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International Journal of Environmental Research and Public Health · 2021 ·Vol. 18 ·期 22 ·12051 · IF 3.39

The Blood Lead Levels of Children and the Loss of Ca2+ from Neurons Owing to Lead

Yifei Duan,Hua Shi,Yongmei Jiang

In order to understand current blood lead levels (BLLs), we investigated the BLLs of children in Sichuan Province from 2011 to 2020. We then monitored the treatment effects of calcium in children with high BLLs to assess their treatment status. Finally, we explored the effects of lead on Ca2+through in-situ experiments. Whole blood samples were used for BLL tests. The BLLs of 76,362 children aged 0–7 years were measured using atomic absorption spectrometry. The median BLL was 35 μg/L (interquartile range: 28–47). The BLLs were significantly higher in boys than in girls (p< 0.001). The BLLs generally decreased annually and increased with age. The overall prevalence of BLLs ≥ 100 μg/L was 1.20%. The children with high BLLs received subsequent check-ups, and the median time required for effective treatment was 18 months. We observed that lead exposure led to a gradual and persistent loss of Ca2+levels in neurons of mice brain slices, and the effect did not subside immediately even after the lead was removed. China has made rapid progress in pediatric healthcare, but the treatment status remains unsatisfactory. Because lead causes an irreversible loss of Ca2+, there is an urgent need to develop new standardized treatments to reduce the treatment duration.Keywords:blood lead levels;treatment status;calcium supplement;Ca2+imaging

研究领域: 公共卫生 · 神经生物学 · 儿科医学
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FOOD CHEMISTRY · 2022 · IF 9.231

Binding mechanism and bioavailability of a novel phosvitin phosphopeptide (Glu-Asp-Asp-pSer-pSer) calcium complex

Kai Si,Tingting Gong,Suyun Ding,Huiping Liu,Shuyuan Shi,Jianqiu Tu,Linxian Zhu,Li Song,Lushan Song,Xiaowei Zhang

Phosvitin has excellent calcium binding capacity, related to its phosphopeptides. The phosphopeptides may be used as functional ingredients for improving calcium bioavailability, but the calcium-binding mechanism is unclear. In this study, a novel phosvitin phosphorylated pentapeptide (Glu-Asp-Asp-pSer-pSer, EDDpSpS) was selected to prepare an EDDpSpS calcium complex (EDDpSpS-Ca), and the calcium-binding mechanism and bioavailability investigated. The calcium-binding capacity of EDDpSpS was up to 468 ± 152.80 mg/g. Calcium ions prompted the folding of the EDDpSpS structure to form spherical nanoparticles. The calcium binding sites of EDDpSpS involved peptide bonds, carboxyl, amino, and phosphate groups. Molecular forces involved in these interactions were electrostatic in nature. Moreover, EDDpSpS-Ca had excellent bioavailability when compared to CaCO 3 , calcium lactate, and d -calcium gluconate. This study revealed the calcium-binding mechanism of phosvitin phosphopeptide, and suggested that EDDpSpS-Ca has the potential to be a novel, efficient, and promising calcium supplement.

CAS / MDL: 10043-52-4
研究领域: 营养学 · 生物化学
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MOLECULAR PHARMACEUTICS · 2021 · IF 4.939

Discovery of a Long-Acting Parathyroid Hormone 1–34 Analogue to Treat Hypoparathyroidism

Sida Ruan,Guiying Yang,Yuanzhen Dong,Wenwen Shangguan,Weigen Lu

Hypoparathyroidism (HP) is a rare disease with clinical manifestations of hypocalcemia and hyperphosphatemia, resulting from deficient or absent parathyroid hormone (PTH) secretion. Conventional treatment for patients with HP involves extensive calcium and vitamin D supplementation. In 2015, PTH1–84 was approved by the United States Food and Drug Administration as an adjunct for HP patients who cannot be well-controlled on conventional treatment. However, PTH1–84 therapy requires a daily injection, leading to poor patient compliance. The purpose of this study was to develop a long-acting PTH1–34 analogue by increasing its affinity to albumin. Three PTH1–34 variants were generated by substituting two of the three lysine (Lys) residues with arginine, reserving a single Lys as the modification site in each sequence. A series of side chains, containing fatty acid, deoxycholic acid, or biotin groups, were synthesized to modify these PTH1–34 variants by using a solid–liquid phase synthesis approach. In vitro bioactivity and albumin affinity tests were used to screen these new PTH1–34 analogues. Finally, Lys27-AAPC was selected from 69 synthesized analogues as a candidate therapeutic compound because it retained potency and exhibited a high albumin-binding capacity. In pharmacodynamic experiments, Lys27-AAPC demonstrated enhanced and prolonged efficacy in serum calcium elevating relative to PTH1–84. Moreover, a lyophilized powder for injection containing Lys27-AAPC was developed for further testing and represented a potential long-acting HP treatment.

