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Homocysteine, methionine, methylmalonic acid and 2-methylcitric acid are clinically relevant markers in the methionine, propionate, and cobalamin metabolism. This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously determining total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots. Three 3.2 mm discs were punched from each calibrator, quality control, and sample dried blood spot into a 96-well U-plate. Each sample was spiked with internal standards and extracted. Then the supernatant was transferred to another 96-well U-plate. After nitrogen drying, the dried residues were reconstituted, centrifuged, and the resulting supernatant was transferred to another 96-well plate for analysis. The method was performed using UPLC-MS/MS within 3 min, validated according to guidance documents, and applied to 72 samples from confirmed patients with methionine, propionate, and cobalamin metabolism disorders. The UPLC-MS/MS method provided satisfactory separation of the four analytes. The R2 values were ≥ 0.9937 for all analytes. The recoveries ranged from 94.17 to 114.29 %, and the coefficients of variation for intraday and interday precision were 0.19 % to 5.23 % and 1.02 % to 6.89 %, respectively. No significant carry-over was detected for the four analytes, and most of confirmed samples exhibited biomarker patterns characteristic of the relevant disorders. A simple and fast UPLC-MS/MS method was successfully developed, validated, and applied to clinical samples for the simultaneous determination of total homocysteine, methionine, methylmalonic acid, and 2-methylcitric acid in dried blood spots.
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Citratos , Pruebas con Sangre Seca , Homocisteína , Límite de Detección , Metionina , Ácido Metilmalónico , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Homocisteína/sangre , Homocisteína/análogos & derivados , Ácido Metilmalónico/sangre , Ácido Metilmalónico/análogos & derivados , Pruebas con Sangre Seca/métodos , Reproducibilidad de los Resultados , Metionina/sangre , Metionina/análogos & derivados , Metionina/química , Modelos Lineales , Citratos/sangre , Citratos/química , Masculino , Femenino , PreescolarRESUMEN
Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates. We have developed a novel MALDI-TOF MS assay that can identify common variants and deletions of CYP21A2 in the Chinese population. Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two CYP21A2 variants were detected in 30 patients and one CYP21A2 variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct CYP21A2 variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C > G (37.84%), followed by c.518T > A (21.62%) and exon 1-7 deletion (17.57%). The high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of CYP21A2. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.
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Hiperplasia Suprarrenal Congénita , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Esteroide 21-Hidroxilasa , Humanos , Esteroide 21-Hidroxilasa/genética , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/normas , Femenino , Masculino , Recién Nacido , Tamizaje Neonatal/métodos , Lactante , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Eliminación de GenRESUMEN
BACKGROUND: Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization. METHODS: We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis. RESULTS: Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15-1.63], P = 5.02 × 10-4) and waist circumference (OR [95% CI] = 1.39[1.21-1.61], P = 7.38 × 10-6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02-1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05-1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15-1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18-1.47], P < 0.001) and colorectal cancer. CONCLUSION: Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.
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Phosphorus-solubilizing bacteria (PSB) assisted phytoremediation of cadmium (Cd) pollution is an effective method, but the mechanism of PSB-enhanced in-situ remediation of Cd contaminated sediment by submerged plants is still rare. In this study, PSB (Leclercia adecarboxylata L1-5) was inoculated in the rhizosphere of Potamogeton crispus L. (P. crispus) to explore the effect of PSB on phytoremediation. The results showed that the inoculation of PSB effectively improved the Cd extraction by P. crispus under different Cd pollution and the Cd content in the aboveground and underground parts of P. crispus all increased. The µ-XRF images showed that most of the Cd was enriched in the roots of P. crispus. PSB especially showed positive effects on root development and chlorophyll synthesis. The root length of P. crispus increased by 51.7 %, 80.5 % and 74.2 % under different Cd pollution, and the Ca/Cb increased by 38.9 %, 15.2 % and 8.6 %, respectively. Furthermore, PSB enhanced the tolerance of P. crispus to Cd. The contents of soluble protein, MDA and H2O2 in 5 mg·kg-1 and 7 mg·kg-1 Cd content groups were decreased and the activities of antioxidant enzymes were increased after adding PSB. The results showed that the application of PSB was beneficial to the in-situ remediation of submerged plants.
