Ionized Calcium Levels Research Articles

Exploring the Effect of Arsenic-Containing Hydrocarbon on the Bidirectional Synaptic Plasticity of the Dorsal Hippocampus.

Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 μg As L-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 μg As L-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability.

Embryo thermal manipulation enhances mitochondrial function in the skeletal muscle of heat-stressed broilers by regulating transient receptor potential V2 expression

Heat stress induces mitochondrial dysfunction, thereby impeding skeletal muscle development and significantly impacting the economic efficiency of poultry production. This study aimed to investigate the effects of embryo thermal manipulation (TM, 41.5°C, 65% RH, 3 h/d during 16-18th embryonic age) on the mitochondrial function of the pectoralis major (PM) in broiler chickens exposed to thermoneutral (24 ± 1°C, 60% RH) or cyclic heat stress (35 ± 1°C, 60% RH, 12 h/d) from day 22 to 28, and to explore potential mechanisms involving transient receptor potential V2 (TRPV2). Additionally, in vitro experiments were conducted to assess the regulatory effects of TRPV2 pharmacological activation and inhibition on mitochondrial function in primary myotubes. The results revealed that TM had no discernible effect on the body weight and feed intake of broiler chickens under heat stress conditions (P > 0.05). However, it did delay the increase in rectal temperature and accelerate the decrease in serum T3 levels (P < 0.05). Furthermore, TM promoted the development of PM muscle fibers, significantly increasing myofiber diameter and cross-sectional area (P < 0.05). Under heat stress conditions, TM significantly upregulated the expression of mitochondrial electron transport chain (ETC) genes and TRPV2 in broiler PM muscle (P < 0.05), with a clear positive correlation observed between the two (P < 0.05). In vitro, pharmacological activation of TRPV2 not only increased its own expression but also enhanced mitochondrial ETC genes expression and oxidative phosphorylation function by upregulating intracellular calcium ion levels (P < 0.05). Conversely, TRPV2 inhibition had the opposite effect. Overall, this study underscores the potential of prenatal thermal manipulation in regulating postnatal broiler skeletal muscle development and mitochondrial function through the modulation of TRPV2 expression.

The Relationship Between Ionized Calcium Levels and Prognosis in Patients with Spontaneous Subarachnoid Hemorrhage

The serum calcium plays a role as a cofactor in critical steps such as cardiac contractility, vascular tone, and the coagulation cascade. This study aimed to determine if the level of ionized calcium can predict outcomes in patients with spontaneous subarachnoid hemorrhage (SAH) in the emergency department. The study was a retrospective cross-sectional case series. Patients aged 18 and over diagnosed with spontaneous SAH in the emergency department were included in the study. Patients' demographic characteristics, comorbidities, vital signs, laboratory parameters, World Federation of Neurosurgical Societies score, SAH grading according to the Fisher scale, needs of mechanical ventilation and inotropic treatment, administered treatments, complications, Rankin scores at discharge, and outcome were recorded in a standard data form. A total of 267 patients were studied, with a mean age of 55.5 ± 13.4years, and 53.9% (n= 144) were female. Hydrocephalus was present in 16.5% of patients. The average hospital stay was 20.4 ± 19.8days. Mortality rate was 34.8% (n= 93). Mortality was significantly higher in patients with low calcium levels upon admission (P= 0.024). Ionized calcium levels during complication development independently predicted mortality (OR: 0.945, 95% CI: 0.898-0.996, P= 0.034). Patients with poor neurologic outcomes (Rankin: 3-6) had significantly lower initial ionized calcium levels (P= 0.002). The ionized calcium level is a readily accessible blood gas parameter that assists clinicians in predicting functional independence and mortality at discharge in patients presenting to the emergency department with spontaneous SAH.

The Olfactory Receptor Olfr25 Mediates Sperm Dysfunction Induced by Low-Dose Bisphenol A through the CatSper-Ca2+ Signaling Pathway.

