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In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/inmunología , Animales , Sistemas de Liberación de Medicamentos , Neoplasias/terapia , Neoplasias/inmunologíaRESUMEN
Background: The purpose of this study was to analyze the imaging risk factors for the development of 2-3 cm ground-glass nodules (GGN) for invasive lung adenocarcinoma and to establish a nomogram prediction model to provide a reference for the pathological prediction of 2-3 cm GGN and the selection of surgical procedures. Methods: We reviewed the demographic, imaging, and pathological information of 596 adult patients who underwent 2-3 cm GGN resection, between 2018 and 2022, in the Department of Thoracic Surgery, Second Affiliated Hospital of the Air Force Medical University. Based on single factor analysis, the regression method was used to analyze multiple factors, and a nomogram prediction model for 2-3 cm GGN was established. Results: (1) The risk factors for the development of 2-3 cm GGN during the invasion stage of the lung adenocarcinoma were pleural depression sign (OR = 1.687, 95%CI: 1.010-2.820), vacuole (OR = 2.334, 95%CI: 1.222-4.460), burr sign (OR = 2.617, 95%CI: 1.008-6.795), lobulated sign (OR = 3.006, 95%CI: 1.098-8.227), bronchial sign (OR = 3.134, 95%CI: 1.556-6.310), diameter of GGN (OR = 3.118, 95%CI: 1.151-8.445), and CTR (OR = 172.517, 95%CI: 48.023-619.745). (2) The 2-3 cm GGN risk prediction model was developed based on the risk factors with an AUC of 0.839; the calibration curve Y was close to the X-line, and the decision curve was drawn in the range of 0.0-1.0. Conclusion: We analyzed the risk factors for the development of 2-3 cm GGN during the invasion stage of the lung adenocarcinoma. The predictive model developed based on the above factors had some clinical significance.
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This study, using Jinan as a case study, systematically investigates the characteristics and geological genesis of loess-like silty clay in the middle and lower reaches of the Yellow River. The primary distribution of loess-like silty clay is revealed through field surveys, laboratory experiments, and previous literature reviews. The chemical and physical properties of the loess-like silty clay were examined, in addition to investigations into its mineral composition, microstructural characteristics, and engineering mechanical properties, in order to enhance comprehension of its attributes and formation mechanisms. The research suggests that the distinctive soil environment in the area has been influenced by numerous instances of the Yellow River overflow and channel shifts over its history, as well as the impacts of climate change, geological factors, and human activities. The primary sources of material for the loess-like silty clay consist of loess, Hipparion Red Clay, and paleosol layers. The discussion also addresses the impact of regional climate on the formation of mineral components. The aforementioned findings hold significant implications for advancing the understanding of historical climatic and paleogeographic shifts, as well as for addressing engineering challenges associated with the distribution of loess-like silty clay.
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Excessive fat deposition due to impaired fat metabolism in chickens is a major problem in the poultry industry. Nutritional interventions are effective solutions, but current options are limited. A safe phytochemical, rutin, has shown positive effects in animals, but its effect on lipid metabolism in poultry remains unknown. Hence, this study is to investigate the effects of rutin on egg quality, serum biochemistry, fat deposition, lipid peroxidation and hepatic lipid metabolism in post-peak laying hens. A total of 360 Taihang laying hens (49-week-old) were randomly divided into five groups and fed a basal diet (control group, 0%) and a basal diet supplemented with 300 (0.03%), 600 (0.06%), 900 (0.09%), and 1,200 (0.12%) mg rutin/kg feed, respectively. The results showed that eggshell strength was significantly (p < 0.05) higher in the dietary rutin groups, whereas yolk percentage (p < 0.05), total cholesterol (TC) (p < 0.01) and yolk fat ratio (p < 0.01) decreased linearly (p < 0.05) in the dietary rutin groups. Importantly, dietary rutin reduced serum triglyceride (TG) and TC levels, decreased abdominal lipid deposition and liver index (p < 0.05), and which concomitantly decreased hepatic lipid (TG, TC, and free fatty acid) accumulation (p < 0.05). An increase (p < 0.05) in total antioxidant capacity and superoxide dismutase activity and a decrease (p < 0.05) in malondialdehyde levels were also found. At the same time, the activities of hepatic lipase, acetyl-CoA carboxylase and malic enzyme in the liver were decreased (p < 0.05). Dietary rutin also increased (p < 0.05) the expression of fatty acid oxidation-related genes (carnitine palmitoyl transferase 1, peroxisome proliferator-activated receptor α, farnesoid X receptor). Additionally, it decreased fatty acid synthesis genes (sterol regulatory element binding protein-1c, acetyl-CoA carboxylase α, stearoyl-CoA desaturase 1) (p < 0.05). In conclusion, the addition of rutin (0.06-0.12%) to the diet improved the fat metabolism and increased liver antioxidant capacity in post-peak laying hens, and these positive changes improved egg quality to some extent.
