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1.
Small ; 20(27): e2310239, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38299473

ABSTRACT

Solid-state hydrogen storage materials are safe and lightweight hydrogen carriers. Among the various solid-state hydrogen carriers, hydrogen boride (HB) sheets possess a high gravimetric hydrogen capacity (8.5 wt%). However, heating at high temperatures and/or strong ultraviolet illumination is required to release hydrogen (H2) from HB sheets. In this study, the electrochemical H2 release from HB sheets using a dispersion system in an organic solvent without other proton sources is investigated. H2 molecules are released from the HB sheets under the application of a cathodic potential. The Faradaic efficiency for H2 release from HB sheets reached >90%, and the onset potential for H2 release is -0.445 V versus Ag/Ag+, which is more positive than those from other proton sources, such as water or formic acid, under the same electrochemical conditions. The total electrochemically released H2 in a long-time experiment reached ≈100% of the hydrogen capacity of HB sheets. The H2 release from HB sheets is driven by a small bias; thus, they can be applied as safe and lightweight hydrogen carriers with economical hydrogen release properties.

2.
Proc Natl Acad Sci U S A ; 118(8)2021 Feb 23.
Article in English | MEDLINE | ID: mdl-33608458

ABSTRACT

The niobium-92-zirconium-92 (92Nb-92Zr) decay system with a half-life of 37 Ma has great potential to date the evolution of planetary materials in the early Solar System. Moreover, the initial abundance of the p-process isotope 92Nb in the Solar System is important for quantifying the contribution of p-process nucleosynthesis in astrophysical models. Current estimates of the initial 92Nb/93Nb ratios have large uncertainties compromising the use of the 92Nb-92Zr cosmochronometer and leaving nucleosynthetic models poorly constrained. Here, the initial 92Nb abundance is determined to high precision by combining the 92Nb-92Zr systematics of cogenetic rutiles and zircons from mesosiderites with U-Pb dating of the same zircons. The mineral pair indicates that the 92Nb/93Nb ratio of the Solar System started with (1.66 ± 0.10) × 10-5, and their 92Zr/90Zr ratios can be explained by a three-stage Nb-Zr evolution on the mesosiderite parent body. Because of the improvement by a factor of 6 of the precision of the initial Solar System 92Nb/93Nb, we can show that the presence of 92Nb in the early Solar System provides further evidence that both type Ia supernovae and core-collapse supernovae contributed to the light p-process nuclei.

3.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Article in English | MEDLINE | ID: mdl-33836612

ABSTRACT

The age of iron meteorites implies that accretion of protoplanets began during the first millions of years of the solar system. Due to the heat generated by 26Al decay, many early protoplanets were fully differentiated with an igneous crust produced during the cooling of a magma ocean and the segregation at depth of a metallic core. The formation and nature of the primordial crust generated during the early stages of melting is poorly understood, due in part to the scarcity of available samples. The newly discovered meteorite Erg Chech 002 (EC 002) originates from one such primitive igneous crust and has an andesite bulk composition. It derives from the partial melting of a noncarbonaceous chondritic reservoir, with no depletion in alkalis relative to the Sun's photosphere and at a high degree of melting of around 25%. Moreover, EC 002 is, to date, the oldest known piece of an igneous crust with a 26Al-26Mg crystallization age of 4,565.0 million years (My). Partial melting took place at 1,220 °C up to several hundred kyr before, implying an accretion of the EC 002 parent body ca. 4,566 My ago. Protoplanets covered by andesitic crusts were probably frequent. However, no asteroid shares the spectral features of EC 002, indicating that almost all of these bodies have disappeared, either because they went on to form the building blocks of larger bodies or planets or were simply destroyed.

