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Aurantii FructusImmaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network. [ABSTRACT FROM AUTHOR]

Stanniocalcin 1 (Stc1) is well known for its role in regulating calcium uptake in fish by acting on ionocytes or NaR cells. A hallmark of NaR cells is the expression of Trpv6, a constitutively open calcium channel. Recent studies in zebrafish suggest that genetical deletion of Stc1a and Trpv6 individually both increases IGF signaling and NaR cell proliferation. While trpv6-/- fish suffered from calcium deficiency and died prematurely, stc1a-/- fish had elevated body calcium levels but also died prematurely. The relationship between Stc1a, Trpv6, and IGF signaling in regulating calcium homeostasis and organismal survival is unclear. Here we report that loss of Stc1a increases Trpv6 expression in NaR cells in an IGF signaling-dependent manner. Treatment with CdCl2, a Trpv6 inhibitor, reduced NaR cell number in stc1a-/- fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures in stc1a-/- fish. Double knockout or pharmacological inhibition of Trpv6 alleviated these phenotypes, suggesting that Stc1a inhibit epithelial Ca2+ uptake by regulating Trpv6 expression and activity. stc1a-/- mutant fish developed cardiac edema, body swelling, and died prematurely. Treatment of stc1a-/- fish with CdCl2 or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microorganisms living on the surface and inside the human body play an important role in the physiological activities of the human body. The largest microecosystem in the human body is the gut microbiome. Calcium disorders are found in many diseases. For example, patients with chronic renal insufficiency present with secondary hyperparathyroidism, which is caused by a calcium imbalance in the body. In addition, calcium dysregulation may affect lipid metabolism in the liver through the calmodulator pathway, leading to cirrhosis, etc. Currently, a considerable number of probiotics have been proven to enhance the body’s absorption of calcium. This paper reviews the effects of intestinal flora and related factors such as short-chain fatty acids, estrogen, immune factors and vitamin D on calcium balance. [ABSTRACT FROM AUTHOR]

There is controversy about the choice of dialysate calcium concentration (DCa), with strong arguments both in favor of and against the use of a low or high DCa, as they can both be potentially harmful. Evidence suggests that calcium mass balance is positive with a DCa 3.5 mEq/L, negative or neutral with the use of DCa 2.5 mEq/L, whereas both positive and negative balances have been observed with the use of DCa 3.0 mEq/L. Overall, the use of DCa >2.5 mEq/L is usually associated with an increase in serum calcium level and a decrease in serum PTH level and use of lower vitamin D analogue dose, with the opposite effects usually observed with the use of lower DCa. Most of the available evidence is from small-sized and crossover studies; hence, evidence should be regarded with caution and applied in a patient-specific manner. As there are a lot of significant unanswered questions regarding calcium balance and the optimal DCa in hemodialysis patients, further high-quality research is needed to clarify many still unclear aspects of calcium homeostasis and balance in these patients. In conclusion, with the existing evidence the choice of DCa needs to be individualized and contextualized in the setting of each patient's calcium balance needs and homeostatic response, taking also into account oral calcium intake (dietary and medicinal), any other relevant therapy administered, such as vitamin D analogues, the type of renal mineral bone disorder, and associated cardiovascular comorbidity. [ABSTRACT FROM AUTHOR]

Introduction: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. Methods: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients' treatment remained unchanged during the study period. Results: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. Conclusions: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes. [ABSTRACT FROM AUTHOR]

This article discusses the importance of calcium balance in the bone response to exercise, particularly in preventing stress fractures in military populations, especially female recruits. The study used dual calcium isotope methodology to assess calcium kinetics in 21 healthy women during load carriage exercise or rest. The results showed that exercise increased total and fractional calcium absorption and improved calcium balance compared to rest. However, the study also highlighted the need for further research to understand calcium kinetics during exercise in different populations and modes of exercise, as well as the role of calcium intake and supplementation in the bone response to exercise. [Extracted from the article]

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use. [ABSTRACT FROM AUTHOR]

Purpose of Review: The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent Findings: Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Summary: Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes. [ABSTRACT FROM AUTHOR]

