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1.
Artigo em Japonês | MEDLINE | ID: mdl-39284725

RESUMO

Objective Ota City, located in southeastern Tokyo, including Haneda Tokyo International Airport, has numerous scattered lodging facilities. Shortly after the first case of SARS-CoV-2 B.1.1.529 (Omicron) variant was reported abroad, the Japanese government strengthened border control measures, including quarantine procedures and public health official involvement, for incoming travelers. This study aims to propose effective and efficient border control measures to prevent future outbreaks of emerging and re-emerging infectious diseases.Methods Border control measures implemented between November 2021 and mid-January 2022 were analyzed from three perspectives: chronological changes in government notifications, the situation of in-flight contacts and Omicron cases, and the support system for coronavirus-disease 2019 control department of the Ota City Public Health Center. Additionally, a questionnaire survey was conducted among public health centers with jurisdiction over the top four international airports. This survey aimed to assess the effectiveness of the support system, evaluate cooperation with related organizations, identify common issues faced by public health concerns, and gather suggestions for improvements in future border control measures.Results The definition and treatment of in-flight contacts of Omicron-positive individuals were initially outlined on November 30, 2021, and underwent frequent revisions until January 14, 2022. Between December 1, 2021, and January 12, 2022, only one Omicron case was identified among the 470 tests conducted on in-flight contacts. However, out of 136 additional domestic specimens collected (including 57 positives for genetic analysis), 40 were confirmed Omicron positive. The results of the questionnaire survey across the four public health centers largely mirrored the issues and suggestions identified by Ota City officials. A significant portion of these issues arose from managing temporary non-Japanese residents staying near international airports.Conclusion Border control measures should be implemented to delay the domestic spread of the virus. In this reason, it is crucial to avoid placing an undue burden on public health officials responsible for handling domestic infections. Since response policies and target definitions may need to adapt to unknown pathogens, they may be changed frequently, baffling the officials; however, a system for collecting real-time data from frontline sites and making evidence-based decisions is essential. Additionally, deploying liaisons from national and prefectural governments to focal points of emergency response would strengthen the support system by promoting unified instructions and information sharing.

2.
FASEB J ; 36(4): e22277, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35319792

RESUMO

Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). ß-Lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine tetrapeptide, has been previously reported to prevent AD-like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of ß-lactolin on neuronal cells and neuronal mitochondrial functions remains unknown. Here, we investigated the effects of ß-lactolin on mitochondrial functions in amyloid ß (Aß)-treated mouse hippocampal neuronal HT22 cells and human induced-pluripotent cell (hiPSC)-derived AD model neurons. Adding ß-lactolin to Aß-treated HT22 cells increased both the oxygen consumption rate and cellular ATP concentrations, suggesting that ß-lactolin improves mitochondrial respiration and energy production. Using high content image analysis, we found that ß-lactolin improved mitochondrial fragmentation, membrane potential, and oxidative stress in Aß-treated cells, eventually preventing neuronal cell death. From a mechanistic perspective, we found that ß-lactolin increased gene expression of mitofusin-2, which contributes to mitochondrial fusion events. Finally, we showed that ß-lactolin improves both mitochondrial morphologies and membrane potentials in hiPSC-derived AD model neurons. Taken together, ß-lactolin improved mitochondrial functions AD-related neuronal cell models and prevented neuronal cell death. The dual function of ß-lactolin on both neuron and microglia marks an advantage in maintaining neuronal health.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Linhagem Celular , Hipocampo/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Oligopeptídeos , Proteínas do Soro do Leite
3.
Pharmacol Res ; 186: 106524, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36349594