CAS / MDL: 58-85-5
研究领域: 内分泌学 · 药理学 · 药物化学
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Advanced Healthcare Materials · 2025 · IF 9.6

Dual-Functional Nanoparticles to Reverse Osteoblast Senescence and Enhance Calcium Supplementation for Alleviating Senile Osteoporosis

Caini Yu,Yanling Peng,Tong Yu,Jia Ke,Qi Jiang,Peirong Li,Renxiang Yuan,Tingting Meng,Fuqiang Hu,Jianwei Wang,Hong Yuan

Senile osteoporosis (SOP) primarily arises from an imbalance between bone formation and bone resorption. The tightly regulated coupling between osteoblasts and osteoclasts limits the therapeutic efficacy of conventional anti-resorptive agents and anabolic agents. Anti-aging therapy offers a potential strategy to modify the senescent phenotype of bone-associated cells, restore cellular function, and re-establish homeostasis between bone resorption and formation. Calcium-based nanoparticles can effectively deliver therapeutic agents to target sites while simultaneously supplying exogenous calcium. Moreover, restored osteoblast function enhances the cellular capacity to process supplemented exogenous calcium ions, ultimately increasing bone density and further alleviating osteoporosis. In this context, a dual-functional calcium carbonate nanoparticle is engineered. This nanoparticle facilitates the complexation of nicotinamide mononucleotide, enabling targeted delivery to osteoblasts, reversing osteoblast senescence, and restoring their osteogenic function. Simultaneously, through calcium supplementation, the nanoparticle promotes osteoblast differentiation and mineralization. In vitro and in vivo studies have demonstrated the promising therapeutic efficacy of this nanoparticle in treating SOP, providing critical insights for the future development of integrated anti-senescence therapies and calcium supplementation strategies.

研究领域: 纳米技术 · 生物医学工程 · 老年医学 · 骨骼生物学 · 药学
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Foods · 2024 ·Vol. 13 ·期 12 ·1943 · IF 4.7

Enhancement of Calcium Chelating Activity in Peptides from Sea Cucumber Ovum through Phosphorylation Modification

Lingyu Han,Yaoyao Li,Bing Hu,Wei Wang,Jianming Guo,Jixin Yang,Nuo Dong,Yingmei Li,Tingting Li

Recently, phosphorylation has been applied to peptides to enhance their physiological activity, taking advantage of its modification benefits and the extensive study of functional peptides. In this study, water-soluble peptides (WSPs) of sea cucumber ovum were phosphorylated in order to improve the latter’s calcium binding capacity and calcium absorption. Enzymatic hydrolysis methods were screened via ultraviolet-visible absorption spectroscopy (UV–Vis), the fluorescence spectrum, and calcium chelating ability. Phosphorylated water-soluble peptides (P-WSPs) were characterized via high-performance liquid chromatography, the circular dichroism spectrum, Fourier transform infrared spectroscopy (FTIR), UV–Vis spectroscopy, surface hydrophobicity, and fluorescence spectroscopy. The phosphorus content, calcium chelation rate and absorption rate were investigated. The results demonstrated that phosphorylation enhanced the calcium chelating capacity of WSPs, with the highest capacity reaching 0.96 mmol/L. Phosphate ions caused esterification events, and the carboxyl, amino, and phosphate groups of WSPs and P-WSPs interacted with calcium ions to form these bonds. Calcium-chelated phosphorylated water-soluble peptides (P-WSPs-Ca) demonstrated outstanding stability (calcium retention rates > 80%) in gastrointestinal processes. Our study indicates that these chelates have significant potential to develop into calcium supplements with superior efficacy, bioactivity, and stability.

CAS / MDL: 7758-29-4 9007-43-6
研究领域: 生物化学 · 食品科学 · 营养学 · 药学
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