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Sjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with GBJ effectively prevented the decrease in aquaporin-5 (AQP-5) mRNA and protein levels induced by TNF-α. GBJ also inhibited histone H4 deacetylation and suppressed the generation of intracellular reactive oxygen species (ROS). Furthermore, GBJ pretreatment reserved mitochondrial membrane potential and suppressed the upregulation of Bax and caspase-3, indicating that GBJ exerted an antiapoptotic effect. These findings suggest that GBJ provides protection against TNF-α in human salivary gland cells and prevents the reduction of AQP-5 expression on the cell membrane. Altogether, these results highlight the potential role of GBJ in preventing oral dryness caused by SS.
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Lycium , Síndrome de Sjögren , Xerostomía , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Lycium/metabolismo , Glándulas Salivales/metabolismo , Glándulas Salivales/patología , Xerostomía/inducido químicamente , Xerostomía/prevención & control , Xerostomía/complicaciones , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Acuaporina 5/genéticaRESUMEN
Seabuckthorn pulp oil (SBO) is used in beauty products because of its rich lipophilic substances with high nutraceutical and cosmeceutical potential. However, the mechanism through which SBO enhances skin elasticity remains unclear. Therefore, in this study, we examined the anti-photoaging activity of SBO in normal human dermal fibroblasts (NHDF) under ultraviolet (UV) irradiation. Pretreatment with SBO significantly suppressed UV-B-induced cell toxicity and collagen degradation, suggesting that SBO contains anti-photoaging substances. Further, palmitoleic acid, the main component of SBO, maintained cell viability and collagen levels in UV-B-irradiated NHDF by suppressing the expression of matrix metalloproteinase 1 and acted on the inhibition of p38 and JNK phosphorylation and nuclear translocation of nuclear factor-kappa B. These findings suggest the utility of SBO as an anti-photoaging agent.
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Supervivencia Celular , Fibroblastos , Hippophae , Metaloproteinasa 1 de la Matriz , Aceites de Plantas , Rayos Ultravioleta , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Rayos Ultravioleta/efectos adversos , Hippophae/química , Metaloproteinasa 1 de la Matriz/metabolismo , Aceites de Plantas/farmacología , Aceites de Plantas/química , Supervivencia Celular/efectos de los fármacos , Ácidos Grasos Monoinsaturados/farmacología , FN-kappa B/metabolismo , Colágeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiaciónRESUMEN
BACKGROUND: Fibrosis is a common final pathway leading to end-stage renal failure. As the renal medulla and cortex contain different nephron segments, we analyzed the factors associated with the progression of renal medullary and cortical fibrosis. METHODS: A total of 120 patients who underwent renal biopsy at Kawashima Hospital between May 2019 and October 2022 were enrolled in this retrospective study. Renal medullary and cortical fibrosis and stiffness were evaluated using Masson's trichrome staining and shear wave elastography, respectively. Maximum urine osmolality in the Fishberg concentration test was also examined. RESULTS: Medullary fibrosis was positively correlated with cortical fibrosis (p < 0.0001) and log-converted urinary ß2-microglobulin (MG) (log urinary ß2-MG) (p = 0.022) and negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.0002). Cortical fibrosis also correlated with log urinary ß2-MG, eGFR, and maximum urine osmolality. Multivariate analysis revealed that cortical fibrosis levels (odds ratio [OR]: 1.063) and medullary stiffness (OR: 1.089) were significantly associated with medullar fibrosis (â§45%). The severe fibrosis group with both medullary fibrosis (â§45%) and cortical fibrosis (â§25%) had lower eGFR and maximum urine osmolality values and higher urinary ß2-MG levels than the other groups. CONCLUSIONS: Patients with disorders involving both renal medullary and cortical fibrosis had decreased maximum urine osmolality but had no abnormalities in the urinary concentrating capacities with either condition. Renal medullary and cortical fibrosis were positively correlated with urinary ß2-MG, but not with urinary N-acetyl-beta-D-glucosaminidase.
