RESUMEN
Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.
RESUMEN
BACKGROUND: Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipids, the formation of lesion plaques, and the narrowing of arterial lumens. Rhubarb has significant effects against AS, but there is a lack of analysis and exploration of the mechanism of action of the transitional components in serum containing rhubarb. OBJECTIVE: This work aims to combine serum pharmacochemistry, network pharmacology, and molecular docking to explore active ingredients and mechanism of rhubarb against AS. METHOD: Firstly, the components of rhubarb in blood samples were identified using HPLC-QTOF/MS. The ingredients-targets-disease interaction network of rhubarb was constructed through network pharmacology. Then, molecular docking between the ingredients and the core targets was carried out using the Autodock Vina software. RESULTS: Eleven active ingredients and five metabolites were preliminarily identified. The network pharmacology results showed that chrysophanol, resveratrol, and emodin might have potential pharmacological effects on AS. The PPI network showed that the key proteins were PTGS2, ESR1, PTGS1, and ELANE. GO analysis revealed that genes were mainly enriched in the inflammatory response and response to exogenous stimuli. Moreover, these genes were related to IL-17 signaling pathways, lipid and atherosclerosis, and other pathways. Molecular docking analyses showed that chrysophanol and emodin have strong binding affinities with the target proteins PTGS2 and PTGS1. CONCLUSION: A comprehensive strategy combining serum pharmacochemistry with network pharmacology and molecular docking was employed to investigate the active ingredients and the mechanism of rhubarb in treating AS, which provided a basis for studying the pharmacological effects and action mechanisms of rhubarb.
RESUMEN
In order to characterize and identify the chemical components in different parts of Artemisia argyi(roots, stems, leaves, and seeds), compounds with antioxidant activity were screened. In this study, ultra-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt-quadrupole time-of-flight-tandem mass spectrometry(UPLC-ABTS-Q-TOF-MS) was used as an online combination technique. Poroshell 120 SB-Aq(3.0 mm×150 mm, 2.7 µm) was used as the column, and acetonitrile(A)-0.2% formic acid water(B) was adopted as the mobile phase to perform gradient elution and was scanned in positive and negative ion modes. MassLynx software was utilized, and combined with reference substances and related literature, the chemical components of different parts of A. argyi were identified and compared. The antioxidant active components were detected by using the online detection system, and the antioxidant activities of active components of different parts of A. argyi were compared and evaluated by scavenging efficiency. As a result, a total of 87 compounds were identified from extracts of different parts of A. argyi, and 38, 72, 85, and 33 components were identified from roots, stems, leaves, and seeds. 22 compounds with antioxidant activity were screened, and 14, 17, 20, and 11 compounds with antioxidant activity were identified from roots, stems, leaves, and seeds. The results show that there are certain differences in chemical components and antioxidant components of different parts of A. argyi, which provides data support for the resource utilization and further research and development of A. argyi.
Asunto(s)
Antioxidantes , Artemisia , Artemisia/química , Antioxidantes/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Hojas de la Planta/química , Espectrometría de Masas/métodos , Ácidos Sulfónicos/química , Semillas/química , Benzotiazoles/química , Raíces de Plantas/químicaRESUMEN
Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.