RESUMO

BACKGROUND AND AIMS: Nephrolithiasis is a common renal disease with no effective medication. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, an anti-diabetic agent, have diuretic and anti-inflammatory properties and could prevent nephrolithiasis. Here, we investigated the potential of SGLT2 inhibition against nephrolithiasis using large-scale epidemiological data, animal models, and cell culture experiments. METHODS: This study included the data of diabetic patients (n = 1,538,198) available in the Japanese administrative database and divided them according to SGLT2 inhibitor prescription status. For animal experiments, renal calcium oxalate stones were induced by ethylene glycol in Sprague-Dawley rats, and phlorizin, an SGLT1/2 inhibitor, was used for the treatment. The effects of SGLT2-specific inhibition for renal stone formation were assessed in SGLT2-deficient mice and a human proximal tubular cell line, HK-2. RESULTS: Nephrolithiasis prevalence in diabetic men was significantly lower in the SGLT2 inhibitor prescription group than in the non-SGLT2 inhibitor prescription group. Phlorizin attenuated renal stone formation and downregulated the kidney injury molecule 1 (Kim1) and osteopontin (Opn) expression in rats, with unchanged water intake and urine volume. It suppressed inflammation and macrophage marker expression, suggesting the role of the SGLT2 inhibitor in reducing inflammation. SGLT2-deficient mice were resistant to glyoxylic acid-induced calcium oxalate stone formation with reduced Opn expression and renal damages. High glucose-induced upregulation of OPN and CD44 and cell surface adhesion of calcium oxalate reduced upon SGLT2-silencing in HK-2 cells. CONCLUSION: Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis.


Assuntos
Diabetes Mellitus , Cálculos Renais , Inibidores do Transportador 2 de Sódio-Glicose , Masculino , Humanos , Ratos , Camundongos , Animais , Oxalato de Cálcio/metabolismo , Florizina , Ratos Sprague-Dawley , Cálculos Renais/tratamento farmacológico , Cálculos Renais/prevenção & controle , Cálculos Renais/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Glucose , Inflamação , Sódio
4.
Biochem Biophys Res Commun ; 533(4): 704-709, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33160623

RESUMO

Matured hop bitter acids (MHBA) are bitter acid oxides derived from hops, widely consumed as food ingredients to add bitterness and flavor in beers. Previous studies have suggested a potential gut-brain mechanism in which MHBA simulates enteroendocrine cells to produce cholecystokinin (CCK), a gastrointestinal hormone which activates autonomic nerves, resulting in body fat reduction and cognitive improvement; however, the MHBA recognition site on enteroendocrine cells has not been fully elucidated. In this study, we report that MHBA is recognized by specific human and mouse bitter taste receptors (human TAS2R1, 8, 10 and mouse Tas2r119, 130, 105) using a heterologous receptor expression system in human embryonic kidney 293T cells. In addition, knockdown of each of these receptors using siRNA transfection partially but significantly suppressed an MHBA-induced calcium response and CCK production in enteroendocrine cells. Furthermore, blocking one of the essential taste signaling components, transient receptor potential cation channel subfamily M member 5, remarkably inhibited the MHBA-induced calcium response and CCK production in enteroendocrine cells. Our results demonstrate that specific bitter taste receptor activation by MHBA drives downstream calcium response and CCK production in enteroendocrine cells. These findings reveal a mechanism by which food ingredients derived from hops in beer activate the gut-brain axis for the first time.


Assuntos
Cerveja/análise , Colecistocinina/metabolismo , Células Enteroendócrinas/metabolismo , Hormônios Gastrointestinais/metabolismo , Humulus/química , Receptores Acoplados a Proteínas G/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Técnicas de Silenciamento de Genes , Humanos , Camundongos , RNA Interferente Pequeno , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/fisiologia , Paladar
5.
J Biol Chem ; 293(22): 8342-8361, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29674317

RESUMO

Epithelia contribute to physical barriers that protect internal tissues from the external environment and also support organ structure. Accordingly, establishment and maintenance of epithelial architecture are essential for both embryonic development and adult physiology. Here, using gene knockout and knockdown techniques along with gene profiling, we show that extracellular signal-regulated kinase 3 (ERK3), a poorly characterized atypical mitogen-activated protein kinase (MAPK), regulates the epithelial architecture in vertebrates. We found that in Xenopus embryonic epidermal epithelia, ERK3 knockdown impairs adherens and tight-junction protein distribution, as well as tight-junction barrier function, resulting in epidermal breakdown. Moreover, in human epithelial breast cancer cells, inhibition of ERK3 expression induced thickened epithelia with aberrant adherens and tight junctions. Results from microarray analyses suggested that transcription factor AP-2α (TFAP2A), a transcriptional regulator important for epithelial gene expression, is involved in ERK3-dependent changes in gene expression. Of note, TFAP2A knockdown phenocopied ERK3 knockdown in both Xenopus embryos and human cells, and ERK3 was required for full activation of TFAP2A-dependent transcription. Our findings reveal that ERK3 regulates epithelial architecture, possibly together with TFAP2A.


