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1.
Nanoscale ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860292

RESUMO

Efficient and environmentally friendly synthesis of silanols is a crucial issue across the broad fields of academic and industrial chemistry. Herein, we describe the dehydrogenative oxidation of hydrosilane using a gold nanoparticle catalyst supported by fibrillated citric acid-modified cellulose (F-CAC). Au:F-CAC catalysts with various particle sizes (1.7 nm, 4.9 nm, and 7.7 nm) were prepared using the trans-deposition method, a technique previously reported by our group. These catalysts exhibited significant catalytic activity to produce silanols with high turnover frequency (TOF) of up to 7028 h-1. Recycling experiments and transmission electron microscopy (TEM) observation represented the high durability of Au:F-CAC under the reaction conditions, allowing kinetic studies on size dependency. Mechanistic studies were conducted, including isotope labelling experiments, kinetics, and various spectroscopies. Notably, the near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) of the model catalyst (Au:PVP) revealed the formation of catalytically active cationic Au sites on the surface through the adsorption of molecular oxygen, providing a new insight into the reaction mechanism.

2.
Cell Stem Cell ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38772377

RESUMO

Aging generally predisposes stem cells to functional decline, impairing tissue homeostasis. Here, we report that hematopoietic stem cells (HSCs) acquire metabolic resilience that promotes cell survival. High-resolution real-time ATP analysis with glucose tracing and metabolic flux analysis revealed that old HSCs reprogram their metabolism to activate the pentose phosphate pathway (PPP), becoming more resistant to oxidative stress and less dependent on glycolytic ATP production at steady state. As a result, old HSCs can survive without glycolysis, adapting to the physiological cytokine environment in bone marrow. Mechanistically, old HSCs enhance mitochondrial complex II metabolism during stress to promote ATP production. Furthermore, increased succinate dehydrogenase assembly factor 1 (SDHAF1) in old HSCs, induced by physiological low-concentration thrombopoietin (TPO) exposure, enables rapid mitochondrial ATP production upon metabolic stress, thereby improving survival. This study provides insight into the acquisition of resilience through metabolic reprogramming in old HSCs and its molecular basis to ameliorate age-related hematopoietic abnormalities.

3.
Geriatr Gerontol Int ; 24 Suppl 1: 44-48, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37837183

RESUMO

Aging shows biologically complex features with high individual variability, which reflects the exposure to several stimuli and the adaptation to them. Among them, metabolic changes are well observed as consequences or possible causes of aging. Calorie restriction extends organismal life span in experimental models. Several metabolites; for example, resveratrol or nicotinamide mononucleotide, are reported to mimic calorie restriction effects in vivo. Metabolomic research would be useful to evaluate metabolites as biomarkers in aging-relevant events and to identify metabolic regulation of aging. We recently developed the metabolomic approach for whole blood analysis, which functions as strong tool for this purpose. We review the update findings in aging-relevant metabolites detected by this method. Geriatr Gerontol Int 2024; 24: 44-48.


Assuntos
Disfunção Cognitiva , Fragilidade , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Envelhecimento/fisiologia , Longevidade
4.
ACS Catal ; 13(16): 10734-10750, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37614518

RESUMO

Low temperature and high pressure are thermodynamically more favorable conditions to achieve high conversion and high methanol selectivity in CO2 hydrogenation. However, low-temperature activity is generally very poor due to the sluggish kinetics, and thus, designing highly selective catalysts active below 200 °C is a great challenge in CO2-to-methanol conversion. Recently, Re/TiO2 has been reported as a promising catalyst. We show that Re/TiO2 is indeed more active in continuous and high-pressure (56 and 331 bar) operations at 125-200 °C compared to an industrial Cu/ZnO/Al2O3 catalyst, which suffers from the formation of methyl formate and its decomposition to carbon monoxide. At lower temperatures, precise understanding and control over the active surface intermediates are crucial to boosting conversion kinetics. This work aims at elucidating the nature of active sites and active species by means of in situ/operando X-ray absorption spectroscopy, Raman spectroscopy, ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Transient operando DRIFTS studies uncover the activation of CO2 to form active formate intermediates leading to methanol formation and also active rhenium carbonyl intermediates leading to methane over cationic Re single atoms characterized by rhenium tricarbonyl complexes. The transient techniques enable us to differentiate the active species from the spectator one on TiO2 support, such as less reactive formate originating from spillover and methoxy from methanol adsorption. The AP-XPS supports the fact that metallic Re species act as H2 activators, leading to H-spillover and importantly to hydrogenation of the active formate intermediate present over cationic Re species. The origin of the unique reactivity of Re/TiO2 was suggested as the coexistence of cationic highly dispersed Re including single atoms, driving the formation of monodentate formate, and metallic Re clusters in the vicinity, activating the hydrogenation of the formate to methanol.

