Calcium Imbalance Research Articles

Pathological role of the calcium-sensing receptor in sepsis-induced hypotensive shock: Therapeutic possibilities and unanswered questions.

Sepsis is a life-threatening disease involving multiorgan dysfunction, prompted by an unregulated host response to infection. Shock is a complication of sepsis in which the circulatory and cellular metabolism anomalies are significant enough to raise the risk of death. Calcium dyshomeostasis occurs during sepsis condition due to imbalance between calcium uptake and excessive release induced by inflammatory cytokines. This calcium imbalance can cause activation of calcium-sensing receptors (CaSRs) located on the surface of T cells and thereby promote release of reactive oxygen species (ROS). The elevated ROS and inflammatory cytokines during sepsis condition have been reported to directly damage the endothelial cells, disrupt the barrier functions that might result in leakage of fluids, and inflammatory cells in tissues Moreover, several evidence have revealed that the calcium mediated activation of CaSR could produce systemic vasodilatory response by stimulating the nitric oxide production and opening of calcium-activated potassium channels, while infusion of its antagonist elevated the blood pressure. These evidence indicate that activation of CaSR during sepsis conditions results in release of ROS and inflammatory cytokines, which could produce an endothelial barrier damage, cardiomyocyte apoptosis. These pathological events could produce loss of fluid in tissues and cardiac dysfunction. Further the direct vasodilatory effects of CaSR activation might add to the shock-like condition. Thus, we hereby propose that inhibition of CaSR could suppress the release of ROS, inflammatory mediators, and thereby prevent the endothelial damage, cardiac dysfunction, and maintain systemic vascular tone.

Molecular mechanisms of doxorubicin-induced cardiotoxicity based on mitochondrial function and traditional Chinese medicine treatment

<p indent="0mm">Doxorubicin (DOX), an anthracycline chemotherapeutic drug, is one of the most effective drugs for the treatment of various cancers. However, its therapeutic effect is seriously limited by related cardiotoxicity. Although this field has yielded many studies, the exact molecular mechanism of DOX-induced cardiotoxicity (DIC) is still worthy of further study. DOX is a mitochondrial toxin, and mitochondrial damage is the core of DIC. This paper reviews a large amount of literature and summarizes the mechanisms related to DIC that depend on mitochondrial dysfunction, including the effects of DOX on mitochondrial electron transport chain, redox cycle, oxidative stress, calcium imbalance, apoptosis pathway and mitophagy. In addition, it discusses the existing strategies of traditional Chinese medicine based on mitochondrial function to prevent and/or reduce DIC, to provide a scientific basis for combination of DOX and traditional Chinese medicine in the treatment of cancer.

ENDOPLASMIC RETICULUM STRESS PATHWAY AS TARGETING THERAPY IN NON COMMUNICABLE DISEASES: A NARRATIVE REVIEW

Background: World Health Organization (WHO) declared that non-communicable diseases still become the main health problem by including it in goal 3.4 in sustainable development goals and also a major cause of mortality worldwide. Based on prevalence, mortality in non communicable diseases is dominated by cancer, cardiovascular disease, diabetes mellitus, and chronic lung disease. Although non-communicable diseases have complex mechanisms and signalling pathways, the role of endoplasmic reticulum stress has been known for its association with abnormal metabolism in non-communicable diseases. This narrative review aims to investigate targeting therapy in non-communicable diseases based on the endoplasmic reticulum stress pathway. Method: The literature search was carried out through several electronic databases (PubMed and Google Scholar), using keywords “endoplasmic reticulum stress”, “non-communicable disease”, “therapy”, “drugs”. Full English text publication between 2010 to 2021 was selected for identification. Result: The endoplasmic reticulum stress occurs due to adaptive and defensive response to lack of oxygen (hypoxia), hypoglycemia and hyperglycemia, hyperthermia, starvation, calcium imbalance, the redox milieu, and also the imbalance between oxidants and antioxidants. Those conditions can impact protein folding in endoplasmic reticulum stress cause accumulation of unfolded and/or misfolded protein that leads to activation of unfolded protein response (UPR). A number of studies in non-communicable diseases such as diabetes mellitus, cardiovascular disease, and cancer showing that some compounds can ameliorate endoplasmic reticulum stress by targeting the pathway. Conclusion: Targeting therapy in the endoplasmic reticulum pathway can be a novel strategy for the treatment of non-communicable diseases. Keywords: Endoplasmic reticulum stress, non-communicable disease, therapy.