Bisphenol A (BPA), a typical endocrine disruptor, is known to have various adverse effects on the male reproductive system. However, the toxic effects and mechanisms of low-dose BPA have not yet been fully explored. In this study, male Kunming mice were orally administered low-dose BPA (0.03, 0.3 and 3 mg/kg/d) for ten consecutive weeks. Pathological sections of testicular tissue showed no significant morphological differences after BPA exposure. An analysis of the functional parameters of sperm revealed that exposure to low-dose BPA significantly decreased sperm motility, chemotaxis, and the acrosome reaction. An in vitro BPA exposure model combined with an omics data analysis showed that the olfactory receptor-related pathway was significantly enriched after BPA treatment. Subsequent experiments verified the reduced mRNA level of a novel olfactory receptor gene, Olfr25, in vivo and in vitro exposure models. Meanwhile, exposure to low-dose BPA reduced the intracellular calcium ion concentration and the mRNA levels of pore-forming subunits of the CatSper channel in sperm. Importantly, the knockdown of Olfr25 inhibited calcium ion levels and CatSper subunit expression in GC-2 cells. Olfr25 overexpression attenuated the BPA-induced downregulation of CatSper subunit expression in GC-2 cells. These findings indicate that Olfr25 might participate in low-dose BPA-induced sperm dysfunction by affecting the CatSper-Ca2+ signaling pathway. This study reveals a new mechanism underlying the effects of low-dose BPA on sperm function and provides a reference for assessing the safety of low-dose BPA exposure.

Citrate and low-dose heparin combined anticoagulation in pediatric continuous renal replacement therapy

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT.

A microfluidic chip for immobilization and imaging of Ciona intestinalis larvae.

Sea squirts (Tunicata) are chordates and develop a swimming larva with a small and defined number of individually identifiable cells. This offers the prospect of connecting specific stimuli to behavioral output and characterizing the neural activity that links these together. Here, we describe the development of a microfluidic chip that allows live larvae of the sea squirt Ciona intestinalis to be immobilized and recorded. By generating transgenic larvae expressing GCaAMP6m in defined cells, we show that calcium ion levels can be recorded from immobilized larvae, while microfluidic control allows larvae to be exposed to specific waterborne stimuli. We trial this on sea water carrying increased levels of carbon dioxide, providing evidence that larvae can sense this gas.

The neonicotinoid, imidacloprid, disrupt the chicken sperm quality through calcium efflux

Imidacloprid (IMI), an insecticide from the neonicotinoid group widely used in agriculture, has drawn attention due to its potential harmful effects on non-target species, including bird populations. In the present work, we investigated the effect of IMI on avian semen by in vitro exposure of rooster spermatozoa to this pesticide. The semen was collected twice a week. Samples collected on one day were pooled and incubated with the following IMI concentrations: 0 mM, 0.5 mM, 5 mM, 10 mM, and 50 mM at 36°C for 3 h. Comprehensive semen analysis was carried out after 1 h and 3 h of incubation, evaluating sperm motility parameters with the CASA system and using flow cytometry to assess membrane integrity, mitochondrial activity, acrosome integrity, chromatin structure, intracellular calcium level and apoptosis markers such as: early apoptosis and caspase activation and lipid peroxidation. The results of the first experiment suggest that low concentrations of IMI have a different effect on sperm motility compared to higher concentrations. In IMI samples, we also observed a lower percentage of cells with a high level of calcium ions compared to the control, and a lower level of lipid peroxidation. We concluded that IMI may act as a blocker of calcium channels, preventing the influx of these ions into the cell. To confirm this mechanism, we conducted a second experiment with calcium channel blockers: SNX 325, MRS-1845, and Nifedipine. The results of this experiment confirmed that the mechanism of action of IMI largely relies on the blockade of calcium channels in rooster sperm. Blocking the influx of calcium ions into the cell prevents the formation of Ca²⁺-dependent pores, thereby preventing an increase in cell membrane permeability, ultimately blocking early apoptosis and lipid peroxidation in chicken spermatozoa.

