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1.
Arch Med Sci ; 20(2): 517-527, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38757035

RESUMO

Introduction: To elucidate the candidate biomarkers involved in the pathogenesis process of heart failure (HF) via analysis of differentially expressed genes (DEGs) of the dataset from the Gene Expression Omnibus (GEO). Material and methods: The GSE76701 gene expression profiles regarding the HF and control subjects were respectively analysed. Briefly, DEGs were firstly identified and subjected to Cytoscape plug-in ClueGO + CluePedia and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was then built to analyse the interaction between DEGs, followed by the construction of an interaction network by combining with hub genes with the targeted miRNA genes of DEGs to identify the key molecules of HF. In addition, potential drugs targeting key DEGs were sought using the drug-gene interaction database (DGIdb), and a drug-mRNA-miRNA interaction network was also constructed. Results: A total of 489 DEGs were verified between HF and control, which mainly enriched in type I interferon and leukocyte migration according to molecular function. Significantly increased levels of GAPDH, GALM1, MMP9, CCL5, and GNAL2 were found in the HF setting and were identified as the hub genes based on the PPI network. Furthermore, according to the drug-mRNA-miRNA network, FCGR2B, CCND1, and NF-κb, as well as corresponding miRNA-605-5p, miRNA-147a, and miRNA-671-5p were identified as the drug targets of HF. Conclusions: The hub genes GAPDH, GALM1, MMP9, CCL5, and GNAL2 were significantly increased in HF. miRNA-605-5p, miRNA-147a, and miRNA-671-5p were predicted as the drug target-interacted gene-miRNA of HF.

2.
Polymers (Basel) ; 16(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38399863

RESUMO

The advanced Gas Insulated Switchgear/Gas Insulated Lines (GIS/GIL) transmission equipment serves as an essential physical infrastructure for establishing a new energy power system. An analysis spanning nearly a decade on faults arising from extra/ultra-high voltage discharges reveals that over 60% of such faults are attributed to the discharge of metal particles and dust. While existing technical means, such as ultra-high frequency and ultrasonic sensing, exhibit effectiveness in online monitoring of particles larger than sub-millimeter dimensions, the inherent randomness and elusive nature of micron-nano dust pose challenges for effective characterization through current technology. This elusive micron-nano dust, likely concealed as a latent threat, necessitates special attention due to its potential as a "safety killer". To address the challenges associated with detecting micron-nano dust and comprehending its intricate mechanisms, this paper introduces a micron-nano dust adsorption experimental platform tailored for observation and practical application in GIS/GIL operations. The findings highlight that micron-nano dust's adsorption state in the electric field predominantly involves agglomerative adsorption along the insulator surface and diffusive adsorption along the direction of the ground electrode. The pivotal factors influencing dust movement include the micron-nano dust's initial position, mass, material composition, and applied voltage. Further elucidation emphasizes the potential of micron-nano dust as a concealed safety hazard. The study reveals specific physical phenomena during the adsorption process. Agglomerative adsorption results in micron-nano dust speckles forming on the epoxy resin insulator's surface. With increasing voltage, these speckles undergo an "explosion", forming an annular dust halo with deepening contours. This phenomenon, distinct from the initial adsorption, is considered a contributing factor to flashovers along the insulator's surface. The physical mechanism behind flashovers triggered by micron-nano dust is uncovered, highlighting the formation of a localized short circuit area and intense electric field distortion constituted by dust speckles. These findings establish a theoretical foundation and technical support for enhancing the safe operational performance of AC and DC transmission pipelines' insulation.