Effects of feeding 25-hydroxyvitamin D3 with an acidogenic diet during the prepartum period in dairy cows: Mineral metabolism, energy balance, and lactation performance of Holstein dairy cows

Our objective was to determine the effects of feeding 25-hydroxyvitamin D3 [25(OH)D3], or vitamin D3 (cholecalciferol) on plasma, mineral, and metabolite concentrations, mineral balance, mineral excretion, rumination, energy balance, and milk production of dairy cows. We hypothesized that supplementing 3 mg/d of 25(OH)D3 during the prepartum period would be more effective than supplementing vitamin D3 at the National Research Council (2001) levels to minimize calcium imbalance during the transition period and improve milk production of dairy cows. Forty multiparous, pregnant nonlactating-Holstein cows were enrolled in this study. Body weight, body condition score, parity, and milk yield in the previous lactation (mean ± standard deviation) were 661 ± 59.2, 3.46 ± 0.35, 1.79 ± 0.87, and 33.2 ± 6.43 kg/d, respectively. Cows were enrolled into the blocks (n = 20 for each treatment) at 30 d of the expected day of calving to receive an acidogenic diet (373 g/kg of neutral detergent fiber and 136 g/kg of crude protein, dry matter basis; -110 mEq/kg) associated with the treatments: (1) control (CTRL), vitamin D3 at 0.625 mg/d (equivalent to 25,000 IU of vitamin D3/d) or (2) 25(OH)D3 at 3 mg/d (equivalent to 120,000 IU of vitamin D3/d). All cows were fed with the base ration for 49 d after calving. Blood samples were taken on d 7, 0, 1, 2, 21, and 42, relative to calving. No effect of treatment was observed for prepartum dry matter intake or body condition score. A trend for increase of ionized Ca was observed for the cows fed 25(OH)D3, compared with the CTRL, but no effect of treatment was detected for total Ca or total P. Feeding 25(OH)D3 increased colostrum yield. The plasmatic concentration of 25-hydroxyvitamin D3 was increased with 25(OH)D3 supplementation. 25-Hydroxyvitamin D3 supplementation increased plasma glucose concentration at parturition. The postpartum dry matter intake was not influenced by treatments. Feeding 25(OH)D3 increases milk yield, 3.5% fat-corrected milk, and energy-corrected milk and improves milk yield components in early lactation. Overall, these findings suggest that 25(OH)D3 at 3 mg/d can improve the energy metabolism and lactation performance, compared with the current-feeding practice of supplementing vitamin D3 at 0.625 mg/d.

A calcification-related calmodulin-like protein in the oyster Crassostrea gigas mediates the enhanced calcium deposition induced by CO2 exposure

Calcium transportation and homeostasis are essential for marine bivalves to maintain basic metabolism and build their shells. Calmodulin-like proteins (CaLPs) are important calcium sensors and buffers and can respond to ocean acidification (OA) in marine calcifiers. However, no further study of their physiological function in calcium metabolism under elevated CO2 has been performed. Here, we identified a novel CaLP (designated CgCaLP) in the Pacific oyster Crassostrea gigas and demonstrated its participation in the calcification process: the mRNA expression level of CgCaLP peaked at the trochophore larval stage and remained high at stages when shells were shaped; the mRNA and protein of CgCaLP were more highly expressed in mantle tissue than in other tissues. Under elevated CO2 levels, the protein expression level of CgCaLP in hemocytes increased, while in contrast, significantly decreased protein levels were detected in gill and mantle tissues. Shell dissolution caused the imbalance of calcium in hemocytes and decreased calcium absorption and transportation demand in gill and mantle tissues, inducing the molecular function allocation of CgCaLP under CO2 exposure. Despite the decreased protein level in mantle tissue, CgCaLP was found to translocate to outer mantle epithelium (OME) cells where condensed calcium-rich deposits (CRDs) were detected. We further demonstrated that CgCaLP mRNA and protein expression levels could respond to seawater Ca2+ availability, suggesting that the calcium deposition capacity of oysters might be enhanced to fight against shell dissolution problems and that CgCaLP might serve as an essential participator of the process. In summary, CgCaLP might enhance calcium deposition under CO2 exposure and thus play a significant and flexible molecular function involved in a compensation strategy of oysters to fight against the acidified ocean.