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Biodegradación Ambiental , Cadmio , Enterobacteriaceae , Enzimas , Sedimentos Geológicos , Fosfatos , Potamogetonaceae , Cadmio/metabolismo , Clorofila/metabolismo , Enterobacteriaceae/metabolismo , Enzimas/metabolismo , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiología , Oxidación-Reducción , Fosfatos/metabolismo , Proteínas de Plantas/metabolismo , Potamogetonaceae/enzimología , Potamogetonaceae/crecimiento & desarrollo , Potamogetonaceae/metabolismo , Potamogetonaceae/microbiología , Solubilidad , Rizosfera , Raíces de Plantas/metabolismo , Contaminantes del Suelo/metabolismo , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismoRESUMEN
The precision of workpiece machining is critically influenced by the geometric errors in the kinematics of grind robots, which directly affect their absolute positioning accuracy. To tackle this challenge, this paper introduces a logistic-tent chaotic mapping Levenberg Marquardt algorithm designed to accurately identify and compensate for this geometric error. the approach begins with the construction of a forward kinematic model and an error model specific to the robot. Then the algorithm is adopted to identify and compensate for the geometric error. The method establishes a mapping interval around the initial candidate solutions derived from iterative applications of the Levenberg Marquardt algorithm. Within this interval, the logistic-tent chaotic mapping method generates a diverse set of candidate solutions. These candidates are evaluated based on their fitness values, with the optimal solution selected for subsequent iterations. Empirical compensation experiments have validated the proposed method's precision and effectiveness, demonstrating a 6% increase in compensation accuracy and a 47.68% improvement in efficiency compared to existing state-of-the-art approaches. This process not only minimizes the truncation error inherent in the Levenberg Marquardt algorithm but also significantly enhances solution efficiency. Moreover, simulation experiments on grind processes further validate the method's ability to significantly improve the quality of workpiece machining.
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The role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes remains unclear. In this study, we explored the role of miR-92a-3p in the ethanol-induced apoptosis of H9c2 cardiomyocytes and identified its target genes and signaling pathways. H9c2 cells were cultured with or without 100 mM ethanol for 24 h. The differential expression of miR-92a-3p was verified in H9c2 cells through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To manipulate the expression of miR-92a-3p, both a mimic and an inhibitor were transfected into H9c2 cells. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit and apoptosis-related antibodies were used for apoptosis detection through flow cytometry and Western blotting, respectively. Target genes were verified through RT-qPCR, Western blotting, and double luciferase reporter gene assays. miR-92a-3p was significantly overexpressed in ethanol-stimulated H9c2 cardiomyocytes (P < 0.001). After ethanol stimulation, H9c2 myocardial cells exhibited increased apoptosis. The apoptosis rate was higher in the miR-92a-3p mimic group than in the control group. However, the apoptosis rate was lower in the miR-92a-3p inhibitor group than in the control group, indicating that miR-92a-3p promotes the ethanol-induced apoptosis of H9c2 myocardial cells. RT-qPCR and Western blotting revealed that the miR-92a-3p mimic and inhibitor significantly regulated the mRNA and protein expression levels of mitogen- and stress-activated protein kinase 2 and cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2), suggesting that miR-92a-3p promotes the apoptosis of H9c2 cardiomyocytes by inhibiting the MSK2/CREB/Bcl-2 pathway. Therefore, the apoptosis of H9c2 cardiomyocytes increases after ethanol stimulation, and miR-92a-3p can directly target MSK2 and CREB3L2, thereby promoting the ethanol-induced apoptosis of H9c2 myocardial cells.
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Apoptosis , Etanol , MicroARNs , Miocitos Cardíacos , Apoptosis/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Etanol/farmacología , Animales , Ratas , Línea Celular , Transducción de Señal/efectos de los fármacosRESUMEN
The role of hypoxia in terms of affecting mammary epithelial cells (MECs) proliferation is closely associated with the milk synthesis of lactating mammals. Primary bovine MECs were cultured at 1, 6, 11, 16, and 21% O2 for 24 h. The results showed that cell proliferation decreased linearly, and hypoxic inducible factor (HIF)-1α expression increased linearly along with the declining O2. The linear increase in oxidative stress resulted in the accumulation of malondialdehyde and reactive oxygen species and decreased antioxidant enzyme activities following the reduced O2. Concerning mitochondria, the dynamin-related protein 1 showed improved expression, and optin atrophy protein 1 decreased along with the decreasing O2 gradient, which led to decreased mitochondrial mass and mitophagy emerging under 1% O2. Oxygen concentration-trend RNA-seq analysis was conducted. Specifically, HIF-1-MAPK (1% O2), PI3K-Akt-MAPK (6% O2), and p53-Hippo (11 and 16% O2) were found to primarily regulate cell proliferation in response to hypoxia compared with normoxia (21%), respectively. In conclusion, our study suggests that bMEC proliferation is suppressed in low-oxygen conditions, and is exacerbated following the reduced oxygen supply. The cross-oxygen gradient comparisons suggest that MAPK and Hippo, which are core pathways of mammary cell proliferation, are repressed by hypoxia via oxidative-stress-dependent signals.
