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Keywords = calcium citrate

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18 pages, 6085 KB  
Article
Influence of Organic Salts on Molecular Interactions, Film Performance, and Antimicrobial Activity of TPS/PBAT Blown Films
by Vannet Roschhuk, Phanwipa Wongphan, Yeyen Laorenza, Phatthranit Klinmalai and Nathdanai Harnkarnsujarit
Foods 2026, 15(7), 1148; https://doi.org/10.3390/foods15071148 - 27 Mar 2026
Viewed by 286
Abstract
This study investigates the effects of organic salts, including sodium citrate (SC), calcium citrate (CC), and calcium lactate (CL), on the structure–property–function relationships of thermoplastic starch/poly(butylene adipate-co-terephthalate) (TPS/PBAT) films for active packaging applications. TPS incorporated with organic salts was prepared via twin-screw extrusion, [...] Read more.
This study investigates the effects of organic salts, including sodium citrate (SC), calcium citrate (CC), and calcium lactate (CL), on the structure–property–function relationships of thermoplastic starch/poly(butylene adipate-co-terephthalate) (TPS/PBAT) films for active packaging applications. TPS incorporated with organic salts was prepared via twin-screw extrusion, blended with PBAT, and further processed into blown films. The films were systematically characterized using 1H NMR, FTIR, and SEM, together with optical, mechanical, water vapor permeability, and antimicrobial evaluations against Staphylococcus aureus. The results revealed that SC primarily modulated hydrogen-bonding interactions within the starch matrix, resulting in improved structural homogeneity, balanced mechanical properties, and the highest antimicrobial activity among all formulations. In contrast, CL and CC promoted ionic crosslinking through Ca2+–starch interactions, leading to increased stiffness and Young’s modulus but reduced polymer chain mobility and limited release of active species, particularly in CC-containing systems. These differences in molecular interactions were consistent with variations in film microstructure, where SC-containing films exhibited more uniform morphologies, while calcium-based systems showed denser but less permeable structures. Furthermore, films containing SC and CL at appropriate concentrations achieved a favorable balance between transparency, water vapor barrier properties, and antimicrobial performance. Overall, this study provides new mechanistic insights into how monovalent and divalent organic salts govern intermolecular interactions, microstructure, and functional performance in TPS/PBAT systems. The findings highlight the critical role of additive type and concentration in designing biodegradable active packaging materials with tunable mechanical, barrier, and antimicrobial properties. Full article
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24 pages, 4484 KB  
Article
Polycarboxylic Acid/Calcium Carbonate Nanopowder-Derived Chelates as Sustainable Cross-Linked Wood Coatings with Improved Thermal Properties
by Jovale Vincent Tongco and Armando Gabriel McDonald
Coatings 2026, 16(2), 268; https://doi.org/10.3390/coatings16020268 - 23 Feb 2026
Cited by 1 | Viewed by 475
Abstract
This study presents a sustainable strategy for improving the thermal properties of pine wood through the application of calcium carbonate nanopowder (CCNP) chelated with polycarboxylic acids (citric acid (CA) and tartaric acid (TA)) as coatings. The chelation reaction was confirmed by the detection [...] Read more.
