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Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages.
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Privação do Sono , Ácido Tióctico , Humanos , Camundongos , Animais , Privação do Sono/complicações , Privação do Sono/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/farmacologia , Retina/metabolismo , Ácido Tióctico/farmacologia , Ácido Tióctico/metabolismoRESUMO
BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.
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Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Medição de Risco/métodos , Programas de Rastreamento/métodos , Reprodutibilidade dos TestesRESUMO
In traditional Chinese medicine, the two commodity forms of Cassiae Semen Raw and Prepared Cassiae Semen, exert different clinical applications, in which Prepared Cassiae Semen is commonly used to treat liver and eye diseases. However, the material basis of Raw and Prepared Cassiae Semen remains unclear due to the limited studies on their overall composition and metabolism in vivo. In this study, an integrated analysis strategy based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry was established to systematically screen the prototype and metabolite constituents of Raw and Prepared Cassiae Semen. Automatic matching analysis of metabolites was performed on Compound Discoverer software based on the function of predicting metabolites. Using this strategy, a total of 77 compounds in Raw Cassiae Semen and 71 compounds in Prepared Cassiae Semen were identified. Furthermore, in vivo study, 46 prototype components and 104 metabolites from the Raw Cassiae Semen group and 41 prototype components and 87 metabolites from the Prepared Cassiae Semen group were unambiguously or preliminarily identified in mice (plasma, urine, feces, eye, and liver). This is the first study of chemical component analysis and in vivo metabolite profiling of Raw and Prepared Cassiae Semen.
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Medicamentos de Ervas Chinesas , Camundongos , Animais , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Sementes/químicaRESUMO
Lanbuzheng (Geum japonicum Thunb. var. chinense Bolle), a plant found in Southwest China, is a traditional Chinese medicine that promotes hematopoiesis and antioxidant functions. Many of its chemical constituents remain unknown, posing challenges both to understanding its pharmacological mechanisms and to conducting quality control research. In this work, ultra-high performance liquid chromatography coupled with quadrupole Exactive Orbitrap high-resolution mass spectroscopy was used for profiling the composition of Lanbuzheng. Using positive ion mass spectrometry data enriched from Lanbuzheng extract, feature-based molecular networking (FBMN) was constructed and associated with Mass2Motifs substructures using MS2LDA. Prediction and validation of unknown constituents of Lanbuzheng using a custom-built compound library, SIRIUS, and network annotation propagation, achieved a semi-automated annotation of the molecular network. Based on the custom-built library comprising 206 compounds and the FBMN clustering results, the constituents in Lanbuzheng primarily include tannins, triterpenes, flavonoids, and phenolics. Using only 65 pre-identified compounds as references, 210 unknown compounds were annotated in various polarity regions of Lanbuzheng. Results of the current work indicate that molecular networks enable the efficient annotation of compounds in complex systems, laying the groundwork for the preliminary identification of pharmacologically active constituents of Lanbuzheng.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Estrutura MolecularRESUMO
In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.
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Doenças Cardiovasculares , Aprendizado de Máquina , Humanos , Reprodutibilidade dos Testes , AlgoritmosRESUMO
INTRODUCTION: Schisandrae Chinensis Fructus (SCF), a traditional Chinese medicine, has been used in treating virtual injury and strain since ancient times. The Chinese Pharmacopoeia reveals that SCF includes raw (RSCF) and vinegar-processed (VSCF) decoction pieces. OBJECTIVE: This study developed an effective method combining the electronic eye (e-eye), electronic tongue (e-tongue), and chemometrics to discriminate RSCF and VSCF from the perspective of chemical composition, color, and taste. MATERIAL AND METHODS: First, RSCF were collected and processed into VSCF, and their color parameters, e-tongue sensory properties, high-performance liquid chromatography (HPLC) and ultra-HPLC (UPLC) characteristic fingerprints, and nominal ingredients were determined. Multivariate statistical analyses, including principal component, linear discriminant, similarity, and partial least squares discriminant analyses, were conducted. RESULTS: HPLC and UPLC fingerprints were established, demonstrating a > 0.900 similarity. The content determination indicated increased schisantherin A, schisantherin B, and schisandrin A contents in VSCF. The e-eye data demonstrated a > 1.5 total color difference before and after processing ΔE*ab, indicating the significantly changed sample color and appearance before and after processing. The e-tongue technology was used to quantitatively characterize the taste of RSCF and VSCF. The t-test revealed significantly reduced sourness, aftertaste-bitter, and aftertaste-astringent values of SCF after vinegar processing. Principal component and partial least squares discriminant analyses indicated that e-eye and e-tongue realize the rapid RSCF and VSCF identification. CONCLUSION: The proposed comprehensive strategy of electronic eye and electronic tongue combined with chemometrics demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be developed into a novel and accurate method for discriminating RSCF and VSCF.