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Introduction: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms. Methods: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation. Results: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1ß in MTX-induced rats. Discussion: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
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Enteritis , Inflamasomas , Metotrexato , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Ratas , Masculino , Enteritis/inducido químicamente , Enteritis/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Tea saponins have high surface-active and biological activities and are widely used in chemicals, food, pharmaceuticals, and pesticides. Tea saponins are usually extracted using ethanol or water, but both methods have their disadvantages, including a negative impact on the environment, high energy consumption, and low purity. In this study, we explored an effective process for extracting tea saponins from tea meal using deep eutectic solvents combined with ultrasonic extraction and enzymatic techniques. The experimental results showed that a high extraction efficiency of 20.93 ± 0.48% could be achieved in 20 min using an ultrasonic power of 40% and a binary DES consisting of betaine and ethylene glycol (with a molar ratio of 1:3) at a material-liquid ratio of 1:35 and that the purity of the tea saponins after purification by a large-pore adsorption resin reached 95.94%, which was higher than that of commercially available standard tea saponin samples. In addition, the extracted tea saponins were evaluated for their antioxidant and bacteriostatic activities using chemical and biological methods; the results showed that the tea saponins extracted using these methods possessed antioxidant properties and displayed significant antibacterial activity. Therefore, the present study developed a method for using deep eutectic solvents as an environmentally friendly technological solution for obtaining high-purity tea saponins from tea meal oil. This is expected to replace the current organic solvent and water extraction process and has great potential for industrial development and a number of possible applications.
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Lactobacillus acidophilus (L. acidophilus), the most prevalent probiotic, has demonstrated the ability to improve the relative abundance of intestinal microorganisms and boost immunity. However, the underlying mechanisms of these effects remain unclear. This study evaluated body weight, nutrient apparent digestibility, serum indices, and bacterial communities in Chinese rural dogs from a L. acidophilus supplementation group (Lactobacillus acidophilus, n = 6) and a control group (CON, n = 6). The results indicated that L. acidophilus had no significant impact on the body weight and apparent nutrient digestibility of Chinese rural dogs. In comparison with the CON group, L. acidophilus significantly reduced the levels of cholesterol (CHO) and increased the levels of IgA, IFN-α, and T-AOC. Bacterial diversity indices were significantly reduced in the LAC group compared to the CON groups, and MetaStat analysis demonstrated notable distinctions in 14 bacterial genera between the groups. These bacterial genera exhibited correlations with physiological indices such as CHO, IgA, IFN-α, and T-AOC. In conclusion, L. acidophilus can modulate lipid metabolism, immunity, and antioxidant capacity by regulating the relative abundance of specific bacterial communities, which helps dogs to adapt to today's lifestyle.