3.
Int Ophthalmol ; 43(12): 4689-4700, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37688652

RESUMO

PURPOSE: The current study aimed to reveal a novel immune-related signature to evaluate immune infiltration status and the survival outcome for patients with uveal melanoma (UM). METHODS: Based on 80 UM samples from the Cancer Genome Atlas, the transcriptome gene expression and clinical characteristics were analyzed to identify immune-related genes that contributed most to prognosis based on LASSO Cox regression. By combining the gene expression level with the corresponding regression coefficient, a risk score was calculated and all patients were divided into high- and low-risk groups. Survival, tumor-infiltrating immune cell abundance, dysregulated signaling pathways, immunophenoscore and tumor mutation burden were compared between two groups. Validation of the risk signature was performed in GSE22138 and GSE44295 cohort. For evaluating the immunotherapy efficacy, 348 advanced urothelial cancer patients treated with immune checkpoint inhibitor (ICI) were used for external validation. RESULTS: Nine immune-related prognostic genes were identified under the LASSO Cox regression in the TCGA cohort; they are ACKR2, AREG, CCL5, CLEC11A, IGKV1-33, IL36B, NROB1, TRAV8-4 and TRBV28. Better prognosis, elevated immune cell infiltration, decreased immune-suppressive cell infiltration, immune response-related pathways and higher immunophenoscore were found in low-risk patients, with better ICI treatment response rate. CONCLUSION: The identified immune risk signature was demonstrated to be associated with the favorable immune infiltration, prognosis and immunotherapeutic efficacy, which may provide clues for survival evaluation and immune treatment.


Assuntos
Melanoma , Neoplasias Uveais , Humanos , Melanoma/genética , Neoplasias Uveais/genética , Prognóstico
4.
Sleep Biol Rhythms ; 21(4): 471, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38476189

RESUMO

[This corrects the article DOI: 10.1007/s41105-023-00456-2.].

5.
Sleep Biol Rhythms ; 21(3): 369-375, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38476314

RESUMO

Sleep disorders affect more than one-quarter of the world's population, resulting in reduced daytime productivity, impaired immune function, and an increased risk of cardiovascular disease. It is important to identify the physiological and psychological factors related to sleep for the prevention and treatment of sleep disorders. In this study, we correlated measurements of emotional state, sleep quality, and some brain neural activity parameters to better understand the brain and psychological factors related to sleep. Resting-state functional magnetic resonance imaging (rs-fMRI) of 116 healthy undergraduates were analyzed using graph theory to assess regional topological characteristics. Among these, the left thalamic cluster coefficient proved to be the ablest to reflect the characteristics of the sleep neural graph index. The Profile of Mood States (POMS) was used to measure vigor, and the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. The results showed that the left thalamic clustering coefficient was negatively correlated with sleep quality and vigor. Further, the left thalamic clustering coefficient moderated the relationship between vigor and sleep quality. When the left thalamic clustering coefficient was very low, there was a significant positive correlation between vigor and sleep quality. However, when the left thalamic clustering coefficient was high, the correlation between vigor and sleep quality became insignificant. The relationship between vigor and sleep quality is heterogeneous. Analyzing the function of the left thalamic neural network could help understand the variation in the relationship between vigor and sleep quality in different populations. Such observations may help in the development of personalized interventions for sleep disorders.

6.
Materials (Basel) ; 15(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955267

RESUMO

N-type bismuth telluride (Bi2Te3) based thermoelectric (TE) fibers were fabricated by thermal drawing and Bridgman annealing, and the influence of Bridgman annealing on the TE properties of n-type Bi2Te3-based TE fibers was studied. The Bridgman annealing enhanced the electrical conductivity and Seebeck coefficient because of increasing crystalline orientation and decreasing detrimental elemental enrichment. The TE performance of n-type Bi2Te3-based TE fibers was improved significantly by enhancing the power factor. Hence the power factor increased from 0.14 to 0.93 mW/mK2, and the figure-of-merit value is from 0.11 to 0.43 at ~300 K, respectively.

7.
J Phys Condens Matter ; 34(27)2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35439734

RESUMO

Using mean field method and random phase approximation, we studied the phase driven topological exotic states in correlated Haldane model on a honeycomb lattice. It is found that topological spin density waves emerge with the phase change of next-nearest-neighbor hopping. We also investigated the topological properties of these spin density waves, including Chern number, edge state and Hall conductivity. Our work provides a new insight for topological phase transitions in correlated quantum anomalous Hall insulators.

8.
Polymers (Basel) ; 14(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35406249

RESUMO

Metal contaminants can distort the surface electric field of the tri-post epoxy insulator and cause serious surface charge accumulation, significantly reducing the insulation performance of the insulator under the superimposed DC and lightning impulse voltage. In this paper, an experimental platform for charge accumulation and surface flashover of tri-post epoxy insulators under the superimposed DC and lightning impulse voltage was built, by surface point measurement and charge inversion calculation, the surface charge distribution characteristics of tri-post insulators with attached particles was experimentally explored and the influence law of attached metal particles on the charge accumulation was discussed. The results show that metal particles can cause a surge in the surface charge density of the tri-post epoxy insulator, forming bipolar charge spots whose polarity is opposite to that of the adjacent electrodes. The adsorbed metal dust can cause the polarity reversal of adjacent surface charges, forming a large-area unipolar charge spot. Moreover, the flashover voltage of a tri-post insulator under DC superimposed lightning impulse voltage with a clean surface and attached metal particle was measured, and the synergistic induction mechanism of charge spot accumulation and metal particle discharge on the flashover along the face of the tri-post insulator is thereby revealed. Compared with the clean insulators, the surface flashover voltages of tri-post epoxy insulators with metal contaminants adhered decrease under the superimposed voltages of different polarities, but the decline amplitude is greater under the heteropolar composite voltage. When adhered to the middle of the insulator leg, the distribution range of bipolar charge spots is the widest, and the surface flashover voltage decreases sharply, which can drop by 32% compared with the absence of particles. In addition, when the metal dust adsorbed by the tri-post epoxy insulator has a wide distribution range, the impact of metal dust on the flashover voltage is greater than that of the attached metal particles, and its hazard cannot be ignored. The research results can provide a reference for the insulation test method and optimal design of the DC tri-post epoxy insulator.

9.
Invest Ophthalmol Vis Sci ; 63(3): 3, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35238868

RESUMO

PURPOSE: To determine the effect of obstructive sleep apnea syndrome (OSA) on lacrimal gland function and its mechanism. METHODS: Male mice aged seven to eight weeks were housed in cages with cyclic intermittent hypoxia to mimic OSA, and the control group was kept in a normal environment. Slit-lamp observation, fluorescein staining, and corneal sensitivity detection are used to assess cornea changes. Tear secretion was detected by phenol red cotton thread, and the pathological changes of lacrimal gland were observed by hematoxylin and eosin staining, oil red O staining, cholesterol and triglyceride kits, immunofluorescence staining, immunohistochemical staining, real-time polymerase chain reaction, transmission electron microscopy, and Western blot. RESULTS: Studies revealed a decreased tear secretion, corneal epithelial defects and corneal hypersensitivity. Myoepithelial cell damage, abnormal lipid accumulation, reduced cell proliferation, increased apoptosis and inflammatory cell infiltration in the lacrimal gland were also seen. Hifα and NF-κB signaling pathways, moreover, were activated, while Pparα was downregulated, in the lacrimal glands of OSA mice. Fenofibrate treatment significantly alleviated pathological changes of the lacrimal gland induced by OSA. CONCLUSION: OSA disturbs the Hifα/Pparα/NF-κB signaling axis, which affects lacrimal gland structure and function and induces dry eye.


Assuntos
Síndromes do Olho Seco , Aparelho Lacrimal , Apneia Obstrutiva do Sono , Animais , Síndromes do Olho Seco/metabolismo , Aparelho Lacrimal/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , PPAR alfa/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Lágrimas/metabolismo
10.
Biosci Biotechnol Biochem ; 86(4): 455-463, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35044455

