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1.
J Physiol ; 601(18): 3995-4012, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37488944

RESUMEN

Asthma is a chronic airway inflammatory disease whose global incidence increases annually. The role of innate lymphoid cells (ILCs) is a crucial aspect of asthma research with respect to different endotypes of asthma. Based on its pathological and inflammatory features, asthma is divided into type 2 high and type 2 low endotypes. Type-2 high asthma is distinguished by the activation of type 2 immune cells, including T helper 2 (Th2) cells and ILC2s; the production of cytokines interleukin (IL)-4, IL-5 and IL-13; eosinophilic aggregation; and bronchial hyper-responsiveness. Type-2 low asthma represents a variety of endotypes other than type 2 high endotype such as the IL-1ß/ILC3/neutrophil endotype and a paucigranulocytic asthma, which may be insensitive to corticosteroid treatment and/or associated with obesity. The complexity of asthma is due to the involvement of multiple cell types, including tissue-resident ILCs and other innate immune cells including bronchial epithelial cells, dendritic cells, macrophages and eosinophils, which provide immediate defence against viruses, pathogens and allergens. On this basis, innate immune cells and adaptive immune cells combine to induce the pathological condition of asthma. In addition, the plasticity of ILCs increases the heterogeneity of asthma. This review focuses on the phenotypes of tissue-resident ILCs and their roles in the different endotypes of asthma, as well as the mechanisms of tissue-resident ILCs and other immune cells. Based on the phenotypes, roles and mechanisms of immune cells, the therapeutic strategies for asthma are reviewed.


Asunto(s)
Asma , Inmunidad Innata , Humanos , Linfocitos/metabolismo , Citocinas/metabolismo
2.
Chem Pharm Bull (Tokyo) ; 71(2): 120-128, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36436947

RESUMEN

Mechanistic target of rapamycin (mTOR) is an effective anti-tumor drug target. Several mTOR kinase inhibitors have entered clinical research, but there are still challenges of potential toxicity. As a new type of targeted drug, proteolysis targeting chimeras (PROTACs) have features of low dosage and low toxicity. However, this approach has been rarely reported to involve mTOR degradation. In this study, the mTOR kinase inhibitor MLN0128 was used as the ligand to the protein of interest and conjugated with pomalidomide by diverse intermediate linkage chains. Several potential small molecule PROTACs for the degradation of mTOR were designed and synthesized. PROTAC compounds exhibited mTOR inhibitory activity and suppressed MCF-7 cell proliferation. The representative compound P1 could inhibit the expression of mTOR downstream proteins and the growth of cancer cells by inducing autophagy but not affecting the cell cycle and not inducing apoptosis.


Asunto(s)
Inhibidores de Proteínas Quinasas , Sirolimus , Humanos , Sirolimus/farmacología , Proteolisis , Inhibidores de Proteínas Quinasas/farmacología , Serina-Treonina Quinasas TOR/metabolismo
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121871, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36155929

RESUMEN

Myricitrin is a natural polyhydroxy flavonoid and is mainly derived from the bark and leaves of the Chinese Bayberry tree (Myrica rubra). It has different pharmacological activities, including antioxidative, anti-inflammatory, hypoglycemic, antiviral, liver protection and cholagogue properties, and may be added to foods, pharmaceuticals, and cosmetic products for antioxidant purposes. In this study, the interaction mechanism between myricitrin and human serum albumin (HSA) was investigated using spectroscopic methods, molecular docking techniques, and molecular dynamic simulations. We showed that the HSA/myricitrin interaction exhibited a static fluorescence quenching mechanism, and that binding processes were spontaneous in nature, with the main forces exemplified by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, synchronous fluorescence spectroscopy, three-dimensional (3D) fluorescence spectroscopy, micro-Fourier transform infrared spectroscopy (micro-FTIR), and circular dichroism (CD) spectroscopy showed that myricitrin binding altered the HSA conformation to some extent. Competitive binding and molecular docking studies showed that the preferred binding of myricitrin on HSA was in the sub-structural domain IIA (Site I); molecular dynamic simulations revealed that myricitrin interacted with HSA to produce a well stabilized complex, and it also generated a conformational change in HSA. The antioxidant capacity of the HSA-myricitrin complex was reduced when compared with free myricitrin. The identification of HSA-myricitrin binding mechanisms provides valuable insights for the application of myricitrin to the food and pharmaceutical industries.