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Supramolecularly assembled high-order supercrystals (SCs) help control the dielectric, electronic, and excitonic properties of semiconductor nanocrystals (NCs) and quantum dots (QDs). Ligand-engineered perovskite NCs (PNCs) assemble into SCs showing shorter excitonic lifetimes than strongly dielectric PNC films showing long photoluminescence (PL) lifetimes and long-range carrier diffusion. Monodentate to bidentate ligand exchange on ≈ 8 nm halide perovskite (APbX3 ; A:Cs/MA, X:Br/I) PNCs generates mechanically stable SCs with close-packed lattices, overlapping electronic wave functions, and higher dielectric constant, providing distinct excitonic properties from single PNCs or PNC films. From Fast Fourier Transform (FFT) images, time-resolved PL, and small-angle X-ray scattering, structurally and excitonically ordered large SCs are identified. An Sc shows a smaller spectral shift (<35 meV) than a PNC film (>100 meV), a microcrystal (>100 meV), or a bulk crystal (>100 meV). Also, the exciton lifetime (<10 ns) of an SC is excitation power-independent in the single exciton regime ãNã<1, comparable to an isolated PNC. Therefore, bidentate-ligand-assisted SCs help overcome delayed exciton or carrier recombination in halide perovskite nanocrystal assemblies or films.
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Halide perovskites are ideal for next-generation optical devices and photovoltaics. Although perovskite single-crystals show reproducible optoelectronic properties, significant variations in the crystal size, anisotropy, density, defects, photoluminescence (PL), and carrier lifetime affect the sample properties and device performances. Homogenous size and shape FA/MAPbBr3 single microcrystals (MCs) with controlled edge lengths, crystal densities, PL lifetimes, and PL intensities are prepared by thermodynamically controlling and kinetically separating the crystal nucleation-growth processes using optimum N-cyclohexyl-2-pyrrolidone (CHP) concentration. The crystal growth kinetics at different CHP concentrations and temperatures are estimated spectroscopically by measuring the concentration of Pb (II). High-density cubic MCs with a homogenous size distribution, high PL intensities, and long PL lifetimes are obtained within minutes at high temperatures by the controlled addition of the pyrrolidone derivative. Conversely, the crystal size nonlinearly increases with time at low temperatures. The isotropically grown high-density single crystals at controlled nucleation-growth rates at 190 °C with 20% CHP show the highest PL intensity and the longest PL lifetimes. This method offers thermodynamic and kinetic control of perovskite single-crystal growth with shape control.
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We generate 1.7-cycle and 35-µJ pulses at a 1-MHz repetition rate by using two-stage multiple plate continuum compression of Yb-laser pulses with 80-W average input power. By adjusting the plate positions with careful consideration of the thermal lensing effect due to the high average power, we compress the output pulse with a 184-fs initial duration to 5.7 fs by using only group-delay-dispersion compensation. This pulse achieves a sufficient beam quality (M2 < 1.5) reaching a focused intensity over 1014 W/cm2 and a high spatial-spectral homogeneity (98%). Our study holds promise for a MHz-isolated-attosecond-pulse source for advanced attosecond spectroscopic and imaging technologies with unprecedentedly high signal-to-noise ratios.
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BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.
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Glomerulonefritis por IGA , Hipoalbuminemia , Síndrome Nefrótico , Embarazo , Femenino , Humanos , Adulto , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/tratamiento farmacológico , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Hematuria/etiología , ProteinuriaRESUMEN
X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.
