Excess Calcium Research Articles

The STIM1/2-Regulated Calcium Homeostasis Is Impaired in Hippocampal Neurons of the 5xFAD Mouse Model of Alzheimer’s Disease

Alzheimer's disease (AD) is the most common cause of age-related dementia. Neuronal calcium homeostasis impairment may contribute to AD. Here we demonstrated that voltage-gated calcium (VGC) entry and store-operated calcium (SOC) entry regulated by calcium sensors of intracellular calcium stores STIM proteins are affected in hippocampal neurons of the 5xFAD transgenic mouse model. We observed excessive SOC entry in 5xFAD mouse neurons, mediated by STIM1 and STIM2 proteins with increased STIM1 contribution. There were no significant changes in cytoplasmic calcium level, endoplasmic reticulum (ER) bulk calcium levels, or expression levels of STIM1 or STIM2 proteins. The potent inhibitor BTP-2 and the FDA-approved drug leflunomide reduced SOC entry in 5xFAD neurons. In turn, excessive voltage-gated calcium entry was sensitive to the inhibitor of L-type calcium channels nifedipine but not to the T-type channels inhibitor ML218. Interestingly, the depolarization-induced calcium entry mediated by VGC channels in 5xFAD neurons was dependent on STIM2 but not STIM1 protein in cells with replete Ca2+ stores. The result gives new evidence on the VGC channel modulation by STIM2. Overall, the data demonstrate the changes in calcium signaling of hippocampal neurons of the AD mouse model, which precede amyloid plaque accumulation or other signs of pathology manifestation.

Microelement provision of cows of the western region of Ukraine

The article presents the results of research on the content of trace elements: Cobalt, Zinc, Copper and Manganese in the soils, fodder and blood of cows of the black and spotted Ukrainian breed in farms from the mountain, foothill and plain zones of the Western region of Ukraine. The western biogeochemical zone of Ukraine includes Zakarpattia, Lviv, Chernivtsi, Ternopil, Volyn and Rivne regions.
 It was established (mg per 1 kg of soil) that the amount of Cobalt was 0.5 mg/kg; Cuprum – 7.2; Zinc – 3.1; Manganese – 6.5; in the foothills – Cobalt – 0.6; Cuprum – 4.5; Zinc – 1.8; Manganese – 32; in the plain – Cobalt – 0.55; Cuprum – 5.0; Zinc – 1.5; Manganese – 39. During the analysis of the rations, it was established that the provision of other mineral substances did not meet the physiological needs. Thus, in the diets of cows from mountain, foothill and plain regions, an excess of Calcium, Magnesium, Potassium and Ferrum and a deficiency of Phosphorus, Sulfur, Zinc, Cobalt, Iodine and Copper were observed.
 Clinical studies of cows indicate the prevalence of trace element diseases in them. Anemia of visible mucous membranes and non-pigmented areas of the skin was recorded in cows, the number of erythrocytes in animals of the mountain zone was 5.7±0.29 T/l, in the foothills – 5.8±0.29, and in the plains – 6.2±0.30 T / l. The hemoglobin content in the blood of cows in the mountain zone was at the level of 97.0±5.40 g/l, in the foothills – 94.0±5.30, and in the plain zone – 98.0±3.70 g/l. Physiological values of the number of erythrocytes in the blood of cows range from 5.0–7.5 T/l, and the hemoglobin content – 95–125 g/l.

Review of the Role of Enteral Factor in the Development of Secondary Hyperoxaluria

Objectives: Discuss the role of the enteric factor in the hyperoxaluria development.
 Methods: Using the Internet and written materials, the relevant factors of enteral factor; hyperoxaluria; oxalotrophia; Oxalobacter formigenes; kidney stones, and with 36 references, were comprehensively analyzed and studied.
 Results: Under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis.
 Discussion: Hyperoxaluria is a disease caused by metabolism disorder of oxalic acid and intestinal factors have significant influence on its progression. This disease can occur under the condition of excessive intake of oxalate and its precursors, increased intestinal absorption of oxalate and imbalance of intestinal flora, resulting in increased urine oxalate and calcium oxalate crystal, which lead to hematuria, proteinuria, recurrent kidney stones and nephrocalcinosis. Some patients may further progress to the AKI and CKD. With progressive decline in renal function, oxalate is reduced and deposits in the body can affect other tissues and organs. And adjustment of enteral factors is helpful for the treatment of hyperoxaluria.
 In this article we discuss the role of the enteric factor in the hyperoxaluria development. Hyperoxaluria is a metabolic disease characterized by excessive urinary oxalic acid excretion and calcium oxalate crystal deposition, whose intestinal factors affecting its onset includes the increased intake of oxalic acid and its precursors, the increased intestinal absorption of oxalate and the imbalance of intestinal flora, etc. Severe hyperoxaluria can lead to kidney stones. At present, the influence of intestinal factors on hyperoxaluria has become a research focus, this paper will give a comprehensive description of its related research.