Asunto(s)
Autofagia , Estrés Oxidativo , Epitelio Pigmentado de la Retina , Humanos , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Autofagia/fisiología , Estrés Oxidativo/fisiología , Inflamasomas/metabolismo , Lipofuscina/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Atrofia Geográfica/metabolismo , Atrofia Geográfica/patologíaRESUMEN
Although uncoupling protein 4 (UCP4) is the most abundant protein reported in the brain, the biological function of UCP4 in cerebellum and pathological outcome of UCP4 deficiency in cerebellum remain obscure. To evaluate the role of Ucp4 in the cerebellar Purkinje cells (PCs), we generated the conditional knockdown of Ucp4 in PCs (Pcp2cre;Ucp4fl/fl mice) by breeding Ucp4fl/fl mice with Pcp2cre mice. Series results by Western blot, immunofluorescent staining, and triple RNAscope in situ hybridization confirmed the specific ablation of Ucp4 in PCs in Pcp2cre;Ucp4fl/fl mice, but did not affect the expression of Ucp2, the analog of Ucp4. Combined behavioral tests showed that Pcp2cre;Ucp4fl/fl mice displayed a characteristic bradykinesia in the spontaneous movements. The electromyogram recordings detection excluded the possibility of hypotonia in Pcp2cre;Ucp4fl/fl mice. And the electrical patch clamp recordings showed the altered properties of PCs in Pcp2cre;Ucp4fl/fl mice. Moreover, transmission electron microscope (TEM) results showed the increased mitochondrial circularity in PCs; ROS probe imaging showed the increased ROS generation in molecular layer; and finally, microplate reader assay showed the significant changes of mitochondrial functions, including ROS, ATP, and MMP in the isolated cerebellum tissue. The results suggested that the specific knockdown of mitochondrial protein Ucp4 could damage PCs possibly by attacking their mitochondrial function. The present study is the first to report a close relationship between UCP4 deletion with PCs impairment, and suggests the importance of UCP4 in the substantial support of mitochondrial function homeostasis in bradykinesia. UCP4 might be a therapeutic target for the cerebellar-related movement disorder.
Asunto(s)
Hipocinesia , Células de Purkinje , Animales , Ratones , Encéfalo , Cerebelo , Hipocinesia/metabolismo , Células de Purkinje/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
PURPOSE: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with lung adenocarcinoma (LUAD) harboring activating EGFR mutations. However, the emergence of drug resistance to EGFR-TKIs remains a critical obstacle for successful treatment and is associated with poor patient outcomes. The overarching objective of this study is to apply bioinformatics tools to gain insights into the mechanisms underlying resistance to EGFR-TKIs and develop a robust predictive model. METHODS: The genes associated with gefitinib resistance in the LUAD cell Gene Expression Omnibus (GEO) database were identified using gene chip expression data. Functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed to comprehensively explore the mechanism of gefitinib resistance. Furthermore, a GRRG_score was constructed by integrating genes related to LUAD prognosis from The Cancer Genome Atlas (TCGA) database with the screened Gefitinib Resistant Related differentially expressed genes (GRRDEGs) using the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. Furthermore, we conducted an in-depth analysis of the tumor microenvironment (TME) features and their association with immune infiltration between different GRRG_score groups. A prognostic model for LUAD was developed based on the GRRG_score and validated. The HPA database was used to validate protein expression. The CTR-DB database was utilized to validate the results of drug therapy prediction based on the relevant genes. RESULTS: A total of 110 differentially expression genes were identified. Pathway enrichment analysis of DEGs showed that the differentially expressed genes were mainly enriched in Mucin type O-glycan biosynthesis, Cytokine-cytokine receptor interaction, Sphingolipid metabolism. Gene set enrichment analysis showed that biological processes strongly correlated with gefitinib resistance were cell proliferation and immune-related pathways, EPITHELIAL_MESENCHYMAL_TRANSITION, APICAL_SURFACE, and APICAL_JUNCTION were highly expressed in the drug-resistant group; KRAS_SIGNALING_DN, HYPOXIA, and HEDGEHOG_SIGNALING were highly expressed in the drug-resistant group. The GRRG_score was constructed based on the expression levels of 13 genes, including HSPA2, ATP8B3, SPOCK1, EIF6, NUP62CL, BCAR3, PCSK9, NT5E, FLNC, KRT8, FSCN1, ANGPTL4, and ID1. We further screened and validated two key genes, namely, NUP62CL and KRT8, which exhibited predictive value for both prognosis and drug resistance. CONCLUSIONS: Our study identified several novel GRRDEGs and provided insight into the underlying mechanisms of gefitinib resistance in LUAD. Our results have implications for developing more effective treatment strategies and prognostic models for LUAD patients.
RESUMEN
Various lung diseases endanger people's health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future.