Assuntos
Neoplasias da Mama/patologia , Embrião não Mamífero/enzimologia , Células Epiteliais/química , Proteína Quinase 6 Ativada por Mitógeno/metabolismo , Fator de Transcrição AP-2/metabolismo , Xenopus laevis/fisiologia , Animais , Neoplasias da Mama/enzimologia , Sistemas CRISPR-Cas , Adesão Celular , Membrana Celular , Células Cultivadas , Embrião não Mamífero/citologia , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Feminino , Células Hep G2 , Humanos , Proteína Quinase 6 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 6 Ativada por Mitógeno/genética , Junções Íntimas , Fator de Transcrição AP-2/antagonistas & inibidores , Fator de Transcrição AP-2/genética , Xenopus laevis/embriologia
6.
Clin Exp Nephrol ; 23(4): 455-464, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30426292

RESUMO

BACKGROUND: Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan. METHODS: Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses. RESULTS: Groups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex. CONCLUSION: HCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Diuréticos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Doenças Renais Policísticas/tratamento farmacológico , Poliúria/tratamento farmacológico , Tolvaptan/uso terapêutico , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Aquaporina 2/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Taxa de Filtração Glomerular , Masculino , Óxido Nítrico Sintase Tipo I/genética , Doenças Renais Policísticas/fisiopatologia , Poliúria/induzido quimicamente , Prostaglandina-E Sintases/genética , RNA Mensageiro/metabolismo , Ratos , Renina/genética , Tolvaptan/efeitos adversos , Urina
7.
Nutr J ; 17(1): 98, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376838

RESUMO

BACKGROUND: We recently reported that successive ingestion of matured hop extract (MHE), produced by oxidation of hops, results in a reduction of body fat in healthy overweight participants. A combined effect of MHE and physical activity on body fat has not been investigated. Thus, we re-analyzed data from the previous study to explore the relationship between the effect of MHE and walking as an index of physical activity. METHODS: This analysis uses existing data from a randomized, double-blind, placebo-controlled parallel group study in which MHE (active) or placebo was given for 12 w to 200 healthy overweight Japanese, from May to December 2014. Correlation between the change in abdominal fat areas at 12 w and the number of steps taken per day was tested by Spearman's correlation coefficient test. The subjects were stratified using the average number of steps per day of Japanese into walking less and walking more subgroups (WL and WM, respectively) as follows: placebo (WL, n = 43; WM, n = 44) and active (WL, n = 49; WM, n = 42). Reductions in total, visceral, and subcutaneous fat area (TFA, VFA and SFA, respectively) were evaluated. The interaction effect between ingestion (active/placebo) and walking (WL/WM) was analyzed using two-way analysis of variance (ANOVA). RESULTS: There was a significant negative correlation between the change in VFA and daily steps taken in the active group (r = - 0.208, P = 0.048). No significant correlation in TFA or SFA. Although the interaction effect in TFA was not significant, the main effect of ingestion was significant (P = 0.045). In contrast, the interaction effect in VFA was suggested to be synergistic (P = 0.055). CONCLUSION: The results suggested that MHE ingestion combined with light intensity exercise would induce a greater reduction in VFA which would be beneficial for obese or overweight individuals in reducing obesity and obesity-related diseases. TRIAL REGISTRATION: UMIN-CTR UMIN000014185 registered 6 June 2014.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Exercício Físico , Humulus , Sobrepeso/dietoterapia , Extratos Vegetais/administração & dosagem , Adulto , Idoso , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Caminhada , Redução de Peso/efeitos dos fármacos , Adulto Jovem
8.
Adv Perit Dial ; 34(2018): 53-57, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30480539

