Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 223
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
J Enzyme Inhib Med Chem ; 35(1): 72-84, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31682465

RESUMO

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.

2.
Biotechnol Lett ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720971

RESUMO

OBJECTIVE: Ferritin is an attractive vector for the delivery of drug molecules and antigen proteins because of its unique structural and biochemical features. In this study, recombinant ferritin from Helicobacter pylori was expressed in the soluble form employing the baculovirus expression system. RESULTS: The optimum conditions for producing recombinant ferritin comprised MOI 5 of rBV-ferritin for 96 h of infection. The recombinant ferritin was purified by Ni Sepharose™ 6 Fast Flow, with a purity and yield of 92.5% and 11.25 mg/L, respectively. In addition, the recombinant ferritin showed a multimeric structure under non-denaturing conditions, as well as self-assembled spherical cage architecture with a diameter of approximately 12 nm. Dot-ELISA results suggested that the His-tag at the N-terminus likely existed on the surface of the recombinant ferritin. CONCLUSION: Recombinant ferritin was produced by the baculovirus expression system, which has the potential to display exogenous proteins, and may aid in the delivery of drugs for disease prevention and treatment.

3.
Nucleic Acids Res ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617563

RESUMO

LnCeVar (http://www.bio-bigdata.net/LnCeVar/) is a comprehensive database that aims to provide genomic variations that disturb lncRNA-associated competing endogenous RNA (ceRNA) network regulation curated from the published literature and high-throughput data sets. LnCeVar curated 119 501 variation-ceRNA events from thousands of samples and cell lines, including: (i) more than 2000 experimentally supported circulating, drug-resistant and prognosis-related lncRNA biomarkers; (ii) 11 418 somatic mutation-ceRNA events from TCGA and COSMIC; (iii) 112 674 CNV-ceRNA events from TCGA; (iv) 67 066 SNP-ceRNA events from the 1000 Genomes Project. LnCeVar provides a user-friendly searching and browsing interface. In addition, as an important supplement of the database, several flexible tools have been developed to aid retrieval and analysis of the data. The LnCeVar-BLAST interface is a convenient way for users to search ceRNAs by interesting sequences. LnCeVar-Function is a tool for performing functional enrichment analysis. LnCeVar-Hallmark identifies dysregulated cancer hallmarks of variation-ceRNA events. LnCeVar-Survival performs COX regression analyses and produces survival curves for variation-ceRNA events. LnCeVar-Network identifies and creates a visualization of dysregulated variation-ceRNA networks. Collectively, LnCeVar will serve as an important resource for investigating the functions and mechanisms of personalized genomic variations that disturb ceRNA network regulation in human diseases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31646376

RESUMO

PURPOSE: We conducted a network meta-analysis of randomized controlled trials comparing the efficacy and safety of multiple endovascular treatments for femoropopliteal lesions. METHODS: Nine treatments for femoropopliteal lesions were identified. We compared major amputation and all-cause mortality at 12-month follow-ups and primary patency at 6-, 12- and 24-month follow-ups of the treatments. RESULTS: Altogether, 26 studies (52 study arms; 4102 patients) were considered eligible. In terms of primary patency, drug-eluting stent (DES) placement was the most effective treatment at 6- and 12-month follow-ups and covered stent (CS) placement at 24-month follow-ups, whereas directional atherectomy (DA) was the least effective treatment during all follow-up periods; both DES and CS placements were better than the majority of other single treatments, including balloon angioplasty, DA, nitinol stent (NS) placement and drug-coated balloon use, during all follow-up periods. In terms of 12-month major amputation and all-cause mortality, DA was the most safe treatment, whereas NS placement was the least safe single treatment. CONCLUSIONS: DES and CS placements have shown encouraging results in terms of primary patency for femoropopliteal lesions, DES placement performs better within 12 months after operation and CS placement at approximately 24 months, while DA seems to be less effective. DA may be better than other treatments in terms of major amputation and all-cause mortality, while NS seems to be less safe.