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OBJECTIVES: The study aimed to investigate the knowledge, attitude and practice (KAP) of contraceptive methods among women with an unplanned pregnancy, aiming to improve their reproductive health and increase their understanding of contraceptive methods. DESIGN: This is a cross-sectional study. SETTING: The study was conducted at the Maternity and Child Healthcare Hospital of Hubei between 20 November 2022 and 20 January 2023. PARTICIPANTS: Women with an unplanned pregnancy were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The questionnaire was in the Chinese language and included demographic data, KAP assessments. Multivariate linear regression was performed to explore the factors associated with knowledge or practice scores. RESULTS: During the study period, 510 participants with valid questionnaires were included. The KAP scores were 7.30±2.91, 32.61±3.13 and 28.58±3.59, respectively. Place of residence (urban vs non-urban; B=0.66, 95% CI 0.02 to 1.29, p=0.043) and educational level (master's degree or above vs post secondary or below; B=1.07, 95% CI 0.17 to 1.96, p=0.020) were positively associated with knowledge. Knowledge (B=0.25, 95% CI 0.17 to 0.32, p<0.001) and attitude (B=0.26, 95% CI 0.19 to 0.32, p<0.001) were positively associated with practice. CONCLUSIONS: This study indicates a low level of KAP regarding contraceptive methods among women facing unplanned pregnancies. Place of residence and educational level were positively associated with knowledge scores. These findings may help improve future sex education policies and programmes.
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Conocimientos, Actitudes y Práctica en Salud , Embarazo no Planeado , Embarazo , Niño , Femenino , Humanos , Estudios Transversales , Anticoncepción , EscolaridadRESUMEN
Sasanquasaponin (SQS), a secondary metabolite that is derived from Camellia seeds, reportedly possesses notable biological properties. However, the anti-inflammatory effects of SQS and its underlying mechanisms remain poorly explored. Herein, we aimed to investigate the anti-inflammatory properties of SQS against lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells, focusing on the nuclear factor-κB (NF-κB) and MAPK signaling pathways. SQS was isolated using a deep eutectic solvent and D101 macroporous adsorption resin and analyzed using high-performance liquid chromatography. The viability of LPS-stimulated RAW264.7 was assessed using the CCK-8 assay. The presence of reactive oxygen species (ROS) was evaluated using 2',7'-dichlorofluorescein-diacetate. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using reverse transcription-quantitative PCR and ELISA. Western blot was performed to analyze the protein expression of LPS-induced RAW264.7 cells. Herein, SQS exhibited anti-inflammatory activity: 30 µg/mL of SQS significantly reduced ROS generation, inhibited the LPS-induced expression of iNOS and COX-2, and attenuated the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. The anti-inflammatory activity was potentially mediated by inhibiting the phosphorylation of IκBα and p65 in the NF-κB signaling pathway and the phosphorylation of ERK and JNK in the MAPK signaling pathway. Accordingly, SQS could inhibit inflammation in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPK signaling pathways. This study demonstrated the potential application of SQS as an anti-inflammatory agent.