#1250 Measurement of ionized calcium with a point-of-care ionometer during treatment with etelcalcetide

Abstract Background and Aims Etelcalcetide is an intravenous calcimimetic indicated for the treatment of mineral and bone disorders in hemodialysis patients by lowering parathyroid hormone (PTH), calcium and phosphorus. The assessment of ionized calcium versus total calcium has not yet been studied during treatment with etelcalcetide, and there are no real data on the occurrence of hypocalcemia as measured by ionized calcium in the pre- and post-hemodialysis period during treatment with etelcalcetide. The aim of this study was to describe the time course of ionized and total serum calcium levels during chronic treatment with etelcalcetide and to assess the occurrence of hypocalcemia in patients treated with etelcalcetide by measuring ionized calcium levels. Method This was an observational, non-interventional, prospective, single-arm phase IV study. A total of 20 chronic hemodialysis patients (15 men and 5 women) aged 55.9 ± 18.2 years undergoing dialysis for 5.5 ± 4.3 years in two hemodialysis centers of the University Medical Centre Ljubljana were enrolled in the study between January 2020 and March 2021. All patients received etelcalcetide as a bolus injection into the venous line of the dialysis circuit three times a week, immediately after each hemodialysis session. Ionized calcium levels were determined using a point-of-care ionometer (GEM Premier 3000) before starting treatment with etelcalcetide prior to dialysis, then during treatment in the first week before and after dialysis, then once a week until the maintenance phase was reached and at least once a month thereafter. Hypocalcemia was defined by a pre-dialysis ionized calcium concentration below 0.90 mmol/L. The corrected total calcium values was measured prior to dialysis at least once a month according to routine clinical practice. The data of all these patients were included in the analysis, except for one, who underwent a kidney transplantation after receiving only 4 doses of etelcalcetide. Results We demonstrated that both corrected total calcium and ionized calcium before dialysis decreased over time during treatment with etelcalcetide. Of 240 measurements of ionized calcium with a point-of-care ionometer at the bedside, the concentration of ionized calcium was below 0.90 mmol/L three times in two patients (0.81, 0.84, 0.85). In one patient, we increased a calcium level in the dialysate from 1.50 to 1.75 mmol/L and in the other from 1.25 to 1.50 mmol/L. In addition, we observed 2 further measurements of ionized calcium of 0.90 mmol/L and 18 measurements between 0.91 and 0.96 mmol/L. However, this corresponds to 1.25% of hypocalcemias with ionized calcium below 0.90 mmol/L and 8.3% of those with calcium between 0.90 and 0.96 mmol/L. As calcium concentration in the bath increased, the pre-dialysis calcium concentrations also appeared to increase. At the beginning of the study, the calcium concentration in the dialysate was 1.5 mmol/L in 16 of 20 patients. 2 patients were treated with a calcium concentration in the dialysate of 1.75 mmol/L and 2 others with 1.25 mmol/L. The proportion of patients using higher dialysate calcium concentration was higher at the end of the study, as two patients switched to 1.75 mmol/L, and one from 1.25 to 1.50 mmol/L. This probably indicates a co-intervention triggered by a reduction in serum calcium levels prior to dialysis during treatment with etelcalcetide. Visual comparisons of the time course of ionized and corrected calcium concentrations before dialysis during chronic treatment with etelcalcetide in 19 patients showed a good correlation between point-of-care ionized calcium and routinely measured total calcium. Conclusion A point-of-care ionometer for the determination of ionized calcium at the bedside has the potential to guide etelcalcetide therapy by optimizing serum calcium levels and also to prevent potentially threatening hypocalcemia.

Polystyrene nanoplastics exert cardiotoxicity through the Notch and Wnt pathways in zebrafish (Danio rerio)