Paleoenvironment-driven organic matter accumulation in lacustrine shale mixed with shell bioclasts: A case study from the Jurassic Da'anzhai member, Sichuan Basin (China)

The sedimentary environment governs the depositional processes, ecological environments, and hydrodynamics, which affect the accumulation of organic-rich sediments. Some particular issues are unsolved about the organic matter accumulations of lacustrine shale mixed with shell bioclasts due to their alternating deposition. Freshwater bivalve remains are a familiar constituent of the Da'anzhai lacustrine calcareous shale, which indicates enhanced activities of benthic organisms. Under this background, favorable environmental conditions for the deposition and preservation of abundant organic matter may be different from classical models. Total organic carbon and elemental concentration analyses of lacustrine calcareous shale samples from the Jurassic Da'anzhai Member in the Sichuan Basin were carried out to reconstruct the paleoenvironment and reveal the organic enrichment mechanism. Results show that the samples are notably enriched in strontium, phosphorus and biogenic calcium (indicated by excess calcium concentrations) and reveal the mass death event of benthic organisms (including freshwater mussels and gastropods) in paleolakes under the control of climatic transformation. Such enrichment strongly supports the hypothesis that CaO is considered to be a paleoproductivity proxy to some extent. The paleolake was dominated by a warm and humid climate and rapid sedimentation rates and experienced intense chemical weathering, which are characteristic of freshwater input and a high flux of detrital fractions. The variations in the redox state and paleoproductivity are due to climatic shifts, hydrographic restrictions and biological behavior. Furthermore, the organic matter was enriched during both oxygenated and oxygen-deficient conditions. The combination of high sedimentation rates and high sinking influxes of particulate organic carbon reduced the chances of decomposition and thereby facilitated the efficiency of organic matter accumulation in an oxic environment. The low degree of organic matter degradation, moderate sedimentation rates and enhanced phosphorus recycling were responsible for the organic carbon accumulation and preservation in sediments for dysoxic bottom conditions.

PSAT192 Hypercalcemia of Immobility in a Patient with Post-Surgical Hypoparathyroidism