This study presents a sustainable strategy for improving the thermal properties of pine wood through the application of calcium carbonate nanopowder (CCNP) chelated with polycarboxylic acids (citric acid (CA) and tartaric acid (TA)) as coatings. The chelation reaction was confirmed by the detection of carbon dioxide (CO2) gas. CCNP was characterized using microscopy and particle size analysis. The formation of crystalline calcium citrate and calcium tartrate was verified using FTIR and Raman spectroscopies, and XRD analysis. Wood treatment was conducted using different volumetric ratios of CA and TA. The CA-TA-treated (coated) wood blocks achieved the highest mass gain after treatment of around 89%, while the pure TA treatment exhibited enhanced leaching resistance, maintaining around 69% mass gain after leaching test. TGA conducted under oxidative (air) conditions showed that the coatings promoted char formation and produced inorganic residues from 6.4% to 7.8%, with the control resulting in negligible residual mass. Flame retardancy tests showed that the chelated coatings effectively delayed combustion and inhibited heat transfer, with the TA treatment showing improved flame retardancy performance by limiting the surface temperature to ~200 °C after 60 s of exposure, as compared to >550 °C for the control. Full article
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17 pages, 3197 KB  
Article
Copper Removal from Water by Citrate-Stabilized Amorphous Calcium Phosphate Nanoparticles: Adsorption Performance and Mechanisms
by Miaomiao Wang, Yuwei Jiang and Junjun Tan
Appl. Nano 2026, 7(1), 7; https://doi.org/10.3390/applnano7010007 - 20 Feb 2026
Viewed by 494
Abstract
Amorphous calcium phosphate (ACP), a key calcium-phosphorus compound, has been widely applied in fields such as dentistry, orthopedics, and biomedicine. However, its potential for removing copper ions from aqueous solutions remains largely unexplored. In this study, sodium citrate-stabilized amorphous calcium phosphate (Cit-ACP) and [...] Read more.
Amorphous calcium phosphate (ACP), a key calcium-phosphorus compound, has been widely applied in fields such as dentistry, orthopedics, and biomedicine. However, its potential for removing copper ions from aqueous solutions remains largely unexplored. In this study, sodium citrate-stabilized amorphous calcium phosphate (Cit-ACP) and its calcined derivatives at various temperatures were successfully synthesized as adsorbents for copper ions. The adsorption behavior of Cit-ACP was best described by the Langmuir isotherm, with kinetics following a pseudo-second-order model. Under conditions of pH 5.5 and an initial copper ion concentration of 200 mg/L, Cit-ACP exhibited a maximum adsorption capacity of 323.96 mg/g. Thermodynamic analysis confirmed that the adsorption process was spontaneous and endothermic. Comprehensive characterization via XRD, XPS, and zeta potential measurements before and after adsorption revealed a two-stage adsorption mechanism. At low initial copper concentrations, adsorption occurred predominantly through surface complexation between copper ions and sodium citrate molecules on Cit-ACP nanoparticles. At higher concentrations, the mechanism extended to include co-precipitation of copper ions with hydroxyl groups, which promoted the transformation of Cit-ACP into copper-substituted calcium phosphate phases, such as copper-containing hydroxyapatite. Owing to its straightforward synthesis, high adsorption capacity, and inherent biocompatibility, Cit-ACP presents a promising, cost-effective, and efficient adsorbent for the removal of copper ions from aqueous environments. Full article
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16 pages, 1847 KB  
Article
Fertilization Effects of Recycled Phosphorus with CaAl-LDH Under Controlled Conditions
by Yunsheng Jia, Liangkai Wang, Sijie Huang, Yun Chen, Mingqing Liu, Fei Liu, Jianyu Zhang, Jibing Zhang, Lifei Yang and Huoyan Wang
Agronomy 2026, 16(3), 385; https://doi.org/10.3390/agronomy16030385 - 5 Feb 2026
Viewed by 444
Abstract
To mitigate the exhausting of phosphate rock (PR) reserves and the widespread water eutrophication due partially to excessive phosphorus (P), efficient adsorbents are valuable. Calcium (Ca) and aluminum (Al) containing layered double hydroxides (CaAl-LDHs) showed high P adsorption capacity and potential as slow-release [...] Read more.