5.
J Phys Chem Lett ; 13(36): 8546-8552, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36067214

RESUMO

The Pt-Rh thin-film sensors exhibit excellent sensitivity and selectivity for H2 gas detection. Here, we studied the mechanism of highly selective detection of H2 by the Pt-Rh thin-film sensors with ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) measurements at working conditions, which were paralleled with electric resistivity measurements. The elemental composition and chemical state of surface Pt and Rh drastically change depending on the background gas environments, which directly link to the sensor response. It is revealed that surface segregated Pt atoms accelerate dissociative adsorption of H2, resulting in a reduction of the sensor surface and then a decrease of electric resistivity of the film, whereas a thin oxidized Rh layer blocks dissociation of the other reducing agent, that is, NH3. This is supported from the adsorption energetics obtained by the density functional theory (DFT) calculations.

6.
Cancers (Basel) ; 14(14)2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35884373

RESUMO

Endoscopic submucosal dissection (ESD) is a safe and minimally invasive method for the treatment of early gastric cancer (EGC). However, whether ESD for EGC is also safe and feasible in patients aged ≥85 years is unclear. The patients enrolled in this study were divided into three groups: age ≥85 years (44 patients, 49 lesions), age 65−84 years (624 patients, 687 lesions), and age ≤64 years (162 patients, 174 lesions). We evaluated the incidence of adverse events (AEs) and overall survival (OS) and disease-specific survival (DSS). We analyzed the factors that had a significant impact on the prognosis of patients aged ≥85 years. No significant differences were found in the incidence of AEs among the three groups (p = 0.612). The OS was significantly lower in patients aged ≥85 years (p < 0.001). Conversely, DSS was not significantly worse in patients aged ≥85 years (p = 0.100). The poor Geriatric Nutritional Risk Index correlated with poor prognosis in patients aged ≥85 years (p < 0.001). ESD is a safe and valid treatment for EGC in patients aged ≥85 years. However, the indications should be carefully decided because it is difficult to estimate the survival contribution of ESD for EGC in patients aged ≥85 years, especially in those with poor nutritional status.