RESUMO

Exit-site infection poses a risk for peritonitis and can shorten peritoneal dialysis (PD) vintage. A loose fit of the skin around the catheter at the exit site can push bacteria surrounding the catheter into the subcutaneous tunnel. Negative-pressure wound therapy (NPWT) has been used to hasten healing of the wound after an operation or to treat pressure ulcers. We hypothesized that NPWT could speed the healing of the exit site and tighten the fit of the skin around the catheter. Using a V.A.C. Therapy system [vacuum-assisted closure (KCI, San Antonio, TX, U.S.A.)], NPWT was therefore applied in 9 patients for 1 - 2 weeks after the PD catheter insertion operation. Results in those patients were compared with results in patients who did not receive NPWT.The healed exit site was classified as either tightly fitted (when the skin was tightly connected around the PD catheter) or loosely fitted (when the skin was not tightly connected around the catheter). The relevant data were retrieved from the medical record and analyzed retrospectively.Patients who received NPWT had a tight exit site after 1 - 2 weeks. Those who did not receive NPWT did not have a tight exit site after 1 - 2 weeks. No bleeding was observed in patients receiving NPWT. Bleeding from the exit site after the catheter insertion operation was observed in 3 patients not receiving NPWT.Because we use a fine trocar to make the subcutaneous catheter tunnel, bleeding from the vasculature can often be observed. That bleeding could be minimized with the application of NPWT. Negative pressure could also hasten wound healing and result in a tight fit of the skin around the catheter within in 1 - 2 weeks compared with the 1 month typically required with the use of conventional film dressings.Negative-pressure wound therapy is beneficial for creating a tight fit of the skin to the catheter within 1 - 2 weeks and might reduce the number of exit-site and tunnel infections, which could result in a reduction in the peritonitis rate.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Diálise Peritoneal , Bandagens , Humanos , Estudos Retrospectivos , Cicatrização
9.
J Biol Chem ; 290(5): 3161-71, 2015 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-25525269

RESUMO

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is activated by various noxious or irritant substances in nature, including spicy compounds. Many TRPA1 chemical activators have been reported; however, only limited information is available regarding the amino acid residues that contribute to the activation by non-electrophilic activators, whereas activation mechanisms by electrophilic ligands have been well characterized. We used intracellular Ca(2+) measurements and whole-cell patch clamp recordings to show that eudesmol, an oxygenated sesquiterpene present at high concentrations in the essential oil of hop cultivar Hallertau Hersbrucker, could activate human TRPA1. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. This activation was completely blocked by a TRPA1-specific inhibitor, HC03-0031. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely threonine at 813, tyrosine at 840, and serine at 873, for activation by ß-eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil and provide a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals.


Assuntos
Aminoácidos/química , Aminoácidos/metabolismo , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Humulus/química , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Óleos Voláteis/química , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia , Sesquiterpenos/química , Canais de Potencial de Receptor Transitório/química , Canais de Potencial de Receptor Transitório/metabolismo , Humanos , Canal de Cátion TRPA1
10.
Genes Cells ; 20(4): 324-39, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25652037

RESUMO

Cannabinoid receptor interacting protein 1 (CNRIP1), which has been originally identified as the binding partner of cannabinoid receptor 1 (CNR1), is evolutionarily conserved throughout vertebrates, but its physiological function has been unknown. Here, we identify a developmental role of CNRIP1 using Xenopus laevis embryos. During early embryogenesis, expression of Xenopus laevis cnrip1 is highly restricted to the animal region of gastrulae where neural and eye induction occur, and afterward it is seen in neural and other tissues with a temporally and spatially regulated pattern. Morpholino-mediated knockdown experiments indicate that cnrip1 has an essential role in early eye and neural development by regulating the onset of expression of key transcription factor genes, sox2, otx2, pax6 and rax. Also, over-expression experiments suggest that cnrip1 has a potential to expand sox2, otx2, pax6 and rax expression. These results suggest an instructive role of Xenopus laevis cnrip1 in early eye and neural development. Furthermore, Xenopus laevis cnr1 knockdown leads to eye defects, which are partly similar to, but milder than, those caused by cnrip1 knockdown, suggesting a possible functional similarity between CNRIP1 and CNR1. This study is the first characterization of an in vivo role of CNRIP1 in the context of whole organisms.