Asunto(s)
Lesión Pulmonar Aguda , Neoplasias Pulmonares , Fibrosis Pulmonar , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/química , Fibrosis Pulmonar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Lesión Pulmonar Aguda/tratamiento farmacológicoRESUMEN
Mitochondrial networks are defined as a continuous matrix lumen, but the morphological feature of neuronal mitochondrial networks is not clear due to the lack of suitable analysis techniques. The aim of the present study is to develop a framework to capture and analyze the neuronal mitochondrial networks by using 4-step process composed of 2D and 3D observation, primary and secondary virtual reality (VR) analysis, with the help of artificial intelligence (AI)-powered Aivia segmentation an classifiers. In order to fulfill this purpose, we first generated the PCs-Mito-GFP mice, in which green fluorescence protein (GFP) could be expressed on the outer mitochondrial membrane specifically on the cerebellar Purkinje cells (PCs), thus all mitochondria in the giant neuronal soma, complex dendritic arborization trees and long projection axons of Purkinje cells could be easily detected under a laser scanning confocal microscope. The 4-step process resolved the complicated neuronal mitochondrial networks into discrete neuronal mitochondrial meshes. Second, we measured the two parameters of the neuronal mitochondrial meshes, and the results showed that the surface area (µm2) of mitochondrial meshes was the biggest in dendritic trees (45.30 ± 53.21), the smallest in granular-like axons (3.99 ± 1.82), and moderate in soma (27.81 ± 22.22) and silk-like axons (17.50 ± 15.19). These values showed statistically different among different subcellular locations. The volume (µm3) of mitochondrial meshes was the biggest in dendritic trees (9.97 ± 12.34), the smallest in granular-like axons (0.43 ± 0.25), and moderate in soma (6.26 ± 6.46) and silk-like axons (3.52 ± 4.29). These values showed significantly different among different subcellular locations. Finally, we found both the surface area and the volume of mitochondrial meshes in dendritic trees and soma within the Purkinje cells in PCs-Mito-GFP mice after receiving the training with the simulating long-term pilot flight concentrating increased significantly. The precise reconstruction of neuronal mitochondrial networks is extremely laborious, the present 4-step workflow powered by artificial intelligence and virtual reality reconstruction could successfully address these challenges.
RESUMEN
Hyperlipidemia has been highlighted as one of the most prominent and global chronic conditions nowadays. Bidens bipinnata L. (BBL), a folk medicine in contemporary China, has efficacy in the treatment of hyperlipidemia (HLP) in China. Although some physiological and pathological function parameters of hyperlipidemia have been investigated, little information about the changes in small metabolites in biofluids has been reported. In the present study, global metabolic profiling with high-performance liquid chromatography-linear ion trap/Orbitrap high-resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) combined with a pattern recognition method was performed to discover the underlying lipid-regulating mechanisms of BBL on hyperlipidemic rats induced by high-fat diet (HFD). The total of four metabolites, up- or down-regulated (p < 0.05 or 0.01), were identified and contributed to the progression of hyperlipidemia. These promising identified biomarkers underpin the metabolic pathway, including glyoxylate and dicarboxylate metabolism, the TCA cycle, sphingolipid metabolism and purine metabolism. They are disturbed in hyperlipidemic rats, and are identified using pathway analysis with MetPA. The altered metabolite indices could be regulated closer to normal levels after BBL intervention. The results demonstrated that urinary metabolomics is a powerful tool in the clinical diagnosis and treatment of hyperlipidemia to provide information on changes in metabolite pathways.