7.
Front Endocrinol (Lausanne) ; 13: 869414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432205

RESUMO

Increased insulin resistance and impaired insulin secretion are significant characteristics manifested by patients with type 2 diabetes mellitus (T2DM). The degree and extent of these two features in T2DM vary among races and individuals. Insulin resistance is accelerated by obesity and is accompanied by accumulation of dysfunctional adipose tissues. In addition, dysfunction of pancreatic ß-cells impairs insulin secretion. T2DM is significantly affected by aging, as the ß-cell mass diminishes with age. Moreover, both obesity and hyperglycemia-related metabolic changes in developing diabetes are associated with accumulation of senescent cells in multiple organs, that is, organismal aging. Cellular senescence is defined as a state of irreversible cell cycle arrest with concomitant functional decline. It is caused by telomere shortening or senescence-inducing stress. Senescent cells secrete proinflammatory cytokines and chemokines, which is designated as the senescence-associated secretory phenotype (SASP), and this has a negative impact on adipose tissues and pancreatic ß-cells. Recent advances in aging research have suggested that senolysis, the removal of senescent cells, can be a promising therapeutic approach to prevent or improve aging-related diseases, including diabetes. The attenuation of a SASP may be beneficial, although the pathophysiological involvement of cellular senescence in diabetes is not fully understood. In the clinical application of senotherapy, tissue-context-dependent senescent cells are increasingly being recognized as an issue to be solved. Recent studies have observed highly heterogenic and complex senescent cell populations that serve distinct roles among tissues, various stages of disease, and different ages. For example, in high-fat-diet induced diabetes with obesity, mouse adipose tissues display accumulation of p21Cip1-highly-expressing (p21high) cells in the early stage, followed by increases in both p21high and p16INK4a-highly-expressing (p16high) cells in the late stage. Interestingly, elimination of p21high cells in visceral adipose tissue can prevent or improve insulin resistance in mice with obesity, while p16high cell clearance is less effective in alleviating insulin resistance. Importantly, in immune-deficient mice transplanted with fat from obese patients, dasatinib plus quercetin, a senolytic cocktail that reduces the number of both p21high and p16high cells, improves both glucose tolerance and insulin resistance. On the other hand, in pancreatic ß cells, p16high cells become increasingly predominant with age and development of diabetes. Consistently, elimination of p16high cells in mice improves both glucose tolerance and glucose-induced insulin secretion. Moreover, a senolytic compound, the anti-Bcl-2 inhibitor ABT263 reduces p16INK4a expression in islets and restores glucose tolerance in mice when combined with insulin receptor antagonist S961 treatment. In addition, efficacy of senotherapy in targeting mouse pancreatic ß cells has been validated not only in T2DM, but also in type 1 diabetes mellitus. Indeed, in non-obese diabetic mice, treatment with anti-Bcl-2 inhibitors, such as ABT199, eliminates senescent pancreatic ß cells, resulting in prevention of diabetes mellitus. These findings clearly indicate that features of diabetes are partly determined by which or where senescent cells reside in vivo, as adipose tissues and pancreatic ß cells are responsible for insulin resistance and insulin secretion, respectively. In this review, we summarize recent advances in understanding cellular senescence in adipose tissues and pancreatic ß cells in diabetes. We review the different potential molecular targets and distinctive senotherapeutic strategies in adipose tissues and pancreatic ß cells. We propose the novel concept of a dual-target tailored approach in senotherapy against diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Células Secretoras de Insulina , Tecido Adiposo/metabolismo , Animais , Senescência Celular/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Humanos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Camundongos , Obesidade/metabolismo
8.
Stud Health Technol Inform ; 289: 496-497, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35062201

RESUMO

In this study, we developed an authentication rangefinder (AR) system for hospital information system (HIS) terminals to support the user authentication workflows. The logoff process of the AR system is triggered if no object is placed at least 90 cm in front of the HIS terminal laptop for ≥5 s. We conducted an anonymous survey of medical staff who used the AR system. 33/42(78%) respondents acknowledged an improvement in the logoff process. This study indicates that the AR system improves the user authentication workflow.


Assuntos
Segurança Computacional , Sistemas de Informação Hospitalar , Humanos , Estudo de Prova de Conceito , Fluxo de Trabalho
10.
Phys Chem Chem Phys ; 24(5): 2988-2996, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35037674

RESUMO

We report a newly designed compact cell to measure XAFS spectra with the conversion electron yield (CEY) method in the soft X-ray region under ambient-pressure gas conditions. Secondary electrons generated from the gas and sample by collision of X-ray-absorption-induced Auger electrons are collected by a positively biased collector electrode to obtain XAFS spectra. It was confirmed that this cell is applicable to soft X-ray surface XAFS measurements for different types of materials such as insulating organic materials and metal oxides under 1 bar gas conditions. During the measurements, photoinduced side effects were observed; i.e. photoinduced degradation of organic materials and photoinduced reduction/oxidation of metal oxides. We found that these photoinduced side effects can be sufficiently suppressed by controlling the measuring conditions. The presented measuring approach will enable surface XAFS spectra to be obtained in the soft X-ray region for various types of functional materials under ambient-pressure working conditions.

