As the population ages worldwide, the importance of maintaining the metabolism of the skeletal system becomes increasingly important. The skeleton is the core of the locomotor and oral structure. ...Moreover, infection control is an essential part of orthopedic and oral surgery. This paper investigates new bone substitutes fabricated by the ionic substitution method leading to octacalcium phosphate (OCP) with excellent contact antibacterial ability, biocompatibility, and bone replacement. To improve the functionality of OCP-based materials as a bone substitute, we introduce a novel OCP block fabrication method based on the dissolution–precipitation method, study the factors that induce OCP in solution, and propose a robust method for cation substitution in the OCP unit lattice named the ionic insertion method. We then fabricate Ag-substituted OCP (OCP–Ag) blocks using this method and evaluate their antibacterial activity in vivo. These techniques will contribute to new-generation medical services and improve the quality of life of individuals requiring implants.
Octacalcium phosphate (OCP), a layered calcium phosphate compound, has attracted attention in areas such as biomaterial and pharmacy, as well as the environmental industry, because of its excellent ...biocompatibility and low environmental load. However, little is known about the effect of alkaline metal ions on OCP formation, even though the Na ion is always present as a pH neutralizing or ionic strength-adjusting agent. Therefore, in this study, we investigated the role of the Na ion in OCP formation from dicalcium phosphate dihydrate through hydrolysis by using solutions with various Na concentrations. When the Na concentration in the treatment solutions increased, the formation of hydroxyapatite as a residual material was inhibited and the purity of OCP was increased. Furthermore, at higher concentrations, OCP crystals evolved layer structures because Na affects the P5 PO4 in the OCP lattice and enhances the HPO4-OH layer structure, which significantly contributes to OCP crystallinity and crystal structure. Thermal stability measurements indicate that the thermal stability of OCP decreases with increasing Na content. This study suggests that Na incorporation into OCP crystals can induce OCP formation but simultaneously decreases the OCP stability.
Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to ...metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in β-oxidation following suppression of transactivation by PPARα. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARα to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARα activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARα activation upon fasting by promoting degradation of NCoR1 and thus regulates β-oxidation and ketone bodies production.
Display omitted
•Intercalated molecules of OCP could be exchanged by PO4 during phase conversion.・The formed HPO4-OH layer structure is unstable, then, easily convert.•PO4 in buffer solution ...accelerated phase conversion process of OCP to HAp.•During this process, crystals morphology was no obvious changes.
Octacalcium phosphate (OCP) is a layered calcium phosphate compound that has attracted significant attention as a new biomaterial due to its excellent biocompatibility. Its interlayer structure, known as HPO4-OH layer, can be easily replaced by dicarboxylic acid. However, the kinetical ionic and/or molecular exchange process of substituted dicarboxylic acid into OCP interlayer is still unclear. Therefore, in this study, we evaluate the molecular exchange process for thiomalate (SH-malate)-substituted OCP (OCP-SH-malate) during the phase conversion process to other phases in disodium hydrogen phosphate solution (Na2HPO4). When the OCP-SH-malate is immersed in 1 mol/L Na2HPO4 at 40 °C while shaking at 200 rpm, SH-malate, first desorbed from the interlayer of OCP-SH-malate and the HPO4-OH layer structure, is formed at the interlayer where the SH-malate was dissolved. The HPO4-OH layer structure is unstable, making it easily convert to hydroxyapatite (HAp) via dehydration upon further immersion. During this reaction, besides the dissolution of marginal edges of the crystals, crystals morphology was no obvious changes, neither were there evidences of dissolution and collapsing of OCP crystals nor nucleation of newly created crystals.
Abstract
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota ...alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2
Porphyromonas
species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into
Apc
Δ14/+
mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between
Porphyromonas
species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.
Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases
. Here we show that centenarians have a distinct gut microbiome that is ...enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3β-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.