CHARACTERISTICS OF CHANGES IN QUALITATIVE PROPERTIES OF ORAL FLUID IN CHILDREN WITH CONGENITAL NONUNION OF THE PALATE

According to publications in scientific periodicals, children with congenital malformations of the development are increasingly born, including those with localization on the face, head and neck. Anatomical inferiority of tissues in the area of the slit defect of the palate creates the preconditions for the formation of pathological symptom complex, which contributes to the progression of inflammatory-dystrophic changes in the oral cavity.&#x0D; The aim of the study was to study the violations of the qualitative properties of oral fluid in children with congenital nonunion of the palate in the preoperative period.&#x0D; For an in-depth examination of 58 children who were under our supervision, a group of 25 patients aged from 4 to 6 years was formed. Of these, 14 had a unilateral cleft and 11 had a bilateral cleft.&#x0D; The substrate for the study was unstimulated fraction of oral fluid. The salivation rate was studied, the concentration of hydrogen ions in it, its optical density, viscosity, α-amylase activity, levels of medium weight molecules, sialic acids, total protein, oxyproline were determined. The degree of mineralizing potential was determined by magnesium, calcium and phosphorus.&#x0D; At the time of the examination in children with unilateral clefts, a decrease in the amount of oral fluid was found, which was expressed by a decrease in the secretory activity of the large and small salivary glands by 1,3 times. The concentration of ions is visible in it and the activity of α-amylase decreased by 1.3 times. The optical density and viscosity also increased by 1,3 times, the number of medium weight molecules, the level of sialic acid and total protein increased by 1.5 times, and oxyrolin by 1.6 times.&#x0D; The analysis of indexes that showed the mineralizing potential of oral fluid mineralizing potential of oral fluid allowed to determine the fact that in patients of this group it decreased by 1,7 times and this occurred against the background of a decrease in calcium and magnesium by 1,5, with an increase in phosphorus by 1.3 times. This imbalance led to falling in calcium-phosphorus ratio by 1,8 times.&#x0D; In children with congenital malformations of the palate there is a decrease in the functional activity of large and small salivary glands, reduced buffering capacity of oral fluid, which occurs against the background of falling mineralizing potential of oral fluid, imbalance of calcium, phosphorus and magnesium. This affects the calcium-phosphorus ratio, thus creating optimal conditions for demineralization of tooth hard tissues. Changes in physicochemical and biochemical properties of mixed saliva are determined, which is the basis for the prolongation and progression of pathological processes in the oral cavity that take place in them.&#x0D; The complex of treatment-and-prophylactic measures developed by us, aimed at improving the level of components of homeostasis of the oral cavity before surgery, is being tested for the future.

Odontoblast apoptosis and intratubular mineralization of sclerotic dentin with aging

ObjectivesThe aims of the study were to evaluate the roles of odontoblast apoptosis in the progression of tubular sclerosis of teeth from donors at different ages and assess its correlation to chemical composition and mechanical properties. Design: Healthy human teeth were obtained and divided into young (age ≤ 25, n = 12) and old (age ≥ 60, n = 12) groups. Odontoblasts were counted with standard hematoxylin and eosin staining. Odontoblast apoptosis within dentinal tubules was determined by cleaved caspase‐3 immunostaining. Teeth in each group were evaluated by dynamic nanoindentation and energy-dispersive X-ray spectroscopy (EDS). ResultsThe number of odontoblasts decreased significantly with age. The most prominent change occurred in the apical third of roots. Odontoblastic apoptosis was visualized within dentinal tubules. The apoptosis staining fraction was significantly higher in the outer and inner dentin of old teeth when compared with young teeth (p < 0.05). EDS showed increased calcium content in peritubular dentin but a decrease in the intertubular dentin with increasing age. Scanning based nanoindentation showed that the old intertubular dentin exhibited a significantly higher elastic modulus. ConclusionsOdontoblast apoptosis, starting at the cell extension in dentinal tubules and proceeding from outer to inner dentin, contributes to the stoichiometric Ca/P ratio in peritubular dentin, which is potentially responsible for intratubular mineralization due to an imbalance of calcium and phosphorous ions.