5.
IEEE Trans Cybern ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31603831

RESUMO

This article addresses the H∞ stabilization problems for a class of nonlinear distributed parameter systems which is described by the first-order hyperbolic partial differential equations (PDEs). First, the first-order hyperbolic PDE systems are identified as a polynomial fuzzy PDE system and the polynomial fuzzy controller for the polynomial fuzzy PDE system is proposed. By utilizing the proposed homogeneous polynomial Lyapunov functional, Euler's homogeneous function theorem, and the proposed theorems, a spatial derivative sum-of-squares (SDSOS) exponential stabilization condition is proposed. In addition, a recursive algorithm for the SDSOS exponential stabilization condition is developed to find the feasible solution. Furthermore, in order to reduce the conservatism of the proposed results, a relaxed H∞ stabilization condition for the polynomial fuzzy PDE system is provided. Finally, the nonisothermal plug-flow reactor (PFR) is used to demonstrate the effectiveness and feasibility of the proposed method.

6.
Biosci Trends ; 13(5): 394-401, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31611520

RESUMO

Postmenopausal osteoporosis (PMO) has become a public health problem worldwide. Hormonal replacement therapy (HRT) is the most popular treatment for PMO at present, but the side effects, including increased risk of endometrial cancer and breast cancer, limit its clinical use. Therefore, finding a new medication with high efficiency and less side-effects is urgently required. Dioscin is the main ingredient of some medicinal plants such as Dioscorea nipponica Makino and Dioscorea zingiberensis Wrigh. It is reported that dioscin has anti-tumoral and anti-atherosclerotic activity as well as an inhibitory effect on hepatic fibrosis. In this study, the effects of dioscin on PMO were examined and the mechanisms were analyzed. The results indicated that the bone mineral density and ultimate load of PMO rats were increased after being treated with dioscin. H&E staining and immunohistochemical staining showed the bone trabeculae formation and bone differentiation of PMO rats were promoted by dioscin. Western blots revealed that dioscin could activate the PI3K/P38/AKT signaling pathway and inhibit the apoptosis signaling pathway in bone tissue cells of PMO rats. In addition, MTT assays showed that MC3T3-E1 cell viability could be improved by dioscin. These results suggest dioscin is a potential therapeutic reagent for osteoporosis and deserves further investigation.

7.
Int J Mol Sci ; 20(17)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484454

RESUMO

CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides are post-translationally cleaved and modified peptides from their corresponding pre-propeptides. Although they are only 12 to 13 amino acids in length, they are important ligands involved in regulating cell proliferation and differentiation in plant shoots, roots, vasculature, and other tissues. They function by interacting with their corresponding receptors. CLE peptides have been studied in many plants, but not in wheat. We identified 104 TaCLE genes in the wheat genome based on a genome-wide scan approach. Most of these genes have homologous copies distributed on sub-genomes A, B, and D. A few genes are derived from tandem duplication and segmental duplication events. Phylogenetic analysis revealed that TaCLE genes can be divided into five different groups. We obtained functional characterization of the peptides based on the evolutionary relationships among the CLE peptide families of wheat, rice, and Arabidopsis, and expression pattern analysis. Using chemically synthesized peptides (TaCLE3p and TaCLE34p), we found that TaCLE3 and TaCLE34 play important roles in regulating wheat and Arabidopsis root development, and wheat stem development. Overexpression analysis of TaCLE3 in Arabidopsis revealed that TaCLE3 not only affects the development of roots and stems, but also affects the development of leaves and fruits. These data represent the first comprehensive information on TaCLE family members.

8.
J Biol Chem ; 294(37): 13657-13670, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31341023

RESUMO

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.