To mitigate the exhausting of phosphate rock (PR) reserves and the widespread water eutrophication due partially to excessive phosphorus (P), efficient adsorbents are valuable. Calcium (Ca) and aluminum (Al) containing layered double hydroxides (CaAl-LDHs) showed high P adsorption capacity and potential as slow-release P fertilizers, which merits further investigation. Two P proportions (5% and 10%) of P-adsorbed CaAl-LDHs (P-LDHs) were prepared, and its effects on various soil P contents and oilseed rape (Brassica napus L.) growth were evaluated. The main components of 5%P-LDH were P-intercalated CaAl-LDH and brushite, while 10%P-LDH mainly consisted of brushite. The proportions of P were extracted from 10%P-LDH and increased in the order of 4.9% (deionized water) < 48.9% (Olsen method) < 63.5% (Bray method) < 67.4% (citric acid), which suggested that 10%P-LDH could be citrate-soluble P fertilizer. 10%P-LDH showed similar effects on soil available P with single superphosphate (SSP). Both 5%- and 10%P-LDHs showed comparable improvement with SSP on aboveground dry weight of oilseed in the red soil, while being inapparent in the Fluvo-aquic soil. The CaAl-LDH appeared capable of providing Ca for rape growth in the low initial P concentration red soil, which showed the highest dry weight when combined with SSP. The recycled P-LDHs, especially 10%P-LDH, could supply P in a comparable manner with SSP for oilseed rape P uptake. Based on trials conducted under controlled conditions, our study suggested a promising production route of commercial P fertilizer alternatives via water P removal by CaAl-LDH. Further validations with realistic wastewater P removal by CaAl-LDH and via field scale growth trials are still needed before wide application of the alternative P fertilizer production procedure reported in the present study. Full article
(This article belongs to the Section Soil and Plant Nutrition)
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21 pages, 1253 KB  
Review
Clinical Approaches and Emerging Therapeutic Horizons in Primary Hyperoxaluria
by Ruth Martínez-Galindo, María Campuzano-Pérez, Afroditi Konstantouli, María Del Pilar Aguilar-Ramírez, Juan Antonio Mainez Rodríguez, Pablo Abad-López, Amir Shabaka and Ramón Cansino
J. Clin. Med. 2026, 15(3), 940; https://doi.org/10.3390/jcm15030940 - 23 Jan 2026
Cited by 1 | Viewed by 599
Abstract
Primary hyperoxalurias (PHs) are rare autosomal recessive disorders characterized by overproduction of oxalate, a metabolic end product that readily forms calcium oxalate crystals. Excess hepatic oxalate leads to recurrent kidney stones, nephrocalcinosis, and progressive renal injury, often culminating in end-stage kidney disease (ESKD). [...] Read more.
Primary hyperoxalurias (PHs) are rare autosomal recessive disorders characterized by overproduction of oxalate, a metabolic end product that readily forms calcium oxalate crystals. Excess hepatic oxalate leads to recurrent kidney stones, nephrocalcinosis, and progressive renal injury, often culminating in end-stage kidney disease (ESKD). Once renal clearance declines, systemic oxalate accumulation can cause multisystem deposition. PH encompasses three types—PH1, PH2, and PH3—caused by deficiencies in the hepatic enzymes AGT, GRHPR, and HOGA1, respectively, resulting in accumulation of glyoxylate and subsequent oxalate overproduction. Clinical presentation varies from infantile oxalosis to adult-onset recurrent nephrolithiasis, with PH1 generally being the most severe. Diagnosis relies on urinary oxalate measurements, plasma oxalate in advanced chronic kidney disease, urinary metabolite profiling, imaging, and genetic testing. Management includes hyperhydration, citrate supplementation, pyridoxine for responsive PH1 patients, dialysis and transplantation when required, while RNA interference therapies targeting glycolate oxidase or LDHA have demonstrated substantial biochemical efficacy in PH1 and represent promising emerging therapeutic options, although long-term clinical outcome data remain limited and broader applicability to other PH types is still under investigation. Future strategies focus on modulating intestinal oxalate absorption, gut microbiome therapies, oxalate-degrading enzymes, and novel gene-editing approaches. Early diagnosis and individualized management are critical to prevent kidney injury and systemic oxalosis. In this review, we summarize the genetic, biochemical, and clinical features of PH and discuss current and emerging therapeutic strategies. Full article
(This article belongs to the Special Issue Targeted Treatment of Kidney Stones)
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25 pages, 6910 KB  
Article
Early Supplementation with Branched-Chain Amino Acids Ameliorates Lipid Retention in Aortic Valves of ApoE-Knockout Mice
by Daria Shishkova, Anastasia Kanonykina, Egor Kondratiev, Arina Tyurina, Alexandra Morozova, Alena Poddubnyak, Anna Sinitskaya, Maxim Sinitsky, Victoria Markova, Anastasia Lazebnaya, Leo Bogdanov, Alexander Stepanov, Susanna Agalaryan and Anton Kutikhin
Int. J. Mol. Sci. 2025, 26(23), 11259; https://doi.org/10.3390/ijms262311259 - 21 Nov 2025
Viewed by 1001
Abstract
Previous studies suggested a certain efficiency of proteinogenic branched-chain amino acid (BCAA) and magnesium supplementations in reducing cardiovascular risk and increasing quality of life. This investigation assessed the anti-atherogenic and anti-calcific effects of BCAA (55 mg/day, corresponding to a human equivalent dose of [...] Read more.