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Nefritis Hereditaria , Masculino , Humanos , Niño , Adulto , Nefritis Hereditaria/genética , Nefritis Hereditaria/metabolismo , Nefritis Hereditaria/patología , Colágeno Tipo IV/genética , Cápsula Glomerular/metabolismo , Cápsula Glomerular/patología , Membrana Basal Glomerular/patología , ExonesRESUMEN
PURPOSE: To perform endoscopic sinus surgery safely and effectively, surgeons need to visualize the complex anatomy of the anterior ethmoid and frontal sinus region. Because this anatomy is so variable and individualized, the foundation of understanding lies in identifying, following, and visualizing the drainage pathway patterns and anticipating possible variations. METHODS: We studied 100 sides (50 cases: 22 male, 28 female, aged 12-86, average age 46.5 years, ± 19.5) using computed tomography (CT) and multiplanar reconstruction (MPR) to identify and classify the drainage pathways leading to the frontal sinus and anterior ethmoidal cells. RESULTS: Analysis revealed five patterns of drainage pathways defined by their bony walls: between the uncinate process and the lamina papyracea [UP-LP]; between the uncinate process and the middle turbinate [UP-MT]; between the uncinate process and the accessory uncinate process [UP-UPa]; between the uncinate process and the basal lamella of the ethmoidal bulla [UP-BLEB]; and between the basal lamella of the ethmoidal bulla and the basal lamella of the middle turbinate [BLEB-BLMT]. In most cases, BLEB formed the posterior wall of the drainage pathway of the frontal sinus, indicating BLEB could be one of the most important landmarks for approaching the frontal sinus. CONCLUSIONS: As endoscopic sinus surgery depends on an understanding of this anatomy, this study may help surgeons to identify and follow the drainage pathways more accurately and safely through the anterior ethmoid to the frontal sinus.
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Senos Etmoidales , Seno Frontal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Drenaje , Endoscopía , Hueso Etmoides/diagnóstico por imagen , Hueso Etmoides/cirugía , Hueso Etmoides/anatomía & histología , Senos Etmoidales/diagnóstico por imagen , Senos Etmoidales/cirugía , Senos Etmoidales/anatomía & histología , Seno Frontal/diagnóstico por imagen , Seno Frontal/cirugía , Seno Frontal/anatomía & histología , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Little attention has been focused on risk factors for undergoing bilateral total knee arthroplasty (TKA) after primary unilateral TKA among patients with knee osteoarthritis (OA). This study investigated the differences in characteristics between groups with and without additional TKA for the contralateral knee among patients with knee OA who underwent primary unilateral TKA. METHODS: Seventy-six patients who underwent primary unilateral TKA were included in this study. We defined patients who underwent additional TKA for the contralateral knee within one year of the primary TKA as a bilateral TKA group, and patients who did not undergo bilateral TKA as a unilateral TKA group. Femorotibial angle (FTA), percentage of mechanical axis (%MA), Kellgren-Lawrence (KL) grade, range of motion, Japan Orthopaedic Association (JOA) score, 10 m-walking time, C-reactive protein, estimated glomerular filtration rate, and serum albumin levels were selected as independent variables including covariates of age, sex, and body mass index for predicting bilateral TKA. We compared differences in variables between the two groups using the t-test or Mann-Whitney U-test and general linear models. A multivariate stepwise logistic regression model was also used to determine which variables correlated with bailateral TKA. RESULTS: In pairwise comparisons, the KL grade, FTA, %MA, JOA score, and knee flexion angle in the contralateral knee were significantly worse in the bilateral TKA group than in the unilateral TKA group after controlling for covariates (P < 0.01, respectively). A stepwise logistic regression revealed that significant contributors to undergoing the contralateral TKA were FTA (OR = 1.47, P < 0.001) and knee flexion angle (OR = 0.96, P = 0.022) of the contralateral knee. CONCLUSIONS: Severe varus deformity and limitations of flexion in the contralateral knee were found to be risk factors for undergoing additional TKA within one year of primary unilateral TKA among patients with knee OA.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Caminata , Factores de RiesgoRESUMEN
A 78-year-old female patient presented to our hospital with abdominal pain and melena. Abdominal ultrasonography detected a multiple concentric ring sign and retrograde invagination mass near the hepatic flexure. Colonoscopy revealed a 40-mm diameter type 1 tumor in the transverse colon near the splenic flexure, and the biopsy specimen demonstrated a well-differentiated adenocarcinoma. Retrograde intussusception due to transverse colon cancer was diagnosed, and laparoscopic transverse colon resection with lymph node dissection was performed. The resected specimen revealed a 48×40mm diameter type 1 tumor in the transverse colon and was diagnosed as pT2N0M0 pStage I. Contrast-enhanced computed tomography was unavailable, but real-time assessment of the invaginated mass and bowel blood flow was possible by abdominal ultrasonography, which was useful in determining the diagnosis and treatment strategy.