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OBJECTIVES: The objectives of this study were to evaluate the cost-effectiveness and cost-benefit of fluoride varnish (FV) interventions for preventing caries in the first permanent molars (FPMs) among children in rural areas in Guangxi, China. METHODS: This study constituted a secondary analysis of data from a randomised controlled trial, analysed from a social perspective. A total of 1,335 children aged 6-8 years in remote rural areas of Guangxi were enrolled in this three-year follow-up controlled study. Children in the experimental group (EG) and the control group (CG) received oral health education and were provided with a toothbrush and toothpaste once every six months. Additionally, FV was applied in the EG. A decision tree model was developed, and single-factor and probabilistic sensitivity analyses were conducted. RESULTS: After three years of intervention, the prevalence of caries in the EG was 50.85%, with an average decayed, missing, and filled teeth (DMFT) index score of 1.12, and that in the CG was 59.04%, with a DMFT index score of 1.36. The total cost of caries intervention and postcaries treatment was 42,719.55 USD for the EG and 46,622.13 USD for the CG. The incremental cost-effectiveness ratio (ICER) of the EG was 25.36 USD per caries prevented, and the cost-benefit ratio (CBR) was 1.74 USD benefits per 1 USD cost. The results of the sensitivity analyses showed that the increase in the average DMFT index score was the largest variable affecting the ICER and CBR. CONCLUSIONS: Compared to oral health education alone, a comprehensive intervention combining FV application with oral health education is more cost-effective and beneficial for preventing caries in the FPMs of children living in economically disadvantaged rural areas. These findings could provide a basis for policy-making and clinical choices to improve children's oral health.
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Cariostáticos , Análise Custo-Benefício , Índice CPO , Cárie Dentária , Fluoretos Tópicos , Humanos , Cárie Dentária/prevenção & controle , Cárie Dentária/economia , China , Fluoretos Tópicos/uso terapêutico , Fluoretos Tópicos/economia , Criança , Cariostáticos/uso terapêutico , Cariostáticos/economia , Masculino , Feminino , Educação em Saúde Bucal/economia , Escovação Dentária/economia , Cremes Dentais/uso terapêutico , Cremes Dentais/economia , Seguimentos , Dente Molar , Árvores de DecisõesRESUMO
This study aims to reveal the dynamics of the HPLC fingerprint, chromaticity values, and main chemical components of Mori Cortex during the stir-frying process. The fingerprints of raw and processed products of Mori Cortex were established. The content of mulberroside A, oxyresveratrol, kuwanon G, and kuwanon H in the samples and the chromaticity values of the samples were determined. Furthermore, the similarity evaluation of fingerprints and the correlation analysis between fingerprints and chromaticity values were carried out. The results showed that the fingerprints of raw and processed products of Mori Cortex had high similarity, and the overall changes in the content of the main chemical components in the stir-frying process were similar. According to the experience, when the stir-frying is moderate, the total chromaticity value difference |ΔE~*_(ab)| is above 1.5. With the extension of stir-frying time, the L~* and E~*_(ab) values keep decreasing, and the a~* value keeps increasing. The results of the correlation analysis between fingerprints and chromaticity values showed that peaks 1(5-hydroxy maltol), 2(mulberroside A), 3, 4, 6, 7, 11(oxyresveratrol), 14, 17(kuwanon G), and 18(kuwanon H) had significant correlations with the chromaticity values. Quantitative analysis of the four components with higher content showed that the content of the four components decreased to varying degrees when the stir-frying was excessive. In addition, 5-hydroxy maltol was produced after stir-frying of Mori Cortex, and the fingerprint and chromaticity values showed regular changes during the stir-frying process. The chromaticity can be included in the evaluation of the stir-frying process of Mori Cortex, which provides a reference for standardizing the quality of stir-fried Mori Cortex.