11.
Cell Metab ; 34(1): 5-7, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34986338

RESUMO

Senotherapy, the elimination of senescent cells, is a cutting-edge treatment for aging-related and lifestyle diseases. In this issue of Cell Metabolism, Wang et al. report that p21Cip1 highly expressing cells, which represent a senescent cell population, occur in the adipose tissue during obesity. Targeting them genetically or pharmacologically attenuates insulin resistance, suggesting a possible therapeutic approach to treat the metabolic complications of obesity.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Tecido Adiposo , Envelhecimento , Senescência Celular , Humanos
12.
FEBS Lett ; 596(10): 1270-1278, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35090053

RESUMO

Ergothioneine is a well-known antioxidant that is abundant in both human red blood cells and in fission yeast responding to nutritional stress. In frail elderly people, whose ageing organs undergo functional decline, there is a correlation between ergothioneine levels and cognitive, but not skeletal muscle decline. In patients suffering from dementia, including Alzheimer's disease with hippocampal atrophy, deteriorating cognitive ability is correlated with declining ergothioneine levels. S-methyl-ergothioneine, trimethyl-histidine and three other trimethyl-ammonium compounds also decrease sharply in dementia, whereas compounds such as indoxyl-sulfate and quinolinic acid increase, possibly exacerbating the disease. Using these opposing dementia markers, not only diagnosis, but also therapeutic interventions to mitigate cognitive decline may now become possible.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Ergotioneína , Fragilidade , Schizosaccharomyces , Idoso , Cognição/fisiologia , Humanos
13.
Phys Chem Chem Phys ; 23(40): 23280-23287, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633002

RESUMO

The electrolysis of water using renewable energy is a promising approach to developing a sustainable hydrogen-based economy. To improve the efficiency of this process, it will be necessary to develop highly active electrocatalysts that promote the oxygen evolution reaction (OER). In the present study, the OER activity of a nickel oxide electrocatalyst was dramatically improved following the addition of a diamine to the electrolyte solution during electrodeposition. Operando UV/vis absorption spectroscopy was used to assess a number of nickel catalysts containing various diamines and other organic compounds. The data indicate that Ni(II) complexes were formed with the diamines during electrodeposition. Consequently, the catalytic activity of these materials was enhanced based on increased concentrations of active reaction sites for the OER process. Ni K-edge X-ray absorption spectra showed that these catalysts were composed of γ-NiOOH with a Ni3.6+ valence state. The coordination of the diamine molecules to the γ-NiOOH produced structural distortion that contributed to improved OER activity. This structural distortion is likely the most important factor in enhancing the OER activity of inorganic-organic composite catalysts.

14.
Cancer Lett ; 523: 29-42, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34508795

RESUMO

Cancer cells craftily adapt their energy metabolism to their microenvironment. Nutrient deprivation due to hypovascularity and fibrosis is a major characteristic of pancreatic ductal adenocarcinoma (PDAC); thus, PDAC cells must produce energy intrinsically. However, the enhancement of energy production via activating Kras mutations is insufficient to explain the metabolic rewiring of PDAC cells. Here, we investigated the molecular mechanism underlying the metabolic shift in PDAC cells under serine starvation. Amino acid analysis revealed that the concentrations of all essential amino acids and most nonessential amino acids were decreased in the blood of PDAC patients. In addition, the plasma serine concentration was significantly higher in PDAC patients with PHGDH-high tumors than in those with PHGDH-low tumors. Although the growth and tumorigenesis of PK-59 cells with PHGDH promoter hypermethylation were significantly decreased by serine starvation, these activities were maintained in PDAC cell lines with PHGDH promoter hypomethylation by serine biosynthesis through PHGDH induction. In fact, DNA methylation analysis by pyrosequencing revealed that the methylation status of the PHGDH promoter was inversely correlated with the PHGDH expression level in human PDAC tissues. In addition to PHGDH induction by serine starvation, PDAC cells showed enhanced serine biosynthesis under serine starvation through 3-PG accumulation via PGAM1 knockdown, resulting in enhanced PDAC cell growth and tumor growth. However, PHGDH knockdown efficiently suppressed PDAC cell growth and tumor growth under serine starvation. These findings provide evidence that targeting the serine biosynthesis pathway by inhibiting PHGDH is a potent therapeutic approach to eliminate PDAC cells in nutrient-deprived microenvironments.