9.
J Basic Microbiol ; 59(9): 867-878, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347180

RESUMO

Removal of heavy metals from food material by growing micro-organisms is limited by the toxicity to cells. In this study, different preincubation treatments were investigated to analyze their effects on cadmium resistance and removal ability of Pichia kudriavzevii A16 and Saccharomyces cerevisiae CICC1211. Sucrose preincubation improved the cadmium resistance of both yeast cells and increased the cadmium-removal rate of P. kudriavzevii A16. An evident decrease of intracellular and cell-surface cadmium accumulation was observed after sucrose preincubation, which may be the primary reason responsible for the improved cadmium resistance. Flow cytometry assay showed that sucrose significantly reduced the production of reactive oxygen species (ROS) and cell death rate of both yeasts under cadmium compared with those normally cultured cells. Under cadmium stress, the content of both protein carbonyls and malonyldialdehyde were also reduced by the addition of sucrose, the results were in accordance with the tendency of ROS, exhibiting a defending function of sucrose. Osmotic regulators as proline and trehalose were increased by sucrose preincubation in P. kudriavzevii A16 in the presence of cadmium. The results suggested that sucrose preincubation could be applied to improve cadmium resistance and removal rate of yeasts.

10.
ACS Nano ; 13(8): 9005-9015, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31274291

RESUMO

The structure of finite self-assembling systems depends sensitively on the number of constituent building blocks. Recently, it was demonstrated that hard sphere-like colloidal particles show a magic number effect when confined in emulsion droplets. Geometric construction rules permit a few dozen magic numbers that correspond to a discrete series of completely filled concentric icosahedral shells. Here, we investigate the free energy landscape of these colloidal clusters as a function of the number of their constituent building blocks for system sizes up to several thousand particles. We find that minima in the free energy landscape, arising from the presence of filled, concentric shells, are significantly broadened, compared to their atomic analogues. Colloidal clusters in spherical confinement can flexibly accommodate excess particles by ordering icosahedrally in the cluster center while changing the structure near the cluster surface. In between these magic number regions, the building blocks cannot arrange into filled shells. Instead, we observe that defects accumulate in a single wedge and therefore only affect a few tetrahedral grains of the cluster. We predict the existence of this wedge by simulation and confirm its presence in experiment using electron tomography. The introduction of the wedge minimizes the free energy penalty by confining defects to small regions within the cluster. In addition, the remaining ordered tetrahedral grains can relax internal strain by breaking icosahedral symmetry. Our findings demonstrate how multiple defect mechanisms collude to form the complex free energy landscape of colloidal clusters.

11.
IEEE Trans Cybern ; 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31283492

RESUMO

This paper discusses the problem of suboptimal local piecewise H∞ fuzzy control of quasi-linear spatiotemporal dynamic systems with control magnitude constraints. A Takagi-Sugeno fuzzy partial differential equation (PDE) model with space-varying coefficient matrices is first assumed to be derived for exactly describing nonlinear system dynamics. In the light of the fuzzy model, a local piecewise fuzzy feedback controller is then constructed to guarantee the exponential stability with a prescribed H∞ disturbance attenuation level for the resulting closed-loop system, while the control constraints are also ensured. A sufficient condition on the existence of such fuzzy controller is developed by the Lyapunov direct method and an integral inequality and presented in terms of space algebraic linear matrix inequalities (LMIs) coupled with LMIs. By virtue of extreme value theorem, a suboptimal-constrained local piecewise H∞ fuzzy control design in the sense of minimizing the disturbance attenuation level is formulated as a minimization optimization problem with LMI constraints. Finally, the proposed method is applied to solve the feedback control of a quasi-linear FitzHugh-Nagumo equation with space-varying coefficients, and simulation results show its effectiveness and merit.

12.
J Food Biochem ; 43(4): e12771, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31353584

RESUMO

Low-temperature storage is a key method for delaying the ripening of "Nanguo" pears. However, the aroma of "Nanguo" pears fades after long-term refrigeration. We investigated the potential mechanism of fading of aroma in "Nanguo" pears by analyzing differentially expressed proteins in pears stored at room temperature, which had higher level of aromatic esters and those stored at low temperature, having lower esters. We observed that 293 kinds of proteins were down-regulated and 377 were up-regulated. Gene ontology analysis showed that proteins in the "catalytic activity," "metabolic process," "organelle," and "membrane" proteins were affected by low temperature. KEGG analysis showed that the differentially expressed proteins were involved in oxidative phosphorylation, carbon and fatty acid metabolism. Real-time PCR showed that transcription levels of nine selected genes correlated with differentially expressed proteins. The results revealed that the expression of potentially aroma-related proteins, which are important in further research on improving aroma quality of "Nanguo" pears. PRACTICAL APPLICATIONS: "Nanguo" pears aroma is an important character for attracting consumers and many proteins are involved in the synthesis of aroma. However, their aroma is lost after cold storage and the quality of fruits is affected by low temperature. It is, therefore, of great significance to study the potential proteins that regulate the aroma of refrigerated "Nanguo" pears. In addition, the study results could provide basic and scientific data for the study of improving the aroma quality and genetic improvement of "Nanguo" pears.