Effects of Magnesium Application on Tipburn Incidence and Calcium Acquisition in Lisianthus (Eustoma grandiflorum) Cultivars

The occurrence of tipburn is a severe problem in horticulture crop production. A previous study suggested that, in lisianthus, tipburn is caused by imbalanced calcium (Ca) distribution. However, there are few studies on the effects of other cations on tipburn incidence in lisianthus cultivars. In this study, to determine the effect of Magnesium (Mg) concentration in nutrient solution on tipburn incidence and Ca and Mg acquisition, three lisianthus cultivars (‘Celeb Wine’: CW, ‘Reina White’: RW, and ‘Voyage Peach’: VP) were cultivated under different Mg concentrations in nutrient solution (12 ppm, 34.7 ppm, and 75.4 ppm). Under high nutritional Mg concentrations, CW and RW had significantly decreased tipburn severity, while VP showed no significant differences in tipburn severity among the treatments. Total Ca concentrations in all cultivars significantly increased at higher nutritional Mg concentrations, which indicated that Mg application in lisianthus cultivars promoted Ca acquisition. Furthermore, it was suggested that CW and RW had the ability to distribute increased Mg to the tip of the upper leaves, thereby promoting Ca distribution. Thus, a decrease in tipburn severity in CW and RW at higher nutritional Mg concentrations appeared to occur.

Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice

The increased cases of hyperlipemia in China and the crucial role of PM2.5 in inducing and promoting cardiovascular diseases have attracting more and more researchers’ attention. However, the effects and mechanisms of PM2.5 on cardiovascular system of hyperlipidemia people are still unclear. In this study, hyperlipidemia mice model was established by high-fat diet. Then we exposed these mice to PM2.5 or saline to explore the underling mechanism of cardiac injury in hyperlipidemia mice. The hyperlipemia mice are more susceptible to heart damage caused by PM2.5 exposure. The participation of oxidative stress, cell apoptosis and Ca2+ related mechanism could be observed in this model. After NAC (N-acetyl-L-cysteine) treatment, the oxidative stress level induced by PM2.5 exposure significantly decreased in hyperlipemia mice. NAC effectively alleviated cardiac injury, improved the imbalance of calcium and attenuated apoptosis induced by PM2.5 exposure in hyperlipemia mice. The strong oxidative stress in hyperlipemia mice could lead to calcium homeostasis imbalance and activation of apoptosis-related pathways. This mechanism of PM2.5-induced myocardial injury was also verified in vitro. In our present study, we demonstrated the contribution of the PM2.5-ROS-Ryr2-Ca2+ axis in PM2.5-induced heart injury of hyperlipidemia mice, offering a potential therapeutical target for related pathology.

Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for renin.

The human Sec61 complex is a widely distributed and abundant molecular machine. It resides in the membrane of the endoplasmic reticulum to channel two types of cargo: protein substrates and calcium ions. The SEC61A1 gene encodes for the pore-forming Sec61α subunit of the Sec61 complex. Despite their ubiquitous expression, the idiopathic SEC61A1 missense mutations p.V67G and p.T185A trigger a localized disease pattern diagnosed as autosomal dominant tubulointerstitial kidney disease (ADTKD-SEC61A1). Using cellular disease models for ADTKD-SEC61A1, we identified an impaired protein transport of the renal secretory protein renin and a reduced abundance of regulatory calcium transporters, including SERCA2. Treatment with the molecular chaperone phenylbutyrate reversed the defective protein transport of renin and the imbalanced calcium homeostasis. Signal peptide substitution experiments pointed at targeting sequences as the cause for the substrate-specific impairment of protein transport in the presence of the V67G or T185A mutations. Similarly, dominant mutations in the signal peptide of renin also cause ADTKD and point to impaired transport of this renal hormone as important pathogenic feature for ADTKD-SEC61A1 patients as well.

Calcium-Mediated Calpain Activation and Microtubule Dissociation in Cell Model of Hereditary Sensory Neuropathy Type-1 Expressing V144D SPTLC1 Mutation.