Asunto(s)
Bidens , Hiperlipidemias , Ratas , Animales , Ratas Sprague-Dawley , Metabolómica/métodos , Redes y Vías Metabólicas , Hiperlipidemias/metabolismo , Cromatografía Líquida de Alta PresiónRESUMEN
Purpose: This study aimed to evaluate the feasibility of differentiating the atrial fibrillation (AF) subtype and preliminary explore the prognostic value of AF recurrence after ablation using radiomics models based on epicardial adipose tissue around the left atrium (LA-EAT) of cardiac CT images. Method: The cardiac CT images of 314 patients were collected wherein 251 and 63 cases were randomly enrolled in the training and validation cohorts, respectively. Mutual information and the random forest algorithm were used to screen for the radiomic features and construct the radiomics signature. Radiomics models reflecting the features of LA-EAT were built to differentiate the AF subtype, and the multivariable logistic regression model was adopted to integrate the radiomics signature and volume information. The same methodology and algorithm were applied to the radiomic features to explore the ability for predicting AF recurrence. Results: The predictive model constructed by integrating the radiomic features and volume information using a radiomics nomogram showed the best ability in differentiating AF subtype in the training [AUC, 0.915; 95% confidence interval (CI), 0.880-0.951] and validation (AUC, 0.853; 95% CI, 0.755-0.951) cohorts. The radiomic features have shown convincible predictive ability of AF recurrence in both training (AUC, 0.808; 95% CI, 0.750-0.866) and validation (AUC, 0.793; 95% CI, 0.654-0.931) cohorts. Conclusions: The LA-EAT radiomic signatures are a promising tool in the differentiation of AF subtype and prediction of AF recurrence, which may have clinical implications in the early diagnosis of AF subtype and disease management.
RESUMEN
Mitochondria play an essential role in pathophysiology of both inflammatory and neuropathic pain (NP), but the mechanisms are not yet clear. Dynamin-related protein 1 (Drp1) is broadly expressed in the central nervous system and plays a role in the induction of mitochondrial fission process. Spared nerve injury (SNI), due to the dysfunction of the neurons within the spinal dorsal horn (SDH), is the most common NP model. We explored the neuroprotective role of Drp1 within SDH in SNI. SNI mice showed pain behavior and anxiety-like behavior, which was associated with elevation of Drp1, as well as increased density of mitochondria in SDH. Ultrastructural analysis showed SNI induced damaged mitochondria into smaller perimeter and area, tending to be circular. Characteristics of vacuole in the mitochondria further showed SNI induced the increased number of vacuole, widened vac-perimeter and vac-area. Stable overexpression of Drp1 via AAV under the control of the Drp1 promoter by intraspinal injection (Drp1 OE) attenuated abnormal gait and alleviated pain hypersensitivity of SNI mice. Mitochondrial ultrastructure analysis showed that the increased density of mitochondria induced by SNI was recovered by Drp1 OE which, however, did not change mitochondrial morphology and vacuole parameters within SDH. Contrary to Drp1 OE, down-regulation of Drp1 in the SDH by AAV-Drp1 shRNA (Drp1 RNAi) did not alter painful behavior induced by SNI. Ultrastructural analysis showed the treatment by combination of SNI and Drp1 RNAi (SNI + Drp1 RNAi) amplified the damages of mitochondria with the decreased distribution density, increased perimeter and area, as well as larger circularity tending to be more circular. Vacuole data showed SNI + Drp1 RNAi increased vacuole density, perimeter and area within the SDH mitochondria. Our results illustrate that mitochondria within the SDH are sensitive to NP, and targeted mitochondrial Drp1 overexpression attenuates pain hypersensitivity. Drp1 offers a novel therapeutic target for pain treatment.
Asunto(s)
Dinámicas Mitocondriales , Neuralgia , Animales , Dinaminas/genética , Dinaminas/metabolismo , Ratones , Neuralgia/genética , Ratas , Ratas Sprague-Dawley , Asta Dorsal de la Médula Espinal/metabolismo , Regulación hacia ArribaRESUMEN
PURPOSE: To compare conventional diffusion weighted imaging (DWI), intravoxel incoherent motion imaging (IVIM) and diffusion kurtosis imaging (DKI) in differentiating malignant and benign lung lesions. METHOD: Fifty-five consecutive patients with lung lesions underwent multiple b-value DWI. The apparent diffusion coefficient (ADC), IVIM and DKI parameters were calculated using postprocessing software and compared between the malignant and benign groups. Receiver operating characteristic (ROC) analysis was performed for all parameters. RESULTS: ADC and D were lower in malignant lesions than in benign lesions, while Kapp was higher (P < 0.05). The differences in D*, f, and Dapp between the two groups were not significant (P > 0.05). The areas under the curves (AUCs) of ADC, D, and Kapp were 0.816, 0.864, and 0.822. The combination of all the significant parameters yielded an AUC of 0.880. There were no significant differences in diagnostic efficacy among ADC, D, Kapp and the predictor factor (PRE). CONCLUSIONS: In this study, traditional DWI (ADC), IVIM (D), and DKI (Kapp) all had good diagnostic performance in differentiating malignant lung lesions from benign lesions, but the combination of ADC, D, and Kapp value had better diagnostic efficacy than these parameters alone.