The ubiquity of micro(nano)plastics has raised significant concerns among people. Their accumulation in the cardiovascular system necessitates attention to their cardiotoxicity. However, research on the cardiotoxicity of micro(nano)plastics remains scarce. Our study exposed zebrafish embryos to four different concentrations (0, 1, 10, 100 μg/mL) of polystyrene nanoplastics (PSNPs) for a period of 7 days. The results indicated that PSNPs noticeably decreased the hatching and survival rates of zebrafish and also induced cardiac developmental abnormalities. The mRNA level analysis revealed significant upregulations of heart development-related genes nkx2.5, cmlc-2, and myh-7 in response to PSNPs. Additionally, PSNPs significantly up-regulated the mRNA level associated with the Notch signaling pathway (notch-1a, jag-1a, and her-7) while remarkably suppressing the expression of the Wnt signaling pathway gene (wnt-3a). Further research showed that PSNPs significantly increased the expression of endoplasmic reticulum stress genes atf-6 and chop, while noticeably inhibiting mitochondrial copy numbers. Moreover, PSNPs were found to decrease calcium ion level and superoxide dismutase (SOD) activity in zebrafish larvae. Additionally, prolonged exposure to PSNPs for 7 days exacerbated abnormalities in various indicators compared to a 4-day exposure. In conclusion, our study demonstrates that PSNPs induce oxidative stress in zebrafish larvae, thereby activating endoplasmic reticulum stress and inhibiting mitochondrial activity, ultimately disrupting the Notch and Wnt signaling pathways. These disruptions result in abnormalities in cardiac developmental genes, ultimately leading to cardiac developmental abnormalities in zebrafish. The present research contributes to a novel understanding of the cardiotoxicity of PSNPs.

FEATURES OF THE DISTRIBUTION AND COMPOSITION OF SNOW COVER WITHIN THE LANDSCAPES OF CHASHNIKOVO

For landscape conditions in the upper reaches of the river Klyazma, Solnechnogorsk district, Moscow region, the height and reserves of snow cover were investigated, and the chemical composition of the snow was determined. The basis for considering the component composition of snow cover was the geochemical taxonomy of chemical elements based on the characteristics of water migration and abundance. Data from 23 snow sampling points were interpolated in SAGA GIS using the inverse distance weighting (IDW) method. On this basis, zones differing in the chemical composition of snow are identified. One of the zones is confined to the M-10 Moscow-St. Petersburg highway, while the second borders on populated areas. The area close to the highway is characterized by increased levels of calcium, sodium, aluminum, and chloride ions in the snow cover. The second zone, bordering populated areas, is characterized by a high content of calcium, copper, and manganese in the snow. For the third zone, low concentrations of components in the snow were observed which are characteristic of a superaquatic landscape due to the distance from sources of pollution. The studied composition of snow waters belongs to the bicarbonate-sodium-calcium-chloride class. It has been shown that the height and reserves of snow cover are partially controlled by two factors: the type of elementary landscape and the type of ecosystem. Against this background, the spatial distribution of concentrations of elements and anions in snow is predominantly controlled by the anthropogenic factor.

Artesunate promotes cervical cancer cell apoptosis by regulating Bcl2 family molecules and reducing the mitochondrial membrane potential.

Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC50) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca2+) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC50 of ART in SiHa cells was 26.32 µg/ml. According to the IC50 value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca2+ and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca2+ and the reduction of the mitochondrial membrane potential.

Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20years after donation.

In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3months and 36months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared with matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium- and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89pg/mL vs. controls 38.79pg/mL, percent difference = -12.6%; P< .001), increases in both parathyroid hormone (when corrected for ionized calcium; donors mean 52.98pg/mL vs. controls 46.89pg/mL,% difference 13%; P= .03) and ionized calcium levels (donors mean 5.13mg/dL vs. controls 5.04mg/dL; P< .001), and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency toward thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Human benign Leydig cell tumor − Biochemical evaluation

Recently we reported expressional alterations in 219 genes and their transcripts in Leydig cell tumors but nowadays there is still a lack of full basic biochemical characteristics of these tumors. The discovery of potential biochemical markers for tumor management from early detection, treatments, and control of therapy results may markedly supplement genetic data. Leydig cell micronodules were obtained from patients with azoospermia who were qualified for testicular biopsy. The biochemistry of Leydig cell tumors was analyzed using histological staining and spectrophotometric measurements of total proteins, carbohydrates, lipids, and nucleic acids. In addition, the levels of calcium (Ca2 +), copper (Cu2 +), zinc (Zn2 +), and selenium (Se2 +) ions were measured. When compared to healthy testis we revealed, for the first time, that in the interstitial tissue with Leydig cell tumors, great amounts of proteins, carbohydrates, lipids, and acids were dislocated from the seminiferous tubules. Measurements of organic compounds showed a decrease (P < 0.05) only in the Cu2 + content in Leydig cell tumors which may be related to their altered biochemical structure. This specific result may be promising for designing further approaches to manage this tumor based on combining morphological and molecular data.