4.
Biochem Biophys Res Commun ; 684: 149145, 2023 12 03.
Article in English | MEDLINE | ID: mdl-37913587

ABSTRACT

Mechanical stimuli serve as crucial regulators of bone mass, promoting bone formation. However, the molecular mechanisms governing how mesenchymal stem cells (MSCs) respond to mechanical cues during their differentiation into osteogenic cells remain elusive. In this study, we found that cyclic stretching enhances MSC proliferation but does not increase the expression of osteoblast-related genes. We further revealed that this proliferative effect is mediated by fibroblast growth factor 2 (FGF-2), synthesized by MSCs in response to mechanical stress. Cell proliferation induced by cyclic stretching was inhibited upon the addition of either U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK), or early growth response 1 (EGR1)-targeting small-hairpin RNA (shRNA), indicating the involvement of the extracellular signal-regulated kinase (ERK)/EGR1 signaling pathway. Osteoblast differentiation, evaluated through ALP activity, osteoblast-related gene expression, and mineralization, was stimulated by recombinant human FGF-2 (rhFGF-2) when applied during the proliferation phase, but not when applied during the differentiation stage alone. Our results suggest that FGF-2 indirectly promotes osteoblast differentiation as a downstream effect of stimulating cell proliferation. For the first time, we demonstrate that cyclic stretching induces MSCs to produce FGF-2, which in turn encourages cell proliferation through an autocrine/paracrine mechanism, consequently leading to osteoblast differentiation.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Humans , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 2/metabolism , Stress, Mechanical , Cell Differentiation , Cell Proliferation , Osteoblasts/metabolism
5.
Small ; 19(20): e2206893, 2023 May.
Article in English | MEDLINE | ID: mdl-36808827

ABSTRACT

The titanium dioxide (TiO2 ) photocatalyst is only active under UV irradiation due to its wide-gap nature. A novel excitation pathway denoted as interfacial charge transfer (IFCT) has been reported to activate copper(II) oxide nanoclusters-loaded TiO2 powder (Cu(II)/TiO2 ) under visible-light irradiation for only organic decomposition (downhill reaction) so far. Here, the photoelectrochemical study shows that the Cu(II)/TiO2 electrode exhibits a cathodic photoresponse under visible-light and UV irradiation. It originates from H2 evolution on the Cu(II)/TiO2 electrode, while O2 evolution takes place on the anodic side. Based on the concept of IFCT, a direct excitation of electrons from the valence band of TiO2 to Cu(II) clusters initiates the reaction. This is the first demonstration of a direct interfacial excitation-induced cathodic photoresponse for water splitting without any addition of a sacrificial agent. This study is expected to contribute to the development of abundant visible-light-active photocathode materials for fuel production (uphill reaction).

6.
Molecules ; 28(12)2023 Jun 06.
Article in English | MEDLINE | ID: mdl-37375133

ABSTRACT

Conventional hydrogen production, as an alternative energy resource, has relied on fossil fuels to produce hydrogen, releasing CO2 into the atmosphere. Hydrogen production via the dry forming of methane (DRM) process is a lucrative solution to utilize greenhouse gases, such as carbon dioxide and methane, by using them as raw materials in the DRM process. However, there are a few DRM processing issues, with one being the need to operate at a high temperature to gain high conversion of hydrogen, which is energy intensive. In this study, bagasse ash, which contains a high percentage of silicon dioxide, was designed and modified for catalytic support. Modification of silicon dioxide from bagasse ash was utilized as a waste material, and the performance of bagasse ash-derived catalysts interacting with light irradiation and reducing the amount of energy used in the DRM process was explored. The results showed that the performance of 3%Ni/SiO2 bagasse ash WI was higher than that of 3%Ni/SiO2 commercial SiO2 in terms of the hydrogen product yield, with hydrogen generation initiated in the reaction at 300 °C. Using the same synthesis method, the current results suggested that bagasse ash-derived catalysts had better performance than commercial SiO2-derived catalysts when exposed to an Hg-Xe lamp. This indicated that silicon dioxide from bagasse ash as a catalyst support could help improve the hydrogen yield while lowering the temperature in the DRM reaction, resulting in less energy consumption in hydrogen production.