Previous studies suggested a certain efficiency of proteinogenic branched-chain amino acid (BCAA) and magnesium supplementations in reducing cardiovascular risk and increasing quality of life. This investigation assessed the anti-atherogenic and anti-calcific effects of BCAA (55 mg/day, corresponding to a human equivalent dose of 13.5 g/day) and magnesium citrate (MgCit, 1.85 mg/day, corresponding to a human equivalent dose of 450 mg/day) intake in male and female ApoE-knockout mice, with the treatment initiation at either 1, 3, or 6 months of age. At the 12-month time point, lipid retention and calcium deposition in the aortic valve, lipid burden in the aorta, and serum ionized calcium were evaluated. The early BCAA intake (from 1/3 to 12 months of age) significantly reduced lipid retention in the aortic valve, whilst MgCit decreased ionized calcium. Both of these protective effects were higher in male than in female mice. Furthermore, it was tested whether human serum albumin (HSA) or MgCit can be applied to decrease the serum calcification propensity in 100 patients with myocardial infarction. A dual supplementation with HSA and MgCit reduced serum calcification propensity in 68% of cases. Collectively, these results highlight the potential benefits of BCAA/HSA and magnesium supplementations for cardiovascular prevention and justify further clinical trials in this regard. Full article
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16 pages, 3641 KB  
Article
SLC30A3 as a Zinc Transporter-Related Biomarker and Potential Therapeutic Target in Alzheimer’s Disease
by Ruyu Bai, Zhiyun Cheng and Yong Diao
Genes 2025, 16(11), 1380; https://doi.org/10.3390/genes16111380 - 13 Nov 2025
Cited by 1 | Viewed by 1168
Abstract
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative [...] Read more.
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene’s biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database. Results: We identified a single key zinc transporter–related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70–0.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson’s disease, AD, Huntington’s disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators. Conclusions: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD. Full article
(This article belongs to the Section Neurogenomics)
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44 pages, 1698 KB  
Systematic Review
Metabolomics Signatures of Atherosclerosis in Cardiovascular Disease: A Narrative Systematic Review
by Monica Pibiri, Antonio Noto, Antonio Dalu, Sandro Muntoni, Karolina Krystyna Kopeć, Martina Spada, Luigi Atzori and Cristina Piras
J. Clin. Med. 2025, 14(22), 8028; https://doi.org/10.3390/jcm14228028 - 12 Nov 2025
Viewed by 2094
Abstract
Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery [...] Read more.
Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article
(This article belongs to the Section Cardiovascular Medicine)
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34 pages, 8474 KB  
Article
Integrated Metabolomic and Transcriptomic Profiles Provide Insights into the Molecular Mechanisms in Modulating Female Flower of Coconut (Cocos nucifera L.)
by Lilan Lu, Yuan Zhang, Zhiguo Dong, Weibo Yang and Ruoyun Yu
Agriculture 2025, 15(22), 2336; https://doi.org/10.3390/agriculture15222336 - 10 Nov 2025
Viewed by 807
Abstract
Coconut yield and quality are significantly affected by multiple female inflorescences (MFF), which disrupt flower differentiation balance. To elucidate the molecular mechanisms, we compared MFF with normal female inflorescences (NFF) using phenotypic, morphological, physiological, and multi-omics approaches. The results revealed that MFF exhibited [...] Read more.
Coconut yield and quality are significantly affected by multiple female inflorescences (MFF), which disrupt flower differentiation balance. To elucidate the molecular mechanisms, we compared MFF with normal female inflorescences (NFF) using phenotypic, morphological, physiological, and multi-omics approaches. The results revealed that MFF exhibited altered flower structures. MFF showed elevated iron (Fe), nitrogen (N), sulfur (S), potassium (K), calcium (Ca), zinc (Zn), proline (Pro), catalase (CAT), malondialdehyde (MDA), abscisic acid (ABA), and jasmonic acid (JA), but reduced molybdenum (Mo), soluble sugar (SS), soluble protein (SP), superoxide dismutase (SOD), peroxidase (POD), indole acetic acid (IAA), zeatin riboside (ZR), and gibberellic acid (GA). We detected 445 differentially expressed genes (DEGs) mainly enriched in ABA, ETH, BR, and JA pathways in MFF compared to NFF. We identified 144 differentially accumulated metabolites (DAMs) primarily in lipids and lipid-like molecules, phenylpropanoids and polyketides, as well as organic acids and derivatives in the comparison of MFF and NFF. Integrated analysis linked these to key pathways, e.g., “carbon metabolism”, “carbon fixation in photosynthetic organisms”, “phenylalanine, tyrosine, and tryptophan biosynthesis”, “glyoxylate and dicarboxylate metabolism”, “glycolysis/gluconeogenesis”, “pentose and glucuronate interconversions”, “flavonoid biosynthesis”, “flavone and flavonol biosynthesis”, “pyruvate metabolism”, and “citrate cycle (TCA cycle)”. Based on our results. the bHLH137, BHLH062, MYB (CSA), ERF118, and MADS2 genes may drive MFF formation. This study provides a framework for understanding coconut flower differentiation and improving yield. Full article
(This article belongs to the Section Crop Genetics, Genomics and Breeding)
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17 pages, 1925 KB  
Article
Influence of Calcium Crosslinker Form on Alginate Hydrogel Properties
by Solomiia Kapatsila, Roman Taras, Diana Varchuk, Nataliia Nosova, Serhii Varvarenko and Volodymyr Samaryk
Gels 2025, 11(11), 885; https://doi.org/10.3390/gels11110885 - 4 Nov 2025
Cited by 4 | Viewed by 3149
Abstract
Alginate hydrogels are attractive for biomedical applications and drug delivery due to their biocompatibility and biodegradability. However, calcium-crosslinked alginates often exhibit only moderate absorption properties compared with synthetic hydrogels. This study examined how the form of calcium ion delivery affects the mechanical, swelling, [...] Read more.