Asunto(s)
Simulación de Dinámica Molecular , Albúmina Sérica Humana , Humanos , Albúmina Sérica Humana/química , Simulación del Acoplamiento Molecular , Dicroismo Circular , Antioxidantes/farmacología , Antioxidantes/metabolismo , Termodinámica , Flavonoides , Espectrometría de Fluorescencia , Unión Proteica , Sitios de Unión
4.
Molecules ; 27(24)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36558095

RESUMEN

This study investigated the optimization of ultrasonic-assisted aqueous two-phase synchronous extraction of carbohydrates and polyphenols present in artichoke bud, evaluated their antioxidant activities in vitro, and analyzed the composition of carbohydrates and polyphenols by high-performance liquid chromatography (HPLC). The powder mass, ultrasonic time, ammonium sulfate concentration, and alcohol-water ratio were considered the influencing factors based on the single-factor experiment results, and a dual-response surface model was designed to optimize the synchronous extraction process to extract carbohydrates and polyphenols. The antioxidant activity was evaluated by measuring the scavenging capacity of ABTS+· and DPPH· and the reducing capacity of Fe3+. The optimal process conditions in this study were as follows: the powder mass of 1.4 g, ammonium sulfate concentration of 0.34 g/mL, alcohol-water ratio of 0.4, and ultrasonic time of 43 min. The polyphenol content in artichoke bud was 5.32 ± 0.13 mg/g, and the polysaccharide content was 74.78 ± 0.11 mg/g. An experiment on in vitro antioxidant activity showed that both carbohydrates and polyphenols had strong antioxidant activities, and the antioxidant activity of polyphenols was stronger than that of carbohydrates. The HPLC analysis revealed that the carbohydrates in artichoke bud were mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, and the molar ratio was 10.77:25.22:2.37:15.74:125.39:48.62:34.70. The polyphenols comprised chlorogenic acid, 4-dicaffeoylquinic acid, caffeic acid, 1,3-dicaffeoylqunic acid, isochlorogenic acid B, isochlorogenic acid A, cynarin, and isochlorogenic acid C, and the contents were 0.503, 0.029, 0.022, 0.017, 0.008, 0.162, 1.621, 0.030 mg/g, respectively. This study also showed that the carbohydrates and polyphenols in artichoke bud could be important natural antioxidants, and the composition analysis of HPLC provided directions for their future research. Carbohydrates and polyphenols in artichoke buds can be separated and enriched using the optimized process technology, and it is an effective means of extracting ingredients from plants.


Asunto(s)
Antioxidantes , Cynara scolymus , Antioxidantes/química , Polifenoles/análisis , Cynara scolymus/química , Sulfato de Amonio , Polvos , Galactosa/química , Agua , Extractos Vegetales/farmacología , Extractos Vegetales/química
5.
Hereditas ; 159(1): 44, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36451177