7.
Angew Chem Int Ed Engl ; 62(17): e202300640, 2023 Apr 17.
Article in English | MEDLINE | ID: mdl-36914572

ABSTRACT

An unexplored tin oxide crystal phase (Sn3 O4 ) was experimentally synthesized via a facile hydrothermal method. After tuning the often-neglected parameters for the hydrothermal synthesis, namely the degree of filling of the precursor solution and the gas composition in the reactor head space, an unreported X-ray diffraction pattern was discovered. Through various characterization studies, such as Rietveld analysis, energy dispersive X-ray spectroscopy, and first-principles calculations, this novel material was characterized as orthorhombic mixed-valence tin oxide with the composition SnII 2 SnIV O4 . This orthorhombic tin oxide is a new polymorph of Sn3 O4 , which differs from the reported conventional monoclinic structure. Computational and experimental analyses showed that orthorhombic Sn3 O4 has a smaller band gap (2.0 eV), enabling greater absorption of visible light. This study is expected to improve the accuracy of hydrothermal synthesis and aid the discovery of new oxide materials.

8.
Phys Chem Chem Phys ; 25(1): 255-261, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36477553

ABSTRACT

The trade-off relationship between narrowing the bandgap and achieving sufficient redox potentials accounts for the hindrance to the development of an efficient photocatalyst. Most of the previous researchers attempt to narrow the bandgap of semiconductors by impurity doping to achieve visible-light sensitivity, but this approach causes the losses of their oxidation and/or reduction ability. Conversely, this study presents a bandgap widening strategy by doping to improve the redox potential of photogenerated carriers. Employing first-principles simulations, we propose the lanthanum-doped bismuth vanadate (La-BiVO4) photocatalyst as a wider-bandgap semiconductor exhibiting stronger oxidation ability compared to pristine BiVO4, and the results revealed that the bismuth orbital in the valence band (VB) was diluted by lanthanum-ion doping, while the VB shifted to a higher potential (positively shifted). Thereafter, a La-BiVO4 powder was synthesized via a solid-state reaction, after which its activity was evaluated in the photocatalytic oxidation of 2-propanol (IPA). La-BiVO4 exhibited bandgap widening; thus, the number of absorbed photons under visible-light irradiation was lower than that of pristine BiVO4. However, the quantum efficiency (QE) of La-BiVO4 for the oxidation of IPA was higher than that of the pristine BiVO4. Consequently, the photocatalytic reaction rate of La-BiVO4 was superior to that of pristine BiVO4 under the same visible-light irradiation conditions. Although the bandgap of La-BiVO4 is widened, it is still sensitive to the cyan-light region, which is the strongest in the sunlight spectrum. These results demonstrate that the orbital dilution strategy by impurity elemental doping is effective for bandgap widening and contributes to improving the oxidation and/or reduction ability of the photogenerated charge carriers. This study elucidates the possibility of boosting photocatalytic performances via bandgap widening.

9.
J Card Surg ; 37(12): 5616-5618, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36378943

ABSTRACT

Coronary anatomy is key for arterial switch operations as reimplantation for coronary artery patterns originating from the same sinus is often challenging. We experienced an extremely rare coronary artery anatomy case (Leiden convention: 1 R, 1LCx) and successfully performed an arterial switch operation with coronary button extension and neo-pulmonary trunk realignment maneuver.


Subject(s)
Arterial Switch Operation , Coronary Vessel Anomalies , Transposition of Great Vessels , Humans , Transposition of Great Vessels/surgery , Heart , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/surgery , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Coronary Vessels/anatomy & histology , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessel Anomalies/surgery
10.
Heart Surg Forum ; 25(3): E459-E461, 2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35787747

ABSTRACT

Myxoma is the most common benign cardiac tumor. Absent pulmonary valves, often treated surgically in childhood, are associated with 3-6% of tetralogy of Fallot. It is unusual for absent pulmonary valves without other congenital heart diseases to be asymptomatic until adulthood. Here, we report the unique case of an 80-year-old female with right ventricular outflow tract myxoma and absent pulmonary valve that has, to our knowledge, never been reported. We successfully performed a simple mass resection and pulmonary valve implantation.