RESUMEN
Bidens bipinnata L. is a folk medicinal plant in China that shows significant antihyperlipidemia effectiveness. However, studies of the underlying mechanism study are lacking. In order to explore the potential action sites and the underlying mechanism of treating hyperlipidemic, this work undertook tissue distribution and molecular docking research on the markers of B. bipinnata L., which were obtained through serum pharmacochemistry and network database retrieval. The results showed that seven compounds (gallic acid, protocatechuic acid, rutin, hyperoside, bipinnate polyacetylenicloside, luteolin and quercetin) were screened out as markers. Owing to the diversity of chemical structures, they exhibited an inconsistent trend in tissue distribution. However, all of them had high levels in the liver and no specific distribution in other tissues. More interestingly, seven proteins-HMGCR (1HWK), NR3C1 (4P6W), CYP1A2 (2HI4), RXRA (4PP3), CES1 (1MX1), HSD11B1 (2RBE) and CYP1A1 (4I8V)-showed significant binding affinity with three or more markers, suggesting that they may be the target proteins of B. bipinnata L. This study preliminarily sheds light on the tissue distribution and targets of B. bipinnata L., providing some useful information on the underlying mechanisms of the antihyperlipidemia effect.
Asunto(s)
Bidens/química , Medicamentos Herbarios Chinos , Hiperlipidemias/metabolismo , Animales , Catequina/análisis , Catequina/farmacocinética , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacocinética , Ácido Gálico/análisis , Ácido Gálico/farmacocinética , Modelos Lineales , Hígado/química , Hígado/metabolismo , Simulación del Acoplamiento Molecular , Ratas , Reproducibilidad de los Resultados , Rutina/análisis , Rutina/farmacocinética , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem , Distribución TisularRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia (HLP) is a prevalence chronic cardiovascular disease, which is treated by traditional Chinese medicine (TCM) in China. More and more attention has been paid to the application of metabolomics in the study of TCM. Bidens bipinnata L. (BBL), a folk medicine in contemporary China, has the efficacy in the treatment of hyperlipidemia (HLP) in China. However, little is known of the underlying mechanism of BBL. This research aimed to investigate ameliorative effects of BBL on hyperlipidemic rats and explore the mechanism by metabolomics method. MATERIALS AND METHODS: Hyperlipidemic rats were established by high fat diet (HFD). Biochemical assay was used to evaluate the efficacy of BBL. A metabolomics approach based on high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry (HPLC-LTQ/orbitrap MS) was performed to analyze the serum biomarkers from model group, control group and BBL group. Principle component analysis (PCA) and partial least-squares discriminate analysis (PLS-DA) were utilized to identify differences of metabolic profiles in rats among the three groups. In order to identify possible pathways that were affected by HLP, the identified endogenous metabolites were analyzed by using MetaboAnalyst. In the network pharmacology study, our research group found that PPAR signaling pathway was the most important pathway of BBL in the treatment of HLP. Then, it was found that changes in the major metabolic pathways would affect the PPAR signaling pathway through comprehensive analysis based on KEGG database. Therefore, the expression of key genes in the PPAR signaling pathway was detected by real-time quantitative fluorescence PCR (RT-qPCR). RESULTS: Six metabolites, which showed a significantly restoring trend from HLP to normal condition, were regarded as potential biomarkers of BBL treatment. The levels of phosphorylcholine, mevalonic acid and leukotriene B4 (LTB4) increased significantly (P < 0.01) in hyperlipidemic rats, while the levels of linoleic acid, arachidonic acid (AA) and lysophosphatidylcholine (18:0) (Lyso PC (18:0)) decreased significantly (P < 0.01) in comparison with control rats. Those endogenous metabolites were chiefly involved in linoleic acid metabolism, AA metabolism and terpenoid backbone biosynthesis. According to the results of RT-qPCR analysis, the mRNA expressions of PPAR α, PPAR ß and PPARγ in model group were difference compared with control group. And the expression difference could be regulated closer to normal level after BBL intervention. CONCLUSIONS: The results of biochemical assay, serum metabolic pattern and RT-qPCR analysis showed that BBL could exert a significant improvement on lipid levels, liver function, renal function, as well as the mRNA expression level of PPAR signaling pathway.