RESUMEN

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic Liver Disease prevalent all over the world. It has become more and more common in Japan, China and most western developed countries. The global prevalence rate is 25.24%, and the trend is increasing year by year. Related studies have shown that Cynarine has certain liver protection, lipid lowering and immune intervention effects. So, this study to systematically predict and analyze the mechanism of Cynarine in the treatment of non-alcoholic fatty liver disease (NAFLD) based on the integration of network pharmacology, molecular docking, and cell experiment. METHODS: We performed Heatmap and Venn diagram analyses to identify genes and targets in Cynarine treat NAFLD. The network of Cynarine-therapeutic targets and the protein-protein interaction network (PPI) was constructed. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. The Sybyl tool was used to dock the Cynarine with key therapeutic targets molecularly. Finally, cell experiments were applied to validate the role of Cynarine in the treatment of NAFLD. RESULTS: The Cynarine could act on 48 targets of NAFLD, and the role of CASP3, TP53, MMP9, ELANE, NOTCH1 were more important. The PPI network showed that immune and inflammation-related targets played a pivotal role. The KEGG analysis found that the PI3K-Akt signaling pathway, cell cycle and MAPK signaling pathway may be the main pathways for Cynarine to prevent and treat NAFLD. Molecular docking studies confirmed that Cynarine has good binding activity with therapeutic targets. Cynarine reduced the fat deposition ability of NAFLD model cells, and effectively reduced the levels of ALT and AST released by liver cells due to excessive lipid accumulation. We also found that Cynarine inhibited the expression of AKT1 and MAPK1. CONCLUSIONS: This study revealed that Cynarine could significantly reduce the fat deposition ability of NAFLD model cells, which may be closely related to the effective regulation of AKT1 and MAPK1 expression by Cynarine.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Lípidos
6.
Front Mol Biosci ; 9: 1031861, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36419933

RESUMEN

Background: The incidence of respiratory diseases and the respiratory disease mortality rate have increased in recent years. Recent studies have shown that long non-coding RNA (lncRNA) MALAT1 is involved in various respiratory diseases. In vascular endothelial and cancer cells, MALAT1 expression triggers various changes such as proinflammatory cytokine expression, cancer cell proliferation and metastasis, and increased endothelial cell permeability. Methods: In this review, we performed a relative concentration index (RCI) analysis of the lncRNA database to assess differences in MALAT1 expression in different cell lines and at different locations in the same cell, and summarize the molecular mechanisms of MALAT1 in the pathophysiology of respiratory diseases and its potential therapeutic application in these conditions. Results: MALAT1 plays an important regulatory role in lncRNA with a wide range of effects in respiratory diseases. The available evidence shows that MALAT1 plays an important role in the regulation of multiple respiratory diseases. Conclusion: MALAT1 is an important regulatory biomarker for respiratory disease. Targeting the regulation MALAT1 could have important applications for the future treatment of respiratory diseases.

7.
Artículo en Inglés | MEDLINE | ID: mdl-36330226

RESUMEN

Asthma is a common chronic respiratory disease characterized by wheezing and shortness of breath. Its risk factors include genetic and acquired factors. The acquired factors are closely related to the environment, especially cold conditions. Autophagy plays a regulatory role in asthma. Therefore, we hypothesized that asthma can be controlled by drug intervention at the autophagy level under cold conditions. The Xiaoqinglong decoction (XQLT) was freeze-dried. The compounds in the freeze-dried powder were identified and quantified using reference standards via the high-performance liquid chromatography method. Ovalbumin (OVA)-sensitized rats were subjected to cold stimulation. The effect of cold stimulation on autophagy levels was determined, and it was confirmed that cold stimulation affected autophagy. The effects and mechanisms of XQLT in an asthmatic rat model (OVA-sensitized rats stimulated with cold) were explored. The concentrations of paeoniflorin, liquiritin, trans-cinnamic acid, glycyrrhizic acid, 6-gingerol, schisandrol A, and asarinin in XQLT freeze-dried powder were 14.45, 3.85, 1.03, 3.93, 0.59, 0.24, and 0.091 mg/g, respectively. Cold stimulation is an important cause of asthma. The inflammatory factors in bronchoalveolar lavage fluid and serum were increased in the model group, accompanied by a decline in autophagy level. The treatment with XQLT increased the expression of autophagy genes and decreased the expression of inflammatory factors. Histological studies showed that XQLT improved inflammatory infiltration and collagen fiber deposition in the lungs of rats. XQLT intervention increased autophagy in asthmatic rats. Autophagy plays a role in phagocytosis and reduces the accumulation of abnormal metabolites in the body to reduce airway inflammation and promote asthma recovery.

