calcium

Overview

Calcium (Ca; atomic number 20) is the most abundant mineral in the human body and a divalent cation (Ca²⁺) essential to a wide range of physiological processes. Beyond its structural role as the primary mineral constituent of bones and teeth—where it exists predominantly as hydroxyapatite—calcium functions as a ubiquitous intracellular second messenger regulating cell signaling, muscle contraction, neurotransmitter release, enzyme activation, and apoptotic pathways. Intracellular Ca²⁺ concentrations are tightly maintained at nanomolar levels in the cytoplasm, while organelles such as the endoplasmic reticulum (ER), mitochondria, and lysosomes serve as dynamic Ca²⁺ reservoirs whose coordinated release and uptake govern excitability, metabolic coupling, and cell death decisions. Dysregulation of calcium homeostasis is implicated in a broad spectrum of pathologies, including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, acute pancreatitis, eryptosis, and neoplastic transformation, making Ca²⁺ signaling axes a prominent target in pharmacological and biomaterial research.

In pharmaceutical and materials science contexts, the Ca²⁺ ion is exploited for its ability to ionically crosslink anionic polymers—most notably sodium alginate—forming stable hydrogel and capsule networks used in drug delivery, wound management, and food science. The versatility of calcium across biological signaling, clinical diagnostics, nutritional supplementation, and advanced biomaterial engineering has positioned it as one of the most actively investigated chemical entities in contemporary biomedical research.

Focus of Latest Publications

Recent studies have investigated calcium's roles as both a pharmacological target and therapeutic agent in disease treatment and prevention. Machine learning and protein language model approaches have been applied to predict proteins that modulate calcium channels, supporting drug discovery and safety assessment of therapeutic biologics. In contrast, blocking calcium influx through ion channels such as TRPM7 has been explored as a strategy to prevent hypoxic ischemic brain injury by triggering apoptotic cell death.

In cancer immunotherapy, multiple research groups have engineered nanomaterials to deliberately release calcium ions within tumors to remodel immunosuppressive microenvironments. A nanoreactor designed to trap intracellular lactate simultaneously released calcium to amplify Ca2+-mediated immunogenic stress, promoting mitochondrial dysfunction and shifting immune populations toward pro-inflammatory phenotypes (including dendritic cell maturation and M1 macrophage polarization), thereby enhancing responsiveness to checkpoint inhibitor blockade. Calcium peroxide-based nanoplatforms have similarly been developed to induce mitochondrial calcium overload in combination with copper-mediated cuproptosis and reactive oxygen species generation, demonstrating enhanced tumor suppression in preclinical studies.

Calcium levels and supplementation have been investigated as clinical markers and preventive interventions. In acute pancreatitis, combined measurement of serum uric acid and calcium provided superior predictive capability (AUC 0.9504) for disease severity. In enamel formation, calcium and vitamin D supplementation were tested as protective factors against fluoride- and amoxicillin-induced enamel disorganization and ameloblast apoptosis, though supplementation did not significantly restore normal enamel architecture or matrix protein profiles in experimental models. Long-term pharmacological calcium supplementation's association with cognitive decline in aging women remains under investigation in prospective cohort studies.

In food science and biomedical materials, calcium and divalent cations have been employed to engineer stable protein-polysaccharide networks. Calcium ions enhanced gelation strength and structural organization in potato protein-sesbania gum composites, while calcium-mediated cross-linking of soy protein amyloid fibrils and sodium alginate produced mechanically robust, high-stretch hydrogels with tensile strains exceeding 91%. In restorative dentistry, calcium phosphate nanoparticles were incorporated into resin composites to achieve controlled release of calcium and phosphate ions for secondary caries prevention.

Key Publications

• NEWJul A PLM-based method for predicting protein ion channel modulators for drug discovery and safety evaluation. (Protein science : a publication of the Protein Society, 2026, PMID 42321971): "including channel-specific (such as sodium, potassium, calcium, and others) and moonlighting proteins capable of modulating multiple ion channels."
• NEWJun Stage-specific associations of mineralization markers with CKM syndrome: Nationwide survey and genetic evidence for Alkaline phosphatase's unique clinical role. (PloS one, 2026, PMID 42313881): "Herein, we investigated the serum alkaline phosphatase (ALP), calcium, and phosphorus across CKM stages."
• NEWJun Pharmacophore Directed Retrosynthesis Applied to Waixenicin A: Synthesis and Bioactivity of Derivatives Bearing a Minimal Proposed Pharmacophore. (Organic letters, 2026, PMID 42276815): "WaixA specifically blocks the divalent ion channel transient receptor potential melastatin 7 (TRPM7), preventing the influx of calcium into the cell and triggering apoptotic pathways."
• NEWJun Engineering Hypoxia-Lactate-Ca Coupling for Metabolic-Ion Intervention in Cancer Immunotherapy. (ACS applied materials & interfaces, 2026, PMID 42268380): "...increases susceptibility to Ca2+-associated stress."
• Jun Hyperuricemia aggravates acute pancreatitis through CNR1-mediated inflammatory signaling and gut-pancreas axis dysregulation: a multi-omics and clinical study. (Scientific reports, 2026, PMID 42243316): "The combination of uric acid and calcium demonstrated superior predictive capability for AP severity (AUC 0.9504)."
• May Morphological, Histochemical, and Proteomic Analysis of the Effects of Fluoride and Amoxicillin, with Calcium and Vitamin D Supplementation, on Dental Enamel Formation. (Calcified tissue international, 2026, PMID 42184017): "Calcium and vitamin D supplementation have been proposed as potential protective factors against fluoride-induced enamel alterations."
• Jun Association Between Calcium Supplement Use and Cognitive Impairment in Ageing Women: A Longitudinal Analysis. (Australasian journal on ageing, 2026, PMID 42159347): "This study assessed the association between pharmacological calcium supplementation and cognitive decline over 7 years in cognitively healthy older women."
• May CaO2-Powered Nanomotors with Enhanced Cellular Uptake and Lysosomal Escape for Cuproptosis and Reactive Oxygen Species-Mediated Synergistic Cancer Therapy. (ACS applied materials & interfaces, 2026, PMID 42126988): "In acidic tumor microenvironments, sustained release of Ca2+, Cu2+, hydrogen peroxide (H2O2), and hesperidin occurs, triggering a cascade of therapeutic effects."
• May Synergistic effect of TGase and Ca2+ in regulating the gel network structure and stability of potato protein-sesbania gum composite gels. (International journal of biological macromolecules, 2026, PMID 41967536): "In this study, synergistic effect of TGase and Ca2+ on potato protein-sesbania gum composite gels was investigated to overcome the problems of poor network structure and gel performance."
• Jun Compact hydrogels network structures reinforced by soy protein amyloid fibrils and sodium alginate. (Food research international (Ottawa, Ont.), 2026, PMID 41895961): "SA was a vital compound capable of constructing a hydrogel network in the presence of Ca2+."