Subject(s)
Myxoma , Pulmonary Atresia , Pulmonary Valve , Tetralogy of Fallot , Adult , Aged, 80 and over , Female , Humans , Myxoma/complications , Myxoma/diagnosis , Myxoma/surgery , Pulmonary Valve/abnormalities , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Tetralogy of Fallot/diagnosis , Tetralogy of Fallot/surgery , Treatment Outcome
11.
J Bone Miner Metab ; 39(5): 737-747, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33830351

ABSTRACT

BACKGROUND: Bisphosphonate and denosumab are widely used for the treatment of osteoporosis and bone metastasis of cancer to prevent excessive bone resorption. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate or denosumab referred to as bisphosphonate-related osteonecrosis of the jaw (BRONJ) or denosumab-related osteonecrosis of the jaw (DRONJ), respectively. Since bisphosphonate and denosumab inhibit bone resorption by different mechanism, we evaluated whether these drug types result in different histopathological characteristics related to bone resorption. MATERIALS AND METHODS: We histopathologically investigated 10 cases of BRONJ, DRONJ, and suppurative osteomyelitis. Paraffin sections prepared from decalcified dissected jaw bones were used for histopathological observation, second harmonic generation imaging, and bone histomorphometry. The samples were also observed by a scanning electron microscope. RESULTS: Numerous bone resorption lacunae were observed on the necrotic bone surface in almost all cases of BRONJ; however, such resorption lacunae were limited in DRONJ and suppurative osteomyelitis. Prominent bone resorption lacunae were also confirmed by second harmonic generation imaging and scanning electron microscopy in BRONJ, but not in DRONJ or suppurative osteomyelitis. As determined by bone histomorphometry, the number of bone resorption lacunae and the length of the erosion surface of resorption lacunae were significantly higher in BRONJ group than in the DRONJ and suppurative osteomyelitis groups. These parameters were correlated between the necrotic bones and the vital bones in BRONJ. CONCLUSIONS: Persistent bone resorption lacunae on the necrotic bone surface are unique to BRONJ, providing a basis for distinguishing BRONJ from DRONJ and OM in histopathological diagnosis.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Bone Neoplasms , Bone Resorption , Osteonecrosis , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging , Bone Density Conservation Agents/adverse effects , Denosumab/adverse effects , Diphosphonates , Humans , Osteonecrosis/chemically induced , Osteonecrosis/diagnostic imaging
12.
Appl Microbiol Biotechnol ; 105(16-17): 6173-6181, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34402937

ABSTRACT

Corynebacterium glutamicum, a gram-positive and facultative anaerobic bacterium, is widely used for the industrial production of amino acids, such as L-glutamate and L-lysine. C. glutamicum grows and produces amino acids under aerobic conditions. When restricted under anaerobic conditions, it produces organic acids, such as L-lactate and succinate, through metabolic shift. With the increasing threat of global warming, these organic acids have drawn considerable attention as bio-based plastic monomers. In addition to the organic acids, the anaerobic bioprocess is also used to produce other value-added compounds, including isobutanol, ethanol, 3-methyl-1-butanol, 2,3-butanediol, L-alanine, and L-valine. Therefore, C. glutamicum is now a versatile cell factory for producing a wide variety of useful chemicals under both aerobic and anaerobic conditions. The growth and metabolism of the bacterium depend on the oxygen levels, which modulate the rearrangement of the carbon flux by reprogramming gene expression patterns and intracellular redox states. Anaerobic cell growth and L-lysine production as well as aerobic succinate production have been demonstrated by engineering the metabolic pathways or supplying a terminal electron acceptor instead of oxygen. In this review, we discuss the physiological and metabolic changes in C. glutamicum associated with its application as a cell factory under different oxygen states. Physiological switching in bacteria is initiated with the sensing of oxygen availability. While such a sensor has not been identified in C. glutamicum yet, the molecular mechanism for oxygen sensing in related bacteria is also discussed. KEY POINTS: • C. glutamicum produces a wide variety of useful compounds under anaerobic conditions. • C. glutamicum is a versatile cell factory under both aerobic and anaerobic conditions. • Metabolic fate can be overcome by engineering metabolic pathways.


