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1.
J Asian Nat Prod Res ; : 1-6, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349545

RESUMO

Three new alkaloids (1-3) were isolated from the rhizomes of Menispermum dauricum. The structures and configurations were established by extensive spectroscopic analyses, including 1D, 2D NMR, and ECD.[Formula: see text].

2.
J Agric Food Chem ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32392414

RESUMO

Athetis lepigone is a polyphagous pest found around the world that feeds on maize, wheat, and various other important crops. Although it exhibits a degree of resistance to various chemical insecticides, an effective pest-control method has not yet been developed. The sex pheromone communication system plays an essential role in the mating and reproduction of moths, in which pheromone-binding proteins (PBPs) are crucial genes. In this study, we cloned and purified the protein AlepPBP1 using an E. coli expression system and found it had a higher binding affinity to two sex pheromones of A. lepigone, namely, Z7-12:Ac and Z9-14:Ac (with Ki 0.77 ± 0.10 and 1.10 ± 0.20 µM, respectively), than to other plant volatiles. The binding-mode analysis of protein conformation with equilibrium stabilization was obtained using molecular dynamics (MD) simulation and indicated that hydrophobic interactions involving several nonpolar residues were the main driving force for the binding affinity of AlepPBP1 with sex pheromones. Computational alanine scanning (CAS) was performed to further identify key amino acid residues and validate their binding contributions. Each key residue, including Phe36, Trp37, Val52, and Phe118, was subsequently mutated into alanine using site-directed mutagenesis. Binding assays showed that the efficient binding abilities to Z7-12:Ac (F36A, W37A, and F118A) and Z9-14:Ac (F36A, W37A, V52A, and F118A) were almost lost in the mutated proteins. Our results demonstrated that these key amino acid residues are crucial for determining the binding ability of AlepPBP1 to sex pheromones. These findings provide a basis for the use of AlepPBP1 in the studies as a specific target for the development of novel behavioral antagonists with marked inhibition or mating-disruption abilities using computer-aided drug design (CADD).

3.
J Hazard Mater ; 397: 122777, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32388456

RESUMO

Athetis lepigone is one of the most severe polyphagous pests, and it has developed resistance to different chemical insecticides. Insects primarily rely on the olfactory system to recognize various environmental chemicals, including xenobiotics such as insecticides. Here, we expressed two A. lepigone pheromone-binding proteins (AlepPBP2 and AlepPBP3), and observed they had higher binding affinities to phoxim than other insecticides, with Ki was 3.30 ±â€¯0.38 µM and 3.27 ±â€¯0.10 µM, respectively. Molecular dynamics simulation, binding mode analysis, and computational alanine scanning showed that six residues (Phe15, Phe39, Ile55, Leu65, Ile97, and Phe122) of AlepPBP2 and three residues (Phe12, Ile52, and Ile134) of AlepPBP3 maybe as potential residues that can change protein ability to bind an organophosphorus insecticide phoxim. Then, we used site-directed mutagenesis assay to mutate these residues into alanine, respectively. Subsequently, the binding assays displayed that Phe15, Phe39, and Ile97 of AlepPBP2, Phe12 and Ile134 of AlepPBP3 caused a significant decrease of AlepPBPs binding ability to phoxim, suggesting they should play crucial roles in the AlepPBPs/phoxim interactions. Our findings could further advance in using PBPs as unique targets to design and develop precise and environmentally-friendly pest control agents with high insecticidal potential using a computer-aided drug design (CADD) approach.

4.
Pestic Biochem Physiol ; 164: 173-182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284124

RESUMO

Athetis lepigone (Alep) is a polyphagous pest native to Europe and Asia that has experienced major outbreaks in the summer maize area of China since 2011 and has shown evidence of resistance to some insecticides. Insect olfaction is crucial for recognition of sex pheromones, host plant volatiles and even insecticides, in which two general-odorant binding proteins (GOBPs) play important roles. To elucidate the functions of GOBPs in A. lepigone, we first expressed the two AlepGOBP proteins in the E. coli expression system. Then, the results of fluorescence competitive binding assays demonstrated that the high binding affinity of AlepGOBP2 with sex pheromones [(Z)-7-dodecenyl acetate (Z7-12:Ac), Ki = 0.65 µM; (Z)-9-tetradecenyl acetate (Z9-14:Ac), Ki = 0.83 µM], two maize plant volatiles [Ocimene, Ki = 9.63 µM; (E)-ß-Farnesene, Ki = 4.76 µM] and two insecticides (Chlorpyrifos Ki =5.61 µM; Phoxim, Ki = 4.38 µM). However, AlepGOBP1 could only bind Ocimene (Ki = 13.0 µM) and two insecticides (Chlorpyrifos Ki =4.46 µM; Phoxim, Ki = 3.27 µM). These results clearly suggest that AlepGOBP1 and AlepGOBP2 differentiate among odorants and other ligands. The molecular docking results further revealed different key residues involved in the ligand binding of AlepGOBPs. In summary, this study provides a foundation for exploring the olfactory mechanism of A. lepigone and identified two potential target genes for the development of highly effective insecticides in the future.