Asunto(s)
Bidens , Análisis de Datos , Medicamentos Herbarios Chinos/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Metabolómica/métodos , Animales , Cromatografía Líquida de Alta Presión/métodos , Dieta Alta en Grasa/efectos adversos , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/aislamiento & purificación , Hiperlipidemias/etiología , Hiperlipidemias/metabolismo , Hipolipemiantes/análisis , Hipolipemiantes/aislamiento & purificación , Masculino , Análisis Multivariante , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem/métodosRESUMEN
To evaluate the impact of an iterative reconstruction (IR) algorithm (advanced modeled iterative reconstruction, ADMIRE) on machine learning-based coronary computed tomography angiography-derived fractional flow reserve (CT-FFRML) measurements compared with filtered back projection (FBP). 170 plaque-containing vessels in 107 patients were included. CT-FFRML values were measured and compared among 5 imaging reconstruction algorithms (FBP and ADMIRE at strength levels of 1, 2, 3 and 5). The plaques were classified as, 'calcified" or "noncalcified" and "≥ 50% stenosis" or "< 50% stenosis', a total of four subgroups by consensus. There were no significant differences of CT-FFRML values among the FBP and ADMIRE 1, 2, 3 and 5 groups wherever comparisons were done at the level of subgroups (P = 0.676, 0.414, 0.849, 0.873, respectively) or overall (P = 0.072). There were 20, 21, 19, 19 and 29 vessels with lesion-specific ischemia (CT-FFRML ≤ 0.80) in FBP and ADMIRE 1, 2, 3 and 5 datasets, respectively, but no statistical differences were found (P = 0.437). Compared with CT-FFRML value of FBP dataset, the CT-FFRML values of 9 (5.3%) vessels from 8 patients (7.5%) in ADMIRE5 dataset switched from above 0.8 to below or equal to 0.8. There were no significant differences of the CT-FFRML values among the FBP and IR image algorithms at different strength levels. However, high iterative strength level (ADMIRE 5) was not recommended, which might have an impact on diagnosis of lesion-specific ischemia, although changes only occurred in a modest number of subjects.
Asunto(s)
Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Reserva del Flujo Fraccional Miocárdico , Aprendizaje Automático , Interpretación de Imagen Radiográfica Asistida por Computador , Anciano , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/fisiopatologíaRESUMEN
5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) is a highly effective, safe, and promising treatment for human papillomavirus (HPV)-induced anogenital condyloma acuminata (CA). Specific HPV subtypes are responsible for the pathogenesis of CA and dynamic changes in viral loads may reflect the efficiency of PDT. Here we present two cases of anogenital CA successfully treated by ALA-PDT under the guidance of HPV DNA detection including genotype identification and viral load measurement, which provided clues for unexpected intra-anal infection. Both of these male patients were free of detectable HPV at the end of the treatment and no recurrence was observed after 1 year. We conclude that the HPV DNA detection can accurately guide ALA-PDT, indicate unnoticed lesions, as well as improve and evaluate the efficiency.