Assuntos
Carcinoma Ductal Pancreático/patologia , Ácidos Glicéricos/metabolismo , Neoplasias Pancreáticas/patologia , Fosfoglicerato Desidrogenase/fisiologia , Serina/biossíntese , Animais , Linhagem Celular Tumoral , Ilhas de CpG , Metilação de DNA , Indução Enzimática , Humanos , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Fosfoglicerato Desidrogenase/antagonistas & inibidores , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Mutase/fisiologia
15.
Aging (Albany NY) ; 13(17): 20915-20934, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492634

RESUMO

Due to global aging, frailty and sarcopenia are increasing. Sarcopenia is defined as loss of volume and strength of skeletal muscle in elderlies, while frailty involves multiple domains of aging-related dysfunction, impaired cognition, hypomobility, and decreased social activity. However, little is known about the metabolic basis of sarcopenia, either shared with or discrete from frailty. Here we analyzed comprehensive metabolomic data of human blood in relation to sarcopenia, previously collected from 19 elderly participants in our frailty study. Among 131 metabolites, we identified 22 sarcopenia markers, distinct from 15 frailty markers, mainly including antioxidants, although sarcopenia overlaps clinically with physical frailty. Notably, 21 metabolites that decline in sarcopenia or low SMI are uremic compounds that increase in kidney dysfunction. These comprise TCA cycle, urea cycle, nitrogen, and methylated metabolites. Sarcopenia markers imply a close link between muscle and kidney function, while frailty markers define a state vulnerable to oxidative stress.


Assuntos
Envelhecimento , Antioxidantes/metabolismo , Idoso Fragilizado , Fragilidade/metabolismo , Rim/metabolismo , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Ciclo do Ácido Cítrico , Feminino , Humanos , Masculino , Força Muscular , Músculo Esquelético/fisiopatologia , Nitrogênio/sangue , Ureia/sangue , Uremia/metabolismo
16.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34493657

RESUMO

Dementia is caused by factors that damage neurons. We quantified small molecular markers in whole blood of dementia patients, using nontargeted liquid chromatography-mass spectroscopy (LC-MS). Thirty-three metabolites, classified into five groups (A to E), differed significantly in dementia patients, compared with healthy elderly subjects. Seven A metabolites present in plasma, including quinolinic acid, kynurenine, and indoxyl-sulfate, increased. Possibly they act as neurotoxins in the central nervous system (CNS). The remaining 26 compounds (B to E) decreased, possibly causing a loss of support or protection of the brain in dementia. Six B metabolites, normally enriched in red blood cells (RBCs), all contain trimethylated ammonium moieties. These metabolites include ergothioneine and structurally related compounds that have scarcely been investigated as dementia markers, validating the examination of RBC metabolites. Ergothioneine, a potent antioxidant, is significantly decreased in various cognition-related disorders, such as mild cognitive impairment and frailty. C compounds also include some oxidoreductants and are normally abundant in RBCs (NADP+, glutathione, adenosine triphosphate, pantothenate, S-adenosyl-methionine, and gluconate). Their decreased levels in dementia patients may also contribute to depressed brain function. Twelve D metabolites contains plasma compounds, such as amino acids, glycerophosphocholine, dodecanoyl-carnitine, and 2-hydroxybutyrate, which normally protect the brain, but their diminution in dementia may reduce that protection. Seven D compounds have been identified previously as dementia markers. B to E compounds may be critical to maintain the CNS by acting directly or indirectly. How RBC metabolites act in the CNS and why they diminish significantly in dementia remain to be determined.


