Kaempferia parviflora extract and its component polymethoxyflavones suppress adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via the AMPK pathway.

BACKGROUND: Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). METHODS AND RESULTS: KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0-3) but not during the mid (days 3-7) or late (days 7-14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. CONCLUSIONS: Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.

Primordial aqueous alteration recorded in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu.

We report primordial aqueous alteration signatures in water-soluble organic molecules from the carbonaceous asteroid (162173) Ryugu by the Hayabusa2 spacecraft of JAXA. Newly identified low-molecular-weight hydroxy acids (HO-R-COOH) and dicarboxylic acids (HOOC-R-COOH), such as glycolic acid, lactic acid, glyceric acid, oxalic acid, and succinic acid, are predominant in samples from the two touchdown locations at Ryugu. The quantitative and qualitative profiles for the hydrophilic molecules between the two sampling locations shows similar trends within the order of ppb (parts per billion) to ppm (parts per million). A wide variety of structural isomers, including α- and ß-hydroxy acids, are observed among the hydrophilic molecules. We also identify pyruvic acid and dihydroxy and tricarboxylic acids, which are biochemically important intermediates relevant to molecular evolution, such as the primordial TCA (tricarboxylic acid) cycle. Here, we find evidence that the asteroid Ryugu samples underwent substantial aqueous alteration, as revealed by the presence of malonic acid during keto-enol tautomerism in the dicarboxylic acid profile. The comprehensive data suggest the presence of a series for water-soluble organic molecules in the regolith of Ryugu and evidence of signatures in coevolutionary aqueous alteration between water and organics in this carbonaceous asteroid.

Effects of various prosthetic methods for patients with Kennedy Class I partial edentulism on oral hypofunction, subjective symptoms, and oral health-related quality of life.

PURPOSE: This propensity score matching, multicenter, cross-sectional study was performed to examine the effects of various prosthetic methods for dental clinic outpatients with Kennedy Class I partial edentulism (KCIPE) on oral hypofunction, subjective frailty symptoms, and oral health-related quality of life (QOL). METHODS: Patients (n = 348) were classified into the following three groups for analysis: NT, patients with natural dentition providing intermaxillary contact in four occlusal supporting zones; RPD, patients with KCIPE who received removable partial dentures; and ISFP, patients with KCIPE who received implant-supported fixed prostheses. Participants' basic characteristics were recorded, and oral function tests were conducted. Subjective symptoms of physical and oral frailty were investigated via questionnaire. Oral health-related QOL was assessed using the Japanese short version of the Oral Health Impact Profile (OHIP-JP16). Propensity score matching was performed to adjust for patient background factors that could influence oral hypofunction in each group. RESULTS: Compared with the ISFP group, the RPD group had significantly higher rates of poor oral hygiene, reduced occlusal force, decreased masticatory function, and declines in swallowing function and oral hypofunction; the odds ratio for oral hypofunction was 4.67. Compared with the ISFP group, the RPD group had significantly greater subjective symptoms of physical frailty and oral frailty, as well as higher OHIP scores. CONCLUSIONS: Prosthetic treatment of KCIPE affected oral hypofunction, subjective frailty symptoms, and oral health-related QOL in dental clinic outpatients.

Nonmagnetic framboid and associated iron nanoparticles with a space-weathered feature from asteroid Ryugu.

Extraterrestrial minerals on the surface of airless Solar System bodies undergo gradual alteration processes known as space weathering over long periods of time. The signatures of space weathering help us understand the phenomena occurring in the Solar System. However, meteorites rarely retain the signatures, making it impossible to study the space weathering processes precisely. Here, we examine samples retrieved from the asteroid Ryugu by the Hayabusa2 spacecraft and discover the presence of nonmagnetic framboids through electron holography measurements that can visualize magnetic flux. Magnetite particles, which normally provide a record of the nebular magnetic field, have lost their magnetic properties by reduction via a high-velocity (>5 km s-1) impact of a micrometeoroid with a diameter ranging from 2 to 20 µm after destruction of the parent body of Ryugu. Around these particles, thousands of metallic-iron nanoparticles with a vortex magnetic domain structure, which could have recorded a magnetic field in the impact event, are found. Through measuring the remanent magnetization of the iron nanoparticles, future studies are expected to elucidate the nature of the nebular/interplanetary magnetic fields after the termination of aqueous alteration in an asteroid.

DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES.

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

Effect of soft denture liners on complete denture treatments: A systematic review.

PURPOSE: This systematic review examined the effectiveness of soft denture relining (SDR) materials. STUDY SELECTION: A comprehensive search of MEDLINE, Cochrane Library, and ICHUSHI was conducted up to July 26, 2020. Target outcomes were patient satisfaction, oral health-related quality of life (OHRQOL), masticatory ability (MA), denture functional duration, residual ridge resorption (RRR), and microbial contamination. An organization specializing in literature searches performed the reference searches, and two reviewers independently selected the literature sources, extracted the data, and assessed the risk of bias. The reviewers resolved any disagreements concerning the assortment of literature sources through discussion. SDR included acrylic- and silicone-based materials, which were evaluated separately. RESULTS: Reviewers selected 7, 5, 11, 1, 4, and 6 studies to assess patient satisfaction, OHRQOL, MA, functional duration, RRR, and microbial contamination, respectively. The results confirmed that SDR improved patient satisfaction, OHRQOL, MA, and RRR. However, the functional duration of SDR material is shorter than that of hard denture relining (HDR) or acrylic resin material. Furthermore, SDR material is more susceptible to microbial contamination in the long term. The risk of bias for the included studies tended to be high because of specific issues (difficulty in blinding SDR versus HDR). CONCLUSIONS: For patients who wear complete dentures, SDR often provides beneficial outcomes such as pain reduction and recovery from MA. However, caution should be exercised regarding their use owing to insufficient functional duration and the possibility of microbial contamination during long-term use.

Genome-wide mapping and cryo-EM structural analyses of the overlapping tri-nucleosome composed of hexasome-hexasome-octasome moieties.

The nucleosome is a fundamental unit of chromatin in which about 150 base pairs of DNA are wrapped around a histone octamer. The overlapping di-nucleosome has been proposed as a product of chromatin remodeling around the transcription start site, and previously found as a chromatin unit, in which about 250 base pairs of DNA continuously bind to the histone core composed of a hexamer and an octamer. In the present study, our genome-wide analysis of human cells suggests another higher nucleosome stacking structure, the overlapping tri-nucleosome, which wraps about 300-350 base-pairs of DNA in the region downstream of certain transcription start sites of actively transcribed genes. We determine the cryo-electron microscopy (cryo-EM) structure of the overlapping tri-nucleosome, in which three subnucleosome moieties, hexasome, hexasome, and octasome, are associated by short connecting DNA segments. Small angle X-ray scattering and coarse-grained molecular dynamics simulation analyses reveal that the cryo-EM structure of the overlapping tri-nucleosome may reflect its structure in solution. Our findings suggest that nucleosome stacking structures composed of hexasome and octasome moieties may be formed by nucleosome remodeling factors around transcription start sites for gene regulation.

Microstructural and chemical features of impact melts on Ryugu particle surfaces: Records of interplanetary dust hit on asteroid Ryugu.

The Hayabusa2 spacecraft delivered samples of the carbonaceous asteroid Ryugu to Earth. Some of the sample particles show evidence of micrometeoroid impacts, which occurred on the asteroid surface. Among those, particles A0067 and A0094 have flat surfaces on which a large number of microcraters and impact melt splashes are observed. Two impact melt splashes and one microcrater were analyzed to unveil the nature of the objects that impacted the asteroid surface. The melt splashes consist mainly of Mg-Fe-rich glassy silicates and Fe-Ni sulfides. The microcrater trapped an impact melt consisting mainly of Mg-Fe-rich glassy silicate, Fe-Ni sulfides, and minor silica-rich glass. These impact melts show a single compositional trend indicating mixing of Ryugu surface materials and impactors having chondritic chemical compositions. The relict impactor in one of the melt splashes shows mineralogical similarity with anhydrous chondritic interplanetary dust particles having a probable cometary origin. The chondritic micrometeoroids probably impacted the Ryugu surface during its residence in a near-Earth orbit.

Feasibility and perceptions of a benzodiazepine deprescribing quality improvement initiative for primary care providers in Japan.