Asunto(s)
Ácido Aminolevulínico/uso terapéutico , Condiloma Acuminado/tratamiento farmacológico , Papillomaviridae/genética , Infecciones por Papillomavirus/tratamiento farmacológico , Fotoquimioterapia/métodos , Adulto , Condiloma Acuminado/virología , ADN Viral , Genotipo , Humanos , Láseres de Gas , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/genética , Fármacos Fotosensibilizantes/uso terapéutico , Reacción en Cadena de la Polimerasa , Carga ViralRESUMEN
The present research aimed to establish an associated two-dimensional fingerprint of Huanglian between characteristic chemical composition and antioxidant activity, which was applied to on-line screen the active constituents. In this study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in Huanglian. Fourteen compositions were discovered, and eight of them displayed antioxidant activity. The antioxidant activity of different ingredients was evaluated by antioxidant efficiency. The data showed that 2, 3, 4-trihydroxy phenylpropionic acid, chlorogenic acid, ferulic acid, cularine, 3-O-feruloylquinic acid and feruloyltyramine showed stronger antioxidant activity than that of alkaloids. These experimental data can provide data support for the basic research of the antioxidant ingredients of Huanglian.
Asunto(s)
Antioxidantes/farmacología , Medicamentos Herbarios Chinos/farmacología , Cromatografía Líquida de Alta PresiónRESUMEN
Yudanshen, the genuine medicinal materials of Danshen (Salvia miltiorrhiza), is a well-known traditional Chinese medicine (TCM) used to treat cardiovascular and cerebrovascular diseases. Although its pharmacological and antioxidative activities have been well-documented, there is little research on the hydroxyl radical (OH) scavenging capacity of Yudanshen. In this study, we established multiple on-line high-performance liquid chromatography- chemiluminescence detector-diode-quadrupole-time of flight mass spectrometry (HPLC-CL-DAD-Q-TOF/MS) methods to rapidly screen and identify the OH scavengers in Yudanshen simultaneously. The chromatographic and potency fingerprints revealed seventeen peaks that showed the inhibition of OH. Fourteen of them were identified as danshensu, protocatechuic aldehyde, caffeic acid, ferulic acid, salvianolic acid F, salvianolic acid H/L, salvianolic acid G, salvianolic acid D, salvianolic acid E, rosmarinic acid, salvianolic acid B, isosalvianolic acid B, salvianolic acid A, and salvianolic acid C. This study explores the OH scavenging activities of Yudanshen, and provides novel and powerful multiple on-line methods in the field of TCM for rapid screening and identification of OH scavengers.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Medicamentos Herbarios Chinos/química , Depuradores de Radicales Libres/análisis , Salvia miltiorrhiza/química , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Contaminación de Medicamentos/prevención & control , Evaluación Preclínica de Medicamentos/instrumentación , Depuradores de Radicales Libres/química , Radical Hidroxilo/metabolismo , Mediciones Luminiscentes/instrumentación , Mediciones Luminiscentes/métodos , Espectrometría de Masas/instrumentación , Espectrometría de Masas/métodosRESUMEN
Xiexin Tang (XXT) is a traditional Chinese medicine (TCM) that has been used in herbal clinics for more than 1800 years. Many studies have shown that XXT has therapeutic effects on patients with arteriosclerosis owing to its antioxidant activity. However, there is little information about the relationship between the chemical composition of XXT and its antioxidant activity. In this study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in XXT. The 15 compounds identified were gluco-syringic acid, adenine, gallic acid, biflorin, cularine, 6-C-arabinose-8-C-glucose-chrysin, 6-C-glucose-8-C-arabinose-chrysin, baicalin, rhein-8-O-ß-d-glucopyranoside, coptisine, epiberberine, jatrorrhizine, norwogonin, 5,7,2'-trihydroxy-6- methoxyflavone and baicalein. In addition, the data showed that the antioxidant activity of peaks 4, 6, and 11 was lower in XXT than in its constituent herbs, while the activity of peaks 1, 2, 3, 5, 7, 8, 10, 12, 13, 14 and 15 was higher in XXT. Compound 5 had the strongest antioxidant activity in XXT, while compound 1 showed the strongest antioxidant activity among its constituent herb. The differences between antioxidant activities of major components of XXT and those of its constituent herbs might be due to the interaction of crude drugs that changes the solubility of active components during the decoction process. The results show that the HPLC-ABTS-DAD-Q-TOF/MS method can successfully combine on-line mass spectrometry with activity detection system. It is a useful tool for the rapid detection and identification of antioxidants, and for quantitative analysis of individual antioxidants in complex mixtures such as plant extracts. Furthermore, this method does not require extensive extract purification and fraction collection.