RESUMO

F-box protein 17 (FBXO17) is associated with high-grade glioma and acted as a promotor of glioma development. This study investigated the effect and underlying pathway of FBXO17 on glioma. The Cancer Genome Atlas database was applied to analyze FBXO17 expression information in glioma. First, high FBXO17 expressions are associated with glioma and poor prognosis. Then, FBXO17 was upregulated in glioma cells. Meanwhile, knock-down of FBXO17 inhibited cell proliferation, migration, and invasion, but increased the cell apoptosis. Besides, knock-down of FBXO17 inhibited mitochondrial membrane potential and increased reactive oxygen species. Furthermore, knock-down of FBXO17 decreased level of adenosine triphosphate, glucose, lactate, GLUT1, HK2, PFKP, PKM2, and LDHA. In conclusion, FBXO17 was high expression in glioma, and FBXO17 regulates glioma by regulating glycolysis pathway, providing novel theoretical for the treatment of glioma.


Assuntos
Proteínas F-Box , Glioma , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas F-Box/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Glicólise , Humanos
11.
Polymers (Basel) ; 13(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34641216

RESUMO

In this paper, we studied the space charge phenomena of a solid polymer under thermal and electrical stresses with different frequencies and waveforms. By analyzing the parameter selection method of a protection capacitor and resistor, the newly built pulsed electro-acoustic (PEA) system can be used for special electrical stresses under 500 Hz, based on which the charge phenomena are studied in detail under positive and negative DC and half-wave sine and rectangular wave voltages. Experimental results show that the charge accumulated in the polyimide polymer under DC conditions mainly comes from the grounded electrode side, and the amount of charge accumulated with electric field distortion becomes larger in a high-temperature environment. At room temperature, positive charges tend to accumulate in low-frequency conditions under positive rectangular wave voltages, while they easily appear under high-frequency situations of negative ones. In contrast, the maximum electric field distortion and charge accumulation under both half-wave sine voltages occur at 10 Hz. When the measurement temperature increases, the accumulated positive charge decreases, with a more negative charge appearing under rectangular wave voltages, while a more positive charge accumulates at different frequencies of half-wave sine voltages. Therefore, our study of the charge characteristics under different voltage and temperature conditions can provide a reference for applications in the corresponding environments.

12.
ACS Omega ; 6(36): 23281-23292, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34549128

RESUMO

HFO1234ze(E) is an environmentally friendly SF6 substitute gas with prominent application potential. To suppress the generation of the HFO1234ze(E) solid decomposition products, which may cause great hazards to the gas-solid insulation strength, a gas mixing scheme screening method based on the reactive force field (ReaxFF) molecular dynamics (MD) simulation was innovatively proposed. The simulation results show that the inhibitory effect of O2 on the formation of HFO1234ze(E) solid products is better than those of CO2 and CF4. Further study shows that when O2 accounts for 3.33% of the gas mixture, the solid precipitate content is reduced by 48%. The experimental study shows that an O2 content of 3.33% can inhibit the generation of solid products by more than 50%. Besides, compared with HFO1234ze(E)-N2, the DC breakdown voltage of HFO1234ze(E)-N2-O2 is slightly increased, and the breakdown voltage dispersion degree and continuous breakdown voltage drop rate are decreased. This work gives a feasible solution for the suppression of HFO1234ze(E) solid decomposition products and provides an efficient method for solving similar problems of environmentally friendly insulating gas in C/F/O/N systems.

13.
Cell Death Discov ; 7(1): 240, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526481

RESUMO

Histone deacetylases (HDACs) and microRNAs (miRs) have been reported to exert pivotal roles on the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). Therefore, the present study was performed to define the underlying role of HDAC4 and miR-206 in the pathological process of MIRI. An IRI rat model was established. The interaction between HDAC4 and the promoter region of miR-206 was determined using ChIP, and that between miR-206 and mitogen-activated protein kinase kinase kinase 1 (MEKK1) was determined using dual luciferase reporter gene assay. After the loss- or gain-of-function assay in cardiomyocytes, western blot analysis, RT-qPCR, TUNEL, and ELISA assay were performed to define the roles of HDAC4, miR-206, and MEKK1. Up-regulation of HDAC4 and down-regulation of miR-206 occurred in rat myocardial tissues and cardiomyocytes in MIRI. HDAC4 down-regulation or miR-206 up-regulation contributed to reduced cell apoptosis and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), while elevating the superoxide dismutase (SOD) and glutathione (GSH) contents. Meanwhile, HDAC4 silencing promoted the expression of miR-206, which targeted and negatively regulated MEKK1. Then inhibition of JNK phosphorylation reduced the cardiomyocyte apoptosis to alleviate MIRI. Coherently, HDAC4 silencing could up-regulate the expression of miR-206 to reduce cardiomyocyte apoptosis and inhibit oxidative stress, and exerting a protective effect on MIRI via the MEKK1/JNK pathway.

14.
J Phys Condens Matter ; 33(39)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34243171

RESUMO

We investigate the interacting spinful Haldane model with on-site and nearest-neighbor repulsions on honeycomb lattices. Interactions drive spin-density and charge-density waves competing with each other. This competition enriches the phase diagram of the system greatly, where both topological and non-topological coexistence phases emerge with spin-density and charge-density wave orders. Moreover, the topological phase transition accompanied by the energy gap closure in coexistence phases is of third order. Finally, we study the topological properties consisting ofChernnumbers and edge states for different phases.

15.
Polymers (Basel) ; 13(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671766

RESUMO

To reliably detect the latent defects and accurately evaluate the remaining life of gas insulated switchgear (GIS) basin insulators, more effective detection and characterization methods need to be explored. The study of pyrolysis kinetic parameters based on the intrinsic characteristics of materials provides a new way to solve this problem. First, an integral expression model of the reaction mechanism function with four parameters is proposed in this paper, which can represent various existing reaction mechanism functions with better universality and more application fields. Then, on the basis of the temperature transformation equation, an improved method for calculating the activation energy is presented, which shows higher computational accuracy than the existing methods. Further, based on a non-isothermal kinetic equation, the structure of the experimental function is given. It is a method for solving the pyrolysis reaction mechanism function of insulating materials, which can also be used to calculate the pre-exponential factor simultaneously. The thermogravimetric analysis experiment is carried out on a certain basin insulator sample at different heating rates. The pyrolysis kinetic state parameters, including the activation energy, reaction mechanism function and pre-exponential factor of the basin insulator, are calculated. Finally, the life prediction method of basin insulators is established, and the key factors affecting the life of insulators are discussed.

16.
ACS Omega ; 5(41): 26518-26526, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33110979

RESUMO

The ReaxFFSFO force field for a SF6-O2 system is developed based on the density functional theory (DFT) calculation data. Then, a series of molecular dynamics (MD) simulations were performed. The results show that the main oxygen-containing compounds that appeared in the MD simulation include SOF4, SOF2, and SO2F2. The relative quantitative relationship between SOF2 and SOF4 can be used to determine the fault temperature. Besides, under overheating conditions, O2 rarely undergoes a self-cracking process to generate free O atoms. Instead, the basic route for O2 to participate in the SF6 pyrolysis process is X + Y + O2 = XO + YO. Furthermore, the reactivity order of various groups to O2 is (SF2)* > (SF3)* > (SF4)* > F*, so O2 is more likely to participate in the reaction by attacking (SF3)* or (SF2)* groups. This study laid the foundation for the application of ReaxFF MD simulations to study the microscopic dynamic mechanism of SF6 pyrolysis in more complex systems.