Assuntos
Inseticidas , Mariposas , Atrativos Sexuais , Animais , China , Escherichia coli , Proteínas de Insetos , Simulação de Acoplamento Molecular , Odorantes , Feromônios
5.
Anal Chem ; 92(8): 6072-6080, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32216261

RESUMO

Hypochlorite (ClO-) and singlet oxygen (1O2) commonly coexist in living systems and exert important interplaying roles in many diseases. To dissect their complex inter-relationship, it is urgently required to construct a fluorescent probe that can discriminate ClO- and 1O2 in living organisms. Herein, by taking the 3-(aliphaticthio)-propan-1-one group as the unique recognition unit for both ClO- and 1O2, we proposed the first fluorescent probe, Hy-2, to simultaneously discriminate ClO- and 1O2 with high sensitivity and selectivity. Probe Hy-2 itself showed fluorescence in blue channel. After treatment with ClO- and 1O2, respectively, pronounced fluorescence enhancements were observed in the green channel and red channel correspondingly. Moreover, upon development of the probe with aggregation-induced emission (AIE) characteristics, the probe could work well in a solution with high water volume fraction. Probe Hy-2 was also able to accumulate into mitochondria and was utilized as an effective tool to image exogenous and endogenous ClO- and 1O2 in mitochondria. Significantly, as the first trial, probe Hy-2 was employed to simultaneously monitor the variation of ClO- and 1O2 level in cecal tissues of rat in the cecal ligation and puncture (CLP)-induced polymicrobial sepsis model. The results demonstrated that the expressed ClO- and 1O2 levels were tightly correlated with the severity of sepsis, inferring that the overproduction of ClO- and 1O2 is an important factor in the pathogenesis of sepsis. The probe illustrated herein may provide a guide for further exploring the functions of ClO- and 1O2 in various diseases.

6.
Diabetes Metab Syndr Obes ; 12: 1297-1309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447572

RESUMO

Background: Diabetic nephropathy (DN) is a lethal diabetic microvascular complication characterized by chronic low-grade inflammation. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is implicated in the progression of DN. MCC950 is a selective and potent inhibitor of NLRP3; however, its efficacy in DN requires further investigation. Methods: To investigate the efficacy of MCC950 in DN, eight-week-old type 2 diabetic db/db mice received injections of MCC950 intraperitoneally (10 mg/kg) twice per week for 12 weeks. Urinary albumin-to-creatinine ratio (ACR) and neutrophil gelatinase-associated lipocalin (NGAL), renal function, pathological changes, markers of podocyte and fibrosis and NLPR3/caspase-1/IL-1ß expression in the renal cortices of db/db mice were evaluated. High-glucose (HG)-treated rat glomerular mesangial cells were treated with various concentrations of MCC950 for 48 hrs. Markers of fibrosis and NLPR3/caspase-1/IL-1ß expression in the glomerular mesangial cells were measured. Results: The NLRP3 inflammasome was activated in db/db mice and HG-induced mesangial cells by upregulating NLRP3/caspase-1/IL-1ß pathway. Inhibition of the NLRP3 inflammasome with MCC950 reduced the production of active caspase-1 and active IL-1ß in db/db mice and HG-induced mesangial cells. MCC950 reduced serum creatinine, urinary ACR and NGAL, attenuated mesangial expansion with increased matrix and tubular dilatation, alleviated thickened glomerular basement membrane (GBM) and foot process fusion without affecting body weight and blood glucose levels in db/db mice. MCC950 increased the expression of podocin in db/db mice, and decreased the expression of TGF-ß1, fibronectin, collagen I and α-smooth muscle actin (α-SMA) in renal cortices of db/db mice and HG-induced mesangial cells. Conclusion: MCC950 ameliorated renal function, thickened GBM, podocyte injury and renal fibrosis in db/db mice, and decreased the production of fibrosis markers in HG-induced mesangial cells. MCC950 effectively ameliorated diabetic kidney injury by inhibiting NLRP3/caspase-1/IL-1ß pathway, which may be a potential therapeutic strategy to prevent the progression of DN.