Abstract Background Hypercalcemia of immobility is a rare diagnosis in the general population, and thus requires careful evaluation to rule out other causes of non-PTH mediated calcium excess. The pathogenesis is not clearly established, however, likely involves a reduction in mechanical loading stimulus from osteocytes with resultant decreased bone formation and increased bone resorption. Management requires careful assessment to maintain normal calcium. We present a case of hypercalcemia of immobility in a patient with a known history of surgical hypoparathyroidism. Clinical Case A 64-year-old man with a history of transglottic cancer s/p total laryngectomy and tracheostomy with resulting post-surgical hypoparathyroidism and hypothyroidism presented for a tracheostomy change and was found to be hypercalcemic. Since his laryngectomy four years ago, the patient had a low PTH of 2.9 pg/mL (10.0 - 65.0 pg/mL) with resulting prolonged hypocalcemia from 5.9 to 7.9 mg/dL (8.5-10.5 mg/mL) requiring calcium and daily calcitriol treatment. Four months prior to current hospitalization, he developed avascular necrosis of the hip and became essentially bedbound from severe hip pain. Since immobilization, his calcium was noted to increase, with the highest corrected calcium of 10.9 mg/dL (8.5-10.5 mg/mL), necessitating tapering and eventual discontinuation of calcium supplements and calcitriol. During this admission, corrected calcium was 12 mg/dL (8.5-10.5 mg/mL). PTH-rP was 16 pg/mL (14 - 27 pg/mL), PTH was 11.2 pg/mL (15-65 pg/mL), vitamin D 25-hydroxy total was 14.7 ng/mL (30-60 ng/mL), 1,25 dihydroxy vitamin D was 18.2 pg/mL (19.9 to 79.3 pg/mL), SPEP did not detect monoclonal protein, thyroid function was normal and bone scan showed no evidence of metastasis, thus excluding other causes of hypercalcemia. Bone specific alkaline phosphatase was 11.7 (7.6-14.9 mcg/L). C-telopeptide, a marker of bone resorption, was markedly elevated at 2079 (87-345 pg/mL), suggesting hypercalcemia of immobility. The patient was started on vitamin D supplementation, intravenous fluid hydration and physical therapy was initiated to encourage mobilization. The patient was carefully monitored with regular labs to avoid the risk of hypocalcemia once mobilization improved. His calcium began to decline to 10.5 (8.5-10.5 mg/mL) at time of discharge, eventually requiring calcium and calcitriol supplementation to maintain normocalcemia. Conclusion Hypercalcemia of immobility should be suspected in patients witha history of post-surgical hypoparathyroidism who present with new onset hypercalcemia that persists despite titrating or discontinuing calcium and calcitriol therapy. It is a diagnosis of exclusion and thorough laboratory assessment is needed to rule out other causes of hypercalcemia. These patients are at risk of hypocalcemia once the underlying etiology is corrected i.e restoration of mobility. Therefore, bisphosphonates should be avoided for acute treatment of hypercalcemia unless refractory to intravenous hydration. Once mobilization improves, calcium levels should be carefully monitored, and calcitriol and calcium supplementation should be resumed to maintain normocalcemia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Probing the Stoichiometry Dependence of Enzyme-Catalyzed Junction Zone Network Formation in Aiyu Pectin Gel via a Reaction Kinetics Model.

We investigate the enzymatic self-catalyzed gelation process in aiyu gel, a natural ion crosslinked polysaccharide gel. The gelation process depends on the concentration ratio (Rmax) of the crosslinking calcium ions and all galacturonic acid binding sites. The physical gel network formation relies on the assembly of calcium-polysaccharide crosslink bonds. The crosslinks are initially transient and through break-up/rebinding gradually re-organizing into long, stable junction zones. Our previous study formulated a reaction kinetics model to describe enzymatic activation, crosslinker binding, and crosslink microstructural reorganization, in order to model the complex growth of elasticity. In this study, we extend the theory for the time-dependent profile of complex moduli and examine the interplay of enzyme conversion, crosslink formation, and crosslink re-organization. The adjusted model captures how the gelation and structural rearrangement characteristic times vary with the polymer and calcium concentrations. Furthermore, we find that calcium ions act as both crosslinkers and dopants in the excess calcium ion scenario and the binding dynamics is determined by Rmax. This study provides perspectives on the dynamic binding behaviors of aiyu pectin gel system and the theoretical approach can be generalized to enzyme-catalyzed ionic gel systems.

Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells.

The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated. To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring. Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. Bone MSCs (BMSCs) were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk, along with normal-fat diet as the control. Then the serum was collected for the measurement of biochemical indicators. Meanwhile, the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration. And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction. Compared with the control group, maternal deficient, low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity, with larger adipocytes, more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation (PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and/or Leptin) among their male offspring (P < 0.05). And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro, respectively (P < 0.05). Meanwhile, it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups. Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring, with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood.

Carbonised fluidised fly ash (CFFA); A new product for mining engineering purposes (discussion of possible applications)

The article presents and summarises the current state of research and laboratory results on the carbonation of fly ash with carbon dioxide in the context of its use in mining engineering. Based on previous publications and patent applications, the possibilities of using carbonated fly ash from fluidised bed boilers for the following applications were discussed: securing excavations particularly susceptible to fire hazards, shotcreting and securing longwalls and supports, constructing cases, securing decommissioned shafts, and others, which means wherever the use of cement is required. It was pointed out that the removal of excess free calcium oxide makes it possible to use carbonated fly ash in mining applications for placement in workings requiring increased tightness. It was also stated that carbonation allows the removal of hydrogen from fluidised fly ash (FFA) obtained during co-combustion. The research highlighted the potential and importance of granulating carbonised FFA in expanding the applications of this innovative product in mining engineering.