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FN-kappa B , Saponinas , Factor de Necrosis Tumoral alfa , Animales , Ratones , Antiinflamatorios/farmacología , Ciclooxigenasa 2/metabolismo , Interleucina-6/farmacología , Lipopolisacáridos/farmacología , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismoRESUMEN
Salvia miltiorrhiza, a prominent traditional Chinese medicinal resource, has been extensively employed in the management of cardiovascular and cerebrovascular ailments. Ensuring the consistency of S. miltiorrhiza raw materials revolves around the imperative task of maintaining stable tanshinones content and composition. An effective approach in this regard involves the utilization of endophytic fungi as inducers. Within this context, our study spotlights an endophytic fungus, Penicillium steckii DF33, isolated from the roots of S. miltiorrhiza. Remarkably, this fungus has demonstrated a significant capacity to boost the biosynthesis and accumulation of tanshinones. The primary objective of this investigation is to elucidate the underlying regulatory mechanism by which DF33 enhances and regulates the biosynthesis and accumulation of tanshinones. This is achieved through its influence on the differential expression of crucial CYP450 genes within the S. miltiorrhiza hairy roots system. The results revealed that the DF33 elicitor not only promotes the growth of hairy roots but also enhances the accumulation of tanshinones. Notably, the content of cryptotanshinone was reached 1.6452 ± 0.0925 mg g-1, a fourfold increase compared to the control group. Our qRT-PCR results further demonstrate that the DF33 elicitor significantly up-regulates the expression of most key enzyme genes (GGPPS, CPS1, KSL1, CYP76AH1, CYP76AH3, CYP76AK1, CYP71D411) involved in the tanshinone biosynthesis pathway. This effect is particularly pronounced in certain critical CYP450 genes and Tanshinone â ¡A synthase (SmTâ ¡AS), with their expression levels peaking at 7 days or 14 days, respectively. In summary, endophytic P. steckii DF33 primarily enhances tanshinone biosynthesis by elevating the expression levels of pivotal enzyme genes associated with the modification and transformation stages within the tanshinone biosynthesis pathway. These findings underscore the potential of employing plant probiotics, specifically endophytic and root-associated microbes, to facilitate the biosynthesis and transformation of vital constituents in medicinal plants, and this approach holds promise for enhancing the quality of traditional Chinese medicinal materials.
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Penicillium , Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Abietanos , Hongos , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
The aim of the study was to identify potent antioxidant peptides sourced from coix seed, analyze the structure-activity relationship through molecular docking and quantum chemical calculation. Molecular docking results showed that among thirteen peptides selected in silico, eight had favourable binding interaction with the Keap1-Kelch domain (2FLU). Promising peptides with significant binding scores were further evaluated using quantum calculation. It was shown that peptide FFDR exhibited exceptional stability, with a high energy gap of 5.24 eV and low Highest Occupied Molecular Orbitals (HOMO) and Lowest Unoccupied Molecular Orbitals (LUMO) values. Furthermore, FFDR displayed the capacity to enhance the expression of Nrf2-Keap1 antioxidant genes (CAT, SOD, GSH-Px) and improved cellular redox balance by increasing reduced glutathione (GSH) while reducing oxidized glutathione (GSSG) and malonaldehyde (MDA) levels. These findings highlight the potential of coix seed peptides in developing novel, effective and stable antioxidant-based functional foods.
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Antioxidantes , Coix , Humanos , Antioxidantes/análisis , Simulación del Acoplamiento Molecular , Células Hep G2 , Coix/química , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Péptidos/metabolismo , Semillas/químicaRESUMEN
Jinhua dry-cured ham (JDH) is a traditional fermented Chinese meat product. We studied the dynamic sensory and emotional profiles of JDHs obtained by five preparation methods and the corresponding release of sodium ions (Na+), potassium ions (K+), and volatile organic compounds (VOCs) during oral processing. The VOCs with salty taste enhancement abilities were screened based on the correlations of VOCs with salty flavor and concentration of Na and K ions with salty flavor. A trained sensory panel evaluated the saltiness enhancements of selected VOCs by using static and dynamic sensory methods. The results revealed that Na+, K+, and selected VOCs were mainly released during 0-10 s of the chewing process. The release of Na+ and K+ in JDH residue samples exhibited consistently decreasing trends, while in saliva, their concentrations increased. The VOCs showing a high correlation with Na+ and K+ and salty flavor have saltiness enhancement abilities in both NaCl solutions and NaCl + MSG mixtures. Odor-induced saltiness was pronounced at low salt concentrations (0.2% NaCl). The investigation demonstrated 16 VOCs exhibiting saltiness enhancement abilities, including 4 pyrazines, 5 acids, 4 sulfur-containing compounds, and 3 other compounds. The sensory evaluation suggested pyrazines and sulfur-containing compounds as good saltiness enhancers. 2-Furfuryl mercaptan significantly enhanced the salty sensation in the NaCl + MSG solutions when compared with MSG alone (p < 0.05). This research provides evidence that certain odorants identified in JDHs exhibit salty-enhancing properties, indicating their potential for salt reduction at the industrial level.