BACKGROUND: Quality improvement (QI) initiatives in primary care in Japan are rare. One crucial area for QI is the appropriate prescription of benzodiazepines due to the large and growing elderly population in the country. OBJECTIVE: This study aimed to determine the feasibility and other perceptions of a Benzodiazepine receptor agonist medications (BZRAs) deprescribing QI initiative for primary care providers (PCPs) in Japanese primary care clinics. DESIGN: A qualitative study within a QI initiative. PARTICIPANTS: We recruited 11 semi-public clinics and 13 providers in Japan to participate in a BZRAs deprescribing initiative from 2020 to 2021. After stratifying the clinics according to size, we randomly allocated implementation clinics to either an Audit only or an Audit plus Coaching group. INTERVENTIONS: For the Audit, we presented clinics with two BZRAs-related indicators. We provided monthly web-based meetings for the Coaching to support their QI activities. APPROACH: After the nine-month initiative, we conducted semi-structured interviews and used content analysis to identify themes. We organized the themes and assessed the key factors of implementation using the Consolidated Framework for Implementation Research (CFIR) framework. KEY RESULTS: Audit plus Coaching was perceived as more valuable than Audit only intervention. Participants expressed intellectual curiosity about the QI initiative from resources outside their clinic. However, adopting a team-based QI approach in a small clinic was perceived as challenging, and selecting the indicators was important for meaningful QI. CONCLUSION: The small size of the clinic could be a potential barrier, but enhancing academic curiosity may facilitate QI initiatives in primary care in Japan. Further implementation trials are needed to evaluate the possibility of QI with more various indicators and a more extended period of time.

Effect of denture adhesives on masticatory performance: Multicenter randomized controlled trial.

PURPOSE: The purpose of this study is to investigate the effects of denture adhesives on masticatory performance via a 10-center, parallel, randomized, controlled trial of complete denture wearers in Japan. METHODS: The trial was conducted between September 2013 and October 2016. The inclusion criteria were complete edentulism, willingness to undergo new complete denture treatment, and willingness to return for recall treatment. The exclusion criteria were age 90 years or older, presence of severe systemic illness, inability to understand the questionnaires, wearing metal base complete dentures, denture adhesive user, wearing prosthetics for maxillofacial defects, wearing complete dentures with tissue conditioners, and severe xerostomia. Randomization of the powder-type denture adhesive (powder), cream-type denture adhesive (cream), and control (saline) groups was performed using a sealed envelope system. Masticatory performance was measured using color-changeable chewing gum. Intervention blinding was not feasible. RESULTS: Sixty-seven control, 69 powder, and 64 cream participants are analyzed using the intention-to-treat principle. The participants in all groups show significantly improved masticatory performance at post-intervention (paired t-test with Bonferroni correction P < 0.0001). However, no significant difference in masticatory performance is detected among the three groups (one-way analysis of variance). A significant negative correlation between pre- and post-changes in masticatory performance and intraoral condition scores is observed (Pearson's correlation coefficient, P < 0.0001). CONCLUSIONS: Although denture adhesives improved the masticatory performance of complete denture wearers, their clinical effects are comparable to those of saline solution. The use of denture adhesives is more effective in complete denture wearers with unsatisfactory intraoral conditions.

Reassigning CI chondrite parent bodies based on reflectance spectroscopy of samples from carbonaceous asteroid Ryugu and meteorites.

The carbonaceous asteroid Ryugu has been explored by the Hayabusa2 spacecraft to elucidate the actual nature of hydrous asteroids. Laboratory analyses revealed that the samples from Ryugu are comparable to unheated CI carbonaceous chondrites; however, reflectance spectra of Ryugu samples and CIs do not coincide. Here, we demonstrate that Ryugu sample spectra are reproduced by heating Orgueil CI chondrite at 300°C under reducing conditions, which caused dehydration of terrestrial weathering products and reduction of iron in phyllosilicates. Terrestrial weathering of CIs accounts for the spectral differences between Ryugu sample and CIs, which is more severe than space weathering that likely explains those between asteroid Ryugu and the collected samples. Previous assignments of CI chondrite parent bodies, i.e., chemically most primitive objects in the solar system, are based on the spectra of CI chondrites. This study indicates that actual spectra of CI parent bodies are much darker and flatter at ultraviolet to visible wavelengths than the spectra of CI chondrites.

Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium.

Polycyclic aromatic hydrocarbons (PAHs) contain ≲20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures ≳1000 kelvin), by reactions within cold (~10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-13C substituted compositions (Δ2×13C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51‰ higher than values expected for a stochastic distribution of isotopes. The Δ2×13C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Δ2×13C values consistent with formation by higher-temperature reactions.

Soluble organic matter Molecular atlas of Ryugu reveals cold hydrothermalism on C-type asteroid parent body.

The sample from the near-Earth carbonaceous asteroid (162173) Ryugu is analyzed in the context of carbonaceous meteorites soluble organic matter. The analysis of soluble molecules of samples collected by the Hayabusa2 spacecraft shines light on an extremely high molecular diversity on the C-type asteroid. Sequential solvent extracts of increasing polarity of Ryugu samples are analyzed using mass spectrometry with complementary ionization methods and structural information confirmed by nuclear magnetic resonance spectroscopy. Here we show a continuum in the molecular size and polarity, and no organomagnesium molecules are detected, reflecting a low temperature and water-rich environment on the parent body approving earlier mineralogical and chemical data. High abundance of sulfidic and nitrogen rich compounds as well as high abundance of ammonium ions confirm the water processing. Polycyclic aromatic hydrocarbons are also detected in a structural continuum of carbon saturations and oxidations, implying multiple origins of the observed organic complexity, thus involving generic processes such as earlier carbonization and serpentinization with successive low temperature aqueous alteration.

Chemical evolution of primordial salts and organic sulfur molecules in the asteroid 162173 Ryugu.

Samples from the carbonaceous asteroid (162173) Ryugu provide information on the chemical evolution of organic molecules in the early solar system. Here we show the element partitioning of the major component ions by sequential extractions of salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition of the primitive asteroid. Sodium is the dominant electrolyte of the salt fraction extract. Anions and NH4+ are more abundant in the salt fraction than in the carbonate and phyllosilicate fractions, with molar concentrations in the order SO42- > Cl- > S2O32- > NO3- > NH4+. The salt fraction extracts contain anionic soluble sulfur-bearing species such as Sn-polythionic acids (n < 6), Cn-alkylsulfonates, alkylthiosulfonates, hydroxyalkylsulfonates, and hydroxyalkylthiosulfonates (n < 7). The sulfur-bearing soluble compounds may have driven the molecular evolution of prebiotic organic material transforming simple organic molecules into hydrophilic, amphiphilic, and refractory S allotropes.

Visualization of nanoscale magnetic domain states in the asteroid Ryugu.

In the samples collected from the asteroid Ryugu, magnetite displays natural remanent magnetization due to nebular magnetic field, whereas contemporaneously grown iron sulfide does not display stable remanent magnetization. To clarify this counterintuitive feature, we observed their nanoscale magnetic domain structures using electron holography and found that framboidal magnetites have an external magnetic field of 300 A m-1, similar to the bulk value, and its magnetic stability was enhanced by interactions with neighboring magnetites, permitting a disk magnetic field to be recorded. Micrometer-sized pyrrhotite showed a multidomain magnetic structure that was unable to retain natural remanent magnetization over a long time due to short relaxation time of magnetic-domain-wall movement, whereas submicron-sized sulfides formed a nonmagnetic phase. These results show that both magnetite and sulfide could have formed simultaneously during the aqueous alteration in the parent body of the asteroid Ryugu.

Role of reactive oxygen species (ROS) in the regulation of adipogenic differentiation of human maxillary/mandibular bone marrow-derived mesenchymal stem cells.