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Colon Transverso , Neoplasias del Colon , Intususcepción , Femenino , Humanos , Anciano , Colon Transverso/diagnóstico por imagen , Colon Transverso/cirugía , Colon Transverso/patología , Intususcepción/diagnóstico por imagen , Intususcepción/etiología , Intususcepción/cirugía , Neoplasias del Colon/complicaciones , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/cirugía , Abdomen/patología , ColonoscopíaRESUMEN
Halide perovskites are materials for future optical displays and solar cells. Electron donor-acceptor perovskite heterostructures with distinguishing halide compositions are promising for transporting and harvesting photogenerated charge carriers. Combined e-beam lithography and anion exchange are promising to develop such heterostructures but challenging to prepare multiple heterojunctions at desired locations in single crystals. We demonstrate swift laser trapping-assisted band gap engineering at the desired locations in MAPbBr3 microrods, microplates, or nanocrystal thin films. The built-in donor-acceptor double and multi-heterojunction structures let us transport and trap photogenerated charge carriers from wide-band gap bromide to narrow-band gap iodide domains. We discuss the charge carrier transport and trapping mechanisms from the viewpoints of engineered bands and band continuity. This work offers a convenient method for designing single-, double- and multi-heterojunction donor-acceptor halide perovskites for photovoltaic, photonic, and electronic applications.
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Colorectal cancer (CRC) is a heterogenous disease, and patients have differences in therapeutic response. However, the mechanisms underlying interpatient heterogeneity in the response to chemotherapeutic agents remain to be elucidated, and molecular tumor characteristics are required to select patients for specific therapies. Patient-derived organoids (PDOs) established from CRCs recapitulate various biological characteristics of tumor tissues, including cellular heterogeneity and the response to chemotherapy. Patient-derived organoids established from CRCs show various morphologies, but there are no criteria for defining these morphologies, which hampers the analysis of their biological significance. Here, we developed an artificial intelligence (AI)-based classifier to categorize PDOs based on microscopic images according to their similarity in appearance and classified tubular adenocarcinoma-derived PDOs into six types. Transcriptome analysis identified differential expression of genes related to cell adhesion in some of the morphological types. Genes involved in ribosome biogenesis were also differentially expressed and were most highly expressed in morphological types showing CRC stem cell properties. We identified an RNA polymerase I inhibitor, CX-5641, to be an upstream regulator of these type-specific gene sets. Notably, PDO types with increased expression of genes involved in ribosome biogenesis were resistant to CX-5461 treatment. Taken together, these results uncover the biological significance of the morphology of PDOs and provide novel indicators by which to categorize CRCs. Therefore, the AI-based classifier is a useful tool to support PDO-based cancer research.