Subject(s)
Corynebacterium glutamicum , Anaerobiosis , Base Composition , Corynebacterium glutamicum/genetics , Metabolic Engineering , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA
13.
Proc Natl Acad Sci U S A ; 115(29): 7497-7502, 2018 07 17.
Article in English | MEDLINE | ID: mdl-29967181

ABSTRACT

Calcium-aluminum-rich inclusions (CAIs) and amoeboid olivine aggregates (AOAs), a refractory component of chondritic meteorites, formed in a high-temperature region of the protoplanetary disk characterized by approximately solar chemical and oxygen isotopic (Δ17O ∼ -24‰) compositions, most likely near the protosun. Here we describe a 16O-rich (Δ17O ∼ -22 ± 2‰) AOA from the carbonaceous Renazzo-type (CR) chondrite Yamato-793261 containing both (i) an ultrarefractory CAI and (ii) forsterite, low-Ca pyroxene, and silica, indicating formation by gas-solid reactions over a wide temperature range from ∼1,800 to ∼1,150 K. This AOA provides direct evidence for gas-solid condensation of silica in a CAI/AOA-forming region. In a gas of solar composition, the Mg/Si ratio exceeds 1, and, therefore, silica is not predicted to condense under equilibrium conditions, suggesting that the AOA formed in a parcel of gas with fractionated Mg/Si ratio, most likely due to condensation of forsterite grains. Thermodynamic modeling suggests that silica formed by condensation of nebular gas depleted by ∼10× in H and He that cooled at 50 K/hour at total pressure of 10-4 bar. Condensation of silica from a hot, chemically fractionated gas could explain the origin of silica identified from infrared spectroscopy of remote protostellar disks.

14.
Acta Med Okayama ; 75(2): 115-123, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33953417

ABSTRACT

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited.


Subject(s)
Angiogenesis Inhibitors/adverse effects , Dentists/statistics & numerical data , Health Knowledge, Attitudes, Practice , Immunosuppressive Agents/adverse effects , Oral Surgical Procedures , Postoperative Complications/etiology , Humans , Japan , Surveys and Questionnaires
15.
Bull Tokyo Dent Coll ; 62(3): 171-180, 2021 Sep 08.
Article in English | MEDLINE | ID: mdl-34393144

ABSTRACT

Bone marrow is the principal site of hematopoiesis in mammals. Amphibians were the first phylogenetic group in vertebrates to acquire bone marrow, but the distribution of hematopoietic cells in the bone marrow of the primitive frog, Xenopus laevis (X. laevis) has not been well documented. The purpose of this study was to perform a histological investigation of the distribution of hematopoietic cells in femoral bone marrow at various stages of development in X. laevis. Hematopoietic cells showed preferential distribution on the endosteal surface of cortical bone throughout all stages of development, from tadpole to aged frog. In mature frogs, hematopoietic cells appeared at the boundary between the epiphysis and the bone marrow. The distribution of hematopoietic cells around the blood vessels was limited to a small number of vessels in the bone marrow. Abundant adipose tissue was observed in the bone marrow cavity from the tadpole stage to the mature frog stage. Hematopoietic cells showed preferential distribution in a belt-like fashion on the surface of newly-formed bones in a bone regeneration model in the diaphysis of X. laevis. These results indicate that the distribution of hematopoietic cells in bone marrow in X. laevis differs from that in mammals, and that the bone marrow of X. laevis constitutes a useful model for exploring the mechanism underlying the phylogenetic differentiation of bone marrow hematopoiesis.