BACKGROUND: Maxillary/mandibular bone marrow-derived mesenchymal stem cells (MBMSCs) exhibit a unique property of lower adipogenic potential than other bone marrow-derived MSCs. However, the molecular mechanisms regulating the adipogenesis of MBMSCs remain unclear. This study aimed to explore the roles of mitochondrial function and reactive oxygen species (ROS) in regulating the adipogenesis of MBMSCs. METHODS AND RESULTS: MBMSCs exhibited significantly lower lipid droplet formation than iliac BMSCs (IBMSCs). Moreover, the expression levels of CCAAT/enhancer-binding protein ß (C/EBPß), C/EBPδ, and early B cell factor 1 (Ebf-1), which are early adipogenic transcription factors, and those of peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which are late adipogenic transcription factors, were downregulated in MBMSCs compared to those in IBMSCs. Adipogenic induction increased the mitochondrial membrane potential and mitochondrial biogenesis in MBMSCs and IBMSCs, with no significant difference between the two cell types; however, intracellular ROS production was significantly enhanced only in IBMSCs. Furthermore, NAD(P)H oxidase 4 (NOX4) expression was significantly lower in MBMSCs than in IBMSCs. Increased ROS production in MBMSCs by NOX4 overexpression or treatment with menadione promoted the expression of early adipogenic transcription factors but did not induce that of late adipogenic transcription factors or lipid droplet accumulation. CONCLUSIONS: These results suggest that ROS may be partially involved in the process of MBMSC adipogenic differentiation from undifferentiated cells to immature adipocytes. This study provides important insights into the tissue-specific properties of MBMSCs.

Uracil in the carbonaceous asteroid (162173) Ryugu.

The pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft enabled us to analyze the pristine extraterrestrial material without uncontrolled exposure to the Earth's atmosphere and biosphere. The initial analysis team for the soluble organic matter reported the detection of wide variety of organic molecules including racemic amino acids in the Ryugu samples. Here we report the detection of uracil, one of the four nucleobases in ribonucleic acid, in aqueous extracts from Ryugu samples. In addition, nicotinic acid (niacin, a B3 vitamer), its derivatives, and imidazoles were detected in search for nitrogen heterocyclic molecules. The observed difference in the concentration of uracil between A0106 and C0107 may be related to the possible differences in the degree of alteration induced by energetic particles such as ultraviolet photons and cosmic rays. The present study strongly suggests that such molecules of prebiotic interest commonly formed in carbonaceous asteroids including Ryugu and were delivered to the early Earth.

Insights into the formation and evolution of extraterrestrial amino acids from the asteroid Ryugu.

All life on Earth contains amino acids and carbonaceous chondrite meteorites have been suggested as their source at the origin of life on Earth. While many meteoritic amino acids are considered indigenous, deciphering the extent of terrestrial contamination remains an issue. The Ryugu asteroid fragments (JAXA Hayabusa2 mission), represent the most uncontaminated primitive extraterrestrial material available. Here, the concentrations of amino acids from two particles from different touchdown sites (TD1 and TD2) are reported. The concentrations show that N,N-dimethylglycine (DMG) is the most abundant amino acid in the TD1 particle, but below detection limit in the other. The TD1 particle mineral components indicate it experienced more aqueous alteration. Furthermore, the relationships between the amino acids and the geochemistry suggest that DMG formed on the Ryugu progenitor body during aqueous alteration. The findings highlight the importance of aqueous chemistry for defining the ultimate concentrations of amino acids in primitive extraterrestrial samples.

Effects of denture adhesives on denture retention and occlusal forces in complete denture wearers: A multicenter, randomized controlled trial.

PURPOSE: This study aimed to determine the effects of denture adhesives on denture retention and occlusal force in complete denture wearers in a multicenter, randomized, parallel-group controlled trial. METHODS: Two hundred edentulous patients wearing complete dentures were allocated to three groups: powder-type denture adhesive, cream-type denture adhesive, and control (saline solution). Denture adhesives and saline solution were applied to the dentures for 4 days. The retentive force of the dentures and occlusal force were measured using a force transducer occlusal force meter at baseline and after 4 days of intervention. In addition to between-group comparisons, subgroup analyses of denture retention and occlusal force were performed based on the level of difficulty of the edentulism treatment. The levels were ranked as I (easy), II, III, and IV (difficult). RESULTS: Cream-type denture adhesives significantly improved the retentive force of the dentures (P<0.01) and occlusal force (P<0.05), with no significant differences between baseline and post-intervention forces in the powder-type denture adhesive and control groups. In within-group comparisons, cream-type denture adhesives improved both the retentive and occlusal forces at Level II (P<0.05), and powder-type denture adhesives improved the occlusal force at Level II (P<0.01). CONCLUSIONS: Application of cream-type denture adhesives effectively improves the denture retention and occlusal force in complete denture wearers with a moderate degree of difficulty during edentulism treatment.