Hereditary sensory neuropathy type 1A (HSN1A) is an autosomal, dominantly inherited peripheral neuropathy caused by mutations in serine palmitoyl transferase long chain 1 (SPTLC1), involved in the de novo synthesis of sphingolipids. We have previously reported calcium imbalance, as well as mitochondrial and ER stress in both HSN1 patient lymphoblasts and a transiently transfected cell model. In this study, we investigated the role of the Ca2+-activated protease calpain in destabilizing the cell cytoskeleton, by examining calpain activity in SH-SY5Y cells overexpressing the V144D mutant and changes in microtubule-associated proteins (MAP). Intramitochondrial Ca2+ was found to be significantly depleted and cytoplasmic Ca2+ increased in the V144D mutant. Subsequently, calpain and proteasome activity were increased and calpain substrates, microtubule associated proteins MAP2, and tau were significantly reduced in the microtubule fraction of the mutant. Significant changes were also found in motor proteins dynein and KIF2A detected in the microtubule fraction of cells overexpressing the V144D mutation. There was also a reduction in anterograde and retrograde mitochondrial transport velocities in the V144D mutant. These findings strongly implicate cytoskeletal aberration caused by Ca2+ dysregulation and subsequent loss of microtubule transport functions as the cause of axonal dying back that is characteristic of HSN1.

High Doses of Phytase Alleviate the Negative Effects of Calcium and Phosphorus Imbalance on Growth Performance and Bone Mineralization in Broiler Chickens

This study investigated the effect of calcium (Ca) and phytase interaction on growth performance and bone quality in 1-42-day-old broiler chickens. A total of 624 female one-day-old Ross 308 broilers were allotted to 13 treatments with four replicates and 12 birds per replicate. A 2 × 6 factorial experiment was designed to test the combinations of 0.50% and 1.00% Ca with 0, 500, 1,000, 2,500, 5,000, and 10,000 FTU/kg phytase in the basal diet (0.25% non-phytate phosphorus, NPP). The control diet contained adequate Ca and phosphorus (P). Dietary Ca, phytase, and their interaction affected growth performance and bone mineralization of broilers at 1-42 days of age (p<0.05). The broilers fed with 1.00% Ca had lower body weight gain (BWG) and feed intake (FI) compared with the birds fed with 0.50% Ca (p<0.05). The BWG, FI, leg bone weight, and ash weight of the broilers fed with 0.25% NPP were lower than those of birds fed with the control diet (p<0.05). The addition of 500-10,000 FTU/kg phytase improved growth rate and leg bone quality, especially at 1.00% Ca (p<0.05). No differences were observed in growth performance and bone quality of 42-day-old broilers fed with 1.00% Ca + 2,500-10,000 FTU/kg phytase and the control diet (p>0.05). These data indicated that high doses of phytase (2,500-10,000 FTU/kg) alleviate the negative effects of Ca and P imbalance (Ca-to-NPP ratio = 4.0) on growth performance and bone mineralization of broiler chickens.

Calcium-regulating hormonal system in cardiac functional activity

The variance of calcium homeostasis is known as a risk factor for the development of heart failure. A study of calcium-regulating hormones is a crucial element to understand underlying pathophysiological mechanisms of heart failure. Pro-inflammatory factors, released during mechanical, hypoxic or bacterial damage of myocardial cells, lead to an imbalance of calcium and disrupt to heart function. The investigation of mentioned factors influence mechanism on the heart, is an urgent solution for preventing the development of heart failure. Present study aimed to reveal the role of calcium-regulating hormones in heart functional activity and their possible involvement in the development of heart failure. The pharmacological analysis of the action mechanism of bacterial lipopolysaccharides on heart functional activity was carried out using a calcium channel blocker. The concentrations of calcium-regulating hormones in blood serum in patients suffering from heart failure was determined by immunoassay enzyme method, and ionized calcium and inorganic phosphate concentrations - by spectrophotometric method. The photoelectrical method was used to determine the direct effect of calcium-regulating hormones and possible calcium-dependent action mechanism of bacterial lipopolysaccharides on the isolated frog’s heart. Clinical findings show that chronic heart failure is accompanied by shifts in the calcium-regulating hormonal system and blood electrolyte balance. In vitro experiments on isolated frog hearts have shown the potentiating effect of parathyroid hormone, its related protein, calcitonin, and vitamin D3 on myocardial contractility. It has been shown, that bacterial lipopolysaccharides suppress the contractile and rhythmogenic functions of the myocardium, and their action can be mediated through a calcium-dependent mechanism. The increase of parathyroid hormone in chronic heart failure has a protective significance aimed at maintaining the contractile ability of a weakened myocardium and preserving cardiac output. Bacterial lipopolysaccharides are able to suppress functional activity of the heart by calcium-dependent mechanism.