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Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH. The combined effect of respiratory flow rates and particle size on delivery efficiency was systematically analyzed. The results showed that the nasopharyngeal peak deposition efficiency (DE) for BDS was approximately 2.25-3.73 times higher than that for MDS under low-flow, resting and high-flow respiratory conditions. Overall nasopharyngeal DEs for MDS were at a low level of below 16 %. For each respiratory flow rate, the BDS tended to achieve higher peak DEs (36.36 % vs 9.74 %, 37.80 % vs 14.01 %, 34.58 % vs 15.35 %) at smaller particle sizes (15 µm vs 17 µm, 10 µm vs 14 µm, 6 µm vs 9 µm). An optimal particle size exists for each respiratory flow rate, maximizing the drug delivery efficiency to the nasopharynx. The BDS is more effective in delivering drug aerosols to the nasal cavity and nasopharynx, which is crucial for early intervention in children with AH.
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Tonsila Faríngea , Humanos , Niño , Administración Intranasal , Aerosoles/uso terapéutico , Nasofaringe , Administración por Inhalación , Hipertrofia/tratamiento farmacológico , Tamaño de la PartículaRESUMEN
Microglia, as the intrinsic immune cells in the brain, are activated following ischemic stroke. Activated microglia participate in the pathological processes after stroke through polarization, autophagy, phagocytosis, pyroptosis, ferroptosis, apoptosis, and necrosis, thereby influencing the injury and repair following stroke. It has been established that polarized M1 and M2 microglia exhibit pro-inflammatory and anti-inflammatory effects, respectively. Autophagy and phagocytosis in microglia following ischemia are dynamic processes, where moderate levels promote cell survival, while excessive responses may exacerbate neurofunctional deficits following stroke. Additionally, pyroptosis and ferroptosis in microglia after ischemic stroke contribute to the release of harmful cytokines, further aggravating the damage to brain tissue due to ischemia. This article discusses the different functional states of microglia in ischemic stroke research, highlighting current research trends and gaps, and provides insights and guidance for further study of ischemic stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Microglía/metabolismo , Isquemia Encefálica/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular/metabolismo , Isquemia/metabolismoRESUMEN
To understand inhaled nanoparticle transport and deposition characteristics in pediatric nasal airways with adenoid hypertrophy (AH), with a specific emphasis on the olfactory region, virtual nanoparticle inhalation studies were conducted on anatomically accurate child nasal airway models. The computational fluid-particle dynamics (CFPD) method was employed, and numerical simulations were performed to compare the airflow and nanoparticle deposition patterns between nasal airways with nasopharyngeal obstruction before adenoidectomy and healthy nasal airways after virtual adenoidectomy. The influence of different inhalation rates and exhalation phase on olfactory regional nanoparticle deposition features was systematically analyzed. We found that nasopharyngeal obstruction resulted in significant uneven airflow distribution in the nasal cavity. The deposited nanoparticles were concentrated in the middle meatus, septum, inferior meatus and nasal vestibule. The deposition efficiency (DE) in the olfactory region decreases with increasing nanoparticle size (1-10 nm) during inhalation. After adenoidectomy, the pediatric olfactory region DE increased significantly while nasopharynx DE dramatically decreased. When the inhalation rate decreased, the deposition pattern in the olfactory region significantly altered, exhibiting an initial rise followed by a subsequent decline, reaching peak deposition at 2 nm. During exhalation, the pediatric olfactory region DE was substantially lower than during inhalation, and the olfactory region DE in the pre-operative models were found to be significantly higher than that of the post-operative models. In conclusions, ventilation and particle deposition in the olfactory region were significantly improved in post-operative models. Inhalation rate and exhalation process can significantly affect nanoparticle deposition in the olfactory region.