7.
Angew Chem Int Ed Engl ; 58(23): 7647-7651, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30972890

RESUMO

A general strategy for the design of asymmetric cascade reactions using readily available halides and carbon monoxide (CO) as substrates is developed. The key is the catalytic generation of C1-ammonium enolates for the subsequent asymmetric cascade reactions through the combination of palladium-catalyzed carbonylation and chiral Lewis base catalysis. Utilizing this strategy, we have established asymmetric formal [1+1+4] and [1+1+2] reactions to afford chiral dihydropyridones and ß-lactams with high yields and high enantio- and diastereoselectivities.

8.
J Asian Nat Prod Res ; 21(3): 207-216, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30588840

RESUMO

Two new diterpenoid glycosides, fructusnoids D (1) and E (2), and two new monoterpenoid glycosides (3, 4), together with three known diterpenoid glycosides (5-7) and three known monoterpenoid glycosides (8-10), were isolated from the fruits of Xanthium chinense. Their structures were elucidated by spectrometric analyses.


Assuntos
Diterpenos/química , Frutas/química , Glicosídeos/química , Xanthium/química , Estrutura Molecular
9.
Biotechnol Biofuels ; 11: 307, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30455736

RESUMO

Background: The biological production of 2,3-butanediol from xylose-rich raw materials from Klebsiella pneumoniae is a low-cost process. RpoD, an encoding gene of the sigma factor, is the key element in global transcription machinery engineering and has been successfully used to improve the fermentation with Escherichia coli. However, whether it can regulate the tolerance in K. pneumoniae remains unclear. Results: In this study, the kpC mutant strain was constructed by altering the expression quantity and genotype of the rpoD gene, and this exhibited high xylose tolerance and 2,3-butanediol production. The xylose tolerance of kpC strain was increased from 75 to 125 g/L, and the yield of 2,3-butanediol increased by 228.5% compared with the parent strain kpG, reaching 38.6 g/L at 62 h. The RNA sequencing results showed an upregulated expression level of 500 genes and downregulated expression level of 174 genes in the kpC mutant strain. The pathway analysis further showed that the differentially expressed genes were mainly related to signal transduction, membrane transport, carbohydrate metabolism, and energy metabolism. The nine most-promising genes were selected based on transcriptome sequencing, and were evaluated for their effects on xylose tolerance. The overexpression of the tktA encoding transketolase, pntA encoding NAD(P) transhydrogenase subunit alpha, and nuoF encoding NADH dehydrogenase subunit F conferred increased xylose consumption and increased 2,3-butanediol production to K. pneumoniae. Conclusions: These results suggest that the xylose tolerance and 2,3-butanediol production of K. pneumoniae can be greatly improved by the directed evolution of rpoD. By applying transcriptomic analysis, the upregulation of tktA, pntA, and nuoF that were coded are essential for the xylose consumption and 2,3-butanediol production. This study will provide reference for further research on improving the fermentation abilities by means of other organisms.

10.
Int J Ophthalmol ; 11(9): 1482-1488, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30225222

RESUMO

AIM: To uncover the underlying pathogenesis of thyroid associated ophthalmopathy (TAO) and explore potential biomarkers of this disease. METHODS: The expression profile GSE9340, which was downloaded from Gene Expression Omnibus database, included 18 specimens from 10 TAO patients and 8 hyperthyroidism patients without ophthalmopathy. The platform was HumanRef-8 v2 Expression BeadChip. Raw data were normalized using preprocess. Core package and the differentially expressed genes (DEGs) were identified based on t-test with limma package of R. Functional enrichment analyses were performed recruiting the DAVID tool. Based on STRING database, a protein-protein interaction (PPI) network was constructed, from which a module was extracted. The functional enrichment for genes in the module was performed by the BinGO plugin. RESULTS: In total, 861 DEGs (433 up-regulated and 428 down-regulated) between TAO patients and hyperthyroidism patients without ophthalmopathy were identified. Crucial nodes in the PPI network included TPX2, CDCA5, PRC1, KIF23 and MKI67, which were also remarkable in the module and all enriched in cell cycle process. Additionally, MKI67 was highly correlated with TAO. Besides, the DEGs of GTF2F1, SMC3, USF1 and ZNF263 were predicted as transcription factors (TFs). CONCLUSION: Several crucial genes are identified such as TPX2, CDCA5, PRC1 and KIF23, which all might play significant roles in TAO via the regulation of cell cycle process. Regulatory relationships between TPX2 and CDCA5 as well as between PRC1 and KIF23 may exist. Additionally, MKI67 may be a potent biomarker of TAO, and SMC3 and ZNF263 may exert their roles as TFs in TAO progression.