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Adenocarcinoma , Antineoplásicos , Neoplasias Colorrectales , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos/farmacología , Inteligencia Artificial , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Organoides/metabolismoRESUMEN
INTRODUCTION: Hemodialysis patients are at a high risk of bloodstream infection (BSI). The risk factors for BSI-associated mortality, especially of unknown origin, remain uncertain. BSI of unknown origin is highly prevalent and related to high mortality. The present study aimed to investigate the clinical and microbiological characteristics of BSI and risk factors for BSI-associated mortality, including BSI of unknown origin, in hemodialysis patients. METHODS: This study was a single-center, retrospective study conducted from August 2012 to July 2019 in hemodialysis patients with BSI at Kawashima Hospital. Data related to demographics, clinical parameters, BSI sources, causative microorganisms, and initial treatments were collected from the medical records. The predictors for mortality associated with BSI were evaluated by logistic regression. RESULTS: Among 174 patients, 55 (30.9%) had the infection from unknown origin. The most frequent bacterium was Staphylococcus aureus. Low serum albumin level was an independent predictor of mortality due to BSI (odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.13-0.59). A lower serum albumin level (≤2.5 g/dL) was associated with poorer mortality. Methicillin-resistant Staphylococcus aureus (MRSA) was independently associated with mortality due to BSI of unknown origin (OR: 6.20, 95% CI: 1.04-37.1); 87.5% cases with BSI of unknown origin due to MRSA were not initially administrated anti-MRSA antibiotics, and in such patients, the mortality rate was 85.7%. CONCLUSIONS: Serum albumin level of 2.5 g/dL is a cutoff value, which could predict the mortality due to BSI in hemodialysis patients. Considering the high mortality rate of MRSA-associated BSI of unknown origin, wherein no focus of infection was identified in the present study, initial empiric treatment should be considered for MRSA-associated BSI of unknown origin.
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Diálisis Renal/efectos adversos , Sepsis/etiología , Infecciones Estafilocócicas/etiología , Anciano , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Estudios Retrospectivos , Factores de Riesgo , Sepsis/sangre , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Albúmina Sérica Humana/análisis , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
This study measures the acoustic power loss that occurs when an acoustic wave passes through a tube with an abrupt change in area. It is determined that the power loss is proportional to the third power of the velocity amplitude, and that the proportionality coefficient depends upon the area change ratio of the tube. On the other hand, the proportionality coefficient is almost independent of the acoustic impedance and frequency in the 80-250 Hz range. Furthermore, the effect of a tapered tube in reducing the coefficient is experimentally investigated. Based on these experimental results, an empirical estimation method for the acoustic power loss is proposed and validated using a high-pressure-helium-filled tube.
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There is increasing interest in the development of noble metal separation/recovery processes, especially for applications to "urban mining". Common separation/recovery processes for noble metals use a solvent (liquid-liquid) extraction technique in hydrometallurgy. However, these processes are time-consuming and not environmentally friendly, because they use organic solvents for sequential metal ion extractions. Electrowinning is an alternative approach for selective metal precipitation that involves controlling the redox potentials of electrodes but requires specialized equipment and generates hydrogen as a byproduct at the cathode surface under dilute conditions. In the present study, we investigated selective gold recovery from a homogenous aqueous solution containing a mixture of dilute HAuCl4 and H2PtCl6 (5.0 × 10-5 M each) and aromatic amino acid-containing peptides (2.0 × 10-4 M each). Gold selectivity was determined by analyzing the compositions of the solids and supernatants obtained from the reaction mixtures. A much higher gold selectivity (gold/platinum (Au/Pt) atomic ratio = 7.5) was obtained using an anthracene-containing peptide compared to peptides containing one or two naphthalene ring(s). Our proposed approach is applicable to the sequential separation of several noble metal ions, such as Au, palladium (Pd), Pt, iridium (Ir) and rhodium (Rh), and simply requires developing aromatics suitable for each noble metal of interest.
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Aminoácidos Aromáticos/química , Oro/aislamiento & purificación , Péptidos/química , Agua/análisis , Precipitación Química , Oro/análisis , Platino (Metal)/análisis , Platino (Metal)/aislamiento & purificación , SolucionesRESUMEN
The intestinal microbiome produces short-chain fatty acids (SCFAs) from dietary fiber and has specific effects on other organs. During endurance exercise, fatty acids, glucose, and amino acids are major energy substrates. However, little is known about the role of SCFAs during exercise. To investigate this, mice were administered either multiple antibiotics or a low microbiome-accessible carbohydrate (LMC) diet, before endurance testing on a treadmill. Two-week antibiotic treatment significantly reduced endurance capacity versus the untreated group. In the cecum acetate, propionate, and butyrate became almost undetectable in the antibiotic-treated group, plasma SCFA concentrations were lower, and the microbiome was disrupted. Similarly, 6-wk LMC treatment significantly reduced exercise capacity, and fecal and plasma SCFA concentrations. Continuous acetate but not saline infusion in antibiotic-treated mice restored their exercise capacity (P < 0.05), suggesting that plasma acetate may be an important energy substrate during endurance exercise. In addition, running time was significantly improved in LMC-fed mice by fecal microbiome transplantation from others fed a high microbiome-accessible carbohydrate diet and administered a single portion of fermentable fiber (P < 0.05). In conclusion, the microbiome can contribute to endurance exercise by producing SCFAs. Our findings provide new insight into the effects of the microbiome on systemic metabolism.