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Medicamentos de Ervas Chinesas , Morus , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Morus/química , Dissacarídeos , EstilbenosRESUMO
INTRODUCTION: Metabolic reprogramming is one of the important mechanisms of cell differentiation, and different cells have different preferences for energy sources. During the differentiation of naive CD4 + T cells into Th17 and Treg cells, these cells show specific energy metabolism characteristics. Th17 cells depend on enhanced glycolysis, fatty acid synthesis, and glutaminolysis. In contrast, Treg cells are dependent on oxidative phosphorylation, fatty acid oxidation, and amino acid depletion. As a potent antimalarial drug, artesunate has been shown to modulate the Th17/Treg imbalance and regulate cell metabolism. METHODOLOGY: Relevant literatures on ART, cellular metabolism, glycolysis, lipid metabolism, amino acid metabolism, CD4 + T cells, Th17 cells, and Treg cells published from January 1, 2010 to now were searched in PubMed database. CONCLUSION: In this review, we will highlight recent advances in which artesunate can restore the Th17/Treg imbalance in disease states by altering T-cell metabolism to influence differentiation and lineage selection. Data from the current study show that few studies have focused on the effect of ART on cellular metabolism. ART can affect the metabolic characteristics of T cells (glycolysis, lipid metabolism, and amino acid metabolism) and interfere with their differentiation lineage, thereby regulating the balance of Th17/Treg and alleviating the symptoms of the disease.
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Linfócitos T Reguladores , Células Th17 , Células Th17/metabolismo , Artesunato/farmacologia , Artesunato/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Ácidos Graxos/metabolismoRESUMO
In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 â and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.
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Medicamentos de Ervas Chinesas , Vitex , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Vitex/químicaRESUMO
Polygonatum cyrtonema rhizome (PCR), the dried sweet rhizome of Polygonatum cyrtonema Hua, is commonly used as a tonic remedy and a functional food in Asia, Europe, and North America. Multiple components, including secondary metabolites, monosaccharides, oligosaccharides, and polysaccharides, collectively contribute to the therapeutic effects of PCR. Processing time exerts a significant influence on the quality of PCR, but the various processing stages have not been comprehensively chemically profiled. It is urgent to study processing-induced chemical variations in PCR to control the processing degree. In this study, multiple chromatographic and mass spectrometric techniques were used in combination with multivariate statistical analysis to perform qualitative and quantitative research on secondary metabolites and carbohydrates in PCR during processing. The results demonstrated that PCR processing can be divided into three stages, namely the raw stage (0 h), the middle stage (1-6 h), and the late stage (8-18 h). Twenty differential compounds were screened from secondary metabolites and oligosaccharides to distinguish PCR in different processing stages. Furthermore, the chemical variations of Polygonatum cyrtonema polysaccharides (PCP) also entered a new stage after processing for 6 h. Multiple chemical mechanisms, including hydrolysis, oxidative decomposition, dehydration, Maillard reaction, and polymerization were involved in the processing. This work provides a scientific basis to reveal the relationship between processing stage and chemical variations.
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Polygonatum , Carboidratos/química , Glicômica , Monossacarídeos/análise , Polygonatum/química , Polissacarídeos/análise , Rizoma/químicaRESUMO
The underlying mechanisms of complement activation in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD) are not fully understood. Overaccumulation of all-trans-retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b-9 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin-1ß production was provoked in both atRAL-treated RPE cells and microglia/macrophages. Coincubation of RPE cells with interleukin-1 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine/paracrine IL-1/IL-1R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.
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Ativação do Complemento/efeitos dos fármacos , Via Alternativa do Complemento/efeitos dos fármacos , Interleucina-1/metabolismo , Receptores de Interleucina-1/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Retinaldeído/farmacologia , Transdução de Sinais , Acetilcisteína/farmacologia , Animais , Células Cultivadas , Fator B do Complemento/metabolismo , Regulação para Baixo , Humanos , Interleucina-1/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Suínos , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Hyperlipidemia impacts on various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. However, its influence, if any, on ocular tissues is largely unknown. Herein, we developed hyperlipidemic murine models by feeding 4-week-old male wild-type mice with a high-fat diet and apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet or standard diet to investigate the corneal endothelial change under hyperlipidemic conditions. Oil Red O staining showed an accumulation of lipid droplets in corneal endothelial cells (CECs) of hyperlipidemic mice. Other manifestations included a reduced cell density and distorted cell morphology, a disruption of the endothelial cell tight junctions and adhesion junctions, a reduced number of surface microvilli, down-regulation of Na+-K+-ATPase expression and function, activation of oxidative stress, changes in mitochondrial ultrastructure, and increased apoptosis. CEC recovery after injury, moreover, was diminished in hyperlipidemic mice; and high palmitate levels were found in the aqueous humor. In vitro hyperlipemia model, moreover, was found to be associated with dose-dependent CEC cytotoxicity, altered cell morphology, reduced pump function, and an induction of oxidative stress, leading to functional and pathologic changes in the corneal endothelium.