8.
Molecules ; 27(17)2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-36080154

RESUMEN

Radix Asteris (RA), also known as 'Zi Wan', is the dried root and rhizome of Aster tataricus L. f., which has been used to treat cough and asthma in many countries such as China, Japan, Korea and Vietnam. This article summarizes the available information on RA in ancient Chinese medicine books and modern research literature: its botanical properties, traditional uses, chemical composition, pharmacological activity, toxicity and quality control. Studies have shown that RA extracts contain terpenes, triterpenoid saponins, organic acids, peptides and flavonoids, and have various pharmacological activities such as anti-inflammatory, anti-tumor, anti-oxidation, and anti-depression. RA is considered to be a promising medicinal plant based on its traditional use, chemical constituents and pharmacological activities. However, there are few studies on its toxicity and the consistency of its components, which indicates the need for further in-depth studies on the toxicity and quality control of RA and its extracts.


Asunto(s)
Aster , Medicamentos Herbarios Chinos , Plantas Medicinales , Antiinflamatorios , Medicamentos Herbarios Chinos/química , Etnofarmacología , Medicina Tradicional China , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
9.
Medicina (Kaunas) ; 58(9)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36143853

RESUMEN

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components-targets-pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD.


Asunto(s)
Antipiréticos , Medicamentos Herbarios Chinos , Lonicera , Enfermedad del Hígado Graso no Alcohólico , Antibacterianos/uso terapéutico , Antipiréticos/uso terapéutico , Antivirales/uso terapéutico , Caspasa 3 , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Simulación del Acoplamiento Molecular , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Factor de Necrosis Tumoral alfa
10.
Front Immunol ; 13: 937832, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967302

RESUMEN

Background: Although studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking. Methods: Transcriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs. Results: Nineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors. Conclusion: Pyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.


Asunto(s)
Asma , Piroptosis , Remodelación de las Vías Aéreas (Respiratorias) , Animales , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/genética , Ratones , Simulación del Acoplamiento Molecular , Pronóstico , Piroptosis/genética
11.
Molecules ; 27(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36014530

RESUMEN

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. The kinase exists in the forms of two complexes, mTORC1 and mTORC2, and it participates in cell growth, proliferation, metabolism, and survival. The kinase activity is closely related to the occurrence and development of multiple human diseases. Inhibitors of mTOR block critical pathways to produce antiviral, anti-inflammatory, antiproliferative and other effects, and they have been applied to research in cancer, inflammation, central nervous system diseases and viral infections. Existing mTOR inhibitors are commonly divided into mTOR allosteric inhibitors, ATP-competitive inhibitors and dual binding site inhibitors, according to their sites of action. In addition, there exist several dual-target mTOR inhibitors that target PI3K, histone deacetylases (HDAC) or ataxia telangiectasia mutated and Rad-3 related (ATR) kinases. This review focuses on the structure of mTOR protein and related signaling pathways as well as the structure and characteristics of various mTOR inhibitors. Non-rapalog allosteric inhibitors will open new directions for the development of new therapeutics specifically targeting mTORC1. The applications of ATP-competitive inhibitors in central nervous system diseases, viral infections and inflammation have laid the foundation for expanding the indications of mTOR inhibitors. Both dual-binding site inhibitors and dual-target inhibitors are beneficial in overcoming mTOR inhibitor resistance.


Asunto(s)
Inhibidores mTOR , Fosfatidilinositol 3-Quinasas , Adenosina Trifosfato/metabolismo , Humanos , Inflamación , Diana Mecanicista del Complejo 1 de la Rapamicina , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo
12.
Oxid Med Cell Longev ; 2021: 5876841, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34603599