THE COHORT STUDY OF ADIPOCYTES’ SECRETORY ACTIVITY, VITAMIN D, PARATHYROID HORMONE, LEPTIN RESISTANCE AND OBESITY IN HYPERTENSIVE PATIENTS

Objective: Obesity is a major risk factor of essential arterial hypertension (EAH). Therefore, we studied the dependence of 25-OH vitamin D (VitD), parathyroid hormone (PTH), Adiponectine, Leptin and ionized calcium blood values on Obesity degrees in EAH patients. Design and method: Study involves 100 EAH patients with hypertensive-mediated organ damage (moderate-very-high cardiovascular risks, aged 45-65). Obesity was determined by body mass index (BMI) &gt;30 kg/m2: 1st obesity degree – 30-34.9 kg/m2, 2nd – 35-39.9 kg/m2, 3rd – &gt;40 kg/m2. Serum levels of VitD and PTH studied by immunochemiluminescent method, Ca2+– by potentiometric method, Adiponectine and Leptin blood values – by ELISA. Leptin resistance (LR) index calculated by Leptin to Triglycerides Ratio (LTR). Adipocytes Secretory Activity (ASA) calculated by Leptin to BMI Ratio. Results: Adiponectin in EAH with obesity was lower, and leptin, on the contrary, was higher than in EAH without obesity – by 7.54-12.81% (p&lt;0.001) and 1.75-2.63 times (p&lt;0.001) respectively. LR and ASA indexes increased in presence of obesity 1.5-2.2 times (p&lt;0.001) and 1.47-1.85 times (p&lt;0.001), respectively. Adipocytokines concentration depended on the obesity: in 2nd and 3rd degrees EAH patients lower by 5.98% (p&lt;0.001), and leptin, on the contrary, was higher by 50.18% (p&lt;0.001), than in the case of 1st degree obesity, leading to LR and adipocytes’ secretory activity growth by 46.88% (p=0.018) and 26% (p=0.004). In EAH patients with 2nd and 3rd obesity degrees, concentration of 25(OH)VitD was lower by 18.48% (p=0.012), and PTH, was higher by 31.62% (p=0.017), than in obesity-free. Ionized calcium level did not depend on the obesity. Obesity risk in EAH elevated with blood adiponectin decrease (&lt;75ng/ml) by 77 times [OR: 16.25-364.8; p&lt;0.001], leptin augmentation (in women &gt;21 ng/ml, in men &gt;14 ng/ml) – 31 times [OR: 3.93-245.48; p&lt;0.001], LR index increase (&gt;15.0 U) – 5.27 times [OR: 2.04-13.60; p&lt;0.001] and adipocytes’ secretory activity (&gt;0.70 U) – 34.1 times [OR: 4.32-268.7; p&lt;0.001]. Conclusions: Low Adiponectine, Leptin elevation, LR and ASA augmentation increase the obesity risk in EAH 5-77 times (p&lt;0.001). The 2nd and 3rd obesity degrees associate with lower 25(OH)VitD, higher PTH (p&lt;0.05), independetly on ionized calcium.

EVALUATION AND COMPARISON OF DIAGNOSTIC EFFICACY OF INDICATORS TO SCREENING FOR PRIMARY ALDOSTERONISM BEFORE ENDOCRINE PATHWAY