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Apolipoproteínas E/genética , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/complicações , Estresse Oxidativo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Apoptose , Sobrevivência Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Hiperlipidemias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Mitocôndrias/ultraestrutura , Palmitatos/toxicidade , ATPase Trocadora de Sódio-Potássio/genética , Junções Íntimas/metabolismo , Junções Íntimas/patologiaRESUMO
This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.
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Córtex Cerebral/fisiopatologia , Conectoma , Corpo Caloso/fisiopatologia , Oftalmopatia de Graves/fisiopatologia , Rede Nervosa/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Feminino , Oftalmopatia de Graves/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Doenças do Nervo Óptico/diagnóstico por imagemRESUMO
An UPLC-MS/MS method was developed to simultaneously determine complanatoside A and complanatoside B in rat plasma with rutin as the internal standard and applied to examine the effect of salt-processing on pharmacokinetics of these two flavonoid glycosides. The pharmacokinetic parameters were estimated using DAS 3.2.6 and subjected to independent sample t-test with SPSS 23.0. No significant difference in T_(max) of complanatoside B was observed between the raw and processed groups; however, in the processed group, C_(max) and AUC_(0-12 h) of complanatoside B increased obviously(P<0.05), while MRT_(0-12 h) decreased from(3.34±0.44) h to(1.81±0.36) h(P<0.05). C_(max) [(14.72±11.13) µg·L~(-1)] and MRT_(0-24) [(3.93±0.26) h] of complanatoside A in the raw group were statistically different from those [(35.64±21.99) µg·L~(-1),(1.43±0.24) h] in the processed group(P<0.05). As a result, salt-processing can facilitate the in vivo adsorption and accelerate the excretion of complanatoside A and complanatoside B.
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Astrágalo , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Glicosídeos , Ratos , SêmenRESUMO
Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMP-activated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway.
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Proteínas Quinases Ativadas por AMP/metabolismo , Proteína de Ligação a CREB/metabolismo , Doença da Artéria Coronariana/enzimologia , GTP Fosfo-Hidrolases/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/toxicidade , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Mitofagia/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Apoptose/efeitos dos fármacos , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , PTEN Fosfo-Hidrolase/genética , Interferência de RNA , Transdução de SinaisRESUMO
As the peroxisome proliferator - activated receptor alpha (PPARα) agonist, fenofibrate has been widely used to be a good lipid-regulating drug in the clinical application. In this study, we investigated the mechanism by which keratocytes inhibit the corneal neovascularization (CNV) through PPARα - activation. To do this, the CNV model was established by alkali burn, followed by being divided into three groups including control, fenofibrate and vehicle group. The expression of VEGFr3, MMP13 and PPARα in corneas of normal mouse and alkali-burned mouse was determined via quantitative RT- PCR (qRT-PCR) and Western blot analysis (WB). The CNV area was observed under a slit lamp microscope. The location of PPARα expression in the corneas was determined via immunohistochemistry. In cultured primary keratocytes, the effect of fenofibrate on PPARα, VEGFr3 and MMP13 expression was determined by qRT-PCR and WB. Besides, PPARα knockout (PPARα-/-) mouse CNV and keratocytes model were established to further confirm the effect of PPARα on VEGFr3 and MMP13 expression. We found that PPARα was expressed in epithelium, stroma and endothelium of the normal cornea, however, with relatively low level in the corneal stroma. Meanwhile, its expression was decreased markedly in the cornea during the stage of CNV formation. After treatment of fenofibrate, PPARα expression was promoted and the expression of VEGFr3 and MMP13 was inhibited in both CNV mice model and primary keratocytes, and CNV areas were decreased in CNV mice model. However, the results in PPARα-/- CNV and keratocytes model were opposite. Our results suggest that keratocytes could promote the expression of VEGFr3 and MMP13, and CNV formation through PPARα downregulation.