13.
Cell Death Dis ; 10(6): 434, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164636

RESUMO

Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.

14.
Sci Rep ; 9(1): 8301, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31165748

RESUMO

DUOII is a multi-ovary wheat line with two or three pistils and three stamens in each floret. The multi-ovary trait of DUOII is controlled by a dominant gene, whose expression can be suppressed by the heterogeneous cytoplasm of TeZhiI (TZI), a line with the nucleus of common wheat and the cytoplasm of Aegilops. DUOII (♀) × TZI (♂) shows multi-ovary trait, while TZI (♀) × DUOII (♂) shows mono-ovary. Observing the developmental process, we found that the critical stage of additional pistil primordium development was when the young spikes were 2-6 mm long. To elucidate the molecular mechanisms that are responsible for the heterogeneous cytoplasmic suppression of the multi-ovary gene, we RNA-sequenced the entire transcriptome of 2-6 mm long young spikes obtained from the reciprocal crosses between DUOII and TZI. A total of 600 differentially expressed genes (DEGs) was identified. Functional annotation of these DEGs showed that the heterogeneous cytoplasmic suppression of additional pistil development mainly involved four pathways, i.e., chloroplast metabolism, DNA replication and repair, hormone signal transduction, and trehalose-6-phosphate in the primordium development stage, which cooperated to modulate the multi-ovary gene expression under heterogeneous cytoplasmic suppression.

15.
Arthritis Res Ther ; 21(1): 153, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234900

RESUMO

INTRODUCTION: Anti-malarial drug artesunate can suppress inflammation and prevent cartilage and bone destruction in collagen-induced arthritis model in rats-suggesting it may be a potent drug for rheumatoid arthritis (RA) therapy. We aimed to investigate its effect on the invasive property of fibroblast-like synoviocytes (FLS) from patients with RA. METHODS: Synovial tissues were obtained by closed needle biopsy from active RA patients, and FLS were isolated and cultured in vitro. RA-FLS were treated with artesunate at various concentrations, while methotrexate or hydroxychloroquine was employed as comparator drugs. Cell viability, proliferation, cell cycle, apoptosis, migration, invasion, and pseudopodium formation of RA-FLS were assessed by CCK-8 assays, EdU staining, Annexin V-FITC/PI staining, transwell assays, or F-actin staining, respectively. Further, relative changes of expressed proteases were analyzed by Proteome profiler human protease array and verified by quantitative real-time PCR (qPCR), Western blot, and ELISA. The expression of signaling molecules of MAPK, NF-κB, AP-1, and PI3K/Akt pathways were measured by qPCR and Western blot. PDK-1 knockdown by specific inhibitor AR-12 or siRNA transfection was used to verify the pharmacological mechanism of artesunate on RA-FLS. RESULTS: Artesunate significantly inhibited the migration and invasion of RA-FLS in a dose-dependent manner with or without TNF-α stimulation. The effect was mediated through artesunate inhibition of MMP-2 and MMP-9 production, and pre-treatment with exogenous MMP-9 reversed the inhibitory effect of artesunate on RA-FLS invasion. Artesunate had a stronger inhibitory effect on migration and invasion of RA-FLS as well as greater anti-inflammatory effect than those of hydroxychloroquine. Similar inhibitory effect was detected between artesunate and methotrexate, and synergy was observed when combined. Mechanistically, artesunate significantly inhibited PDK-1 expression as well as Akt and RSK2 phosphorylation-in a similar manner to PDK-1-specific inhibitor AR-12 or PDK-1 knockdown by siRNA transfection. This inhibition results in suppression of RA-FLS migration and invasion as well as decreased MMP-2 and MMP-9 expression. CONCLUSIONS: Our study demonstrates artesunate is capable of inhibiting migration and invasion of RA-FLS through suppression of PDK1-induced activation of Akt and RSK2 phosphorylation-suggesting that artesunate may be a potential disease-modifying anti-rheumatic drug for RA.