Objective: To evaluate and compare the effectiveness to screen for primary aldosteronism (PA) before the endocrine performing among hypokalemia, the serum sodium to urinary sodium to (serum potassium) to urinary potassium (SUSPPUP) index, combination of urine pH, sex, and serum potassium (PFK score) and PA-nomogram prediction model.2 Design and method: From January 2010 to January 2014, 937 patients with hypertension were admitted in the People's Hospital of Xinjiang Uygur Autonomous Region. Fasting elbow venous blood was collected on admission day, serum, potassium, sodium and calcium ion levels were determined, calcium and phosphorus products were calculated, plasma sitting aldosterone/renin activity (ARR) were measured, and calculated. 24 h urine was collected and the ion level was measured. The pH value of urine was detected by pH test paper in the morning. Serum potassium (&lt;3.5 mmol/L), SUSPPUP (&gt;5.3/ (mmol/L)), PFK score (&gt;2 points), nomogram prediction model (&gt;21%) as positive screening criteria, ARR (&gt;20ng/dL/ ng/mL/h) as positive endocrine screening index, were respectively used to predict and screen PA. The patients with positive ARR were confirmed PA using saline infusion test. The ROC curve was drawn to evaluate the efficacy of serum potassium, SUSPPUP, PFK score, and PA-nomogram prediction model to screen PA. Kappa test was used to evaluate its consistency with ARR screening results. Results: The area under ROC curve of serum potassium &lt;3.5 mmol/L, SUSPPUP &gt;5.3 (mmol/L)-1, PFK score &gt;2 points, nomogram prediction probability&gt;21% to screen PA in patients with hypertensive respectively were 0.61(95%CI:0.56∼0.66, P&lt;0.001), 0.52(0.47∼0.57, P=0.479), 0.57(0.52∼0.62, P=0.005), 0.62(0.57∼0.67, P&lt;0.001), and the sensitivity was 36%, 7%, 24% and 53%, the specificity was 86%, 96%, 90% and 70%, respectively. There was good consistency between nomogram prediction model or PFK score and ARR (Kappa=0.122, P &lt;0.001, Kappa=0.092,P &lt;0.001), and the Kappa value of nomogram prediction model with ARR was higher than the PFK score with ARR (X2=163.577, P &lt; 0.001). Conclusions: The nomogram prediction model, which includes gender, serum potassium, calcium-phosphorus product and urine pH value, is more sensitive to screen PA in patients with hypertension, and the nomogram prediction probability&gt;21% is more consistent with ARR.

Regulation of cardiac fibroblasts reprogramming into cardiomyocyte-like cells with a cocktail of small molecule compounds.

Myocardial infarction results in extensive cardiomyocyte apoptosis, leading to the formation of noncontractile scar tissue. Given the limited regenerative capacity of adult mammalian cardiomyocytes, direct reprogramming of cardiac fibroblasts (CFs) into cardiomyocytes represents a promising therapeutic strategy for myocardial repair, and small molecule drugs might offer a more attractive alternative to gene editing approaches in terms of safety and clinical feasibility. This study aimed to reprogram rat CFs into cardiomyocytes using a small molecular chemical mixture comprising CHIR99021, Valproic acid, Dorsomorphin, SB431542, and Forskolin. Immunofluorescence analysis revealed a significant increase in the expression of cardiomyocyte-specific markers, including cardiac troponin T (cTnT), Connexin 43 (Cx43), α-actinin, and Tbx5. Changes in intracellular calcium ion levels and Ca2+ signal transfer between adjacent cells were monitored using a calcium ion fluorescence probe. mRNA sequencing analysis demonstrated the upregulation of genes associated with cardiac morphogenesis, myocardial differentiation, and muscle fiber contraction during CF differentiation induced by the small-molecule compounds. Conversely, the expression of fibroblast-related genes was downregulated. These findings suggest that chemical-induced cell fate conversion of rat CFs into cardiomyocyte-like cells is feasible, offering a potential therapeutic solution for myocardial injury.

Suppression of Contraction Raises Calcium Ion Levels in the Heart of Zebrafish Larvae.