Background: The potential effects of dietary oxalate (Ox) intake on cardio-renal function have remained unestablished. We evaluated the effect of usual Ox intake and its interaction with dietary calcium (Ca) on incident hypertension (HTN) and chronic kidney disease (CKD). Methods: Adult men and women, free of HTN and CKD at baseline (2006–2008), were recruited. Dietary intakes were assessed using a validated food frequency questionnaire, and the outcomes were documented up to 2014–2017. Multivariate Cox proportional hazard regression models were used to estimate the development of HTN and CKD in relation to Ox intakes. Repeated-measures generalized estimating equation (GEE) linear regression models were used to assess possible effect of Ox-intake on the estimated glomerular filtration rate (eGFR) and blood pressure levels over eight years. Results: Dietary Ox intakes were positively associated with incident CKD (HR = 2.59, 95% CI = 1.46–4.64) and HTN (HR = 1.79, 95% CI = 1.05–3.04). Compared to high-Ca consumers, subjects who had lower Ca intakes (< 990 vs. 1580 mg/d) had a higher incidence of CKD and HTN (HR = 2.43, 95% CI = 1.06–5.55, and HR = 1.72, 95% CI = 0.76–3.78). Participants with higher intakes of Ox (> 220 vs. < 150 mg/d) had lower eGFR values (75.3, 95% CI = 75.0–76.5 vs. 77.3, 95% CI = 76.6–78.1 mL/min/1.73m2, Ptime×group = 0.004) and higher SBP levels (112, 95% CI = 111–113 vs. 109, 95% CI = 108–110 mmHg, Ptime×group = 0.007) overtime. Conclusion: Higher dietary Ox intake may increase the risk of HTN and CKD. The relation between dietary Ox and risk of HTN and CKD seems to be varied by Ca intake, and subjects with lower Ca intakes may be more burdened by excessive amounts of dietary Ox. [ABSTRACT FROM AUTHOR]

Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization. [ABSTRACT FROM AUTHOR]

Previous research documented that furosemide negatively impacted calcium balance for 3 days but did not determine when calcium balance returned to baseline. This study hypothesized that furosemide's impact on calcium would return to control values before 7 days post‐administration. Ten mature geldings were assigned to either control (CON, n = 5) or treatment (FUR, n = 5) for the first of two 8‐day total collections in crossover design. Treatment horses received one administration of furosemide (1 mg/kg, IV). A 10% sample of pooled faeces and urine from each day was kept. Calcium concentrations in hay, faeces and urine were determined by an atomic absorption spectrophotometer. Data were analysed using mixed‐model‐repeated measures ANOVA to determine influence of day and treatment. For urine output, FUR urinated twice as much during the 24 hr after administration than CON (p <.001). Horses in FUR excreted more urinary calcium 24‐hr post‐administration as compared to CON (9.3 ± 1.0 and 4.2 ± 1.0 g, respectively; p <.001). Calcium balance in FUR was more negative on day 1 than day 3 (p <.05). Faecal calcium concentrations remained the same from day 1 to day 7 in CON (6.3 ± 1.3 and 5.5 ± 1.3 g/kg, respectively; p >.10) but were lower in FUR on day 7 as compared to day 1 (4.8 ± 1.3 and 7.3 ± 1.3 g/kg, respectively; p <.001), indicating a potential mechanism to restore calcium balance. These findings corroborate previous studies on furosemide and calcium balance and provide evidence for a possible mechanism to recover net calcium losses after furosemide administration. Since calcium balance returns to baseline in 3 days and previous results have examined frequent, long‐term use, furosemide may not negatively impact bone mineral content even if used over long periods. [ABSTRACT FROM AUTHOR]

The role of estrogen in the regulation of calcium balance is still poorly understood. A calcium balance study was performed to examine the effects of estrogen status in relation to fecal calcium loss as a component of bone loss after oophorectomy (OOX) in the mature rat. The components of the classic calcium balance were compared with calcium balance estimates obtained from whole body bone density. Six month or older Sprague Dawley rats were allocated to either a sham-operated or OOX group and fed a 0.1% calcium diet. The bone mineral density (BMD) and bone mineral content (BMC) were measured at baseline, 6 weeks, and 9 weeks. A calcium balance was done for 6 days before and 6 weeks post OOX. The fall in BMD from baseline to 9 weeks in the OOX group was significantly greater than in the sham-operated group. The calcium balance was more negative at baseline than at 6 weeks in both groups of animals because they had not adapted to the low calcium diet. However, the increase in calcium balance was significantly less in the OOX animals than in the sham-operated animals. The greater the rise in calcium balance from the baseline to the 6 weeks balance the less the fall in the calcium content of the whole body (Spearman correlation: r = 0.604 P = 0.008). The fall in fecal calcium, but not urine calcium or calcium consumed, was negatively correlated with the change in whole body BMC (Spearman correlation: fecal calcium r = -0.763 P = 0.001). Thus, the primary effect of estrogen deficiency on calcium balance in the mature rat appears to be calcium flux in the bowel, rather than renal calcium handling. [ABSTRACT FROM AUTHOR]

