Controlled Release of Oxygen from Calcium Peroxide in a Weak Acidic Condition by Stabilized Amorphous Calcium Carbonate Nanocoating for Biomedical Applications.

Calcium peroxide (CaO2) has recently attracted much attention as an oxygen-releasing biomaterial for tissue engineering. CaO2 has also been used in cancer therapies, such as photodynamic therapy. However, the uncontrollability of oxygen release after immersion in water is a challenge. Furthermore, the nanoscale surface chemistry of CaO2 on the oxygen release properties under cell culture conditions has not been taken into account in these applications. Herein, we report the stabilized amorphous calcium carbonate (ACC) nanocoating on CaO2 in a cell culture medium, which suppressed the reaction between CaO2 and water. Stabilized ACC was produced by the reaction between calcium hydroxide (Ca(OH)2) derived from CaO2 and sodium hydrogen carbonate (NaHCO3) including sodium dihydrogen phosphate (NaH2PO4) in a cell culture medium. In contrast, surface modification of CaO2 by calcium carbonate crystals was difficult due to the crystallization process via dissolution-reprecipitation. Strikingly, ACC-CaO2 showed pH-dependent oxygen release in a cell culture medium probably because of the dissolution of ACC under weak acidic condition. Since the environments in ischemic tissue and cancer are weakly acidic, our findings should be important for understanding and designing properties related to biomaterials and drugs using CaO2.

Ultra-Rapid and Specific Gelation of Collagen Molecules for Transparent and Tough Gels by Transition Metal Complexation.

Collagen is the most abundant protein in the human body and one of the main components of stromal tissues in tumors which have a high elastic modulus of over 50 kPa. Although collagen has been widely used as a cell culture scaffold for cancer cells, there have been limitations when attempting to fabricate a tough collagen gel with cells like a cancer stroma. Here, rapid gelation of a collagen solution within a few minutes by transition metal complexation is demonstrated. Type I collagen solution at neutral pH shows rapid gelation with a transparency of 81% and a high modulus of 1,781 kPa by mixing with K2 PtCl4 solution within 3 min. Other transition metal ions also show the same rapid gelation, but not basic metal ions. Interestingly, although type I to IV collagen molecules show rapid gelation, other extracellular matrices  do not exhibit this phenomenon. Live imaging of colon cancer organoids in 3D culture indicates a collective migration property with modulating high elastic modulus, suggesting activation for metastasis progress. This technology will be useful as a new class of 3D culture for cells and organoids due to its facility for deep-live observation and mechanical stiffness adjustment.

Development of temperature dependent oxygen releasable nanofilm by modulating oxidation state of myoglobin.

Controlled release of oxygen from myoglobin was achieved by modulating autoxidation of oxymyoglobin using ascorbic acid as a reductant by temperature variation. Long-term storage, prompt release and re-storage of oxygen were also available with this system. Furthermore, 20 nm thick nanofilms composed of oxymyoglobin and type I collagen containing ascorbic acid could successfully show autoxidation of oxymyoglobin in response to environmental temperature. The ultrathin nanofilms will be useful as oxygen-controlled releasable scaffolds for tissue engineering application.

Diverse phenotypic expression associated with the same genetic variant in female heterozygote patients of Anderson-Fabry disease: a case series.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder resulting from a mutation of alpha-galactosidase A gene (GLA), causing deficiency in alpha-galactosidase activity. The enzyme deficit can lead to storage of globotriaosylceramide in various organs including heart. Studies suggest that vasospastic angina (VSA) is associated with AFD. CASE SUMMARY: This clinical case series aimed to present two female patients with AFD, including progressive cardiac involvement: a 50-year-old woman (patient number 1) and a 39-year-old woman (patient number 2) who are siblings with a male AFD patient harbouring p. Arg342Glu missense variant in alpha-galactosidase A gene (GLA), who suffered VSA and subsequent ventricular fibrillation. Enzymatic tests and genetic analysis confirmed AFD in both female patients and histological tests revealed globotriaosylceramide deposits in their hearts. In patient number 1, a 12-lead electrocardiography and transthoracic echocardiography revealed cardiac hypertrophy. Coronary angiography revealed no organic coronary artery stenosis and vasospasms was induced by spasm provocation test. In patient number 2, no signs of cardiac hypertrophy were found, and coronary arteries had no organic stenosis with negative spasm provocation test. Both patients received enalapril therapy and enzyme replacement therapy (ERT). DISCUSSION: Different phenotype of AFD was occurred even with the same genetic variant in female heterozygote patients. The duration of exposing accumulation of Gb3 might affect cardiac hypertrophy and vasospasms. Coronary angiography with acetylcholine provocation test should be considered in female AFD patient, especially in case with cardiac hypertrophy.

Peroxisome proliferator-activated receptors (PPARs) have multiple binding points that accommodate ligands in various conformations: phenylpropanoic acid-type PPAR ligands bind to PPAR in different conformations, depending on the subtype.

Human peroxisome proliferator-activated receptors (hPPARs) are ligand-dependent transcription factors that control various biological responses, and there are three subtypes: hPPARα, hPPARδ, and hPPARγ. We report here that α-substituted phenylpropanoic acid-type hPPAR agonists with similar structure bind to the hPPAR ligand binding domain (LBD) in different conformations, depending on the receptor subtype. These results might indicate that hPPAR ligand binding pockets have multiple binding points that can be utilized to accommodate structurally flexible hPPAR ligands.