Zebrafish larvae have emerged as a valuable model for studying heart physiology and pathophysiology, as well as for drug discovery, in part thanks to its transparency, which simplifies microscopy. However, in fluorescence-based optical mapping, the beating of the heart results in motion artifacts. Two approaches have been employed to eliminate heart motion during calcium or voltage mapping in zebrafish larvae: the knockdown of cardiac troponin T2A and the use of myosin inhibitors. However, these methods disrupt the mechano-electric and mechano-mechanic coupling mechanisms. We have used ratiometric genetically encoded biosensors to image calcium in the beating heart of intact zebrafish larvae because ratiometric quantification corrects for motion artifacts. In this study, we found that halting heart motion by genetic means (injection of tnnt2a morpholino) or chemical tools (incubation with para-aminoblebbistatin) leads to bradycardia, and increases calcium levels and the size of the calcium transients, likely by abolishing a feedback mechanism that connects contraction with calcium regulation. These outcomes were not influenced by the calcium-binding domain of the gene-encoded biosensors employed, as biosensors with a modified troponin C (Twitch-4), calmodulin (mCyRFP1-GCaMP6f), or the photoprotein aequorin (GFP-aequorin) all yielded similar results. Cardiac contraction appears to be an important regulator of systolic and diastolic Ca2+ levels, and of the heart rate.

Effects of High-Dose Cyclophosphamide on Ultrastructural Changes and Gene Expression Profiles in the Cardiomyocytes of C57BL/6J Mice.

The pathogenesis of cyclophosphamide (CY)-induced cardiotoxicity remains unknown, and methods for its prevention have not been established. To elucidate the acute structural changes that take place in myocardial cells and the pathways leading to myocardial damage under high-dose CY treatments, we performed detailed pathological analyses of myocardial tissue obtained from C57BL/6J mice subjected to a high-dose CY treatment. Additionally, we analysed the genome-wide cardiomyocyte expression profiles of mice subjected to the high-dose CY treatment. Treatment with CY (400 mg/kg/day intraperitoneally for two days) caused marked ultrastructural aberrations, as observed using electron microscopy, although these aberrations could not be observed using optical microscopy. The expansion of the transverse tubule and sarcoplasmic reticulum, turbulence in myocardial fibre travel, and a low contractile protein density were observed in cardiomyocytes. The high-dose CY treatment altered the cardiomyocyte expression of 1210 genes (with 675 genes upregulated and 535 genes downregulated) associated with cell-cell junctions, inflammatory responses, cardiomyopathy, and cardiac muscle function, as determined using microarray analysis (|Z-score| > 2.0). The expression of functionally important genes related to myocardial contraction and the regulation of calcium ion levels was validated using real-time polymerase chain reaction analysis. The results of the gene expression profiling, functional annotation clustering, and Kyoto Encyclopedia of Genes and Genomes pathway functional-classification analysis suggest that CY-induced cardiotoxicity is associated with the disruption of the Ca2+ signalling pathway.

Correlation of Serum Calcium with Severity and Outcomes in Patients of COVID-19 Pneumonia.

Calcium is an essential electrolyte with critical physiological functions. Recently, it has been implicated in the pathogenesis and outcomes of COVID-19. This retrospective study was conducted to estimate serum ionic calcium and its correlation with clinical severity, inflammatory markers, and in-hospital outcomes in moderate to severe COVID-19 patients. We retrospectively analyzed data from 377 COVID-19 patients, aged between 23 and 79 years, with a mean age of 54.17±11.53 years. Severity of the disease was determined using ICMR criteria. Parameters including age, gender, inflammatory markers, calcium levels, and clinical outcomes were assessed. The study showed a prevalence of moderate and severe COVID-19 in 58.1% and 41.9% patients, respectively. Severity was significantly associated with younger age, higher mean inflammatory markers, notably IL-6, procalcitonin, D-Dimer, and lower ionic and total calcium levels, as well as vitamin D levels. Mortality and referral rate were significantly higher in the severe group. Hypocalcemia was prevalent in 39% of the patients and was significantly associated with disease severity, ARDS, and mortality. On multivariate assessment, only age and ionic calcium were significantly associated with COVID-19 severity. Lower serum ionic calcium levels are associated with increased severity and poor outcomes, including higher mortality in COVID-19 patients, underscoring the potential role of calcium as a diagnostic and prognostic marker in COVID-19 pneumonia and may be an important factor in various other forms of pneumonia.

Naringenin Alleviates Radiation-Induced Intestinal Injury by Inhibiting TRPV6 in Mice.

Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. C57BL/6J mice are exposed to a single dose of 13Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.