Introduction: To assess the safety, efficacy, and calcium flux of an accelerated algorithm for regional citrate anticoagulation in membrane-based plasma exchange. Methods: This was an observational study in patients receiving citrate anticoagulated, membrane-based plasma exchange at the Canberra Hospital between July 2017 and May 2020. Data were collected prospectively using an electronic medical record and compared to data from our previous published algorithm. Results: There were 134 plasma exchange sessions performed during the observational period. Circuit clotting occurred in 4 sessions, and 1 session was affected by symptomatic hypocalcaemia. A systemic ionized calcium <0.96 mmol/L was seen in 19.4% of sessions, which was a similar frequency to that seen in our previous algorithm. A systemic ionized Ca <0.81 mmol/L occurred in 4 sessions (all asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after switching from albumin to fresh frozen plasma replacement fluid. Median treatment time was 135 min, compared to 219 min in our previously published algorithm. Mean net Ca gain/session was 7.7 ± 2.3 mmol. Conclusion: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium <0.81 mmol/L may have been due to recirculation of infused citrate but, probably more likely, are due to the additional citrate load imposed by use of fresh frozen plasma in these sessions. Future algorithms need to better account for the citrate load present in fresh frozen plasma. [ABSTRACT FROM AUTHOR]

Objective: Opposite to lanthanum carbonate (LC), sevelamer hydrochloride (SH) may increase intestinal calcium absorption. The study compared the effects of LC and SH on serum and urine phosphate and calcium, and on hormones regulating mineral-bone metabolism.Patients and Methods: A prospective randomized crossover study included 34 patients with eGFR <60 mL/min. A single oral dose of LC (1,000 mg) or SH (2,400 mg) was administered in random order 15 minutes after a standardized meal fortified with 5 g calcium carbonate. Serum calcium, phosphate, and parathormone were measured before and 3, 6, 12, and 24 hours after each medication. Bone alkaline phosphatase (BAP), sclerostin, calcitriol, and FGF-23 were measured at baseline and after 12 and 24 hours. A 24-hour calcium and phosphate excretion was measured after each drug.Results: Serum calcium increased 3 and 6 hours after SH then returned to baseline. After LC calcium was unchanged for up to 3 hours then transiently increased and eventually returned to baseline. The area under curve (AUC) of serum calcium for 12 hours after SH was larger than after LC (p=0.04). Serum phosphate decreased after each drug with a nadir 3 hours post-SH and 6 hours post-LC. AUC of serum phosphate was similar after both medications. PTH decreased transiently after both drugs. BAP did not change. FGF-23 was constant for the first 12 hours but later decreased after each drug.Conclusion: A 2,400 mg SH and 1,000 mg LC are similarly effective in lowering serum phosphate in CKD, but LC induce in less intestinal calcium absorption after a meal. The trial was registered on February 23, 2018 in the clinicaltrial.gov database - NCT03451019. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed calcium balance after net acid excretion (NAE) as described in the acid-ash hypothesis in healthy adults. It is stated that the meta-analysis used superior methodological quality to examine calcium metabolism. The result of regression analysis to assess the dose-response relationship across the study subjects in terms of change of urinary calcium, calcium balance and marker of bone metabolism is revealed.

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established. Recent studies have shown impairments in the calcium homeostasis in striatal neurons in HD. These cells are extremely sensitive to changes in the cytoplasmic concentration of calcium and its excessive increase leads to their death. One of the possible ways to normalize the balance of calcium in striatal neurons is through the sigma 1 receptor (S1R), which act as a calcium sensor that also exhibits modulating chaperone activity upon the cell stress observed during the development of many neurodegenerative diseases. The fact that S1R is a ligand-operated protein makes it a new promising molecular target for the development of drug therapy of HD based on the agonists of this receptor. [ABSTRACT FROM AUTHOR]

