Ionized Calcium Levels Research Articles

Systemic Mechanisms of Ionic Regulation in Carcinogenesis.

Cancer is a complex disease characterized by uncontrolled cell proliferation at various levels, leading to tumor growth and spread. This review focuses on the role of ion homeostasis in cancer progression. It describes a model of ion-mediated regulation in both normal and cancerous cell proliferation. The main function of this system is to maintain the optimal number of cells in the body by regulating intra- and extracellular ion content. The review discusses the key points of ion regulation and their impact on tumor growth and spread during cancer development. It explains that normal levels of sodium, potassium, calcium, chloride, and hydrogen ions are regulated at different levels. Damage to ion transport mechanisms during carcinogenesis can lead to an increase in sodium cations and water content in cells, disrupting the balance of calcium and hydrogen ions. This, in turn, can lead to chromatin compaction reduction, gene overexpression, and instability at the epigenetic and genomic levels, resulting in increased cell proliferation and mutagenesis. Restoring normal ion balance can reduce the proliferative potential of both normal and tumor cell populations. The proposed model of systemic ionic regulation of proliferation aims to reconcile diverse data related to cell mitotic activity in various physiological conditions and explain tumor growth. Understanding the mechanisms behind pathological cell proliferation is important for developing new approaches to control ion homeostasis in the body, potentially leading to more effective cancer treatment and prevention.

Ionised calcium levels during trauma resuscitation in predicting outcomes-a prospective cohort study.

Haemorrhage remains the leading cause of preventable mortality following trauma, often aggravated by the acidosis, hypothermia and coagulopathy-the lethal triad of trauma. However, the impact of trauma-induced hypocalcemia on the haemorrhage remains unclear. It is intuitive to consider perturbations of ionised calcium early during trauma resuscitation in acutely injured patients given its pathophysiological significance for an improved outcome. Thus, we conducted a prospective study to analyse the role of ionized calcium ion levels during trauma resuscitation and its association with the need for blood transfusion(s) requirement and mortality. A prospective study was conducted on acutely injured patients with haemorrhage getting admitted to a Level 1 trauma center in India between September 2020 and June 2022. Ionised calcium was measured on arrival, after 6h, and on day two of the injury to assess the prevalence. The amount of blood transfusion received by the patient was noted along with other demographic and in-hospital details. The association of hypocalcemia with blood transfusion and mortality was also evaluated. Of the 1961 patients screened for eligibility, 200 patients were recruited and analysed. 72.5% of patients were hypocalcaemic on emergency department (ED) admission. Ionized hypocalcaemia was significantly associated with the need for blood transfusion(s) (p-value < 0.01). A significant association was also noted between ionized hypocalcaemia and mortality (p-value: 0.0085). On the univariate and multivariable analysis, ionized hypocalcaemia was a significant predictor of mortality. Ionized hypocalcaemia is widely prevalent among acutely injured. Trauma-induced hypocalcaemia at admission is associated with increased need for blood transfusions and increased mortality.

Cardiac function evaluation in children with primary nephrotic syndrome

Background Pediatrics with nephrotic syndrome (NS) have an increased prevalence of cardiac difficulties. Several risk factors enhance the increase of cardiac modification such as elevation of blood pressure, cholesterol level, increased BMI, inflammation, prolonged treatment with steroids and other drugs that suppress the immunity, hypercoagulability state, and stress. Aim The aim of this work was to evaluate cardiac function in children with primary NS using echocardiography. Patients and methods This case–control study was conducted on 60 children. They were subdivided into three groups: group Ι; 20 cases steroid sensitive NS. Group II 20 cases with steroid resistant NS. Group ΙΙΙ; 20 healthy children with matched age and sex as controls. All patients undergo medical history taking, clinical examination, and investigations: laboratory investigations (complete blood count, complete urine analysis, 24-h urine collection for proteinuria and urine volume, blood urea, and serum creatinine, total and ionized calcium level, serum proteins and albumin, total serum cholesterol, liver enzymes; alanine aminotransferase, aspartate aminotransferase, erythrocyte sedimentation rate, antinuclear antibody and Complement C3 and C4). Radiological investigations (plain chest radiography, ECG, and echocardiographic examination (M Mode echocardiography, two-dimensional echocardiography). Results There was a significant increase in left ventricular mass and left ventricular mass index in the nephrotic children. Conclusion Echocardiography provides a widespread evaluation of cardiac functions.