Alginate hydrogels are attractive for biomedical applications and drug delivery due to their biocompatibility and biodegradability. However, calcium-crosslinked alginates often exhibit only moderate absorption properties compared with synthetic hydrogels. This study examined how the form of calcium ion delivery affects the mechanical, swelling, and morphological characteristics of calcium-crosslinked alginate hydrogels. We prepared four alginate hydrogel samples in which Ca2+ was introduced on different polyacrylate polymer carriers, and a reference hydrogel crosslinked with calcium citrate. All samples were characterized by equilibrium swelling, gel fraction determination, and rheological frequency-sweep measurements. Also, the average mesh size was estimated using two independent theoretical approaches. Hydrogels prepared with calcium salt of polyacrylic acid (PAA) exhibited higher mechanical strength and higher water swelling than the citrate-crosslinked reference. Calculated mean mesh sizes for the citrate system ranged from 58 to 221 nm, whereas high-molecular-weight crosslinked systems showed a broader distribution (68–708 nm). These results demonstrate that the form of Ca2+ introduction significantly influences network architecture and functional properties and indicates that tuning the carrier form of calcium provides a practical route to design swelling, mesh size, and mechanical behavior of alginate-based hydrogels for specific biomedical or delivery applications. Full article
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19 pages, 4039 KB  
Review
Role of Uropathogenic Escherichia coli and Other Pathogens in Kidney Stone Formation: From Pathogenesis to Treatment
by Beata Zalewska-Piątek, Michalina Nagórka and Rafał Piątek
Pathogens 2025, 14(10), 991; https://doi.org/10.3390/pathogens14100991 - 1 Oct 2025
Cited by 3 | Viewed by 3093
Abstract
Urinary tract infections (UTIs) are among the most prevalent infections in the human population. Uropathogenic Escherichia coli, the primary causative agent of UTIs, may also contribute to the development of metabolic kidney stones, particularly those composed of calcium oxalate. Kidney stone disease [...] Read more.
Urinary tract infections (UTIs) are among the most prevalent infections in the human population. Uropathogenic Escherichia coli, the primary causative agent of UTIs, may also contribute to the development of metabolic kidney stones, particularly those composed of calcium oxalate. Kidney stone disease (KSD), known as nephrolithiasis or urolithiasis, is one of the most common disorders of the urinary system. This review explores the significant clinical association between UTIs and kidney stones, focusing on the mechanisms by which UPEC may promote stone formation, including oxidative stress, inflammation, and altered citrate metabolism. It also examines the role of immune responses, particularly macrophage activity, in the progression of KSD. Recent evidence suggests that the composition of the gut microbiota and metabolic imbalances have an additional impact on stone development. In light of these findings, current prevention and treatment strategies, including microbiota-targeted therapies, probiotics, and immune modulation, are also reviewed. Understanding the complex links between UTI, immunity, and metabolism provide new insights into the pathogenesis of KSD and allows for the development of more effective treatments for this disease. Full article
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23 pages, 1580 KB  
Article
The Distinction of Chemical Profiles of Mountainous Forest Cultivated Ginseng and Garden Ginseng Based on Calcium Oxalate Crystals, Organic Acids, and Ginsenosides
by Xiaotong Zhang, Xiaoku Ran, Yidan Xi and Deqiang Dou
Foods 2025, 14(17), 3073; https://doi.org/10.3390/foods14173073 - 30 Aug 2025
Viewed by 1620
Abstract
This study aims to further analyze the chemical characteristics of mountainous forest cultivated ginseng (MFCG) and garden ginseng (GG), concerning their calcium oxalate crystals, organic acids, and ginsenosides. The results demonstrate that MFCG had higher levels of non-free oxalate, calcium oxalate crystals, and [...] Read more.