In situ crosslinking sodium alginate on oil-water interface to stabilize the O/W emulsions

It has been a great challenge of using natural polysaccharides to stabilize food emulsions, due to their poor amphiphilicity. In this study, a novel strategy of using polysaccharide to stabilize O/W emulsions was developed, through in situ crosslinking of sodium alginate on oil-water interface. During the emulsifying process, the acetic acid migrated across the interface, and induced the released of calcium ions, which immediately crosslinked the sodium alginate on interface. Results showed that the oil droplets were encapsulated in the integral polysaccharide shells. The droplet size of the emulsions located in the range from 20 to 200 μm. The concentration of sodium alginate and HAc, as well as the mixing rates were showed to be positively related with the thickness of the shell. However, excess calcium ions would disintegrate the shell structure. Additionally, the interfacial crosslinked sodium alginate stabilized emulsions exhibited excellent physical stability under centrifugating and freeze-thawing.

A Model Nutrition Control System in Potato Tissue Culture and Its Influence on Plant Elemental Composition.

Low or excessive soil fertility is a major constraint to potato production. The influence of each individual nutrient element on potato plants under field studies remains ambiguous due to the influence of environmental variations. Creating an in vitro model plant with deficient or excessive nutrient content will provide a more controlled study and allow for a better understanding of how the concentration of one element can affect the uptake of other elements. Here we designed a tissue culture-based nutrition control system to systematically analyze the effects of essential nutrients on potato plants. Insufficient or excessive nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) contents were created by modifying the Murashige and Skoog (MS) medium. Deficient to toxic plant nutrient statuses were successfully defined by the evaluation of dry biomass and morphological symptoms. The results showed that plant shoot growth, nutrient uptake and content, and nutrient interactions were all significantly impacted by the changes in the MS media nutrient concentrations. These tissue culture systems can be successfully used for further investigations of nutrient effects on potato production in response to biotic and abiotic stresses in vitro.

Comparative Study on Pavement Performance of Asphalt Mixtures Modified by Calcium Sulfate Whisker and Calcium Carbonate Whisker

In order to study the effect of calcium sulfate whiskers and calcium carbonate whiskers on the road performance of asphalt mixtures, the high temperature stability, low temperature performance, and the change of water stability, the effect of two whiskers with different dosage levels on the road performance of asphalt mixture was obtained. The test results show that the calcium carbonate whiskers can improve the high temperature stability and water stability of the asphalt mixture within a certain dosage level range, but the low temperature performance has no obvious improvement effect, and adding excessive calcium carbonate whiskers will reduce the low temperature performance. The addition of calcium sulfate whiskers can significantly improve the road performance of the asphalt mixture. Under the same dosage level, the effect of calcium sulfate whiskers in improving road performance is better than that of calcium carbonate whiskers. When the content of calcium sulfate whisker is 0.4%, the road performance improvement effect of asphalt mixture is the best.

Effects of gellan gum and calcium fortification on the rheological properties of mung bean protein and gellan gum mixtures.

In this study, the effects of gellan gum types and CaCl2 addition on the rheological characteristics of mung bean protein (MBP)-gellan gum mixtures at varying protein contents (1-7 wt%) were investigated. Two types of gellan gum, high acyl gellan (HAG) and low acyl gellan (LAG), at 0.5 wt% were used. MBP-HAG system showed soft and elastic gels at below 3 wt% MBP content, but gel became weaker due to protein network disruption at higher MBP content. In contrast, MBP-LAG system exhibited a liquid-like behavior and a synergistic interaction between LAG and MBP. High calcium concentration can cause proteins to aggregate leading to protein precipitation. However, such phenomenon could be retarded by both types of gellan gum in the MBP-gellan gum mixtures studied herein. The calcium addition of up to 50 mM did not significantly alter the overall viscoelastic property of MBP-HAG system. In contrast, MBP-LAG system fortified with calcium formed solid gel at low protein content (1 wt%), but excessive calcium ions were required to maintain the strong gel characteristic at higher protein concentration (≥ 3 wt%) due to the competitive binding of calcium between the protein and gellan gum. These results were also supported by their microstructure observed through CLSM and SEM experiments. PRACTICAL APPLICATION: The application of hydrocolloids as rheology modifiers is useful to improve the stability and textural properties of plant-based protein drinks. Results from this study are helpful for the industry to understand the textural properties of mung bean protein at varying concentrations in the presence of gellan gum and calcium. Especially, at high calcium fortification which is desirable in plant-based protein drinks, protein aggregation could be retarded by gellan gum. Overall, the finding demonstrated that a range of rheological characteristics of mung bean protein and gellan gum mixtures could be manipulated as desired to meet both nutritional quality and product stability.