Assuntos
Proteínas de Transporte/metabolismo , Olho/embriologia , Gástrula/metabolismo , Neurogênese , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Animais , Proteínas de Transporte/genética , Olho/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Xenopus/genética
12.
Breed Sci ; 64(3): 252-63, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25320560

RESUMO

To develop a high density linkage map in faba bean, a total of 1,363 FBES (Faba bean expressed sequence tag [EST]-derived simple sequence repeat [SSR]) markers were designed based on 5,090 non-redundant ESTs developed in this study. A total of 109 plants of a 'Nubaria 2' × 'Misr 3' F2 mapping population were used for map construction. Because the parents were not pure homozygous lines, the 109 F2 plants were divided into three subpopulations according to the original F1 plants. Linkage groups (LGs) generated in each subpopulation were integrated by commonly mapped markers. The integrated 'Nubaria 2' × 'Misr 3' map consisted of six LGs, representing a total length of 684.7 cM, with 552 loci. Of the mapped loci, 47% were generated from multi-loci diagnostic (MLD) markers. Alignment of homologous sequence pairs along each linkage group revealed obvious syntenic relationships between LGs in faba bean and the genomes of two model legumes, Lotus japonicus and Medicago truncatula. In a polymorphic analysis with ten Egyptian faba bean varieties, 78.9% (384/487) of the FBES markers showed polymorphisms. Along with the EST-SSR markers, the dense map developed in this study is expected to accelerate marker assisted breeding in faba bean.

13.
Jpn J Infect Dis ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945861

RESUMO

An active epidemiological investigation of COVID-19 cases in the Setagaya ward of Tokyo revealed that household transmission was the main route of infection spread. This study aimed to identify the factors affecting household transmission in patients diagnosed with COVID-19 and their cohabitants, during the wild type virus (December 2020) and alpha variant epidemic (May 2021). Index case factors significantly associated with household transmission for both wild type (WT) and alpha variant (AV), were at least 3 days from onset to diagnosis (WT: risk ratio [RR] 1.44, 95% confidence interval [CI] 1.16-1.79/AV: RR 1.66, CI 1.32-2.08), and a household size of three or more people (WT: RR 1.37, CI 1.10-1.72/AV: RR 1.29, CI 1.05-1.59). There were also significant differences in age ≥ 65 (RR 2.39, CI 1.26-4.54) and symptomatic at diagnosis (RR 3.05, CI 1.22-7.63) in index cases of WT. Among cohabitants, factors associated with household transmission for both strains were being the spouse/partner of the index case (WT: RR 1.68, CI 1.21-1.82/AV: RR 1.97, CI 1.59-2.43) and at least 3 days from onset to diagnosis of the index case (WT: RR 1.48, CI 1.34-2.10/ AV: RR 1.86, CI1.52-2.28). Early diagnosis and isolation are effective for preventing household transmission.

14.
Hypertens Res ; 47(1): 33-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749334

RESUMO

Renal congestion is an issue of cardiorenal syndrome in patients with heart failure. Recent clinical and basic studies suggest a renoprotective potential of sodium-glucose cotransporter (SGLT) 2 inhibitors. However, the effect on renal congestion and its mechanism is not fully understood. Thus, we aimed to clarify the effect of SGLT inhibition in a renal congestion model. Renal congestion was induced in the left kidney of male Sprague-Dawley rats by ligation of the inferior vena cava between the renal veins. The SGLT2 inhibitor tofogliflozin or vehicle was orally administered daily from the day before IVC ligation until two days after surgery. On the third postoperative day, both the right control kidney and the left congested kidney were harvested and analyzed. Kidney weight and water content was increased, and renal injury and fibrosis were observed in the left congested kidney. Kidney weight gain and hydration were improved with tofogliflozin treatment. Additionally, this treatment effectively reduced renal injury and fibrosis, particularly in the renal cortex. SGLT2 expression was observed in the congested kidney, but suppressed in the damaged tubular cells. Molecules associated with inflammation were increased in the congested kidney and reversed by tofogliflozin treatment. Mitochondrial dysfunction provoked by renal congestion was also improved by tofogliflozin treatment. Tofogliflozin protects against renal damage induced by renal congestion. SGLT2 inhibitors could be a candidate strategy for renal impairment associated with heart failure.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Ratos , Masculino , Animais , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Ratos Sprague-Dawley , Rim , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Insuficiência Cardíaca/complicações , Fibrose , Glucose/metabolismo , Glucose/farmacologia , Glucose/uso terapêutico , Diabetes Mellitus Tipo 2/complicações
15.
Sci Rep ; 14(1): 4638, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409370