For people in Western countries, the vegan diet has the advantage of low energy intake, but the calcium status of this strictly plant-based diet is still unclear. The aim of this study was to determine the calcium balance of individuals on a vegan diet in comparison with a lactovegetarian diet in a short-term investigation. Seven women and one man, ranging in age from 19 to 24 years, received during the first 10 days a vegan diet based on plant foods and calcium-rich mineral water and a lactovegetarian diet during the following 10 days. Portion size was adapted to the subjects' individual energy requirements. Calcium status was assessed by means of calcium intake in food and calcium output in feces and urine as measured by flame atomic absorption spectrophotometry. In addition, deoxypyridinoline was measured in urine as a marker of bone resorption. The results show a significantly smaller daily calcium intake with an average of 843 ± 140 mg in the vegan versus 1322 ± 303 mg in the lactovegetarian diet. Apparent calcium absorption rates were calculated as 26% ± 15% in the vegan and 24% ± 8% in the lactovegetarian group (NS). The calcium balance was positive both in the vegan diet (119 ± 113 mg/day) and in the lactovegetarian diet (211 ± 136 mg/day) (NS). Deoxypyridinoline excretion showed no significant difference between the two diets (105 ± 31 and 98 ± 23 nmol/day). The present results indicate that calcium balance and a marker of bone turnover are not affected significantly when calcium is provided either solely by plant foods or by a diet including dairy products, despite the significantly different calcium intake levels in the diets. We conclude that a well-selected vegan diet maintains calcium status, at least for a short-term period. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the efficacy, safety and calcium balance of a membrane based regional citrate anticoagulation plasma exchange protocol. Methods: This was an observational, prospective, single centre study of membrane separation plasma exchange using regional citrate anticoagulation. It was performed using a fixed dose pre‐filter citrate infusion that was based on the plasma flow rate. Patients received a post filter calcium infusion that was modified during treatment based on systemic ionized calcium monitoring. Post filter ionized calcium was not assessed. Safety and efficacy were assessed by extraction of clinical events and laboratory data contemporaneously recorded in electronic health records. Results: Thirty‐six sessions in five patients were performed. No patients developed symptomatic hypocalcaemia, and no patient had a recorded ionized calcium below 0.81 mmol/L. Filter clotting occurred in two sessions. The mean net calcium gained was 9.6 ± 1.8 mmol per session. Conclusion: Regional citrate anticoagulated membrane separation plasma exchange can be performed safely and effectively without the need for post filter ionized calcium monitoring. The algorithm employed resulted in a net calcium gain. [ABSTRACT FROM AUTHOR]

Copyright of Terra Latinoamericana is the property of Sociedad Mexicana de la Ciencia del Suelo A.C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Individuals diagnosed with Parkinson's disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches. [ABSTRACT FROM AUTHOR]

Calcium balance is an overall assessment of the net calcium taken in minus the net calcium taken out. It can only be assessed when patients are in steady state and requires complicated isotope methods that can simultaneously assess intestinal absorption and endogenous secretion, urinary and stool excretion, bone calcium uptake and removal, and dialysate calcium removal. By virtue of the need for steady state, formal balance studies cannot be accurately carried out in patients on dialysis. However, many of the components of calcium balance have been assessed. Importantly, because 99% of calcium is in bone, studies must accurately assess both the rapidly exchangeable calcium from the bone surface and the net bone calcium balance that results from the difference in bone formation minus resorption. While it is tempting to adjust the dialysate calcium concentration to correct the net positive calcium balance that is likely present in patients who receive calcium-based phosphate binders, the reality is that the highly variable, yet important, role of bone cannot be easily assessed at the bedside. Thus, it is best to prevent the calcium overload in the first place by avoiding high-dose calcium-based phosphate binders and optimizing bone remodeling. [ABSTRACT FROM AUTHOR]

The mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU's potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening. [ABSTRACT FROM AUTHOR]