Skeletal and dental tissue mineralization: The potential role of the endoplasmic reticulum/Golgi complex and the endolysosomal and autophagic transport systems.

This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there are sound reasons for considering that they may be liberated from mitochondria during the utilization of ATP for anabolic purposes, perhaps linked to matrix synthesis. Published studies indicate that calcium and phosphate ions or their clusters contained as cargo within the intracellular organelles noted above lead to formation of extracellular mineral. The mineral sequestered in mitochondria has been documented as an amorphous calcium phosphate. The ion-, ion cluster- or mineral- containing vesicles exit the cell in plasma membrane blebs, secretory lysosomes or possibly intraluminal vesicles. Such a cell-regulated process provides a means for the rapid transport of ions or mineral particles to the mineralization front of skeletal and dental tissues. Within the extracellular matrix, the ions or mineral may associate to form larger aggregates and potential mineral nuclei, and they may bind to collagen and other proteins. How cells of hard tissues perform their housekeeping and other biosynthetic functions while transporting the very large volumes of ions required for mineralization of the extracellular matrix is far from clear. Addressing this and related questions raised in this review suggests guidelines for further investigations of the intracellular processes promoting the mineralization of the skeletal and dental tissues.

MINERAL COMPONENT OF ORAL FLUID AS AN INDICATOR OF REPARATIVE OSTEOGENESIS AFTER TOOTH EXTRACTION

Tooth extraction is known to results in the formation of a bone defect and the gradual atrophy of the alveolar process, which can negatively impact the outcomes of dental rehabilitation. Adequate alveolar bone volume and the complete morphology of the alveolar process are essential for achieving aesthetic and functional reconstruction. The aim of this study was to determine the effect of cryopreserved placenta and quercetin on the levels of total and ionized calcium in oral fluid during the process of reparative osteogenesis following tooth extraction. Results. The study found that the content of total calcium in the oral fluid of patients showed a statistically significant increase on the 20th day after the tooth extraction procedure: by 5.2%, 3.7%, and 4.8% in the 1st, 2nd, and 3rd clinical groups, respectively. The dynamics of ionized calcium were even more pronounced. On day 20 after tooth extraction, the levels of ionized calcium increased significantly in all three clinical groups: by 23.0%, 9.6%, and 33.3%, respectively. In the second clinical group, the ionized calcium content was lower by 16.7% compared to the control group, and by 12.1% compared to the group where cryopreserved placenta was used alongside the standard treatment protocol, with these differences being statistically significant. Ninety days after tooth extraction, the levels of ionized calcium showed a statistically significant decrease: by 13.2%, 6.3%, and 13.5%, respectively, in the 1st, 2nd, and 3rd clinical groups. The least change in total and ionized calcium levels in the oral fluid was observed in patients treated with the standard protocol supplemented with cryopreserved placenta and quercetin. This may be attributed to local bone tissue resorption in the lower jaw, resulting in the release of this mineral from the bones.

Experimental Study on Softening High-Calcium Sulfate Reverse Osmosis Concentrate Using Induced Crystallization Method

Reverse osmosis (RO) concentrate often contains high levels of sulfate and calcium ions due to the use of antiscalants, leading to significant calcium sulfate supersaturation and creating favorable conditions for induced crystallization. This study utilized a combination of static and dynamic experiments to investigate the key factors influencing the removal of calcium sulfate from RO concentrate via induced crystallization. The static experiments examined the effects of seed crystal concentration, stirring speed, reaction temperature, and the molar ratio of SO42− to Ca2+ on removal efficiency, with response surface methodology (RSM) employed to analyze the interactions among these factors. In the dynamic experiments, gypsum particles were used as seed crystals in a fluidized bed reactor to study the impact of initial seed crystal dosage and influent flow rate on the removal performance. Optimization strategies for stable operation were also explored. The static experiments revealed that seed crystal concentration was the most critical factor affecting removal efficiency. Under optimal conditions, the calcium ion concentration in the treated water could be reduced to 453 mg/L, achieving a removal rate of 63.8%. In the dynamic experiments, the effluent calcium ion concentration was reduced to 724 mg/L, with a removal rate of 52.5%. However, prolonged continuous operation led to a gradual increase in effluent calcium ion levels, which could be mitigated by recycling seed crystals from the settling zone back to the reaction zone. Characterization of the induced seed crystals and simulation calculations demonstrated that Ca2+ and SO42− reacted to form calcium sulfate crystals, primarily as CaSO4·2H2O, which adhered to the seed crystal surfaces. The growth of the seed crystals, indicated by an increase in particle size, correlated with the volume of water treated. This study provides valuable insights and data for the application of calcium sulfate-induced crystallization as a method to reduce sulfate and calcium ion concentrations in RO concentrate, offering a viable approach to water softening and resource recovery.