Quantification of Parathyroid Hormone and its Fragments in Serum by Liquid Chromatography-High-Resolution Mass Spectrometry.

Parathyroid hormone (PTH), an 84-amino acid peptide hormone, is a major regulator of calcium homeostasis. Quantification of PTH in serum is used clinically to investigate calcium imbalances and for monitoring osteodystrophy in patients with renal failure. In addition to intact PTH, several PTH fragments are found in circulation. Recent studies have shown that accurate quantification of PTH fragments may provide valuable clinical information in certain scenarios. In this chapter, a high-resolution mass spectrometry-based method for quantification of PTH (1-84) and its fragments is described. This method involves immunoaffinity capture of intact PTH and PTH-fragments followed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS).

Overview: prevalence and structure of metabolic diseases of laying chickens, their influence on egg quality and condition of young chickens

The article analyzes and presents statistics on the number of laying hens in Ukraine, production, consumption and import of eggs for the last 5 years, the spread of metabolic diseases of laying hens on the basis of a review of literature sources. Metabolic disorders are the largest group of poultry diseases classified as metabolic diseases and cause significant economic losses. Hepatitis, hepatodystrophy, cirrhosis, liver abscesses, cholecystitis, and gallstone disease are diagnosed in laying hens as a result of impaired carbohydrate, lipid, protein, and mineral metabolism. With a lack or imbalance of calcium and phosphorus or D-hypovitaminosis, in chickens develop diseases such as osteoporosis and hypocalcemia, which reduce egg-laying, quality of hatching eggs and young poultry, and can lead to the death of embryos and adults. Hypovitaminosis (A, D, E) and microelementosis (Co, Cu, Zn, J) in poultry cause decreased immunity, disorders of hormonal system, growth, reproductive functions, egg production, dysfunction of internal organs and nervous system, contribute to the formation of defective eggs, development in embryo of alimentary diseases, which affects the hatchability and quality of young poultry. In view of this, the norms of feeding and keeping poultry are constantly being improved based on an in-depth study of these processes. The subject of this work was a comparative review of the results obtained by various authors on the most common metabolic diseases of laying hens, their impact on productive traits (laying), quality characteristics of eggs, embryogenesis, quality of young laying hens of modern high-yielding crosses. This review of literature sources can serve as a tool for determining the future direction of research, as well as an indicator of its practical application.

Targeting CDK5 in Astrocytes Promotes Calcium Homeostasis Under Excitotoxic Conditions.

Glutamate excitotoxicity triggers overactivation of CDK5 and increases calcium influx in neural cells, which promotes dendritic retraction, spine loss, increased mitochondrial calcium from the endoplasmic reticulum, and neuronal death. Our previous studies showed that CDK5 knockdown (KD) in astrocytes improves neurovascular integrity and cognitive functions and exerts neuroprotective effects. However, how CDK5-targeted astrocytes affect calcium regulation and whether this phenomenon is associated with changes in neuronal plasticity have not yet been analyzed. In this study, CDK5 KD astrocytes transplanted in CA3 remained at the injection site without proliferation, regulated calcium in the CA1 hippocampal region after excitotoxicity by glutamate in ex vivo hippocampal slices, improving synapsin and PSD95 clustering. These CDK5 KD astrocytes induced astrocyte stellation and neuroprotection after excitotoxicity induced by glutamate in vitro. Also, these effects were supported by CDK5 inhibition (CDK5i) in vitro through intracellular stabilization of calcium levels in astrocytes. Additionally, these cells in cocultures restored calcium homeostasis in neurons, redistributing calcium from somas to dendrites, accompanied by dendrite branching, higher dendritic spines and synapsin-PSD95 clustering. In summary, induction of calcium homeostasis at the CA1 hippocampal area by CDK5 KD astrocytes transplanted in the CA3 area highlights the role of astrocytes as a cell therapy target due to CDK5-KD astrocyte-mediated synaptic clustering, calcium spreading regulation between both areas, and recovery of the intracellular astrocyte-neuron calcium imbalance and plasticity impairment generated by glutamate excitotoxicity.