Octacalcium phosphate (OCP), a layered calcium phosphate compound, is an attractive material for new medical combination products, which are hybrid materials consisting of both drugs and biomaterials ...that have shown excellent therapy scores. OCP is fabricated primarily from soluble calcium salt via an aqueous-mediated hydrolysis process. The coexisting cations are likely to be incorporated into the OCP unit lattice during this process and affect the development of the OCP crystal structure and its thermodynamic stability. However, the key parameters of the coexisting cations, such as the ionic radii and charge number, that affect OCP formation are still unclear. In this study, we focused on the ionic radius of each monovalent ion of alkali metal ions (Li+, Na+, K+, Rb+, and Cs+) for OCP incorporation and formation in a CaHPO4·2H2O (DCPD)-(NH4)2HPO4 system with alkali metal salts. There was little incorporation of Li into the OCP unit lattice at low concentrations, whereas Li was incorporated into the OCP unit lattice as a conjugate form of NH4 and K, which have ionic radii that are larger than that of Ca, resulting in a HPO4–OH layered structure in the OCP unit lattice. The Na concentration increased hyperbolically and was incorporated into the OCP unit lattice, resulting in a HPO4–OH layered structure in the OCP unit lattice. By contrast, Li, K, and Rb resulted in the HPO4–OH layer in the OCP unit lattice at low concentrations and attenuated OCP formation at high concentrations. Cs only exhibited an attenuation effect on OCP formation. Considering the differences between the Ca ionic radius (1.00 Å) and those of alkali metal ions, the alkali metal ionic radii that were smaller than ∼1.5 times the Ca ionic radius could be incorporated into the OCP unit lattice, whereas those greater than ∼1.5 times the Ca ionic radius exhibited an inhibiting effect on OCP formation. In addition, Na particularly affects the OCP formation and its crystallinity unlike other alkali metal ions because of its similar ionic radius to Ca.
Here, we introduce Ag substituted octacalcium phosphate (OCP-Ag) blocks with interconnected porous structure and sufficient mechanical strength as bone substitute (i.e., foam). We employed a two-step ...process for fabrication, which includes a setting reaction for acidic calcium phosphate granules using an acidic phosphate solution and a phase conversion process via dissolution-precipitation method in cocktail ((NH
4
)
2
HPO
4
-NH
4
NO
3
-NaNO
3
-AgNO
3
) solutions. The Ag contents in the fabricated OCP-Ag foams were 0.08–0.15 at%, which were sufficient in exhibiting contact antibacterial ability. The mechanical strength and porosity of the OCP-Ag foams were about 0.5 MPa and 70%, respectively. These values were sufficient for the application of the OCP-Ag foams as bone substitute.
Graphical abstract
It is unclear whether long-term sodium–glucose cotransporter 2 (SGLT2) inhibition such as that during the treatment of diabetes has deleterious effects on the kidney. Therefore, we first sought to ...determine whether abnormal glucose metabolism occurs in the kidneys of 22-week-old BTBR ob/ob diabetic mice. Second, the cumulative effect of chronic SGLT2 inhibition by ipragliflozin and 30% calorie restriction, either of which lowered blood glucose to a similar extent, on renal glucose metabolism was evaluated. Mass spectrometry–based metabolomics demonstrated that these diabetic mice exhibited an abnormal elevation in the renal pools of tricarboxylic acid cycle metabolites. This was almost completely nullified by SGLT2 inhibition and calorie restriction. Moreover, imaging mass spectrometry indicated an increased level of the tricarboxylic acid cycle intermediate, citrate, in the cortex of the diabetic mice. SGLT2 inhibition as well as calorie restriction almost completely eliminated citrate accumulation in the cortex. Furthermore, imaging mass spectrometry revealed that the accumulation of oxidized glutathione in the cortex of the kidneys, prominent in the glomeruli, was also canceled by SGLT2 inhibition and calorie restriction. Effects of these beneficial interventions were consistent with improvements in glomerular damage, such as albuminuria, glomerular hyperfiltration, and mesangial expansion. Tubulointerstitial macrophage infiltration and fibrosis were ameliorated only by calorie restriction, which may have been due to autophagy activation, which was observed only with calorie restriction. Thus, chronic SGLT2 inhibition is efficient in normalizing the levels of accumulated tricarboxylic acid cycle intermediates and increased oxidative stress in the kidneys of diabetic mice.
Display omitted
The excellent biocompatibility of apatite (hydroxyapatite, HAp; carbonate apatite, CO3Ap) materials makes them suitable candidates as bone substitutes. However, they have no antibacterial ability. ...Meanwhile, silver (Ag) exhibits excellent antibacterial properties across a wide antibacterial spectrum. However, soluble Ag salts exhibit cytotoxicity and poor aesthetic properties. We dope Ag into an apatite unit lattice in order for the composite material to exhibit antibacterial contact abilities while simultaneously limiting the release of Ag+, which is the primary cause of the unwanted color changes and cytotoxicity. When a crystal structure in which silver ions are substituted for Ca in octacalcium phosphate (OCP) (Ag-OCP) is immersed in water and/or (NH4)2CO3-containing solutions, Ag-OCP is converted into an apatite containing Ag via a solid–solid phase-transformation process. The Ag contents of the apatite and precursor Ag-OCP are the same. The CO3 content of apatite samples depends on the (NH4)2CO3 concentration of the treated solutions. A single-pot, single-step treatment enables the synthesis of both Ag-containing HAp and CO3Ap. Further, these Ag-containing HAp and CO3Ap samples show little color change from that of the precursor Ag-OCP.
Display omitted
PDF