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Carne de Cerdo , Compuestos Orgánicos Volátiles , Cloruro de Sodio/farmacología , Odorantes/análisis , Gusto , Cloruro de Sodio Dietético , Sodio , Potasio , Pirazinas , Iones , AzufreRESUMEN
Mechanical faults are the main causes of abnormal opening, refusal operation, or malfunction of high-voltage circuit breakers. Accurately assessing the operational condition of high-voltage circuit breakers and delivering fault evaluations is essential for the power grid's safety and reliability. This article develops a circuit breaker fault monitoring device, which diagnoses the mechanical faults of the circuit breaker by monitoring the vibration information data. At the same time, the article adopts an improved deep learning method to train vibration information of high-voltage circuit breakers, and based on this, a systematic research method is employed to identify circuit breaker faults. Firstly, vibration information data of high-voltage circuit breakers is obtained through monitoring devices, this vibration data is then trained using deep learning methods to extract features corresponding to various fault types. Secondly, using the extracted features, circuit breaker faults are classified and recognized with a systematic analysis of the progression traits across various fault categories. Finally, the circuit breaker's fault type is ascertained by comparing the test set's characteristics with those of the training set, using the vibration data. The experimental results show that for the same type of circuit breaker, the accuracy of this method is over 95%, providing a more efficient, intuitive, and practical method for online diagnosis and fault warning of high-voltage circuit breakers.
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Aprendizaje Profundo , Reproducibilidad de los Resultados , Fenotipo , Proyectos de Investigación , Análisis de SistemasRESUMEN
Deep eutectic solvents (DESs) have physicochemical characteristics similar to those of ionic liquids but are more cost-effective, easier to produce, and less harmful to the environment, making them viable alternatives to ionic liquids. In this study, various DESs have been created to assess their potential as storage media for enzymes. The impact of the DES composition and water content on the thermal and storage stability of cellulase and pectinase was also investigated. Molecular simulation was used to examine the kinetic parameters of cellulase and pectinase in DESs with varying water levels based on choline chloride. The results demonstrated that the stability of the enzymes initially increased and then decreased with an increase in water content in DESs. The enzymes experienced secondary structural changes, leading to variations in fluorescence values. Ultimately, DESs can be utilized as a stabilizers for long-term enzyme preservation, and this study provides a theoretical basis for the coapplication of DESs and enzymes.
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Groundwater pollution at landfill sites poses a significant risk to human health and ecological security. However, efficiently tracking pollution plumes in a polluted aquifer with variable pollutants remains challenging. In order to track groundwater pollution plumes at landfill sites, an in-situ borehole hydrochemical and hydrodynamic profile (BHHP) method was developed. Total dissolved solids (TDS), oxidation-reduction potential (ORP), and ammonia nitrogen were selected as the hydrochemical indicators. Meanwhile, the hydrodynamic indicators included flow direction and flow velocity of groundwater. Among the three hydrochemical indicators, TDS and ORP were analyzed to be the prior alternative ones for the BHHP application. The BHHP method was successfully applied to track groundwater pollution plumes at a typical valley-type landfill site and its neighboring downstream zone. Consequently, four groundwater pollution plumes of different types and different scales were identified in both horizontal and vertical directions within the depth of 0-50 m, and the various pollution sources for the detected pollution plumes were revealed. Furthermore, the BHHP method was validated using sampling test results of groundwater chloride and chemical oxygen demand at the surveyed landfill site.