The effect of the boiling process on the Oxalic acid content of some vegetables in the Syrian local market

Oxalic acid HOOC-COOH (OA) is the first in the homologous series of dicarboxylic acids. It is one of the most common acids present in vegetable world1, it is one of the abundant organic compound acts as an anti-nutrient present in most vegetables in various quantities. It is found as salts of insoluble complexes with divalent cations, minerals and trace elements. Oxalates react with calcium to precipitate calcium oxalate and accumulation of oxalates in the body prevents the absorption and utilization of calcium; which in turn causes calcium imbalance, rickets and osteomalacia. In the present study oxalate content of various vegetables commonly available in local market of Syria were determined and effect of boiling on oxalate content of selected vegetable were investigated. Most of the samples analyzed were contained more than 100mg/100g on dry weigh basis. The higher value of total oxalate content was found in Parsley (1466.82 mg/100g); spinach and Cabbage contain (478.7, 191.08 mg/100g). Boiling has shown reduction in total oxalate content and least reduction was obtained in Parsely leaves (28.33%) and highest reduction was obtained from Spinach (40.00%)

Protective effect of commercial extracts of oregano (Lippia graveolens) against cardiac ischemia-reperfusion damage

Cardiac ischemia includes severe damage to heart muscle tissue due to decreased or cessation of blood flow, which involves failure to supply nutrients and oxygenation to heart cells. Causes can include blockages due to fat and cholesterol deposits. These damages include cell apoptosis, calcium and sodium concentration imbalance, loss of contraction force, and formation of reactive oxygen species. In the present work, oregano extracts administered to Wistar rats were tested. After 15 days of treatment, the hearts were extracted and the pharmacological response was evaluated in Langendorff isolated perfused heart assay. Left ventricular contractility and perfusion pressure were evaluated before and after inducing an ischemia-reperfusion event by administering three different drugs to stimulate said response. The results, expressed as a percentage of loss of cardiac functionality, suggest a protective effect against cardiac damage in those hearts treated with the extracts after each event. Key words: Wistar rats, cardiac ischemia, Langendorff, oregano extracts.

Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium

BackgroundCholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL).MethodsLiver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1.ResultsER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL−1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression.ConclusionsThese findings suggest that PD-MSCsPRL−1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.

Exercise-Induced Benefits for Alzheimer's Disease by Stimulating Mitophagy and Improving Mitochondrial Function.

Neurons are highly specialized post-mitotic cells that are inherently dependent on mitochondria due to their higher bioenergetic demand. Mitochondrial dysfunction is closely associated with a variety of aging-related neurological disorders, such as Alzheimer’s disease (AD), and the accumulation of dysfunctional and superfluous mitochondria has been reported as an early stage that significantly facilitates the progression of AD. Mitochondrial damage causes bioenergetic deficiency, intracellular calcium imbalance and oxidative stress, thereby aggravating β-amyloid (Aβ) accumulation and Tau hyperphosphorylation, and further leading to cognitive decline and memory loss. Although there is an intricate parallel relationship between mitochondrial dysfunction and AD, their triggering factors, such as Aβ aggregation and hyperphosphorylated Tau protein and action time, are still unclear. Moreover, many studies have confirmed abnormal mitochondrial biosynthesis, dynamics and functions will present once the mitochondrial quality control is impaired, thus leading to aggravated AD pathological changes. Accumulating evidence shows beneficial effects of appropriate exercise on improved mitophagy and mitochondrial function to promote mitochondrial plasticity, reduce oxidative stress, enhance cognitive capacity and reduce the risks of cognitive impairment and dementia in later life. Therefore, stimulating mitophagy and optimizing mitochondrial function through exercise may forestall the neurodegenerative process of AD.