Mitochondrial regulation of acute extrafollicular B‐cell responses to COVID‐19 severity

BackgroundPatients with COVID‐19 display a broad spectrum of manifestations from asymptomatic to life‐threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive.MethodsWe investigated a total of 137 APs infected with SARS‐CoV‐2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD‐, S1‐, SSA/Ro‐ and dsDNA‐specific IgG.ResultsWhile critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection‐induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID‐19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease.ConclusionOur results reveal an immune mechanism that controls SARS‐CoV‐2‐induced detrimental B cell responses and COVID‐19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.

A Rapid Prognostic Score Based on Bedside Arterial Blood Gas Analysis (ABG) Established for Predicting 60-Day Adverse Outcomes in Patients with Acute Pancreatitis in the Emergency Department.

ObjectiveTo establish a rapid and concise prognosis scoring system for pancreatitis in the emergency department based on bedside arterial blood gas analysis (ABG).MethodsA single-center, retrospective cohort study was used to establish the new scoring system, and a validation group was used to verify it. The primary endpoint was 60-day death, and secondary endpoints were 28-day death, admission to the intensive care unit (AICU), requirement for mechanical ventilation (MV) and persistent organ failure (POF). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the new scoring system. The performance of the new scoring system was compared with that of conventional predictive scoring.Results443 patients were in the derivation group and 217 patients in the validation group, of which 27 and 25 died during follow-up. A total of 443 patients in the derivation group, 27 of whom died during the follow-up period. Multivariate regression analysis showed that mental status, hematocrit (HCT), base excess (BE) and Serum ionic calcium (Ca2+) were independent risk factors for 60-day mortality of pancreatitis, and they were used to create a new scoring system (MHBC). In the derivation and validation, the ability of MHBC (AUC= 0.922, 0.773, respectively) to predict 60-day mortality from pancreatitis was no less than that of APACHE II (AUC= 0.838, 0.748, respectively) and BISAP (AUC= 0.791, 0.750, respectively), while, MHBC is more quickly and concisely than APACHE II and BISAP. Compared with MHBC less than or equal to 2, when MHBC is greater than 2, the 28-day mortality, 60-day mortality and the incidence of AICU, MV and POF increased significantly (P <0.001).ConclusionThe MHBC can quickly and concisely evaluate the 60-day mortality, 28-day mortality, and the incidence of AICU, MV and POF of patients with acute pancreatitis in the emergency department.

Morphological and molecular insights of calcium in peanut pod development

Calcium is an important secondary macronutrient after nitrogen, phosphorus and potassium for the proper development of the plant. It is typically important for the formation of cell walls, cell members and accumulates in the plant cells. Calcium deficiency occurs rarely in nature but excess calcium limits plant communities on calcareous soils. In peanut, calcium uptake by plants from the soil will remain in the plant tissues and will not be transported back to developing pods where calcium requirement is more. The geotropic growth of peanut pods had capacity of absorption of calcium from the soil for filling and development of pods. Application of calcium before the pod development stage in peanut is required to have sufficient calcium available to the pods which could help an increase in yield up to 20–30%. The calcium-related genes in different metabolic pathways help in the regulation of embryo abortion in peanut and also a well-documented role in mediating plant responses to abiotic and biotic stimuli. This article provides a summary of the role of calcium, its management details, the transport of calcium into plants through the soil and overview of calcium genes in peanut pod development.

Molybdenum and cadmium co-exposure induces CaMKKβ/AMPK/mTOR pathway mediated-autophagy by subcellular calcium redistribution in duck renal tubular epithelial cells