Subject(s)
Bone Marrow , Hematopoietic Stem Cell Transplantation , Animals , Hematopoiesis , Phylogeny , Xenopus laevis
16.
J Am Chem Soc ; 142(39): 16513-16517, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-32623880

ABSTRACT

Two-dimensional metal-organic frameworks (2D MOFs) have attracted much attention, as they are the crystalline materials that exhibit both conductivity and microporosity. Numerous efforts have been made to advance their application as chemiresistive sensors or electrochemical capacitors. However, the intrinsic physical properties and spin states of these materials remain poorly understood. Most of these 2D MOFs possess a honeycomb lattice, with a Kagomé lattice arrangement of metal cations. These structural characteristics suggest that these MOFs would be candidates for geometrically frustrated spin systems with unprecedented magnetic phenomena. Herein, by performing magnetic susceptibility and specific heat measurements at an ultralow temperature down to 38mK on a 2D semiconductive MOF, Cu3(HHTP)2, a quantum spin liquid state that arises from the geometrical frustration was suggested. This result illustrates the potential of strongly correlated MOFs as systems with emergent phenomena induced by unusual structural topologies.

17.
Biochem Biophys Res Commun ; 524(3): 702-709, 2020 04 09.
Article in English | MEDLINE | ID: mdl-32035618

ABSTRACT

Tissue-nonspecific alkaline phosphatase (TNAP) is expressed in the calcification sites of the skeletal tissue. It promotes hydroxyapatite crystal formation by degrading inorganic pyrophosphate (PPi) and increasing inorganic phosphate (Pi) concentration. However, abnormalities in Alpl-/- mouse-derived osteoblasts are poorly understood, and the involvement of TNAP in osteoblast differentiation remains unclear. Therefore, in this study, we aimed to investigate the precise role of TNAP in osteoblast differentiation. TNAP inhibition by levamisole, a reversible TNAP inhibitor, suppressed the expression of osteoblast differentiation marker genes in wild-type osteoblastic cells. Alpl overexpression increased the expression of master osteoblast transcription factor genes runt-related transcription factor 2 (Runx2) and Sp7 and the mature osteoblast and osteocyte marker genes, bone γ-carboxyglutamate protein 2 (Bglap2) and dentin matrix protein 1 (Dmp1), respectively in Alpl-deficient osteoblastic cells. TNAP regulated Runx2 expression, which in turn regulated the expression of all other osteoblast markers, except Dmp1. Dmp1 expression was independent of RUNX2 but was dependent on extracellular Pi concentration in Runx2-deficient osteogenic cells. These results suggest that TNAP functions as an osteogenic differentiation regulator either by regulating Runx2 expression or by controlling extracellular Pi concentration.


Subject(s)
Alkaline Phosphatase/metabolism , Cell Differentiation , Osteogenesis , Stem Cells/cytology , Stem Cells/metabolism , Animals , Cell Differentiation/drug effects , Core Binding Factor Alpha 1 Subunit/metabolism , Dura Mater/cytology , Extracellular Matrix Proteins/metabolism , Levamisole/pharmacology , Mice, Inbred C57BL , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Phosphates/pharmacology , Skull/cytology
18.
Calcif Tissue Int ; 106(6): 665-677, 2020 06.
Article in English | MEDLINE | ID: mdl-32076747

ABSTRACT

Hypophosphatasia (HPP) is a systemic skeletal disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). We recently reported that survival of HPP model mice can be prolonged using an adeno-associated virus (AAV) vector expressing bone-targeted TNALP with deca-aspartate at the C terminus (TNALP-D10); however, abnormal bone structure and hypomineralization remained in the treated mice. Here, to develop a more effective and clinically applicable approach, we assessed whether transfection with TNALP-D10 expressing virus vector at a higher dose than previously used would ameliorate bone structure defects. We constructed a self-complementary AAV8 vector expressing TNALP driven by the chicken beta-actin (CBA) promoter (scAAV8-CB-TNALP-D10). The vector was injected into both quadriceps femoris muscles of newborn HPP mice at a dose of 4.5 × 1012 vector genome (v.g.)/body, resulting in 20 U/mL of serum ALP activity. The 4.5 × 1012 v.g./body-treated HPP mice grew normally and displayed improved bone structure at the knee joints in X-ray images. Micro-CT analysis showed normal trabecular bone structure and mineralization. The mechanical properties of the femur were also recovered. Histological analysis of the femurs demonstrated that ALP replacement levels were sufficient to promote normal, growth plate cartilage arrangement. These results suggest that AAV vector-mediated high-dose TNALP-D10 therapy is a promising option for improving the quality of life (QOL) of patients with the infantile form of HPP.