RESUMO

Thermodynamically metastable glasses that can contain metastable species are important functional materials. X-ray absorption near-edge structure (XANES) spectroscopy is an effective technique for determining the valence states of cations, especially for the doping element in phosphors. Herein, we first confirm the valence change of silver cations from monovalent to trivalent in aluminophosphate glasses by X-ray irradiation using a combination of Ag L3-edge XANES, electron spin resonance, and simulated XANES spectra based on first-principles calculations. The absorption edge of the experimental and simulated XANES spectra demonstrate the spectral features of Ag(III), confirming that AgO exists as Ag(I)Ag(III)O2. A part of Ag(I) changes to Ag(III) by X-ray irradiation, and the generation of Ag(III) is saturated after high irradiation doses, in good agreement with conventional radiophotoluminescence (RPL) behaviour. The structural modelling based on a combination of quantum beam analysis suggests that the local coordination of Ag cations is similar to that of Ag(III), which is confirmed by density functional theory calculations. This demonstration of Ag(III) in glass overturns the conventional understanding of the RPL mechanism of silver cations, redefining the science of silver-related materials.

16.
Sci Rep ; 14(1): 23444, 2024 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379481

RESUMO

Mental disorders have become one of the most burdensome health concerns. We have previously demonstrated that whey-derived ß-lactolin (glycine-thereonine-tryptophan-tyrosine tetrapeptide) activates dopaminergic systems and improves psychiatric function in rodents. However, the effects of ß-lactolin on human mood states have not been investigated. This randomized, double-blind, placebo-controlled study aimed to evaluate the effects of supplementation with ß-lactolin-rich whey peptide on human mood states. Sixty healthy adults (aged 45-64 years) with relatively low psychological health were randomly allocated to receive either whey peptide (containing ß-lactolin 1.6 mg/day) or placebo for 6 weeks. Mood states (primary outcomes) were evaluated using self-reporting questionnaires. Health-related quality of life (QOL), salivary stress marker and lipid mediator levels were evaluated as secondary outcomes. Compared with placebo, supplementation with ß-lactolin improved changes in trait anxiety (p = 0.046), as assessed using the state-trait anxiety inventory, and in subjective stress (p = 0.043), as assessed using the Perceived Stress Scale. In the assessment of QOL, changes in the vitality subscale and mental health summary score of the 36-Item Short-Form Health Survey were improved in the ß-lactolin group. The levels of salivary immunoglobulin A were significantly higher in the ß-lactolin group. In a subgroup analysis by median age (54.5 years), subjective stress and salivary prostaglandin levels were significantly decreased by ß-lactolin supplementation in the 45-54 -year-old subgroup. In conclusion, supplementation with ß-lactolin improves trait anxiety, subjective stress, and psychological QOL, which may be associated with immunologic responses detected via salivary analysis.


Assuntos
Ansiedade , Suplementos Nutricionais , Qualidade de Vida , Estresse Psicológico , Proteínas do Soro do Leite , Humanos , Pessoa de Meia-Idade , Masculino , Proteínas do Soro do Leite/administração & dosagem , Proteínas do Soro do Leite/farmacologia , Feminino , Método Duplo-Cego , Ansiedade/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Saliva/metabolismo , Estresse Subjetivo
17.
Aging (Albany NY) ; 16(18): 12443-12472, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39302208

RESUMO

Within the same species, individuals exhibiting faster growth tend to have shorter lifespans, even if their fast growth arises from early-life pharmacological interventions. However, in vertebrates, the impact of the early-life environment on the growth rate and lifespan has not been fully elucidated. In this study, by utilizing the short-lived African turquoise killifish, which is suitable for a comprehensive life-stage analysis in a brief timeframe, we explored the effects of housing density during the juvenile stage on holistic life traits. As a result, we found that lower housing densities resulted in faster growth, but led to longer adult lifespan, which was contrary to the common notion. Furthermore, the single-housed adult fish displayed a longer egg-laying period than did their group-housed counterparts. Our transcriptome analysis also demonstrated that, in terms of internal transcriptional programs, the life stage progression and aging process of single-housed fish were slower than those of group-housed fish. Collectively, our results suggest that sharing housing with others in early life might influence whole-life attributes, potentially leading to specific life history traits beyond the typical relationship between the growth rate and lifespan.