16.
BMC Genomics ; 20(1): 377, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088374

RESUMO

BACKGROUND: Sulforaphane is a natural isothiocyanate available from cruciferous vegetables with multiple characteristics including antioxidant, antitumor and anti-inflammatory effect. Single-molecule real-time (SMRT) sequencing has been used for long-read de novo assembly of plant genome. Here, we investigated the molecular mechanism related to glucosinolates biosynthesis in Chinese kale using combined NGS and SMRT sequencing. RESULTS: SMRT sequencing produced 185,134 unigenes, higher than 129,325 in next-generation sequencing (NGS). NaCl (75 mM), methyl jasmonate (MeJA, 40 µM), selenate (Se, sodium selenite 100 µM), and brassinolide (BR, 1.5 µM) treatment induced 6893, 13,287, 13,659 and 11,041 differentially expressed genes (DEGs) in Chinese kale seedlings comparing with control. These genes were associated with pathways of glucosinolates biosynthesis, including phenylalanine, tyrosine and tryptophan biosynthesis, cysteine and methionine metabolism, and glucosinolate biosynthesis. We found NaCl decreased sulforaphane and glucosinolates (indolic and aliphatic) contents and downregulated expression of cytochrome P45083b1 (CYP83b1), S-alkyl-thiohydroximatelyase or carbon-sulfur lyase (SUR1) and UDP-glycosyltransferase 74B1 (UGT74b1). MeJA increased sulforaphane and glucosinolates contents and upregulated the expression of CYP83b1, SUR1 and UGT74b1; Se increased sulforaphane; BR increased expression of CYP83b1, SUR1 and UGT74b1, and increased glucosinolates contents. The desulfoglucosinolate sulfotransferases ST5a_b_c were decreased by all treatments. CONCLUSIONS: We confirmed that NaCl inhibited the biosynthesis of both indolic and aliphatic glucosinolates, while MeJA and BR increased them. MeJA and BR treatments, conferred the biosynthesis of glucosinolates, and Se and MeJA contributed to sulforaphane in Chinese kale via regulating the expression of CYP83b1, SUR1 and UGT74b1.


Assuntos
Brassica/metabolismo , Perfilação da Expressão Gênica/métodos , Isotiocianatos/metabolismo , Proteínas de Plantas/genética , Acetatos/farmacologia , Brassica/genética , Brassinosteroides/farmacologia , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Oxilipinas/farmacologia , Ácido Selênico/farmacologia , Análise de Sequência de RNA/métodos , Análise de Célula Única , Cloreto de Sódio/farmacologia , Esteroides Heterocíclicos/farmacologia , Sequenciamento Completo do Exoma/métodos
17.
Shanghai Kou Qiang Yi Xue ; 28(1): 110-112, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31081012

RESUMO

Dentigerous cyst belongs to one kind of odontogenic cysts, and is also known as follicular cyst. After the formation of the crown or root of the tooth, liquid exudates between the residual enamel epithelium and the crown surface to form odontogenic cysts. Multiple odontogenic cysts are rare in the oral and maxillofacial regions, especially in different areas of the jaw. In this paper, we reported case with multiple odontogenic cysts and discussed its etiology,pathological classification,differential diagnosis and treatment.