RESUMEN

Myocardial fibrosis represents the primary pathological change associated with diabetic cardiomyopathy and heart failure, and it leads to decreased myocardial compliance with impaired cardiac diastolic and systolic function. Quercetin, an active ingredient in various medicinal plants, exerts therapeutic effects against cardiovascular diseases. Here, we investigate whether SIRT5- and IDH2-related desuccinylation is involved in the underlying mechanism of myocardial fibrosis in heart failure while exploring related therapeutic drugs for mitochondrial quality surveillance. Mouse models of myocardial fibrosis and heart failure, established by transverse aortic constriction (TAC), were administered with quercetin (50 mg/kg) daily for 4 weeks. HL-1 cells were pretreated with quercetin and treated with high glucose (30 mM) in vitro. Cardiac function, western blotting, quantitative PCR, enzyme-linked immunosorbent assay, and immunofluorescence analysis were employed to analyze mitochondrial quality surveillance, oxidative stress, and inflammatory response in myocardial cells, whereas IDH2 succinylation levels were detected using immunoprecipitation. Myocardial fibrosis and heart failure incidence increased after TAC, with abnormal cardiac ejection function. Following high-glucose treatment, HL-1 cell activity was inhibited, causing excess production of reactive oxygen species and inhibition of mitochondrial respiratory complex I/III activity and mitochondrial antioxidant enzyme activity, as well as increased oxidative stress and inflammatory response, imbalanced mitochondrial quality surveillance and homeostasis, and increased apoptosis. Quercetin inhibited myocardial fibrosis and improved cardiac function by increasing mitochondrial energy metabolism and regulating mitochondrial fusion/fission and mitochondrial biosynthesis while inhibiting the inflammatory response and oxidative stress injury. Additionally, TAC inhibited SIRT5 expression at the mitochondrial level and increased IDH2 succinylation. However, quercetin promoted the desuccinylation of IDH2 by increasing SIRT5 expression. Moreover, treatment with si-SIRT5 abolished the protective effect of quercetin on cell viability. Hence, quercetin may promote the desuccinylation of IDH2 through SIRT5, maintain mitochondrial homeostasis, protect mouse cardiomyocytes under inflammatory conditions, and improve myocardial fibrosis, thereby reducing the incidence of heart failure.


Asunto(s)
Glucosa/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Sustancias Protectoras/farmacología , Quercetina/farmacología , Sirtuinas/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias Cardíacas/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Quercetina/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo
13.
Oxid Med Cell Longev ; 2021: 5529913, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33859776

RESUMEN

Cardiomyocyte apoptosis is an important pathological mechanism underlying cardiovascular diseases and is commonly caused by hypoxia. Moreover, hypoxic injury occurs not only in common cardiovascular diseases but also following various treatments of heart-related conditions. One of the major mechanisms underlying hypoxic injury is oxidative stress. Quercetin has been shown to exert antioxidant stress and vascular protective effects, making it a promising candidate for treating cardiovascular diseases. Therefore, we examined the protective effect of quercetin on human cardiomyocytes subjected to hypoxia-induced oxidative stress damage and its underlying mechanism. Human cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro with or without quercetin pretreatment; thereafter, flow cytometry, Cell Counting Kit-8 assay, laser scanning confocal microscopy, quantitative PCR, western blotting, and enzyme-linked immunosorbent assay were performed to analyze the effects of quercetin on cardiomyocytes. We found that H/R induced reactive oxygen species overproduction and endoplasmic reticulum stress, as well as inhibited the function of the mitochondria/endoplasmic reticulum and mitophagy, eventually leading to apoptosis and decreasing the viability of human cardiomyocytes. Quercetin pretreatment inhibited H/R-mediated overproduction of reactive oxygen species and damage caused by oxidative stress, increased mitophagy, regulated mRNA and protein expression of transmembrane BAX inhibitor-1 motif-containing 6 (TMBIM6), regulated endoplasmic reticulum stress, and improved the vulnerability of human cardiomyocytes to H/R. Furthermore, transfection with short interfering RNA against silent information regulator protein 1 (SIRT1) counteracted the protective effects of quercetin on cardiomyocytes. Thus, quercetin was predicted to regulate mitophagy and endoplasmic reticulum stress through SIRT1/TMBIM6 and inhibit H/R-induced oxidative stress damage. These findings may be useful for developing treatments for hypoxic injury-induced cardiovascular diseases and further highlight the potential of quercetin for regulating mitochondrial quality control and endoplasmic reticulum function.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Quercetina/farmacología , Sirtuina 1/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Respiración de la Célula/efectos de los fármacos , Células Cultivadas , Humanos , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitofagia/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
14.
Oxid Med Cell Longev ; 2021: 6659240, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33728025