Assuntos
Neovascularização da Córnea/patologia , Regulação da Expressão Gênica , Queratinócitos/patologia , PPAR alfa/antagonistas & inibidores , RNA/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Western Blotting , Células Cultivadas , Neovascularização da Córnea/genética , Neovascularização da Córnea/metabolismo , Modelos Animais de Doenças , Queratinócitos/metabolismo , Camundongos , Camundongos Knockout , PPAR alfa/metabolismo , Coelhos , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND The aim of this study was to explore potential changes in brain function network activity in patients with adult strabismus with amblyopia (SA) using the voxel-wise degree centrality (DC) method. MATERIAL AND METHODS We enrolled 15 patients with SA (6 males, 9 females) and 15 sex-matched healthy controls (HCs). All subjects completed resting functional magnetic resonance imaging scans. Independent-sample t tests and receiver operating characteristic (ROC) curves were used to assess DC value differences between groups, and Pearson correlation analysis was performed to evaluate correlations between DC-changed brain regions and clinical data of patients with SA. RESULTS Compared with the HC group, DC values that were lower in patients with SA included the left middle frontal gyrus and bilateral angular gyri. Increases were observed in the left fusiform gyrus, right lingual gyrus, right middle occipital gyrus, right postcentral gyrus, and left paracentral lobule. However, DC values were not correlated with clinical manifestations. ROC curve analysis showed high accuracy. CONCLUSIONS We found abnormal neural activity in specific brain regions in patients with SA. Specifically, we observed significant changes in DC values compared to HCs. These changes may be useful to identify the specific mechanisms involved in brain dysfunction in SA.
Assuntos
Ambliopia/diagnóstico por imagem , Ambliopia/fisiopatologia , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética , Rede Nervosa/fisiopatologia , Descanso , Estrabismo/diagnóstico por imagem , Estrabismo/fisiopatologia , Adulto , Ambliopia/complicações , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Curva ROC , Estrabismo/complicações , Adulto JovemRESUMO
BACKGROUND We used fractional amplitude of low-frequency fluctuation (fALFF) technology to investigate spontaneous cerebral activity in patients with monocular blindness (MB) and in healthy controls (HCs). MATERIAL AND METHODS Thirty MB patient and 15 HCs were included in this study. All subjects were scanned by resting-state functional magnetic resonance imaging (rs-fMRI). The independent sample t test and chi-squared test were applied to analyze demographics of MB patients and HCs. The 2-sample t test and receiver operating characteristic (ROC) curves were applied to identify the difference in average fALFF values between MB patients and HCs. Pearson's correlation analysis was applied to explore the relationship between the average fALFF values of brain areas and clinical behavior in the MB group. RESULTS MB patients had lower fALFF values in the left anterior cingulate and higher fALFF values in the left precuneus and right and left inferior parietal lobes than in HCs. Moreover, the mean fALFF values of MB patients in the left anterior cingulate had negative correlations with the anxiety scale score (r=-0.825, P<0.001) and the depression scale score (r=-0.871, P<0.001). CONCLUSIONS Our study found that MB patients had abnormal spontaneous activities in the visual and vision-related regions. The finding of abnormal neuronal activity helps to reveal the underlying neuropathologic mechanisms of vision loss.
Assuntos
Cegueira/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cegueira/fisiopatologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Sucrose, an important sugar, is transported from source to sink tissues through the phloem, and plays important role in the development of important traits in plants. However, the SUT gene family is still not well characterized in pomegranate. In this study, we first identified the pomegranate sucrose transporter (SUT) gene family from the whole genome. Then, the phylogenetic relationship of SUT genes, gene structure and their promoters were analyzed. Additionally, their expression patterns were detected during the development of the seed. Lastly, genetic transformation and cytological observation were used to study the function of PgL0145810.1. A total of ten pomegranate SUT genes were identified from the whole genome of pomegranate 'Tunisia'. The promoter region of all the pomegranate SUT genes contained myeloblastosis (MYB) elements. Four of the SUT genes, PgL0328370.1, PgL0099690.1, PgL0145810.1 and PgL0145770.1, were differentially expressed during seed development. We further noticed that PgL0145810.1 was expressed most prominently in the stem parts in transgenic plants compared to other tissue parts (leaves, flowers and silique). The cells in the xylem vessels were small and lignin content was lower in the transgenic plants as compared to wild Arabidopsis plants. In general, our result suggests that the MYB cis-elements in the promoter region might regulate PgL0145810.1 expression to control the structure of xylem, thereby affecting seed hardness in pomegranate.