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (−11.3 mmol/d on 60 mmol/d; −29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (−46 ± 15.9 mg/d) and 90 mmol/d (−59 ± 31.6 mg/d) compared with placebo ( p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus −80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance ( p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (−34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; −71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group ( p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The debate on the most adequate dialysate calcium concentration for intermittent haemodialysis therapy is ongoing. There is probably no one optimal concentration. In general, one would like to maintain a neutral calcium balance in adult haemodialysis patients. However, a slightly negative balance may be preferable to avoid soft-tissue calcium accumulation in face of net calcium loss from the bone with ageing. The problem with measurements of calcium balance is that they are generally imprecise, as are estimations of total body calcium and its distribution in various compartments, unless done with labour-intensive methods and great care. The choice of the dialysate calcium will depend on several factors, including parathyroid and vitamin D status, type and severity of concomitant bone disease, presence or absence of arterial calcification, dietary habits, drug treatment and dialysis modality. Ideally the dialysate calcium would be adapted to each patient's needs. This is not feasible, however, in most dialysis settings and neither is it cost-effective. From a practical point of view, a relatively high dialysate calcium concentration in the range of of 1.50–1.75 mmol/L (3.0–3.5 mEq/L) should probably be preferred in haemodialysis patients with high serum PTH levels who are not prescribed calcium-based phosphate binders or high doses of active vitamin D sterols, and in those who are receiving a calcimimetic. In those who are treated with high doses of calcium-based binders and/or active vitamin D derivatives or who have a very low serum PTH level, the optimal dialysate calcium concentration is probably lower, in the range of 1.25–1.50 mmol/L (2.50–3.0 mEq/L). In the present pro/con debate about the optimal dialysate calcium concentration used for the haemodialysis session, we have accepted to defend the viewpoint that a low calcium concentration may do more harm than benefit in many patients. This viewpoint is opposite to that taken by Gotch [1]. He argues that since calcitriol and other active vitamin D derivatives have become available virtually all haemodialysis patients are in positive calcium balance. We would like to take issue with this statement and warn against the indiscriminate use of a low calcium dialysate in all patients receiving haemodialysis therapy. [ABSTRACT FROM PUBLISHER]

Calcium balance during hemodialysis (HD) is important in determining short-term cardiovascular function, this influences the hemodynamic tolerability of dialysis. In the longer term, calcium flux during HD is an important determinant of overall calcium balance in a patient and may also influence the development and progression of vascular calcification, with its attendant consequences. This article aims to review the assessment and mechanisms of calcium flux during HD, choice of dialysate calcium concentration, influence of HD modality, and potential consequences of therapy choices (cardiovascular and skeletal) resulting from an inappropriate intradialytic calcium balance. [ABSTRACT FROM AUTHOR]

The hair bundle of cochlear hair cells comprises specialized microvilli, the stereocilia, which fulfil the role of mechanotransduction. Genetic defects and environmental noise challenge the maintenance of hair bundle structure, critically contributing to age‐related hearing loss. Stereocilia fusion is a major component of the hair bundle pathology in mature hair cells, but its role in hearing loss and its molecular basis are poorly understood. Here, we utilized super‐resolution expansion microscopy to examine the molecular anatomy of outer hair cell stereocilia fusion in mouse models of age‐related hearing loss, heightened endoplasmic reticulum stress and prolonged noise exposure. Prominent stereocilia fusion in our model of heightened endoplasmic reticulum stress, Manf (Mesencephalic astrocyte‐derived neurotrophic factor)‐inactivated mice in a background with Cadherin 23 missense mutation, impaired mechanotransduction and calcium balance in stereocilia. This was indicated by reduced FM1‐43 dye uptake through the mechanotransduction channels, reduced neuroplastin/PMCA2 expression and increased expression of the calcium buffer oncomodulin inside stereocilia. Sparse BAIAP2L2 and myosin 7a expression was retained in the fused stereocilia but mislocalized away from their functional sites at the tips. These hair bundle abnormalities preceded cell soma degeneration, suggesting a sequela from stereociliary molecular perturbations to cell death signalling. In the age‐related hearing loss and noise‐exposure models, stereocilia fusion was more restricted within the bundles, yet both models exhibited oncomodulin upregulation at the fusion sites, implying perturbed calcium homeostasis. We conclude that stereocilia fusion is linked with the failure to maintain cellular proteostasis and with disturbances in stereociliary calcium balance. Key points: Stereocilia fusion is a hair cell pathology causing hearing loss.Inactivation of Manf, a component of the endoplasmic reticulum proteostasis machinery, has a cell‐intrinsic mode of action in triggering outer hair cell stereocilia fusion and the death of these cells.The genetic background with Cadherin 23 missense mutation contributes to the high susceptibility of outer hair cells to stereocilia fusion, evidenced in Manf‐inactivated mice and in the mouse models of early‐onset hearing loss and noise exposure.Endoplasmic reticulum stress feeds to outer hair cell stereocilia bundle pathology and impairs the molecular anatomy of calcium regulation.The maintenance of the outer hair cell stereocilia bundle cohesion is challenged by intrinsic and extrinsic stressors, and understanding the underlying mechanisms will probably benefit the development of interventions to promote hearing health. [ABSTRACT FROM AUTHOR]