Real-time Monitoring of Peripheral Blood After Electrochemical Therapy by Electrical Impedance Spectroscopy: A Clinical Trial Study

Background: Electrochemical therapy (EChT) is a well-known tumor destruction method, but entering byproducts into the peripheral blood can be a concern. In recent decades, the electrical impedance spectroscopy (EIS) technique has been noticed to help significantly analyze biological materials in real time. Objectives: This study aimed to investigate the role of the EIS technique for the first time in real-time monitoring of peripheral blood after EChT. Methods: This clinical trial study was conducted on 19 women with breast cancer who were routinely treated with EChT between 2022 and 2023 at Shohadaye Tajrish Hospital, Tehran, Iran. Accurate real-time monitoring of dielectric properties of peripheral blood, including Hematologic Factors, blood ions, apoptosis of peripheral blood mononuclear cells, and the balance of peripheral blood properties before and after EChT was measured using EIS in the frequency range of 1 Hz to 500 kHz. Results: peripheral blood impedimetric parameters before and after EChT, based on EIS findings, were similar at all measured frequencies. EIS analysis did not show a significant difference in the mean level of potassium, sodium and calcium ions in the peripheral blood before and after EChT. Also, there was no significant difference in the level of red blood cells (RBC), platelets, and hemoglobin (HGB) before and after EChT. Although the level of white blood cells (WBC) after EChT decreased by about 15%, this difference was not statistically significant. In addition, peripheral blood smear showed no changes in the appearance of peripheral blood cells, and peripheral blood properties were maintained in balance after EChT. Conclusions: EIS can be used as a real-time method to monitor the patient's peripheral blood status without disturbing hematological factors and peripheral blood balance during EChT in breast cancer patients.

The safety and efficacy of regional citrate anticoagulation for multiple consecutive therapeutic plasma exchanges with fresh frozen plasma as a replacement solution.

Therapeutic plasma exchange (TPE) is an important blood purification technology and most patients require multiple consecutive TPEs. Regional citrate anticoagulation (RCA) could be used for membrane therapeutic plasma exchange (mTPE). However, there is no research on the metabolic complications of the RCA for patients receiving multiple consecutive mTPEs with fresh frozen plasma (FFP) as a replacement solution. We retrospectively included patients who used RCA for multiple consecutive mTPEs with FFP as a replacement solution in Xijing Hospital from 2020 to 2022. We collected blood gas analysis and electrolyte results before and after mTPE treatment and analysed the anticoagulation effectiveness and metabolic complications of the RCA. A total of 33 patients who underwent 131 mTPE sessions were included, and 129 (98.5%) sessions were successfully completed. Severe hypocalcemia (19.1%) and metabolic alkalosis (58.5%) were frequently observed. In single mTPE sessions, there was a significant decrease in ionized calcium levels and significant increases in serum sodium, potassium, pH, bicarbonate, and base excess (BE) levels compared to pretreatment values. When comparing the values after the last treatment to the baseline values in all 33 patients, the serum sodium, pH, bicarbonate, and BE levels increased significantly, while the ionized calcium decreased significantly. The levels of pH, bicarbonate, and BE increased with the number of mTPE sessions, and the cumulative incidence of metabolic alkalosis reached 95.2% after the fifth treatment according to the Kaplan-Meier survival analysis. RCA is an effective anticoagulation method for patients undergoing mTPE with FFP as a replacement solution. However, the metabolic complications associated with RCA, especially hypocalcemia and metabolic alkalosis, frequently develop in patients who undergo multiple consecutive mTPEs with FFP.

Calcium Ions in the Physiology and Pathology of the Central Nervous System.

Calcium ions play a key role in the physiological processes of the central nervous system. The intracellular calcium signal, in nerve cells, is part of the neurotransmission mechanism. They are responsible for stabilizing membrane potential and controlling the excitability of neurons. Calcium ions are a universal second messenger that participates in depolarizing signal transduction and contributes to synaptic activity. These ions take an active part in the mechanisms related to memory and learning. As a result of depolarization of the plasma membrane or stimulation of receptors, there is an extracellular influx of calcium ions into the cytosol or mobilization of these cations inside the cell, which increases the concentration of these ions in neurons. The influx of calcium ions into neurons occurs via plasma membrane receptors and voltage-dependent ion channels. Calcium channels play a key role in the functioning of the nervous system, regulating, among others, neuronal depolarization and neurotransmitter release. Channelopathies are groups of diseases resulting from mutations in genes encoding ion channel subunits, observed including the pathophysiology of neurological diseases such as migraine. A disturbed ability of neurons to maintain an appropriate level of calcium ions is also observed in such neurodegenerative processes as Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. This review focuses on the involvement of calcium ions in physiological and pathological processes of the central nervous system. We also consider the use of calcium ions as a target for pharmacotherapy in the future.

MPatch: A Wearable Hydrogel Microneedle Patch for In Vivo Optical Sensing of Calcium.

This study presents an in vivo optical hydrogel microneedle platform that measures levels of analytes in interstitial fluid. The platform builds on a previously published technique for molding hydrogel microneedles by developing a composite hydrogel (i.e., PEGDA and polyacrylamide) that is sufficiently stiff to penetrate skin in the hydrated state and whose fluorescence changes dynamically-via a conjugated aptamer-depending on level of analyte. In a demonstration relevant to hypercalcemia, the hydrogel microneedle distinguished varying concentrations of calcium (within a range of 0 to 2 mM, which spans physiologically meaningful variations for hypoparathyroidism) within 10 minutes. In rats, a compact CMOS sensor measuring fluorescence from microneedles distinguished low hypercalcemic (1.7 mM) from high hypercalcemic (2.3 mM) ionized calcium levels as determined from reference blood measurements. Overall, this work demonstrates in vivo feasibility of a concept-which we call mPatch-for an optical hydrogel microneedle to measure small changes in levels of analytes in interstitial fluid, which does not rely on extraction of interstitial fluid out of the dermis.

MPatch: a wearable hydrogel microneedle patch for in vivo optical sensing of calcium

This study presents an in vivo optical hydrogel microneedle platform that measures levels of analytes in interstitial fluid. The platform builds on a previously published technique for molding hydrogel microneedles by developing a composite hydrogel (i.e., PEGDA and polyacrylamide) that is sufficiently stiff to penetrate skin in the hydrated state and whose fluorescence changes dynamically—via a conjugated aptamer—depending on level of analyte. In a demonstration relevant to hypercalcemia, the hydrogel microneedle distinguished varying concentrations of calcium (within a range of 0 to 2 mM, which spans physiologically meaningful variations for hypoparathyroidism) within 10 minutes. In rats, a compact CMOS sensor measuring fluorescence from microneedles distinguished low hypercalcemic (1.7 mM) from high hypercalcemic (2.3 mM) ionized calcium levels as determined from reference blood measurements. Overall, this work demonstrates in vivo feasibility of a concept—which we call mPatch—for an optical hydrogel microneedle to measure small changes in levels of analytes in interstitial fluid, which does not rely on extraction of interstitial fluid out of the dermis.

DIAGNOSTIC AND CLINICAL ASPECTS OF NORMOCALCEMIC PARATHYROID HYPERPLASIA AND NON-RENAL SECONDARY HYPERPARATHYROIDISM IN EXPOSED AND NON;EXPOSED TO IONIZING RADIATION INDIVIDUALS (LITERATURE REVIEW AND OWN RESEARCH DATA).