11.
Infect Drug Resist ; 11: 995-1005, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087569

RESUMO

Background: CMY-2 is the most prevalent pAmpC ß-lactamase, but the chromosomal blaCMY-2 gene transfer via horizontal transmission has been seldom reported. This study aimed to describe an ISEcp1-mediated transposition of a chromosomal blaCMY-2 gene from Escherichia coli into a small endogenous ColE1-like plasmid, resulting in elevated resistance to extended-spectrum cephalosporins. Methods: Three ESCs-resistant ST641 E. coli strains EC6413, EC4103 and EC5106 harbored the blaCMY-2 gene. S1-PFGE, I-ceu I-PFGE, Southern blotting and electroporation experiments were performed to investigate the location and transferability of blaCMY-2. The genetic context and gene expression of blaCMY-2 in the original isolates and the corresponding electroporants were explored by PCR mapping, primer walking strategy and RT-qPCR. Results: The blaCMY-2-containing region (ISEcp1-blaCMY-2-∆blc-∆yggR-∆tnp1-orf7-orf8-orf9-∆tnp2-∆hsdR) was transposed into endogenous ColE1-like plasmid pSC137 in the process of electroporation at very low frequencies (10-8-10-9). The transpositions resulted in novel larger blaCMY-2-harboring ColE1-like plasmids with size of 14,845 bp, enabling increase in MICs of 2 to 8-fold for cefotaxime, ceftiofur, and ceftazidime in recipient strains over their respective original counterparts. Transcriptional level analysis revealed that the increased blaCMY-2 expression was correlated with elevated MIC values of cephalosporins. The blaCMY-2 transposition unit was identical to that in a clinical isolate E. coli TN44889 from France isolated in 2004. Conclusions: Our results firstly demonstrated that ISEcp1 mediated a transposition of chromosome-borne blaCMY-2 into an endogenous ColE1-like plasmid by electroporation. Amplification of the blaCMY-2 gene facilitates the strain adaptation to a changed environment with an elevated antibiotic pressure.

12.
Org Lett ; 20(8): 2403-2406, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29620907

RESUMO

A palladium-catalyzed asymmetric α-allylation of aldehydes with alkynes has been established by integrating the catalysis of enamine and chiral hydridopalladium complex that is reversibly formed from the oxidative addition of Pd(0) to chiral phosphoric acid. The ternary catalyst system, consisting of an achiral palladium complex, a primary amine, and a chiral phosphoric acid allows the reaction to tolerate a wide scope of α,α-disubstituted aldehydes and alkynes, affording the corresponding allylation products in high yields and with excellent levels of enantioselectivity.

13.
Chemistry ; 24(30): 7626-7630, 2018 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-29532578

RESUMO

An efficient synthesis of highly enantio-enriched tetrahydropyrans from readily available aldehydes, allylboronates, and syngas has been established by multiply relay catalysis of rhodium and chiral phosphoric acid. The cascade reaction integrates the asymmetric allylboration of aldehydes and alkene hydroformylation, providing a structurally diverse range of products with different workup procedures. The concise synthesis of key chiral building blocks to access herboxidiene and leucascandrolide A demonstrates the high synthetic utility of this method. The cascade reaction employing alkenes to replace aldehydes was also successful.