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Tonsila Faríngea , Nanopartículas , Humanos , Niño , Cavidad Nasal , Olfato , Hipertrofia , Simulación por ComputadorRESUMEN
Background and purpose: Revascularization surgery for patients with moyamoya disease (MMD) is very complicated and has a high rate of postoperative complications. This pilot study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) in adult MMD patients undergoing revascularization surgery. Methods: A total of 44 patients with MMD were enrolled in this single-center, open-label, prospective, parallel randomized study, including 22 patients assigned to the sham group and 22 patients assigned to the RIC group. The primary outcome was the incidence of major neurologic complications during the perioperative period. Secondary outcomes were the modified Rankin Scale (mRS) score at discharge, at 90 days post-operation, and at 1 year after the operation. The outcome of safety was the incidence of adverse events associated with RIC. Blood samples were obtained to monitor the serum concentrations of cytokines (VEGF, IL-6). Results: No subjects experienced adverse events during RIC intervention, and all patients could tolerate the RIC intervention in the perioperative period. The incidence of major neurologic complications was significantly lower in the RIC group compared with the control group (18.2% vs. 54.5%, P = 0.027). The mRS score at discharge in the RIC group was also lower than the control group (0.86 ± 0.99 vs. 1.18 ± 1.22, P = 0.035). In addition, the serum IL-6 level increased significantly at 7 days after bypass surgery in the control group and the serum level of VEGF at 7 days post-operation in the RIC group. Conclusion: In conclusion, our study demonstrated the neuroprotective effect of RIC by reducing perioperative complications and improving cerebral blood flow in adult MMD patients undergoing revascularization surgery. Thus, RIC seems to be a potential treatment method for MMD. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05860946.
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Objective:The nasal swell bodyï¼NSBï¼ consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional ï¼3Dï¼ nasal models were reconstructed from computed tomography ï¼CTï¼ scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamicsï¼CFDï¼ method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:â The average width and length of the NSB in healthy adults in Northwest China were ï¼12.85±1.74ï¼ mm and ï¼28.30±1.92ï¼ mm, respectively. â¡After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. â¢There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; â£After NSB removal, the deposition fractionï¼DFï¼ of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal wereï¼22.79±6.61ï¼% vs ï¼30.70±12.27ï¼%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal wereï¼24.12±6.59ï¼% vs ï¼17.00±5.57ï¼%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: â nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; â¡nasal heating and humidification were not significantly changed; â¢the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
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Artemisia , Cavidad Nasal , Adulto , Humanos , Estudios Transversales , Cavidad Nasal/cirugía , Alérgenos , Polen , HidrodinámicaRESUMEN
BACKGROUND: The cognitive impairment after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) has become a crucial clinical concern that cannot be ignored. However, studies on the early warning factors of cognitive impairment after PCI are still insufficient. METHODS: This study reviewed the postoperative cognitive function of 284 patients who underwent PCI in our hospital from June 2019 to June 2022. During the 21-day follow-up, all participants included in the analysis were divided into the cognitive impairment (CI) group (nâ=â82) and the noncognitive impairment (NCI) group (nâ=â186) according to their Montreal cognitive assessment (MoCA) scale. Participants' serum 25(OH)D3 levels on admission and serum neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) and S100ß levels were measured 21âdays after surgery. RESULTS: Age more than 65âyears, hypertension, operation time longer than 60 min, left ventricular ejection fraction less than 50% and serum 25(OH)D3 less than 31.41âng/ml were the risk factors for cognitive dysfunction in ACS patients 21âdays after PCI. Serum levels of 25(OH)D3, NSE, S100ß and GFAP were significantly higher in patients with cognitive impairment than in patients without cognitive impairment. CONCLUSION: Postoperative serum NSE, S100ß and GFAP levels were significantly negatively correlated with serum 25(OH)D3 levels at admission. The serum 25(OH)D3 level is a risk factor and predictor of cognitive impairment in patients with ACS after PCI.
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Síndrome Coronario Agudo , Disfunción Cognitiva , Intervención Coronaria Percutánea , Humanos , Anciano , Vitamina D , Síndrome Coronario Agudo/diagnóstico , Intervención Coronaria Percutánea/efectos adversos , Volumen Sistólico , Función Ventricular Izquierda , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiologíaRESUMEN
Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO2, Au, and NaYF4 nanoparticles at low doses, can promote lipid degradation and alleviate steatosis in the liver of male mice. We show that low-level uptake of nanoparticles evokes an unusual antioxidant response in hepatocytes by promoting Ces2h expression and consequently enhancing ester hydrolysis. This process can be implemented to treat specific hepatic metabolic disorders, such as fatty liver in both genetic and high-fat-diet obese mice without causing observed adverse effects. Our results demonstrate that low-dose nanoparticle administration may serve as a promising treatment for metabolic regulation.