Background: Epilepsy initiation involves multifactorial etiologies, including genetic susceptibility, structural anomalies, and glial cell dysregulations, particularly in astrocytes. Despite advancements in understanding various factors, the mechanisms of astrocyte dysregulation in epilepsy, critical for neural homeostasis, remain elusive, requiring comprehensive evaluation of molecular pathways and cellular interactions for future targeted interventions. Methods: A systematic search of PubMed, ScienceDirect, and the Cochrane databases up to January 1st 2024 identified relevant studies predominantly from experimental models, forming the basis for an in-depth analysis of astrocytic contributions to epileptic pathophysiology. The aims, subjects, epilepsy induction techniques, assessment methods, and findings of each studies were presented. Results: A total of 24 clinical trials met the inclusion criteria and were included in the systematic review. Altered potassium buffering compromises extracellular potassium regulation, fostering hyperexcitability. Aquaporin dysfunction disrupts water homeostasis, aggravating seizure susceptibility. Disturbances in glutamatergic transmission, marked by changes in glutamate transporter function, contribute to excitotoxicity, fueling epileptogenesis. Intricacies in calcium signaling and disruptions in calcium-binding proteins tip intracellular calcium balance towards hyperexcitability. Dysfunctional GABA transporters compromise inhibitory neurotransmission, upsetting excitatory–inhibitory balance. Gap junction protein dysregulation disrupts astroglial networks, impacting neuronal synchronization in epileptogenic circuitry. Compromised BBB allows entry of epileptogenic factors, exacerbating the epileptogenic milieu. Conclusions: Collectively, these astrocytic dysregulations unveil intricate contributors to epilepsy onset and progression. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor (Prlr) gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Materials and Methods: Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess Prlr gene expression in the duodenum, vertebrae, and kidneys. Results: In Group S, Prlr gene expression was notably decreased in the duodenum (p < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum (p < 0.01) alongside elevated expression in the vertebrae and kidneys. Conclusions: In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health. [ABSTRACT FROM AUTHOR]

The use of high ultrafiltration rates in haemodiafiltration (HDF) has been suggested for improving the clearance of small and large molecules. This strategy has become economically applicable with the development of safe techniques for on-line production of sterile infusate from dialysate, which enables us to infuse large substitution fluid volumes without further increasing the cost of the sessions. The effect of increasing the ultrafiltration rate in HDF on electrolyte balance has not yet been evaluated. The aim of this study was to evaluate the effects of variations of the ultrafiltration rate on calcium kinetics in HDF using three different dialysate calcium concentrations. Since the increase in ultrafiltration rate augments the convective calcium loss, variations of intrasession calcium balance could result from modifications of the ultrafiltration rate. In the present study we found no significant variations in calcium balance and serum ionized calcium (iCa) levels during on-line HDF treatment when increasing the mean ultrafiltration rate from 60 to 100 ml/min in the presence of an adequate and corresponding increase in the infusion rate (from 2.5 to 5 l/h). During the balance studies, pretreatment serum iCa was on the average 1.32 mmol/l and weight loss 3.2 kg. Mean calcium loss during treatment was 2.8 and 3.3 mmol at infusion rates of 2.5 and 5 l/h with 1.63 mmol/l of calcium in both the dialysate and infusate; calcium loss rose to 5.9 and 11.2mmol at infusion rates of 2.5 l/h and to 5.7 and 14.2 mmol at infusion rates of 5 l/h when the dialysate and infusate calcium was reduced respectively to 1.5 and 1.25 mmol/l. Serum iCa significantly increased at the end of the session with the higher dialysate concentration, while it decreased to 1.28 mmol/l and 1.20 mmol/l with the lower two concentrations. Linear regression ana lysis showed no variation in serum iCa during treatment when the iCa concentration in the dialysate was equal to pretreatment serum iCa. A neutral calcium balance would be expected using 1.75 mmol/l of calcium in the dialysate. In conclusion, increasing the ultrafiltration rate from 60 to 100 ml/min did not significantly affect calcium kinetics in on-line HDF. The main factors affecting calcium mass transfer and serum iCa fluctuation during treatment were the dialysate calcium concentration and the iCa gradient between dialysate and pretreatment serum levels. [ABSTRACT FROM PUBLISHER]

