensively investigated in terms of its occurrence after injury and as a concomitant disease with various brain diseases, such as tumors, ischemic events, etc. However, in the last decades, there are multiple reports that both genetic and epigenetic factors play an important role in epileptogenesis. Therefore, there is a need for further identification of genes and loci that can be associated with higher susceptibility to epileptic seizures. Use of mouse knockout models of epileptogenesis is very informative, but it has its limitations. One of them is due to the fact that complete deletion of a gene is not, in many cases, similar to human epilepsy-associated syndromes. Another approach to generating mouse models of epilepsy is N-Ethyl-N-nitrosourea (ENU)-directed mutagenesis. Recently, using this approach, we generated a novel mouse strain, soc (socrates, formerly s8-3), with epileptiform activity. Using molecular biology methods, calcium neuroimaging, and immunocytochemistry, we were able to characterize the strain. Neurons isolated from soc mutant brains retain the ability to differentiate in vitro and form a network. However, soc mutant neurons are characterized by increased spontaneous excitation activity. They also demonstrate a high degree of Ca2+ activity compared to WT neurons. Additionally, they show increased expression of NMDA receptors, decreased expression of the Ca2+-conducting GluA2 subunit of AMPA receptors, suppressed expression of phosphoinositol 3-kinase, and BK channels of the cytoplasmic membrane involved in protection against epileptogenesis. During embryonic and postnatal development, the expression of several genes encoding ion channels is downregulated in vivo, as well. Our data indicate that soc mutation causes a disruption of the excitation-inhibition balance in the brain, and it can serve as a mouse model of epilepsy.

The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis in Galleria mellonella (Lepidoptera) Immunocompetent Cells during Conidiobolus coronatus (Entomophthorales) Infection.

Mitochondria have been shown to play an important role in apoptosis using mammalian cell lines. However, their role in insects is not fully understood; thus, more indepth studies of insect cell apoptosis are necessary. The present study investigates mitochondrial involvement during Conidiobolus coronatus-induced apoptosis in Galleria mellonella hemocytes. Previous research has shown that fungal infection could induce apoptosis in insect hemocytes. Our findings indicate that mitochondria undergo several morphological and physiological changes during fungal infection, e.g., loss of mitochondrial membrane potential, megachannel formation, disturbances in intracellular respiration, increased nonrespiratory oxygen consumption in mitochondria, decreased ATP-coupled oxygen consumption and increased non-ATP-coupled oxygen consumption, decreased extracellular and intracellular oxygen consumption, and increased extracellular pH. Our findings confirm that G. mellonella immunocompetent cells demonstrate Ca2+ overload in mitochondria, translocation of cytochrome c-like protein from mitochondrial to cytosol fraction, and higher activation of caspase-9-like protein after C. coronatus infection. Most importantly, several of the changes observed in insect mitochondria are similar to those accompanying apoptosis in mammalian cells, suggesting that the process is evolutionarily conserved.

The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes.

Cartilage is an avascular tissue and sensitive to mechanical trauma and/or age-related degenerative processes leading to the development of osteoarthritis (OA). Therefore, it is important to investigate the mesenchymal cell-based chondrogenic regenerating mechanisms and possible their regulation. The aim of this study was to investigate the role of intracellular calcium (iCa2+) and its regulation through voltage-operated calcium channels (VOCC) on chondrogenic differentiation of mesenchymal stem/stromal cells derived from human bone marrow (BMMSCs) and menstrual blood (MenSCs) in comparison to OA chondrocytes. The level of iCa2+ was highest in chondrocytes, whereas iCa2+ store capacity was biggest in MenSCs and they proliferated better as compared to other cells. The level of CaV1.2 channels was also highest in OA chondrocytes than in other cells. CaV1.2 antagonist nifedipine slightly suppressed iCa2+, Cav1.2 and the proliferation of all cells and affected iCa2+ stores, particularly in BMMSCs. The expression of the CaV1.2 gene during 21 days of chondrogenic differentiation was highest in MenSCs, showing the weakest chondrogenic differentiation, which was stimulated by the nifedipine. The best chondrogenic differentiation potential showed BMMSCs (SOX9 and COL2A1 expression); however, purposeful iCa2+ and VOCC regulation by blockers can stimulate a chondrogenic response at least in MenSCs.

Cerium Oxide Nanoparticles Protect Cortical Astrocytes from Oxygen-Glucose Deprivation through Activation of the Ca2+ Signaling System.

Most of the works aimed at studying the cytoprotective properties of nanocerium are usually focused on the mechanisms of regulation of the redox status in cells while the complex effects of nanocerium on calcium homeostasis, the expression of pro-apoptotic and protective proteins are generally overlooked. There is a problem of a strong dependence of the effects of cerium oxide nanoparticles on their size, method of preparation and origin, which significantly limits their use in medicine. In this study, using the methods of molecular biology, immunocytochemistry, fluorescence microscopy and inhibitory analysis, the cytoprotective effect of cerium oxide nanoparticles obtained by laser ablation on cultured astrocytes of the cerebral cortex under oxygen-glucose deprivation (OGD) and reoxygenation (ischemia-like conditions) are shown. The concentration effects of cerium oxide nanoparticles on ROS production by astrocytes in an acute experiment and the effects of cell pre-incubation with nanocerium on ROS production under OGD conditions were studied. The dose dependence for nanocerium protection of cortical astrocytes from a global increase in calcium ions during oxygen-glucose deprivation and cell death were demonstrated. The concentration range of cerium oxide nanoparticles at which they have a pro-oxidant effect on cells has been identified. The effect of nanocerium concentrations on astrocyte preconditioning, accompanied by increased expression of protective proteins and limited ROS production induced by oxygen-glucose deprivation, has been investigated. In particular, a correlation was found between an increase in the concentration of cytosolic calcium under the action of nanocerium and the suppression of cell death. As a result, the positive and negative effects of nanocerium under oxygen-glucose deprivation and reoxygenation in astrocytes were revealed at the molecular level. Nanocerium was found to act as a "double-edged sword" and to have a strictly defined concentration therapeutic "window".

Calcium inhibits penetration of Alzheimer's Aß1 -42 monomers into the membrane.

Calcium ion regulation plays a crucial role in maintaining neuronal functions such as neurotransmitter release and synaptic plasticity. Copper (Cu2+ ) coordination to amyloid-ß (Aß) has accelerated Aß1-42 aggregation that can trigger calcium dysregulation by enhancing the influx of calcium ions by extensive perturbing integrity of the membranes. Aß1-42 aggregation, calcium dysregulation, and membrane damage are Alzheimer disease (AD) implications. To gain a detail of calcium ions' role in the full-length Aß1-42 and Aß1-42 -Cu2+ monomers contact, the cellular membrane before their aggregation to elucidate the neurotoxicity mechanism, we carried out 2.5 µs extensive molecular dynamics simulation (MD) to rigorous explorations of the intriguing feature of the Aß1-42 and Aß1-42 -Cu2+ interaction with the dimyristoylphosphatidylcholine (DMPC) bilayer in the presence of calcium ions. The outcome of the results compared to the same simulations without calcium ions. We surprisingly noted robust binding energies between the Aß1-42 and membrane observed in simulations containing without calcium ions and is two and a half fold lesser in the simulation with calcium ions. Therefore, in the case of the absence of calcium ions, N-terminal residues of Aß1-42 deeply penetrate from the surface to the center of the bilayer; in contrast to calcium ions presence, the N- and C-terminal residues are involved only in surface contacts through binding phosphate moieties. On the other hand, Aß1-42 -Cu2+ actively participated in surface bilayer contacts in the absence of calcium ions. These contacts are prevented by forming a calcium bridge between Aß1-42 -Cu2+ and the DMPC bilayer in the case of calcium ions presence. In a nutshell, Calcium ions do not allow Aß1-42 penetration into the membranes nor contact of Aß1-42 -Cu2+ with the membranes. These pieces of information imply that the calcium ions mediate the membrane perturbation via the monomer interactions but do not damage the membrane; they agree with the western blot experimental results of a higher concentration of calcium ions inhibit the membrane pore formation by Aß peptides.

Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State.

Many pathological conditions are characterized by a deficiency of metabolic energy. A prominent example is nonhealing or difficult-to-heal chronic wounds. Because of their unique ability to serve as a source of metabolic energy, inorganic polyphosphates (polyP) offer the opportunity to develop novel strategies to treat such wounds. The basis is the generation of ATP from the polymer through the joint action of two extracellular or plasma membrane-bound enzymes alkaline phosphatase and adenylate kinase, which enable the transfer of energy-rich phosphate from polyP to AMP with the formation of ADP and finally ATP. Building on these findings, it was possible to develop novel regeneratively active materials for wound therapy, which have already been successfully evaluated in first studies on patients.

Ca2+ participates in programmed cell death by modulating ROS during pollen cryopreservation.

KEY MESSAGE: After cryopreservation, the Ca2+ content increased, which affected the intracellular ROS content, then participated in the occurrence of programmed cell death in pollen. Programmed cell death (PCD) is one of the reasons for the decline in pollen viability after cryopreservation. However, the role of calcium ions (Ca2+) in PCD during pollen cryopreservation has not been revealed in the existing studies. In this study, Paeonia lactiflora 'Fen Yu Nu' pollen was used as the research material for investigating the effects of Ca2+ changes on PCD indices and reactive oxygen species (ROS) during pollen cryopreservation. The results showed that after cryopreservation, with the decrease of pollen viability, the Ca2+ content significantly increased. The regulation of Ca2+ content had a significant effect on PCD indices, which showed that the Ca2+ carrier A23187 accelerated the decrease of mitochondrial membrane potential level and increased the activity of caspase-3-like and caspase-9-like proteases and the apoptosis rate. The expression levels of partial pro-PCD genes were upregulated, the anti-PCD gene BI-1 was downregulated, and the addition of Ca2+-chelating agent EGTA had the opposite effect. The addition of the Ca2+ carrier A23187 after cryopreservation significantly increased the ROS content of pollen, the addition of the Ca2+-chelating agent EGTA had the opposite effect, and Ca2+ regulators also had significant effects on the contents of ROS production and clearance-related substances. Ca2+ affected intracellular ROS content by acting on the ROS production and clearance system during the cryopreservation of pollen and is thus involved in the occurrence of PCD.

Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.