This study aims to further analyze the chemical characteristics of mountainous forest cultivated ginseng (MFCG) and garden ginseng (GG), concerning their calcium oxalate crystals, organic acids, and ginsenosides. The results demonstrate that MFCG had higher levels of non-free oxalate, calcium oxalate crystals, and most ginsenosides, while GG had higher fumaric acid/total organic acids. The content of non-free oxalate and calcium oxalate crystals in rhizome was the highest, showing a positive correlation with the growth years (5–20 years). In most cases, in MFCG, non-free oxalic acid ≥ 0.8%, calcium oxalate ≥ 160/mg, fumaric acid/total organic acids < 9%, Rb1 ≥ 6 mg/g, PPD/PPT was close to 2, and Rb1/Ro ≥ 2.5, while in GG, non-free oxalic acid < 0.8%, calcium oxalate ≤ 60/mg, fumaric acid/total organic acids ≥ 9%, Rb1 < 6 mg/g, PPD/PPT was close to 1, and Rb1/Ro < 2.5. These results can be used as the basis for distinguishing between GG and MFCG. Chemometric analysis of non-free oxalate, calcium oxalate crystals, and ginsenosides could distinguish MFCG from GG. Chemometric analysis of succinate, citrate, and malonic acids could mostly differentiate MFCG of over 15 years from that of less than 12 years. As far as we know, the present study is the first to determine the difference in the ratio of ginsenosides (Rb1/Ro, PPD/PPT) and the ratio of organic acids, which provides an innovative method for the distinction between the two and a scientific basis for effective quality control of MFCG. Full article
(This article belongs to the Section Food Analytical Methods)
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14 pages, 2150 KB  
Article
Neurotoxicological Evaluation of Intrathecal Citrate Excipients: Calcium Homeostasis Disruption and Safety Implications in CNS Drug Delivery
by Jue Wang, Yuan Zhang, Qing He, Ying Du, Xia Zhang, Xinru Tan, Xinting Zhou, Susu Tang, Baoming Ning, Rui Yang, Xia Zhao, Dejiang Tan, Huimin Sun and Jiasheng Tu
Pharmaceutics 2025, 17(9), 1112; https://doi.org/10.3390/pharmaceutics17091112 - 27 Aug 2025
Viewed by 1592
Abstract
Background/Objectives: Intrathecal drug delivery is essential for treating CNS disorders, but the safety of commonly used excipients such as citric acid/sodium citrate (SC) remains unclear. This study aims to systematically evaluate the potential neuropharmacological effects of repeated intrathecal SC administration. Methods: Multimodal approaches [...] Read more.
Background/Objectives: Intrathecal drug delivery is essential for treating CNS disorders, but the safety of commonly used excipients such as citric acid/sodium citrate (SC) remains unclear. This study aims to systematically evaluate the potential neuropharmacological effects of repeated intrathecal SC administration. Methods: Multimodal approaches were applied across murine and lagomorph models. Doses ranged from 1.833–14.664 μg/g in mice and 0.104–3.290 mg/rabbit. Behavioral, neurophysiological, and fiber photometry analyses were conducted to assess sensorimotor function, cortical activity, and calcium dynamics. Results: SC induced dose-dependent sensorimotor deficits, including hypolocomotion (45.7% reduced distance, p < 0.001) and impaired coordination (latency reduction 48.3–64.1%, p < 0.001). Mortality increased with dosage and repeated exposure. Neurophysiological data revealed biphasic cortical modulation: acute c-Fos suppression followed by delayed hyperactivity. Fiber photometry confirmed calcium chelation-mediated attenuation and subsequent potentiation of Ca2+ signals. Rabbits exhibited similar neurological symptoms, correlating with transient CSF calcium/magnesium depletion, though no structural neural damage was observed. Conclusions: These results provide the first comprehensive evidence that SC buffers can significantly disrupt neuronal calcium homeostasis and induce functional impairments upon intrathecal delivery. The findings emphasize the need for reassessing excipient safety in CNS-targeted formulations. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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10 pages, 306 KB  
Article
Investigation of rs11568476 Polymorphism in the SLC13A2 Gene in Turkish Patients with Hypocitraturia and Calcium-Containing Kidney Stones
by Ekrem Başaran, Dursun Baba, Yusuf Şenoğlu, Alpaslan Yüksel, Muhammet Ali Kayıkçı, Selma Düzenli and Ali Tekin
Biomedicines 2025, 13(8), 1985; https://doi.org/10.3390/biomedicines13081985 - 15 Aug 2025
Viewed by 1129
Abstract
Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption [...] Read more.