Parathyroids are the key regulators of calcium-phosphorus metabolism. By means of parathyroid hormone they respond to any changes in the serum level of calcium and phosphorus ions and determine the integrity of skeleton, affecting almost all systems and cells where calcium and phosphorus are involved in metabolism and/or signaling.Disorders of parathyroid function are associated with significant complications accompanying secondary hyperparathyroidism. Unfortunately, most medical practitioners and scientists underestimate the impact of parathyroid hormone excess and vitamin D deficiency. Usually, medical practitioners do not prescribe the assay of serum level of parathyroid hormone, which should be done as a screening test, so the disease remains unnoticed for a long time.In fact, the incidence of parathyroid disorders, namely hyperparathyroidism, is almost equal to the incidence of thyroid diseases and is more than 10 % for the entire population, depending on the observation groups (gender, age, exposure to ionizing radiation), as demonstrated in our previous studies. Thus, according to our data, the incidence of parathyroid hyperplasia is 24.3 % (with 50-70 % in children and adolescents) in the state of euparathyroidism, and incidence of normocalcemic hyperparathyroidism is up to 14.3 % in the average population of Ukraine. Today, we see much confusion in publications and available recommendations regarding diagnosis, pathogenesis, and course of parathyroid disease. It is often not taken into account that the strain in calcium-phosphorus system usually occurs due to the lack/deficiency of vitamin D, which is very common worldwide. Often a simple administration of vitamin D in optimal and individual dosages solves (prevents) the problem of hyperparathyroidism or reduces the aggressiveness of its course. Review of data from literary sources and results of own research on pathogenetic patterns and clinical course of parathyroid diseases was carried out, and it was determined that the lack/deficiency of vitamin D is the most common ground of development of hyperparathyroidism, which affects the formation of parathyroid hyperplasia or adenoma, and the process itself is of a gradual, staged clinical development.

Comparative Analysis of Adjusted Calcium and Free Ionized Calcium in Patients with Calcium Derangement in Clinical Setting

Background: Calcium derangements, including hypocalcaemia and hypercalcemia, are significant clinical conditions that affect multiple physiological processes. While adjusted calcium and free ionized calcium are both used to assess calcium status, their comparative utility remains a topic of investigation. This study evaluates the demographic patterns, prevalence, and biochemical characteristics of these conditions, focusing on the relationship between adjusted and free ionized calcium levels. Method: This cross-sectional study included 166 patients diagnosed with either hypocalcaemia or hypercalcemia based on hospital laboratory reference values. Venous blood samples were analysed for free ionized calcium using an ion-selective electrode method and O-cresolphthalin complexone method for Total calcium. Adjusted calcium was derived with a formular. Demographic data, including age and gender, were recorded. Results: Among the 166 patients studied, hypocalcaemia was observed in 45% of the participants, while 55% were diagnosed with hypercalcemia, reflecting a slightly higher prevalence of the latter. Gender distribution showed no significant difference between the groups (p = 0.898), with hypocalcaemia affecting 40% males and 60% females, and hypercalcemia affecting 39.6% males and 60.4% females. The highest prevalence was observed in individuals aged 60 and above, comprising 40% of hypocalcaemia and 49.5% of hypercalcemia cases, with no significant differences in age distribution between groups (p = 0.455). The mean ionized calcium in hypocalcaemia was 0.9 ± 0.6 mmol/L, significantly lower than the 1.9 ± 0.9 mmol/L observed in hypercalcemia. Adjusted calcium levels were also significantly lower in the hypocalcaemia group (1.1 ± 0.9 mmol/L) compared to the hypercalcemia group (3.1 ± 1.1 mmol/L). Conclusion: This study demonstrates that free ionized calcium is a reliable indicator of calcium disorders, so also adjusted total calcium particularly in diagnosing hypocalcemia and hypercalcemia. The findings show strong correlation between adjusted calcium and ionized calcium in both groups

Doença mineral e óssea da doença renal crônica em indivíduos em hemodiálise e a suas correlações com as condições clínicas, antropométricas e laboratoriais

Introduction: Chronic Kidney Disease-Mineral and Bone Disease is one of the main complications of individuals on hemodialysis. Objective: this research aims to analyze the correlations of the laboratory components of Chronic Kidney Disease-Mineral and Bone Disease with clinical, anthropometric and laboratory factors of individuals on hemodialysis. Methods: this is a cross-sectional study with 790 patients on hemodialysis, in southeastern Brazil. Chronic Kidney Disease-Mineral and Bone Disease was evaluated according to specific laboratory diagnostic criteria already defined in the literature. Assessment was carried out regarding the existence of a linear correlation between the dependent and independent variables. References used: r &lt; 0.4 (weak correlation); r ≥ 0.4 and &lt; 0.6 (moderate correlation); r ≥ 0.6 (strong correlation). The Significance level adopted was 5%. Results: parathyroid hormone and duration of renal replacement therapy showed a moderate positive correlation with each other (r 0.582, p &lt;0.001). Phosphorus levels had a moderate positive correlation with potassium (r 0.556, p 0.020) and negative correlation with age (r -0.413, p 0.036). 25-hydroxyvitamin D levels had a positive correlation with adductor pollicis muscle thickness (r 0.602, p 0.018) and right hand grip strength (r 0.402, p &lt;0.001), and a negative correlation with tricipital skinfold (r -0.600, p 0.020) and corrected arm muscle area (r -0.769, p 0.024). Ionic calcium levels had a strong positive correlation with duration of renal replacement therapy (r 0.961, p 0.015) and a strong negative correlation with Body Mass Index (r -0.82, p 0.046). Conclusion: all laboratory elements of Chronic Kidney Disease-Mineral and Bone Disease showed important correlations with clinical, anthropometric and laboratory components of individuals on hemodialysis.