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet. [ABSTRACT FROM AUTHOR]

Calcium regulation in sturgeon is of special interest because they are a representative of the ancient fishes possessing mainly cartilaginous skeletons and a supposedly low calcium demand. The present study aimed to characterize the effect of a chronic absence of dietary calcium and the effect of parathyroid hormone-related protein (PTHrPA) (1-34) (7) on calcium balance in juvenile sturgeon (Acipenser naccarii). At rest, sturgeon juveniles are in net positive calcium balance, since whole body calcium uptake is significantly higher than efflux and calcium accumulates in the body. To study the importance of dietary calcium, the sturgeon were kept on a calcium-free diet for 8 wk. This manipulation impaired growth as measured by failure to gain weight or increase in length and indicates that dietary calcium is important for growth in sturgeon. An increased whole body calcium uptake partially compensated dietary calcium deficiency and was associated with increased gill chloride cell number in lamellae and filaments in parallel with increased gill Na+K+-ATPase activity. In addition, a single injection of piscine PTHrP(1-34) significantly increased whole body calcium uptake and decreased whole body calcium efflux. Administration of PTHrP significantly increased circulating plasma calcium 4-24 h postinjection. The increase in net calcium transport and increased plasma levels of calcium is consistent with the actions of a hypercalcemic factor. It would appear that the sturgeon rely on calcium for growth and tightly regulate calcium transport. The action in calcium balance is consistent with PTHrP acting as a hypercalcemic factor in sturgeon. [ABSTRACT FROM AUTHOR]

We studied the role of calcium-regulating structures of slow- ( m. soleus, SOL) and fast-twitch ( m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca balance. [ABSTRACT FROM AUTHOR]

Although the implications of long-term high Ca intakes have been well documented in growing dogs, the health consequences of Ca excess in adult dogs remain to be established. To evaluate the impact of feeding a diet containing 7·1 g/4184 kJ (1000 kcal) Ca for 40 weeks on Ca balance and health parameters in adult dogs, eighteen neutered adult Labrador Retrievers, (nine males and nine females) aged 2·5–7·4 years were randomised to one of two customised diets for 40 weeks. The diets were manufactured according to similar nutritional specifications, with the exception of Ca and P levels. The diets provided 1·7 and 7·1 g/4184 kJ (1000 kcal) (200(SD26) and 881(SD145) mg/kg body weight0·75 per d, respectively) Ca, respectively, with a Ca:P ratio of 1·6. Clinical examinations, ultrasound scans, radiographs, health parameters, metabolic effects and mineral balance were recorded at baseline and at 8-week intervals throughout the study. Dogs in both groups were healthy throughout the trial without evidence of urinary, renal or orthopaedic disease. In addition, there were no clinically relevant changes in any of the measures made in either group (all P>0·05). The high-Ca diet resulted in a 3·3-fold increase in faecal Ca excretion (P<0·001), whereas apparent Ca digestibility (%) and net Ca balance (g/d) did not significantly change from baseline or differ between the groups at any time point (both P>0·05). Ca intakes of up to 7·1 g/4184 kJ (1000 kcal) are well tolerated over a period of 40 weeks, with no adverse effects that could be attributed to the diet or to a high mineral intake. [ABSTRACT FROM AUTHOR]

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A 35-day experimental study consisting of 28-day growth and 7-day calcium (CA) balance periods was conducted to assess the effects of fibre and N ratios on growth and Ca balance of rats. Growth and Ca balance of rats (45 80 g) fed mixtures of cooked (CS) and uncooked (RS) sorghum and dehulled (DB) and undehulled (UB) bean were studied. The diets contained 10% protein. Casein served as the control protein. The control group ate more food except for the group fed the CS:DU (60:40) diets (P less than 0.05) had higher values for all parameters tested than the test groups. There were increases in food and Ca intakes, fecal Ca, weight gain, protein efficiency ration (PER), liver weight and composition except for the low moisture value for the CS:DS (60:40) group when N ratios were changed from 80:20 to 60:40. These results appear to indicate that fiber and N ratio had significant effects on growth liver composition and calcium balance of the rats. [ABSTRACT FROM AUTHOR]