RESUMEN

Atherosclerosis is closely associated with the inflammatory reaction of vascular endothelial cells. Puerarin (Pue), the main active component isolated from the rhizome of Pueraria lobata, is an isoflavone compound with potent antioxidant properties. Although Pue exhibits promising antiatherosclerotic pharmacological effects, only a few studies have reported its protective effect on endothelial cells. This study found that Pue could partly regulate mitochondrial function in human umbilical vein endothelial cells (HUVECs) and reduce or inhibit lipopolysaccharide-induced inflammatory reactions and oxidative stress injury in HUVECs, likely via mitochondrial quality control. Furthermore, the protective effect of Pue on HUVECs was closely related to the SIRT-1 signaling pathway. Pue increased autophagy and mitochondrial antioxidant potential via increased SIRT-1 expression, reducing excessive production of ROS and inhibiting the expression of inflammatory factors and oxidative stress injury. Therefore, Pue may improve mitochondrial respiratory function and energy metabolism, increasing the vulnerability of HUVECs to an inflammatory state.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/patología , Inflamación/patología , Isoflavonas/farmacología , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/farmacología , Metabolismo Energético/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/ultraestructura , Humanos , Lipopolisacáridos , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo
15.
Oxid Med Cell Longev ; 2021: 6620677, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33552385

RESUMEN

Cardiovascular disease has become one of the main causes of human death. In addition, many cardiovascular diseases are accompanied by a series of irreversible damages that lead to organ and vascular complications. In recent years, the potential therapeutic strategy of natural antioxidants in the treatment of cardiovascular diseases through mitochondrial quality control has received extensive attention. Mitochondria are the main site of energy metabolism in eukaryotic cells, including myocardial and vascular endothelial cells. Mitochondrial quality control processes ensure normal activities of mitochondria and cells by maintaining stable mitochondrial quantity and quality, thus protecting myocardial and endothelial cells against stress. Various stresses can affect mitochondrial morphology and function. Natural antioxidants extracted from plants and natural medicines are becoming increasingly common in the clinical treatment of diseases, especially in the treatment of cardiovascular diseases. Natural antioxidants can effectively protect myocardial and endothelial cells from stress-induced injury by regulating mitochondrial quality control, and their safety and effectiveness have been preliminarily verified. This review summarises the damage mechanisms of various stresses in cardiomyocytes and vascular endothelial cells and the mechanisms of natural antioxidants in improving the vulnerability of these cell types to stress by regulating mitochondrial quality control. This review is aimed at paving the way for novel treatments for cardiovascular diseases and the development of natural antioxidant drugs.


Asunto(s)
Antioxidantes/farmacología , Células Endoteliales/patología , Mitocondrias/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Animales , Hipoxia de la Célula/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos
16.
Opt Express ; 28(20): 29865-29875, 2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-33114876

RESUMEN

Photothermal spectroscopy (PTS) working in the mid-infrared region is an effective technique for in-situ characterization of the chemical composition of surface contaminants. The sensitivity relies on the way that the laser-induced response of the sample is detected. We present a highly-sensitive PTS assisted with a dual-wavelength Mach-Zehnder interferometer (MZI), MZI-PST in short. The MZI aims to sense all the phase delays taking place at the sample and air when the heat produced by resonance absorption of the contaminant is transferred into its surroundings and further to amplify the total phase delay to a large intensity difference of a probe beam. To guarantee a stable quadrature phase bias of the MZI working in the balanced detection mode, we employ two separate wavelengths, one for sensing and the other for phase bias feedback, to lock the working point to the quadrature point in real time. The MZI is expected to have a 7.8-fold sensitivity enhancement compared with the conventional phase-sensitive PTS in theory. The results of the proof-of-concept experiment on the olive oil contaminated on a wafer surface verify the spectral fidelity and the sensitivity enhancement as well as the capability of photothermal spectral imaging of the MZI-PST.