Background and Objectives: Hypocitraturia is a major risk factor for calcium-containing kidney stone disease. Citrate inhibits stone formation by binding calcium in the urine. The SLC13A2 gene encodes the sodium-dependent dicarboxylate cotransporter 1 (NaDC1), a membrane transport protein that facilitates citrate reabsorption in the proximal renal tubules. Variants in this gene, such as rs11568476 (V477M), have been shown to significantly impair transporter activity. This study aimed to investigate the presence of the rs11568476 polymorphism in SLC13A2 and its association with hypocitraturia in Turkish patients with calcium-containing kidney stones. To our knowledge, this is the first genetic study evaluating this polymorphism in a Turkish cohort. Materials and Methods: This prospective cross-sectional study included 90 patients diagnosed with calcium-containing kidney stones at Düzce University Faculty of Medicine, Department of Urology. Based on 24 h urinary citrate levels, patients were divided into two groups: normocitraturic (n = 38) and hypocitraturic (n = 52). Blood and 24 h urine samples were analyzed for biochemical parameters. The rs11568476 polymorphism in SLC13A2 was analyzed using Real-Time PCR. Results: There were no significant differences between the two groups in terms of age, gender, and most biochemical parameters. Serum uric acid levels were significantly higher in the hypocitraturic group (p = 0.002), whereas family history of stone disease was more prevalent in the normocitraturic group (p = 0.024). Genetic analysis revealed no polymorphism in the rs11568476 region; all patients exhibited the homozygous wild-type genotype (GG). Conclusions: No association was observed between the rs11568476 polymorphism and hypocitraturia in this cohort. The absence of the polymorphism suggests that this variant may be rare or absent in the Turkish population. These findings highlight the importance of investigating additional genetic and environmental contributors to hypocitraturia and nephrolithiasis through larger, multicenter studies. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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Brief Report
CalOPT: A Specialty Pharmacy–Dietitian Quality Improvement Initiative for Calcium Optimization in Patients with Osteoporosis Risk
by Jennifer Cerulli, Alisha Roberts, Ellie Wilson and Scott Guisinger
Pharmacy 2025, 13(4), 100; https://doi.org/10.3390/pharmacy13040100 - 23 Jul 2025
Viewed by 1305
Abstract
A total of 38% of Americans do not meet the Recommended Dietary Allowance (RDA) for calcium including those at risk for osteoporosis. To increase the percentage of patients at risk for osteoporosis who achieve goal calcium RDA intake, a collaborative specialty pharmacy-registered dietitian-nutritionist [...] Read more.
A total of 38% of Americans do not meet the Recommended Dietary Allowance (RDA) for calcium including those at risk for osteoporosis. To increase the percentage of patients at risk for osteoporosis who achieve goal calcium RDA intake, a collaborative specialty pharmacy-registered dietitian-nutritionist (RDN) quality improvement program was developed. Patients aged 18 to 90 years old receiving osteoporosis therapy (denosumab, teriparatide, zoledronic acid) or medications that increase bone loss (elagolix, oral prednisone) were provided with a structured assessment and educational intervention. Daily calcium intake included patient self-reported dietary intake plus supplement use. Written and verbal education on increasing dietary intake based on patient preferences was provided with 5 calcium-rich food-source store coupons. Recommendations for supplement selection (citrate vs. carbonate) and/or medication-related problem resolution were provided. Follow-up occurred at 3–6 months. Fifty patients enrolled [94% female, mean age 66.6 years (SD 15.3)] were taking denosumab (36), teriparatide (1), zoledronic acid (1), elagolix (7) and prednisone (5). The mean baseline daily dietary calcium intake was 500 mg (SD 247) with none achieving goal intake with diet alone. Average calcium supplement use in 22 (44%) patients was 686 mg daily (SD 284). At baseline, 17 (34%) met goal daily calcium intake compared to 30 (60%) at post intervention follow-up (p = 0.009). Over half of the store coupons were redeemed. A specialty pharmacy-RDN customized intervention program provides a model for aiding patients to modify calcium intake. Full article
(This article belongs to the Section Pharmacy Practice and Practice-Based Research)
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