Comparison of different concentrations of calcium gluconate added in replacement fluid to maintain ionised calcium levels during therapeutic plasma exchange procedures

IntroductionTherapeutic plasma exchange (TPE) is generally well tolerated but Anticoagulant Citrate Dextrose Solution A (ACD-A) can cause citrate mediated hypocalcaemia so, adding calcium gluconate to the replacement fluid is effective in preventing this complication. We aimed to compare the effect of different concentrations of 10 % calcium gluconate (9.3 mg of elemental calcium/100 ml Vs 18.6 mg of elemental calcium/100 ml) added to 5 % Human Serum Albumin (HSA) on intraprocedural and post procedural ionised calcium (iCa2+) levels in patients with neurological conditions undergoing TPE. Material and methodsThis study comprised of 100 TPE procedures divided into two groups of 50 each. In group 1, 5 ml of 10 % calcium gluconate was added in 500 ml of 5 % HSA (9.3 mg of elemental calcium/100 ml) and in group 2, 10 ml of 10 % calcium gluconate was added (18.6 mg of elemental calcium/100 ml) in 5 % of HSA. Ionised calcium was noted-pre, intra and post-procedure and compared within the groups along with other procedural parameters and adverse events if any. ResultsWe observed that mean intraprocedural ionised calcium levels were comparable (p = 0.579) in both the groups, but post-procedural iCa2+ levels significantly decreased (p = 0.003) in group-1 as compared to group-2. Symptomatic hypocalcaemia was seen in 14 % of patients group 1 compared to 2 % in group-2. Vasovagal reactions were 8 % in group-1 % and 2 % in group-2. ConclusionProphylactic addition of 18.6 mg of elemental calcium/100 ml of 5 % HSA is safe to maintain levels of iCa2+ throughout the procedure with lower chances of adverse events related to hypocalcaemia.

Vibrotactile stimulation at 40 Hz inhibits Aβ-induced changes in SH-SY5Y, BV2 cells, and pericytes

Alzheimer’s disease (AD) poses a major societal challenge, yet no definitive cure exists. Noninvasive brain stimulation methods, such as transcranial magnetic stimulation and transcranial direct current stimulation, have shown promise in alleviating cognitive symptoms associated with neurodegenerative disorders. This study investigated the effects of 40 Hz vibrotactile stimulation on AD-related cellular responses using SH-SY5Y neuroblastoma cells, primary human brain pericytes, and BV2 microglia. SH-SY5Y cells and brain pericytes treated with oligomeric beta-amyloid (Aβ) underwent 40 Hz vibrational stimulation for varying durations. Cell viability was determined via the CCK-8 assay, while intracellular calcium levels in pericytes were assessed. Protein expression was measured using western blotting, and gene expression was quantified via a real-time quantitative polymerase chain reaction. Detailed vibrational parameters were employed to ensure precise stimulation. Notably, 40 Hz vibrotactile stimulation improved cell viability in Aβ-exposed SH-SY5Y cells, reduced intracellular calcium ion (Ca2+) levels in Aβ-treated pericytes, activated autophagy, and mitigated tau hyperphosphorylation in SH-SY5Y cells. Additionally, it exhibited anti-neuroinflammatory properties in BV2 microglia. These findings highlight the potential of 40 Hz vibrotactile stimulation as a therapeutic strategy for AD.

The anthraquinone derivative KA-4s reduces energy metabolism and enhances the sensitivity of ovarian cancer cells to cisplatin.

Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP)is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPKand reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.

The identification and correction of pseudohypercalcemia.