17.
Opt Express ; 28(8): 11393-11405, 2020 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-32403651

RESUMEN

The strong coupling effect of thermal and plasma waves disturbs the accurate characterization of thermal properties of semiconductors under super bandgap energy photon excitation. We propose a time-resolved laser scanning photothermal microscopy to decouple the thermo-electronic effect for accurate determination of the thermal diffusivity of a semi-insulating GaAs sample. The distinct advantage of the decoupling principle relies on that the scanning excitation of a laser beam on the sample surface introduces different transient and steady-state characteristics into the thermal and electronic parts of the photothermal response, where the transients between the thermal and electronic parts have a large time-scale separation, and the steady states show an enhanced thermal effect over the electronic effect. Therefore, the plasma wave is simply responsible for a negligible constant background in the thermo-electronic coupling. The theoretical and experimental results confirmed that the time-resolved photothermal signal is insensitive to the electronic transport parameters varying even by several orders of magnitude and can be used to determine the thermal diffusivity from its best fit. Moreover, the scanning excitation nature of this method allows for high-efficiency photothermal imaging of the sample to identify the thermal defects.

18.
Front Cell Dev Biol ; 8: 616139, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33425924

RESUMEN

Mitochondria are double-membraned cellular organelles that provide the required energy and metabolic intermediates to cardiomyocytes. Mitochondrial respiratory chain defects, structure abnormalities, and DNA mutations can affect the normal function of cardiomyocytes, causing an imbalance in intracellular calcium ion homeostasis, production of reactive oxygen species, and apoptosis. Mitochondrial quality control (MQC) is an important process that maintains mitochondrial homeostasis in cardiomyocytes and involves multi-level regulatory mechanisms, such as mitophagy, mitochondrial fission and fusion, mitochondrial energy metabolism, mitochondrial antioxidant system, and mitochondrial respiratory chain. Furthermore, MQC plays a role in the pathological mechanisms of various cardiovascular diseases (CVDs). In recent years, the regulatory effects of natural plants, drugs, and active ingredients on MQC in the context of CVDs have received significant attention. Effective active ingredients in natural drugs can influence the production of energy-supplying substances in the mitochondria, interfere with the expression of genes associated with mitochondrial energy requirements, and regulate various mechanisms of MQC modulation. Thus, these ingredients have therapeutic effects against CVDs. This review provides useful information about novel treatment options for CVDs and development of novel drugs targeting MQC.

19.
Appl Opt ; 58(31): 8665-8672, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31873358

RESUMEN

Digital speckle pattern interferometry and digital shearography are widely used in nondestructive testing due to their advantages of high speed, full field, and high sensitivity. However, traditional speckle pattern interferometry and shearography can only measure a single variable of deformation or strain. This study presents a modified common measurement setup that can simultaneously measure deformation and its first derivative. In the optical setup, a reference beam is introduced behind the shearing device to interfere with the object beams, thereby simplifying the spectrum and improving the quality of the phase maps. Then the spatial carrier technology is used to extract phase and achieve dynamic measurements. The proposed system also expands the measurement range using a ${4}f$4f system. This study also presents a 3D optical setup based on the 1D system, which is more suitable for practical measurement applications in industrial areas. Theoretical derivation and experimental results are described and presented.

20.
Sensors (Basel) ; 19(23)2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31779258

RESUMEN

Shearography has been widely used in non-destructive testing due to its advantages in providing full-field, high precision, real-time measurement. The study presents a pixelated carrier phase-shifting shearography using a pixelated micropolarizer array. Based on the shearography, a series of shearograms are captured and phase maps corresponding to deformation are measured dynamically and continuously. Using the proposed spatiotemporal filtering algorithm in the complex domain, the set of phase maps are simultaneously low-pass filtered in the spatial and temporal domains, resulting in better phase quality than spatial low-pass filtering. By accumulating the temporally adjacent phase, the phase corresponding to large deformation can be evaluated; thus, large deformations can be accurately measured and protected from speckle noise, allowing internal defects to be easily identified. The capability of the proposed shearography is described by theoretical discussions and experiments.

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