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Hígado Graso , Nanopartículas , Enfermedad del Hígado Graso no Alcohólico , Masculino , Ratones , Animales , Antioxidantes/metabolismo , Metabolismo de los Lípidos , Especies Reactivas de Oxígeno/metabolismo , Hígado/metabolismo , Hígado Graso/metabolismo , Hepatocitos/metabolismo , Dieta Alta en Grasa/efectos adversos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratones Endogámicos C57BLRESUMEN
The previous documentation has shown the role of resistant starch in promoting intestinal health, while the effect of starch-lipid complex (RS5) on colitis remains unclear. This study aimed to investigate the effect and potential mechanism of RS5 in colitis. We prepared RS5 complexes by combining pea starch with lauric acid. Mice with dextran sulfate sodium-induced colitis were treated with either RS5 (3.25 g/kg) or normal saline (10 mL/kg) for seven days, and the effects of pea starch-lauric acid complex on mice were observed. The RS5 treatment significantly attenuated weight loss, splenomegaly, colon shortening, and pathological damage in mice with colitis. Compare with the DSS group, cytokines levels, such as tumor necrosis factor-α and interleukin-6 in both serum and colon tissue was significantly decreased in RS5 treatment group, while the gene expression of interleukin-10 and the expression of mucin 2, zonula occludens-1, Occludin, and claudin-1 in the colon was significantly upregulated in RS5 treatment group. In addition, RS5 treatment altered the gut microbiota structure of colitis mice by increasing the abundance of Bacteroides and decreasing Turicibacter, Oscillospira, Odoribacter, and Akkermansia. The dietary composition could be exploited to manage colitis by attenuating inflammation, restoring the intestinal barrier, and regulating gut microbiota.
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Colitis , Pisum sativum , Animales , Ratones , Sulfato de Dextran/toxicidad , Almidón/efectos adversos , Almidón/metabolismo , Ratones Endogámicos C57BL , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon/metabolismo , Modelos Animales de EnfermedadRESUMEN
To improve the diagnostic accuracy of adenoid hypertrophy (AH) in children and prevent further complications in time, it is important to study and quantify the effects of different degrees of AH on pediatric upper airway (UA) aerodynamics. In this study, based on computed tomography (CT) scans of a child with AH, UA models with different degrees of obstruction (adenoidal-nasopharyngeal (AN) ratio of 0.9, 0.8, 0.7, and 0.6) and no obstruction (AN ratio of 0.5) were constructed through virtual surgery to quantitatively analyze the aerodynamic characteristics of UA with different degrees of obstruction in terms of the peak velocity, pressure drop (â³P), and maximum wall shear stress (WSS). We found that two obvious whirlpools are formed in the anterior upper part of the pediatric nasal cavity and in the oropharynx, which is caused by the sudden increase in the nasal cross-section area, resulting in local flow separation and counterflow. In addition, when the AN ratio was ≥ 0.7, the airflow velocity peaked at the protruding area in the nasopharynx, with an increase 1.1-2.7 times greater than that in the nasal valve area; the â³P in the nasopharynx was significantly increased, with an increase 1.1-6.8 times greater than that in the nasal cavity; and the maximum WSS of the posterior wall of the nasopharynx was 1.1-4.4 times larger than that of the nasal cavity. The results showed that the size of the adenoid plays an important role in the patency of the pediatric UA.
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Tonsila Faríngea , Humanos , Niño , Tonsila Faríngea/diagnóstico por imagen , Hidrodinámica , Nariz , Nasofaringe/diagnóstico por imagen , HipertrofiaRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic mucosal inflammation of the nasal cavity and sinuses. It is classified into CRS without nasal polyps and CRS with nasal polyps (CRSwNP). CRSwNP has high recurrence, especially CRSwNP with massive eosinophil infiltration which is mediated by type 2 inflammatory response. Melatonin is a hormone secreted by the pineal gland, it has powerful antioxidant and anti-inflammatory effects in addition to regulating biological rhythms. There are no studies on melatonin for the treatment of CRS, so we aimed to explore whether melatonin could be used for the treatment of CRS. MATERIALS AND METHODS: In this study, we used melatonin to treat a cell model of CRS. Subsequently, MTT assay was performed to examine the cell viability of human nasal epithelial cells (HNEpCs), a reactive oxygen species (ROS) kit to detect ROS production, a malondialdehyde (MDA) kit to detect the MDA content in the cell culture supernatant, and an apoptosis kit and Western blot analysis to detect apoptosis. The expressions of Nrf2, HO-1, IL-33, TSLP, and IL-25 were detected by Western blot analysis. RESULTS: Melatonin improved the viability of HNEpCs, reduced lipopolysaccharide-induced ROS, reduced the MDA content, and inhibited their apoptosis. More importantly, melatonin reduced the expression of IL-33 and TSLP, an important phenomenon for the treatment of CRSwNP. CONCLUSION: Melatonin protects HNEpCs from damage in inflammation and reduces IL-33 and TSLP expression of HNEpCs.