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Contaminantes Ambientales , Agua Subterránea , Humanos , Hidrodinámica , Contaminación Ambiental , Instalaciones de Eliminación de ResiduosRESUMEN
The first primary age-related tauopathy (PART) genome-wide association study confirmed significant associations of Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) genetic variants with PART, and highlighted a novel genetic variant rs56405341. Here, we perform a comprehensive analysis of rs56405341. We found that rs56405341 was significantly associated with C4orf33 mRNA expression, but not JADE1 mRNA expression in multiple brain tissues. C4orf33 was mainly expressed in cerebellar hemisphere and cerebellum, and JADE1 was mainly expressed in thyroid, and coronary artery. Meanwhile, we found significantly downregulated C4orf33 expression both AD and PSP compared with normal controls, respectively.
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Enfermedad de Alzheimer , Parálisis Supranuclear Progresiva , Tauopatías , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Parálisis Supranuclear Progresiva/genética , Parálisis Supranuclear Progresiva/metabolismo , Estudio de Asociación del Genoma Completo , ARN MensajeroRESUMEN
The volatiles in coffee play an important part in the overall flavor profile. In this study, GC-TOF/MS and GC×GC-TOF/MS were used to detect the volatile organic compounds (VOCs) in coffee samples of three different brands at three states (bean, powder, and brew). The differences between the two methods in characterizing VOCs were analyzed using the Venn diagram and PCA (principal component analysis). The important aroma-contributing compounds were further compared and analyzed. The results of the venn diagrams of different coffee samples showed that most VOCs existed in 2-3 kinds of coffee. The PCA of VOCs in different coffee samples showed that the VOCs detected by GC-TOF/MS could distinguish the coffee samples in the different states. GC×GC-TOF/MS was suitable for the further identification and differentiation of the different brands of coffee samples. In addition, pyridine, pyrrole, alcohols, and phenols greatly contributed to distinguishing coffee in three states, and alcohols greatly contributed to distinguishing the three brands of coffee.
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One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1ß. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.
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Enteritis , Inflamasomas , Ratas , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Metotrexato/toxicidad , Autofagia , Enteritis/inducido químicamente , Enteritis/tratamiento farmacológicoRESUMEN
Introduction: This study aimed to investigate the effects of Cyberlindnera jadinii supplementation on the growth performance, nutrient utilization, serum biochemistry, immunity, antioxidant status, and intestinal microbiota of raccoon dogs during the winter fur-growing period. Methods: Forty-five 135 (±5) day-old male raccoon dogs were randomly assigned to three dietary groups supplemented with 0 (group N), 1 × 109 (group L) and 5 × 109 CFU/g (group H) Cyberlindnera jadinii, with 15 raccoon dogs per group. Results: The results showed that Cyberlindnera jadinii in groups L and H improved average daily gain (ADG) and decreased feed-to-weight ratio (F/G) (P < 0.05). No significant difference was found in nutrient digestibility and nitrogen metabolism among the three groups (P > 0.05). Compared with group N, serum glucose levels were lower in groups L and H (P < 0.05). The levels of serum immunoglobulins A and G in group L were higher than those in the other two groups (P < 0.05), and the levels of serum immunoglobulins A and M in group H were higher than those in group N (P < 0.05). Supplementation with Cyberlindnera jadinii in groups L and H increased serum superoxide dismutase activity, and the total antioxidant capacity in group H increased compared with group N (P < 0.05). The phyla Bacteroidetes and Firmicutes were dominant in raccoon dogs. The results of principal coordinate analysis (PCoA) showed that the composition of microbiota in the three groups changed significantly (P < 0.05). The relative abundance of Campylobacterota was increased in the H group compared to the N and L groups (P < 0.05). The relative abundance of Sarcina was increased in group L compared with the other two groups (P < 0.05), while the relative abundance of Subdoligranulum and Blautia were decreased in group H compared with the other two groups (P < 0.05). Also, the relative abundance of Prevotella, Sutterella and Catenibacterium was higher in group L (P < 0.05) compared with group H. Discussion: In conclusion, dietary supplementation with Cyberlindnera jadinii improved growth performance, antioxidant activity, immune status, and improved intestinal microbiota in winter fur-growing raccoon dogs. Among the concentrations tested, 1 × 109 CFU/g was the most effective level of supplementation.