Subject(s)
Alkaline Phosphatase/genetics , Cancellous Bone/pathology , Hypophosphatasia/therapy , Animals , Dependovirus , Disease Models, Animal , Genetic Therapy , Genetic Vectors , Mice , Quality of Life
19.
J Periodontal Res ; 55(5): 734-743, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32583900

ABSTRACT

BACKGROUND/OBJECTIVES: PTH plays an important role in bone remodeling, and different actions have been reported depending on its administration method. iPSCs are promising as a cell source for regeneration of periodontal tissue due to their ability of proliferation and pluripotency. However, the effects of PTH on iPSCs remain mostly unknown. The purpose of this study was to investigate in vitro effects of parathyroid hormone (PTH) on osteoblastic differentiation of induced pluripotent stem cells (iPSCs) in a 3D culture model. MATERIALS AND METHODS: Following embryoid body (EB) induction from mouse iPSCs (miPSCs), dissociated cells (miPS-EB-derived cells) were seeded onto atelocollagen sponge (ACS) in osteoblast differentiation medium (OBM). Cell-ACS constructs were divided into three groups: continuous treatment with human recombinant PTH (1-34) (PTH-C), intermittent PTH treatment (PTH-I) or OBM control. To confirm the expression of PTH receptor-1(PTH1R), the expression of Pth1r and cAMP production over time were assessed. Real-time PCR was used to assess the expression of genes encoding osterix (Sp7), runt-related transcription factor 2 (Runx2), collagen type 1 (Col1a1), and osteocalcin (Bglap) at different time points. Mineralization was assessed by von Kossa staining. Histochemical staining was used to analyze alkaline phosphatase (ALP) activity, and immunolocalization of SP7 and BGLAP was analyzed by confocal laser scanning microscopy (CLSM). RESULTS: On days 7 and 14, expression of the Pth1r in miPS-EB-derived cells was increased in all groups. Production of cAMP, the second messenger of the PTH1R, tended to increase in the PTH-I group compared with PTH-C group on day 14. Expression of Col1a1 in the PTH-I group on day 14 was significantly higher than other groups. There was a time-dependent increase in the expression of Sp7 in all groups. On day 14, the expression level of Sp7 in the PTH-I group was significantly higher than other groups. In von Kossa staining, the PTH-I group showed higher level of staining compared with other groups on day 14, whereas the level was slightly attenuated in the PTH-C group. In histochemical staining, ALP-positive cells were significantly increased in the PTH-I group compared with other groups on day 14. In CLSM analysis, the numbers of SP7- and BGLAP-positive cells showed a gradual increase over time, and on day 14, a significantly greater SP7 expression was observed in the PTH-I group than other groups. CONCLUSION: These results suggested that the intermittent PTH treatment promotes osteoblastic differentiation and mineralization of miPSCs in the ACS scaffold.


Subject(s)
Induced Pluripotent Stem Cells , Osteoblasts , Parathyroid Hormone , Alkaline Phosphatase , Animals , Cell Differentiation , Humans , Mice , Osteoblasts/physiology , Receptor, Parathyroid Hormone, Type 1/genetics
20.
J Infect Chemother ; 26(9): 882-889, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32591324

ABSTRACT

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteria, Anaerobic , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Clindamycin/pharmacology , Clindamycin/therapeutic use , Drug Resistance, Bacterial , Humans , Japan/epidemiology , Microbial Sensitivity Tests , Penicillins
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