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Acetatos/metabolismo , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/fisiología , Condicionamiento Físico Animal , Resistencia Física/fisiología , Animales , Antibacterianos/farmacología , Butiratos/metabolismo , Fibras de la Dieta/metabolismo , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Resistencia Física/efectos de los fármacos , Propionatos/metabolismoRESUMEN
Colorectal cancer (CRC) is caused by genetic alterations, and comprehensive sequence analyses have revealed the mutation landscapes. In addition to somatic changes, genetic variations are considered important factors contributing to tumor development; however, our knowledge on this subject is limited. Familial adenomatous polyposis coli (FAP) is an autosomal-dominant inherited disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. FAP patients are classified into two major groups based on clinical manifestations: classical FAP (CFAP) and attenuated FAP (AFAP). In this study, we established 42 organoids from three CFAP patients and two AFAP patients. Comprehensive gene expression analysis demonstrated a close association between IFN/STAT signaling and the phenotypic features of FAP patients. Genetic disruption of Stat1 in the mouse model of FAP reduced tumor formation, demonstrating that the IFN/STAT pathway is causally associated with the tumor-forming potential of APC-deficient tumors. Mechanistically, STAT1 is downstream target of KRAS and is phosphorylated by its activating mutations. We found that enhanced IFN/STAT signaling in CFAP conferred resistance to MEK inhibitors. These findings reveal the crosstalk between RAS signaling and IFN/STAT signaling, which contributes to the tumor-forming potential and drug response. These results offer a rationale for targeting of IFN/STAT signaling and for the stratification of CRC patients.
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Transformación Celular Neoplásica/metabolismo , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Interferones/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Ratones , Modelos Biológicos , Organoides , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos , Técnicas de Cultivo de Tejidos , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Litotricia , Humanos , Litotricia/métodos , Masculino , Endoscopía del Sistema Digestivo/métodos , Endoscopía del Sistema Digestivo/instrumentación , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Femenino , Cálculos Biliares/cirugía , Cálculos Biliares/terapia , Cálculos Biliares/diagnóstico por imagenRESUMEN
Gold nanoparticles (AuNPs) show unique optical properties and catalytic activities, and their synthesis from gold ions has been widely studied. One of the additive-reagent-free and noncontact production procedures is the reduction of gold ions in solution by femtosecond laser pulses; however, the aggregation of AuNPs is unavoidable in homogeneous solution. Here, we report the synthesis of single-nanometer-sized AuNPs in a mixture of aqueous HAuCl4 solution and n-hexane (the mixture) and in aqueous HAuCl4 solution (the aqueous solution) by femtosecond laser irradiation in the absence of any additive reagents. Transmission electron microscopy revealed that circlelike colonies consisting of well-separated AuNPs were obtained from the mixture, while highly stacked and agglomerated AuNPs were obtained from the aqueous solution. The mean size of AuNPs in the mixture was nearly independent of the laser irradiation time, whereas that obtained in aqueous solution was gradually shifted to smaller size by laser irradiation period. We propose that the adsorption of primary AuNPs on the surface of hexane microdroplets and the fragmentation of large AuNPs in water by successive laser pulses retain single-nanometer-sized AuNPs in the mixture. The use of liquid-liquid interface on hexane microdroplets in aqueous solution provides a simple and useful environment to synthesize small AuNPs without the aid of surfactants or capping agents.