We found that a subset of patients with monoclonal gammopathy exhibited hypercalcemia without apparent causes or clinical manifestations In a cohort of 289 monoclonal gammopathy patients, 2.4% presented with such atypical hypercalcemia, with one notable case exhibiting normal ionized calcium levels, suggesting the presence of pseudohypercalcemia. The aim of this study is to elucidate the factors contributing to pseudohypercalcemia in monoclonal gammopathy and to develop a novel globulin-corrected calcium formula for clinical application. This observational study enrolled 110 monoclonal gammopathy patients from our center. An additional 33 patients were recruited to validate the newly proposed formula. Univariate analysis identified potential risk factors. And multivariate logistic regression identified definitive influential factors. The determined influential factors were utilized to develop a formula by multiple linear regression, which was validated by a paired t-test and the Youden index. This study found that globulin was a risk factor for pseudohypercalcemia. It revealed that pseudohypercalcemia should be considered in patients with globulin levels ≥61 g/L (P=0.014). Both albumin and globulin were confirmed as independent factors associated with bound calcium. Given that, we developed a formula to correct ionized calcium levels, which was consistent with ionized calcium tested by blood gas analysis. The diagnostic accuracy of the new formula (Youden index is 0.906) is better than the traditional formula (Youden index is 0.906). Interestingly, all monoclonal immunoglobulin types, except for light chains, showed an equal propensity to develop pseudohypercalcemia (P=0.306). It also showed a linear correlation between IgA, IgG, and IgM and bound calcium. This study confirmed that elevated globulin affects serum total calcium and offered the threshold of globulin ≥ 61 g/L in the differential diagnosis of peudohypercalcemia from hypercalcemia. The new formula based on albumin and globulin was developed, which was verified to be better than the traditional formula for correctly diagnosing hypercalcemia. In addition, we found that neither light chains nor heavy chains of monoclonal immunoglobulin alone can result in pseudohypercalcemia.

The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells.

Calcium homeostasis is correlated closely with the occurrence and development of various cancers. The role of calcium homeostasis in prostate cancer has remained unclear. The present study aimed to investigate the relationship between transmembrane and crimp-crimp domain 1 (TMCO1) and calreticulin (CALR) in the pathological characteristics of prostate cancer and the mechanism of action on prostate cancer metastasis. Effects of CALR recombinant protein and TMCO1 knockdown on prostate cancer cells were investigated using following methods: cell cloning, Transwell, wound scratch assay, JC-1 assay, Fluo-4 Assay, endoplasmic reticulum (ER) fluorescent probe, mitochondrial fluorescence probe, Western blot and Immunofluorescence. TMCO1 and CALR are overexpressed in prostate cancer and knockdown of TMCO1 significantly inhibited the invasion, migration and cell proliferation. Furthermore, knocking down TMCO1 modulated the intensity of ER probes and mitochondrial fluorescence probes, and affected the levels of intracellular calcium ion and mitochondrial membrane potential. In addition, CALR recombinant protein upregulated the expression of epithelial-mesenchymal transition marker, Vimentin, Conversely, knockout of TMCO1 significantly reduced the expression of CALR and Vimentin. Knockout of TMCO1 can reverse the effect of CALR recombinant protein, elucidating the pivotal roles of TMCO1 and CALR in the regulation of prostate cancer metastasis through modulation of calcium homeostasis.

High glucose elevates intracellular calcium level and induces ferroptosis in glomerular endothelial cells through the miR-223-3p/ITPR3 pathway

We investigated the link between ferroptosis and the miR-223-3p/inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) pathway in diabetic kidney disease (DKD). Blood samples from DKD patients and healthy controls were analysed for iron ions, calcium ions, and lipid peroxidation. High-glucose-induced glomerular endothelial cells were used to simulate DKD. MiR-223-3p overexpression or silencing was achieved using adenoviruses, affecting ferroptosis regulators (glutathione peroxidase 4 [GPX4], cystine/glutamate transporter (xCT), and long-chain acyl-CoA synthetase 4 [ACSL4]) and ITPR3. DKD patients showed elevated levels of iron ions, calcium ions, and lipid peroxidation. High glucose downregulated miR-223-3p, reducing xCT and GPX4 expression and increasing ACSL4 expression. MiR-223-3p was confirmed to target ITPR3 through luciferase reporter assay. MiR-223-3p overexpression reversed high-glucose-induced effects on ferroptosis markers and ITPR3 expression. In summary, high glucose levels decreased miR-223-3p expression, leading to increased calcium ion levels and ferroptosis, potentially through ITPR3 modulation. These findings provide insights into the mechanisms underlying DKD and its potential therapeutic targets.