Assuntos
Envelhecimento , Biomarcadores/sangue , Encéfalo/metabolismo , Demência/patologia , Metaboloma , Idoso , Estudos de Casos e Controles , Demência/sangue , Humanos , Testes Neuropsicológicos , Transdução de Sinais
17.
JMIR Med Inform ; 9(11): e28763, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33993103

RESUMO

BACKGROUND: Medicines may cause various adverse reactions. An enormous amount of money and effort is spent investigating adverse drug events (ADEs) in clinical trials and postmarketing surveillance. Real-world data from multiple electronic medical records (EMRs) can make it easy to understand the ADEs that occur in actual patients. OBJECTIVE: In this study, we generated a patient medication history database from physician orders recorded in EMRs, which allowed the period of medication to be clearly identified. METHODS: We developed a method for detecting ADEs based on the chronological relationship between the presence of an adverse event and the medication period. To verify our method, we detected ADEs with alanine aminotransferase elevation in patients receiving aspirin, clopidogrel, and ticlopidine. The accuracy of the detection was evaluated with a chart review and by comparison with the Roussel Uclaf Causality Assessment Method (RUCAM), which is a standard method for detecting drug-induced liver injury. RESULTS: The calculated rates of ADE with ALT elevation in patients receiving aspirin, clopidogrel, and ticlopidine were 3.33% (868/26,059 patients), 3.70% (188/5076 patients), and 5.69% (226/3974 patients), respectively, which were in line with the rates of previous reports. We reviewed the medical records of the patients in whom ADEs were detected. Our method accurately predicted ADEs in 90% (27/30patients) treated with aspirin, 100% (9/9 patients) treated with clopidogrel, and 100% (4/4 patients) treated with ticlopidine. Only 3 ADEs that were detected by the RUCAM were not detected by our method. CONCLUSIONS: These findings demonstrate that the present method is effective for detecting ADEs based on EMR data.

18.
J Phys Ther Sci ; 33(3): 267-273, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33814715

RESUMO

[Purpose] Global aging has led to a dramatic increase in the number of frail people, who are likely to become bedridden. Since frailty can be partially reversed, early intervention would be beneficial for patients, family members, and clinicians. This study was designed to develop a screening tool for an accurate and comprehensive assessment of frailty by modulating the Edmonton Frail Scale (EFS). [Participants and Methods] The EFS, covering multiple domains, is one of the major diagnostic tools for frailty. Frail and non-frail participants (n=67) were evaluated for each diagnostic item of the EFS to identify the most efficient combination of questions by evaluating its sensitivity and specificity. [Results] The Kyoto Frailty Scale (KFS) was developed as a rapid frailty scale, based on the EFS. The KFS comprises nine questions about health status, polypharmacy, hospitalization, living with a reliable caregiver, shopping, transportation, housework, money management, and forgetting to take medicine. The KFS has an excellent negative predictive value (100%) for screening frailty and a positive predictive value (97%) for screening prefrailty and frailty if we regard KFS ≥4 as a test positive. [Conclusion] The KFS permits clinician to rapidly and accurately screen for frailty and prefrailty, or exclude frailty.

20.
PLoS One ; 16(4): e0250856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914812

RESUMO

Glycolytic metabolism is closely involved in physiological homeostasis and pathophysiological states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been reported to exert certain physiological role in vitro, whereas its impact on glucose metabolism in vivo remains unclear. Here, we report the characterization of Pgam1 knockout mice. We observed that homozygous knockout mice of Pgam1 were embryonic lethal. Although we previously reported that both PGAM-1 and -2 affect global glycolytic profile of cancers in vitro, in vivo glucose parameters were less affected both in the heterozygous knockout of Pgam1 and in Pgam2 transgenic mice. Thus, the impact of PGAM on in vivo glucose metabolism is rather complex than expected before.


Assuntos
Genes Letais , Glucose/metabolismo , Fosfoglicerato Mutase/genética , Animais , Técnicas de Inativação de Genes , Glicólise , Perda de Heterozigosidade , Masculino , Camundongos , Camundongos Transgênicos
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