Assuntos
Fundulidae , Longevidade , Animais , Fundulidae/genética , Abrigo para Animais , Feminino , Masculino , Envelhecimento/fisiologia , Peixes Listrados
18.
Hypertens Res ; 46(12): 2705-2717, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845397

RESUMO

Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.


Assuntos
Insuficiência Cardíaca , Hipertensão , Humanos , Ratos , Animais , Ratos Endogâmicos Dahl , Pericitos/patologia , Cloreto de Sódio , Rim , Insuficiência Cardíaca/etiologia , Cloreto de Sódio na Dieta , Fibrose , Pressão Sanguínea
19.
BMC Plant Biol ; 12: 80, 2012 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22672714

RESUMO

BACKGROUND: Peanut (Arachis hypogaea) is an autogamous allotetraploid legume (2n = 4x = 40) that is widely cultivated as a food and oil crop. More than 6,000 DNA markers have been developed in Arachis spp., but high-density linkage maps useful for genetics, genomics, and breeding have not been constructed due to extremely low genetic diversity. Polymorphic marker loci are useful for the construction of such high-density linkage maps. The present study used in silico analysis to develop simple sequence repeat-based and transposon-based markers. RESULTS: The use of in silico analysis increased the efficiency of polymorphic marker development by more than 3-fold. In total, 926 (34.2%) of 2,702 markers showed polymorphisms between parental lines of the mapping population. Linkage analysis of the 926 markers along with 253 polymorphic markers selected from 4,449 published markers generated 21 linkage groups covering 2,166.4 cM with 1,114 loci. Based on the map thus produced, 23 quantitative trait loci (QTLs) for 15 agronomical traits were detected. Another linkage map with 326 loci was also constructed and revealed a relationship between the genotypes of the FAD2 genes and the ratio of oleic/linoleic acid in peanut seed. CONCLUSIONS: In silico analysis of polymorphisms increased the efficiency of polymorphic marker development, and contributed to the construction of high-density linkage maps in cultivated peanut. The resultant maps were applicable to QTL analysis. Marker subsets and linkage maps developed in this study should be useful for genetics, genomics, and breeding in Arachis. The data are available at the Kazusa DNA Marker Database (http://marker.kazusa.or.jp).


Assuntos
Arachis/genética , Elementos de DNA Transponíveis , Repetições de Microssatélites , Polimorfismo Genético , Mapeamento Cromossômico , DNA de Plantas/genética , Ligação Genética , Marcadores Genéticos , Locos de Características Quantitativas
20.
Artigo em Inglês | MEDLINE | ID: mdl-35805508

RESUMO

A limited number of longitudinal studies have explored factors contributing to decreases in tongue pressure (TP). This longitudinal study aimed to clarify the factors affecting TP decline among community-dwelling older adults. We followed the Takashimadaira Study participants with a baseline TP ≥ 30 kPa for 2 years. A TP of <30 kPa at follow-up was defined as TP decline. We used Poisson regression with robust standard errors to explore the factors related to TP decline. The studied baseline variables were dental status, sociodemographic characteristics, health behaviors, appetite, medical conditions, physical function, cognitive status, and anthropometric and body composition characteristics. Inverse probability weighting (IPW) was used to adjust for selection bias. Overall, 357 individuals (159 men and 198 women) with a mean (standard deviation) age of 75.9 (4.1) years were included in the analyses. Of these, 59 study participants (16.5%) exhibited TP decline. After adjusting for baseline TP and applying IPW, poor appetite (incident rate ratio [95% confidence interval] = 1.58 [1.01−2.48]), low skeletal muscle mass index (1.66 [1.02−2.70]), and cognitive impairment (1.93 [1.12−3.33]) were associated with TP decline. In conclusion, we demonstrated that baseline appetite, body composition, and cognitive status could predict future TP decline among community-dwelling older adults.


Assuntos
Disfunção Cognitiva , Vida Independente , Idoso , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pressão , Língua
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