17.
J Mol Graph Model ; 100: 107671, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32663780

RESUMO

Decomposition experiments under corona discharge and theoretical calculations using the density functional theory (DFT) method were accomplished to clarify the dissociation behavior and decomposition mechanism of HFO1234zeE (trans-1,3,3,3-tetrafluoropropene), an eco-efficient SF6 alternative gas. The discharge decomposition products of HFO are mainly fluorocarbon, unsaturated hydrocarbon and saturated hydrocarbons, which are containing no more than three carbons. Free radicals, CF3·, F· and H·, generated via bond-cleavage reaction are important structures to promote the decomposition, and HFO is more likely to dissociate with them by abstraction reaction to form CF4 and CF3H. Long-chain radicals, such as CF3CHCF·, CF3CHCH· and CF3CCHF·, will be decomposed into CF3CCH and CF3CCF, and small intermediates would be easier to combine to form HF, C2F6, C2F4, C2HF5, CF3HCF3H and C3F8. It is also likely to be converted to Z-isomer. Due to the high discharge intensity and ion bombardment, solid by-products appeared on the electrode surface may contain carbon dust and metal compounds. The solid attached to the surface has little effect on the electric field distribution, and most gas decomposition products still maintain the insulation strength, so the air-gap breakdown voltage only dropped by about 6.2% after long-term corona discharge. The obtained results not only reveal the decomposition mechanism in a comprehensive way, but also present useful reference for exploring the application potentials of HFO1234zeE.


Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Carbono , Eletricidade , Radicais Livres , Humanos
18.
World Neurosurg ; 141: e367-e373, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32454193

RESUMO

OBJECTIVE: To determine the association of sex with serum potassium, sodium, and calcium disorders in patients with hypertensive intracerebral hemorrhage, and meanwhile investigate other risk factors. METHODS: A total of 516 patients with hypertensive intracerebral hemorrhage were retrospectively enrolled. The clinical characteristics were collected. Serum potassium, sodium, and calcium levels were measured. Multivariate analysis was performed to identify risk factors. RESULTS: Hypokalemia is the most common electrolyte disorder (50.2%) after hypertensive intracerebral hemorrhage, followed by hyponatremia (19.8%), hypocalcemia (13.8%), hypernatremia (12.0%), hyperkalemia (2.5%), and hypercalcemia (0.4%). Most of the electrolyte disorders occurred within 1 week after the onset of hypertensive intracerebral hemorrhage. The incidence rate of hypokalemia was higher in women than in men (61.7% vs. 42.3%, χ2 = 18.676; P < 0.001), but the incidence rates of hyponatremia, hypocalcemia, and hypernatremia were not statistically different between women and men (all P > 0.05). Sex was associated with hypokalemia with women having increased risk, whereas sex was not associated with hypernatremia, hypocalcemia, and hyponatremia. In addition, surgical treatment was a risk factor of hypokalemia, hyponatremia, hypocalcemia, and hypernatremia, both breaking into ventricle and age were risk factors of hyponatremia and hypocalcemia, and bleeding site was a risk factor of hypocalcemia and hypernatremia. CONCLUSIONS: In the treatment of female patients with hypertensive cerebral hemorrhage, the clinician should pay attention to potassium chloride supplementation and monitor its intensity. Within 1 week after intracerebral hemorrhage, individuals most prone to electrolyte disorders determined according to the identified risk factors should be monitored as early as possible, and the disorders should be promptly corrected.


Assuntos
Cálcio/sangue , Hemorragia Intracraniana Hipertensiva/sangue , Potássio/sangue , Fatores Sexuais , Sódio/sangue , Adulto , Idoso , Feminino , Humanos , Hipercalcemia/epidemiologia , Hipernatremia/epidemiologia , Hipocalcemia/epidemiologia , Hipopotassemia/epidemiologia , Hiponatremia/epidemiologia , Incidência , Hemorragia Intracraniana Hipertensiva/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Molecules ; 25(4)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098438

RESUMO

Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Sesquiterpenos/farmacologia , Tetralonas/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Neoplasias/patologia , Sesquiterpenos/síntese química , Sesquiterpenos/química , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Tetralonas/síntese química , Tetralonas/química , Triazóis/síntese química , Triazóis/química
20.
J Cell Physiol ; 235(11): 8283-8292, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32052443

RESUMO

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.


Assuntos
Doença da Artéria Coronariana/genética , Metaloproteinase 9 da Matriz/genética , Peroxidase/genética , Receptores de Interleucina-8A/genética , Receptor 6 Toll-Like/genética , Doença da Artéria Coronariana/patologia , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas
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