Excessive molybdenum (Mo) and cadmium (Cd) are toxic environmental pollutants. Our previous research confirmed excessive Mo and Cd co-induced calcium homeostasis disorder and autophagy in duck kidneys, but how calcium ion (Ca2+) regulates autophagy is unclear. The results revealed that the Mo- and/or Cd-induced cytosolic Ca2+ concentration ([Ca2+]c) increase mainly came from intracellular calcium stores. Mo and/or Cd caused mitochondrial Ca2+ content ([Ca2+]mit) and [Ca2+]c increase with endoplasmic reticulum (ER) Ca2+ content ([Ca2+]ER) decrease and upregulated calcium homeostasis-related factor expression levels, but 2-Aminoethoxydiphenyl borate (2-APB) reversed subcellular Ca2+ redistribution. Increased Phospholipase C (PLC) and inositol 1,4,5-trisphosphate (IP3) activities and inositol 1,4,5-trisphosphate receptor (IP3R) expression level were observed in Mo- and/or Cd-treated cells, which was reversed by the PLC inhibitor U-73122. 2-APB and 1,2-Bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM) addition mitigated [Ca2+]c and autophagy (variations in microtubule-associated protein light chain 3 (LC3), LC3B-II/LC3B-I, autophagy related 5 (ATG5), sequestosome-1(P62), programmed cell death-1 (Beclin-1) and Dynein expression levels, LC3 puncta, autophagosomes and acid vesicle organelles) under Mo and/or Cd treatment, respectively, while thapsigargin (TG) had the opposite impacts. Additionally, the calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor STO-609 reversed the increased CaMKKβ, adenosine 5′-monophosphate-activated protein kinase (AMPK), Beclin-1, and LC3B-II/LC3B-I protein expression levels and reduced mammalian target of rapamycin (mTOR) and P62 protein expression levels in Mo- and/or Cd-exposed cells. Collectively, the results confirmed that [Ca2+]c overload resulted from PLC/IP3/IP3R pathway-mediated ER Ca2+ release, and then activated autophagy by the CaMKKβ/AMPK/mTOR pathway in Mo- and/or Cd-treated duck renal tubular epithelial cells.

Vertebral Artery Stenosis: A Narrative Review

Vertebral artery stenosis (VAS) is the cause of approximately 20% of ischemic strokes in the posterior circulation. There are several causes of vertebral artery stenosis, including atherosclerosis, calcification, dissections, fibromuscular dysplasia, giant cell arteritis, neurofibromatosis type 1, and bony compressions. The most common cause of VAS is atherosclerosis which is derived from the macrophage-induced oxidation of low-density lipoproteins (LDLs), alongside the accumulation of cholesterol. Calcification of the vertebral artery occurs when there is excess calcium and phosphate deposition in the vessel. Dissection of the vertebral artery can lead to the formation of a hematoma causing stenosis of the vertebral artery. Fibromuscular dysplasia can result in stenosis due to the deposition of collagen fibers in the tunica media, intima, or adventitia. Giant cell arteritis, an autoimmune disorder, causes inflammation of the internal elastic membrane resulting in eventual stenosis of the artery. Neurofibromatosis type 1, an autosomal dominant disorder, results in the stenosis of the vertebral artery due to the altered function of neurofibromin. Mechanical compression of the vertebral artery by bone can also cause stenosis of the vertebral artery. Digital subtraction angiography (DSA) is considered the current gold standard in diagnosing vertebral artery stenosis; however, its associated morbidity and mortality have led to increased use of non-invasive techniques such as duplex ultrasonography (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Currently, asymptomatic and symptomatic vertebral artery stenoses are treated by risk factor modification and medical treatment. However, it is recommended that surgical (endarterectomy, reconstruction, and decompression) and endovascular (balloon coronary, bare-metal, and drug-eluting stents) treatments are also used for symptomatic vertebral artery stenosis.

New application to remediate drinkable groundwater from excess of hardness ions by using sodalite bearing modified illite

Calcium Hardness (Ca. H) and total Hardness ions in drinkable groundwater cause great problems for the entire world especially, the population communities which are located far from surface water sources. The present study investigates the use of Sodalite Bearing Modified Illite (SBMI) as a sustainable and new technique to eliminate these ions from drinkable groundwater to compatible with the instruction of the World Health Organization. The methodology was achieved by using a new method to remove these ions’ excess calcium Hardness and total Hardness depending on two main processes; the adsorption as a first step and the coagulation-flocculation-sedimentation process as a second step. The results of this study were achieved through conducting three tasks; (1) Chemical analysis surveys for all the groundwater wells, to determine the areas which are more affected by these salts, and plot them on the location maps. (2) Conducting the alkaline modification of the Illite ore to obtain the (SBMI) which has a high surface area and high adsorption ability, and it had been characterized by using XRD, XRF, SEM, and FTIR techniques. (3) The experimental studies were conducted to evaluate the effect of the modified Illite on raw groundwater containing a high concentration of hardness ions, through the batch studies to determine the factors which affected its ability for removing these ions from groundwater. The present study illustrated that the removing efficiency for both total hardness (Ca. H + Mg. H) and calcium hardness (Ca. H) reached about 98%. Finally, the present study recommended using this technique, when there is a requirement for large quantities of treated water at a low cost.