Assuntos
Cisto Dentígero , Cistos Odontogênicos , Cisto Dentígero/diagnóstico , Cisto Dentígero/cirurgia , Epitélio , Humanos , Mandíbula , Cistos Odontogênicos/diagnóstico , Cistos Odontogênicos/cirurgia , Coroa do Dente
18.
Mol Med Rep ; 19(6): 5291-5300, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059055

RESUMO

Atherosclerosis (AS) is an inflammatory disease that occurs in the arterial wall and is characterized by progressive lipid accumulation within the intima of large arteries, leading to the dysfunction of endothelial cells and further destruction of the endothelial barrier and vascular tone. Arterial intima injury accelerates the adhesion and activation of platelets at the injury site. The activation of platelets results in the secretion of growth factors, leading to the migration and proliferation of vascular smooth muscle cells (VSMCs), promoting the formation of plaque, resulting in the formation of thrombus. The present study found that vorapaxar could alleviate the inflammatory response induced by a high concentration of cholesterol stimulation and increase the release of nitric oxide (NO) via the protein kinase B (AKT) signaling pathway and regulation of the intracellular concentration of Ca2+ ([Ca2+]i). We also found that vorapaxar could reduce the damage of DNA caused by cholesterol stimulation and regulate the cell cycle via the AKT/JNK signaling pathway and its downstream molecules glycogen synthase kinase 3ß (GSK­3ß) and connexin 43, maintaining the integrity of the endothelial barrier and proliferation of endothelial cells, serving a protective role in endothelial cells.


Assuntos
Lactonas/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/farmacologia , Conexina 43/metabolismo , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Permeabilidade/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
BMC Plant Biol ; 19(1): 175, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046676

RESUMO

BACKGROUND: DUOII is a multi-ovary wheat (Triticum aestivum L.) line with two or three pistils and three stamens in each floret. The multi-ovary trait of DUOII is controlled by a dominant gene, whose expression can be suppressed by the heterogeneous cytoplasm of TeZhiI (TZI), a line with the nucleus of common wheat and the cytoplasm of Aegilops. Crosses between female DUOII plants and male TZI plants resulted in multi-ovary F1s; whereas, the reciprocal crosses resulted in mono-ovary F1s. Although the multi-ovary trait is inherited as single trait controlled by a dominant allele in lines with a Triticum cytoplasm, the mechanism by which the special heterogeneous cytoplasm suppresses the expression of multi-ovary is not well understood. RESULTS: Observing the developmental process, we found that the critical stage of additional pistil primordium development was when the young spikes were 2-6 mm long. Then, we compared the quantitative proteomic profiles of 2-6 mm long young spikes obtained from the reciprocal crosses between DUOII and TZI. A total of 90 differentially expressed proteins were identified and analyzed based on their biological functions. These proteins had obvious functional pathways mainly implicated in chloroplast metabolism, nuclear and cell division, plant respiration, protein metabolism, and flower development. Importantly, we identified two key proteins, Flowering Locus K Homology Domain and PEPPER, which are known to play an essential role in the specification of pistil organ identity. By drawing relationships between the 90 differentially expressed proteins, we found that these proteins revealed a complex network which is associated with multi-ovary gene expression under heterogeneous cytoplasmic suppression. CONCLUSIONS: Our proteomic analysis has identified certain differentially expressed proteins in 2-6 mm long young spikes, which was the critical stage of additional primordium development. This paper provided a universal proteomic profiling involved in the cytoplasmic suppression of wheat floral meristems; and our findings have laid a solid foundation for further mechanistic studies on the underlying mechanisms that control the heterogeneous cytoplasm-induced suppression of the nuclear multi-ovary gene in wheat.


Assuntos
Citoplasma/metabolismo , Triticum/metabolismo , Cruzamentos Genéticos , Flores/anatomia & histologia , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Proteômica , Triticum/anatomia & histologia , Triticum/genética
20.
Braz J Med Biol Res ; 52(6): e7628, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116255

RESUMO

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Lindera/química , Hepatopatias Alcoólicas/prevenção & controle , Fígado/ultraestrutura , Extratos Vegetais/farmacologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Lipopolissacarídeos/sangue , Hepatopatias Alcoólicas/diagnóstico por imagem , Masculino , Raízes de Plantas/química , Proteínas Serina-Treonina Quinases/sangue , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA