Octacalcium phosphate (OCP), a precursor to apatite, has a layered structure that allows various molecules to be intercalated within its interlayers. Previous research on the phase conversion process ...of OCP to apatite indicated that the layered structures typically collapse due to the shrinking of the OCP layers. In contrast, this study presents a novel phenomenon involving OCP layer expansion during phase conversion. This expansion is based on a forced oxidation process of the intercalated molecules within the hydrous layers of OCP. By introducing NaClO to an OCP interlayer containing dithiodiglycolic acid (DSG), the OCP layers are expanded. This process involves DSG decomposition through its reaction with NaClO. Specifically, the process occurs when a DSG-substituted OCP (containing disulfide bonds (–S–S–)) is immersed in a NaClO solution. This is the first study to report the expansion phenomenon during the phase conversion process from OCP to apatite, providing a new perspective to the conventional understanding that these layers only shrink.
Octacalcium phosphate (OCP) is a layered type of calcium phosphate that shows promise for pharmaceutical and biomedical applications because it offers both excellent biocompatibility and a unique, ...robust crystal structure that readily accepts substitution by various molecules. Although several cations can be incorporated into the OCP crystal lattice by ionic substitution, little is known about the relative probability of different ions to substitute into the OCP crystal lattice. In this study, we focus on Na and NH
4
, which are known to enter the OCP crystal lattice by ionic substitution. We investigate which of these two is most likely to substitute into OCP in a system containing both ions. In this work, OCP is fabricated from monocalcium phosphate monohydrate
via
hydrolysis in a solution containing 1 mol L
−1
(NH
4
)
2
HPO
4
with NaCl concentrations ranging from 0 to 100 mmol L
−1
. X-ray diffraction and thermal analyses indicate that the structure characteristic of NH
4
ionic substitution in OCP is attenuated as the Na concentration increases. Furthermore, when the Na concentration exceeds 50 mmol L
−1
(Na/NH
4
≥ 1/20), the structure characteristic of NH
4
ionic substitution into OCP almost completely disappears. These results indicate that Na is more likely to be ionically substituted into the OCP crystal structure than NH
4
and thereby inhibits the structural change of OCP caused by ionic substitution of NH
4
.
Octacalcium phosphate (OCP) is a layered type of calcium phosphate that shows promise for pharmaceutical and biomedical applications because it offers both excellent biocompatibility and a unique, robust crystal structure that readily accepts substitution by various molecules.
Removal of senescent cells (senolysis) has been proposed to be beneficial for improving age-associated pathologies, but the molecular pathways for such senolytic activity have not yet emerged. Here, ...we identified glutaminase 1 (
) as an essential gene for the survival of human senescent cells. The intracellular pH in senescent cells was lowered by lysosomal membrane damage, and this lowered pH induced kidney-type glutaminase (KGA) expression. The resulting enhanced glutaminolysis induced ammonia production, which neutralized the lower pH and improved survival of the senescent cells. Inhibition of KGA-dependent glutaminolysis in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction. Our results suggest that senescent cells rely on glutaminolysis, and its inhibition offers a promising strategy for inducing senolysis in vivo.
β-caryophyllene (BCP), an essential oil component of many herbs and spices, has various biological activities as a functional food factor. A distinct feature of BCP is its volatile double-ring ...sesquiterpene structure. Orally administered BCP is reportedly detected in its intact form in mice serum; however, the distribution of inhaled volatile BCP throughout the body remains unknown. This study aimed to estimate the distribution properties of inhaled volatile BCP and to investigate its effects on metabolism. After mice were exposed to volatile BCP, it was detected in the lung, olfactory bulb, brain, serum, heart, liver, kidney, epididymal fat, and brown adipose tissue. BCP was further detected in the brain, liver, and brown adipose tissue 24 h after exposure. Metabolites related to glutathione metabolism were significantly altered in the liver. These results suggest that inhaled volatile BCP is widely distributed in murine tissues and affects the dynamics of metabolites in the liver.
•High-purity OCP blocks could be fabricated from DCPD blocks.•Weak basic high-PO4-containing solution induced OCP formation from DCPD.•The mechanical strength of this OCP block is higher than that ...from CaSO4 block.
Octacalcium phosphate (OCP) blocks are attractive as bone substitutes because of their excellent biocompatibility. They can be fabricated from precursor ceramic blocks via a compositional conversion process. Herein, high-purity OCP blocks were fabricated through a dissolution–precipitation reaction from precursor blocks of dicalcium hydrogen phosphate dihydrate (DCPD) immersed in a 1.00-mol/L basic phosphate solution of disodium hydrogen phosphate (NaAP; pH ∼ 9) at 70 °C for 2 days. The results showed that they were completely converted to OCP blocks comprising interlocking ribbon-like crystals while maintaining their shape. The diametral tensile strength of the obtained OCP blocks was ∼6 MPa, which was significantly higher than that of OCP blocks fabricated from calcium sulfate as the precursor.
This paper details the results of the previous research on the fabrication of octacalcium phosphate (OCP)-based bone substitute materials, along with its new findings. OCP has received considerable ...attention as a new bone substitute material because it exhibits excellent biocompatibility. However, its poor formability seriously restricts its implementation in biomedical applications, especially as a bone substitute. OCP has been fabricated in aqueous solution via aqueous mediated reactions. Furthermore, the crystal growth process of OCP as a bone substitute material has also been investigated. Although previous studies have indicated that OCP is preferentially formed under weak acidic solutions, we also introduced Na+ and PO43− as key factors for OCP formation because they strongly enhance the OCP crystal structure. Based on these new findings about OCP formation, we introduced fabrication protocols for an OCP block as a bone substitute. In vivo studies have indicated that the fabricated OCP block exhibits excellent biocompatibility.
Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally ...truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH.
Octacalcium phosphate (OCP) has attracted the interest of researchers looking for new biomaterials due to its excellent biocompatibility and high formability. Furthermore, it was an attraction for ...medical combination products that ions and molecule doping ability of OCP, which originated its distinct crystal structure. Then, as an antibacterial bone substitute, Ag-substituted OCP (OCP-Ag) was a candidate of a centerpiece. However, for OCP-Ag block fabrication, drawback Ag contents of OCP-Ag blocks were significantly reduced compared to OCP-Ag powder when they were fabricated in the same Ag concentration solutions. It was still unclear the role of Na, an important matter for OCP block structure fabrication, in Ag substitution into OCP unit lattice. Thus, in this study, we analyzed the Na and Ag substitution process into OCP during OCP fabrication in the presence of Na and Ag solutions. Both cations improved the OCP’s layer structure, even though both ions co-exist. As the concentration of Na in the solutions increased, Ag contents of samples decreased until threshold values were achieved. According to the ionic species analysis, both PO4 ion complexes of Na and Ag showed no tendency toward other cation concentrations. Spectroscopic investigation showed that both ions were substituted in the conjugated site of P5 PO4, resulting in a competition of Ag and Na substitution into the same.
Carbonate apatite (CO3Ap) is an inorganic component of mature bone and is used as bone substitute instead of autografts. Recently, 100% pure CO3Ap granules formed from calcium carbonate via a ...dissolution-precipitation reaction have been used as a clinical precursor for bone. In this study, the feasibility of fabricating blocks of CO3Ap from blocks of octacalcium phosphate (OCP), which is an analog of the bone composition and serves as a precursor for bone, was investigated by immersion in NaHCO3. The macroscopic structure of the OCP block was retained upon conversion to CO3Ap. In addition, as the NaHCO3 concentration increased from 0.0 to 2.0 mol/L, the carbonate content increased in the resulting CO3Ap, reaching ≈ 14 wt% at maximum NaHCO3 concentration. Moreover, the morphology of the CO3Ap crystals varied as the NaHCO3 concentration increased up to 0.5 mol/L: they were pseudomorphic plate-like when the NaHCO3 concentration was low but formed particles ranging ~ 10 nm in size at high NaHCO3 concentrations. The different phase transformation modes depended on NaHCO3 concentrations closely related to CO3Ap crystal morphology and were associated with a decrease in the mechanical strength of the block.
Different phase conversion modes from OCP to CO3Ap depended on CO3 concentration Display omitted
Octacalcium phosphate (OCP) blocks with substituted dicarboxylic acid are attractive materials for new bioceramics because the substituted dicarboxylic acid enhances and regulates the ...biocompatibility of OCP. Therefore, OCP blocks can be model materials for biological bones and new medical combination products. However, dicarboxylic-acid-substituted OCP blocks are difficult to fabricate using conventional OCP fabrication methods such as dissolution–precipitation and simple precipitation methods because the counter cations in buffer solutions strongly inhibit dicarboxylic acid substitution into the OCP unit lattice. This study proposes a pure OCP-block fabrication method based on the cement setting of CaCO3, H3PO4, and dicarboxylic acid, which inserts dicarboxylic acid into the OCP matrix. OCP blocks with various dicarboxylic-acid substituents (succinate, thiomalate, and citrate) were obtained after optimizing the amount of CaCO3 in the mixtures. The mechanical strength of the dicarboxylic-acid-substituted OCP blocks significantly exceeded that of unsubstituted OCP.
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