Abstract P1095: Analysis Of Pro-arrhythmic Effects Of The Trisulfated Disaccharide Heparin Fragment, A Potential Antiarrhythmic Drug.

Background: The heparin fragment called trisulfated disaccharide (TD) acts on the sodium-calcium exchanger by removing excess calcium from cytoplasm with antiarrhythmic action demonstrated in animal models in the reversal of supraventricular and ventricular arrhythmia. However, it is known that drugs with antiarrhythmic potential can induce arrhythmic phenomena, limiting and interrupting the study of new potentially antiarrhythmic drugs. Objective: To evaluate the arrhythmogenic potential of TD in relation to the stimulation of hERG channels in human cardiomyocytes. Material and Methods: Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in culture were plated onto a fibronectin coated 48 well microelectrode array plate at a density of 25,000 cells per well in iCell® maintenance medium. The plate was incubated for 7 days until a stable beating phenotype was achieved, and the cells were ready for drug treatment. They were dosed with 0.2% DMSO vehicle, E-4031 (0.05μM), or cisapride (0.05μM) as controls (arrhythmogenic drugs). They were also dosed with TD at four concentrations in triplicate. The activity of the cells was recorded prior to dosing and at 1 hour using the Axion Biosystems Maestro MEA system. Beat period (s), fast Na+ slope (V/s), fast Na+ amplitude (mV) and field potential duration (FPD) were evaluated. Results: E-4031 treatment resulted in a significant increase in beat period length (decrease in beat rate) and a decrease in the Na slope and amplitude. There was a very large increase in the FPD. Cisapride showed a very similar response. Both compounds caused an increase in the ratio of the FPD to the beat period length. When the cardiomyocytes were incubated with the different doses of TD, there was a slight increase in the beat period length (decrease in the beat rate), which was observed regarding all the doses. There was an increase in the FPD, which is consistent with the change in beat rates suggesting that the change is purely related to beating and not indicative of any hERG effect or other responses. The ratio of the FPD to the beat period length was the same. There was a slight decrease in the sodium slope and amplitude, but they were not significant. Therefore, the only significant change observed was the beat rate. Conclusion: TD when exposed to human cardiomyocytes did not present an arrhythmogenic potential in relation to the hERG channels, and this is a desirable behavior for an antiarrhythmic drug.

Neuronopathic Gaucher disease: Beyond lysosomal dysfunction.

Gaucher disease (GD) is an inherited disorder caused by recessive mutations in the GBA1 gene that encodes the lysosomal enzyme β-glucocerebrosidase (β-GC). β-GC hydrolyzes glucosylceramide (GluCer) into glucose and ceramide in the lysosome, and the loss of its activity leads to GluCer accumulation in different tissues. In severe cases, enzymatic deficiency triggers inflammation, organomegaly, bone disease, and neurodegeneration. Neuronopathic Gaucher disease (nGD) encompasses two different forms of the disease, characterized by chronic or acute damage to the central nervous system (CNS). The cellular and molecular studies that uncover the pathological mechanisms of nGD mainly focus on lysosomal dysfunction since the lysosome is the key organelle affected in GD. However, new studies show alterations in other organelles that contribute to nGD pathology. For instance, abnormal accumulation of GluCer in lysosomes due to the loss of β-GC activity leads to excessive calcium release from the endoplasmic reticulum (ER), activating the ER-associated degradation pathway and the unfolded protein response. Recent evidence indicates mitophagy is altered in nGD, resulting in the accumulation of dysfunctional mitochondria, a critical factor in disease progression. Additionally, nGD patients present alterations in mitochondrial morphology, membrane potential, ATP production, and increased reactive oxygen species (ROS) levels. Little is known about potential dysfunction in other organelles of the secretory pathway, such as the Golgi apparatus and exosomes. This review focuses on collecting evidence regarding organelle dysfunction beyond lysosomes in nGD. We briefly describe cellular and animal models and signaling pathways relevant to uncovering the pathological mechanisms and new therapeutic targets in GD.