14.
Asian Pac J Cancer Prev ; 18(7): 1769-1772, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28749103

RESUMO

Background: Cervical cancer is the most common gynecological malignant disorder worldwide. Activated platelets play a key role in cancer development and progression. Mean platelet volume (MPV) is an early indicator of platelet activation. The aim of the present study was to evaluate MPV levels in patients with cervical cancer. Materials and methods: A total of 181 patients with cervical cancer and 181 controls between January 2015 and June 2015 were included in the study. Patient characteristics and hematologic test data at initial diagnosis were collected and odds ratios (ORs) and 95% confidence intervals (CIs) for risk of cervical cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: MPV levels were decreased in patients with cervical cancer compared with control subjects. A significant correlation between MPV and FIGO stage was found. Moreover, after adjusting for other risk factors, the ORs (95%CIs) for cervical cancer according to MPV quartiles were 4.450 (1.975-10.026), 2.505 (1.206-5.202), 0.573 (0.261-1.259), and 1.000, respectively. Conclusions: MPV was found to be independently associated with the presence of cervical cancer. Our results suggest that MPV could be potential diagnostic screening tool.

15.
Exp Ther Med ; 14(1): 79-86, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672896

RESUMO

The present study investigated the predictive values of urine paraquat (PQ) concentration, dose of poison, arterial blood lactate and Acute Physiology and Chronic Health Evaluation (APACHE) II score in the prognosis of patients with acute PQ poisoning. A total of 194 patients with acute PQ poisoning, hospitalized between April 2012 and January 2014 at the First Affiliated Hospital of P.R. China Medical University (Shenyang, China), were selected and divided into survival and mortality groups. Logistic regression analysis, receiver operator characteristic (ROC) curve analysis and Kaplan-Meier curve were applied to evaluate the values of urine paraquat (PQ) concentration, dose of poison, arterial blood lactate and (APACHE) II score for predicting the prognosis of patients with acute PQ poisoning. Initial urine PQ concentration (C0), dose of poison, arterial blood lactate and APACHE II score of patients in the mortality group were significantly higher compared with the survival group (all P<0.05). Logistic regression analysis revealed that C0, dose of poison and arterial blood lactate correlated with mortality risk of acute PQ poisoning (all P<0.05). ROC curve analysis suggested that the areas under the curve (AUC) values of C0, dose of poison, arterial blood lactate and APACHE II score in predicting the mortality of patients within 28 days were 0.921, 0.887, 0.808 and 0.648, respectively. The AUC of C0 for predicting early and delayed mortality were 0.890 and 0.764, respectively. The AUC values of urine paraquat concentration the day after poisoning (Csec) and the rebound rate of urine paraquat concentration in predicting the mortality of patients within 28 days were 0.919 and 0.805, respectively. The 28-day survival rate of patients with C0 ≤32.2 µg/ml (42/71; 59.2%) was significantly higher when compared with patients with C0 >32.2 µg/ml (38/123; 30.9%). These results suggest that the initial urine PQ concentration may be the optimal index for predicting the prognosis of patients with acute PQ poisoning. Additionally, dose of poison, arterial blood lactate, Csec and rebound rate also have referential significance.

16.
Curr Microbiol ; 74(8): 921-929, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28516199

RESUMO

Calmodulin (CaM) is a Ca2+-binding protein that plays a role in several Ca2+ signaling pathways, which dynamically regulates the activities of hundreds of proteins. The ice alga Chlamydomonas sp. ICE-L, which has the ability to adapt to extreme polar conditions, is a crucial primary producer in Antarctic ecosystem. This study hypothesized that Cam helps the ICE-L to adapt to the fluctuating conditions in the polar environment. It first verified the overall length of Cam, through RT-PCR and RACE-PCR, based on partial Cam transcriptome library of ICE-L. Then, the nucleotide and predicted amino acid sequences were, respectively, analyzed by various bioinformatics approaches to gain more insights into the computed physicochemical properties of the CaM. Potential involvements of Cam in responding to certain stimuli (i.e., UVB radiation, high salinity, and temperature) were investigated by differential expression, measuring its transcription levels by means of quantitative RT-PCR. Results showed that CaM was indeed inducible and regulated by high UVB radiation, high salinity, and nonoptimal temperature conditions. Different conditions had different expression tendencies, which provided an important basis for investigating the adaptation mechanism of Cam in ICE-L.


Assuntos
Calmodulina/análise , Calmodulina/genética , Chlamydomonas/enzimologia , Perfilação da Expressão Gênica , Regiões Antárticas , Calmodulina/química , Chlamydomonas/efeitos dos fármacos , Chlamydomonas/genética , Chlamydomonas/efeitos da radiação , Clonagem Molecular , Biologia Computacional , Pressão Osmótica , Reação em Cadeia da Polimerase , Salinidade , Temperatura , Raios Ultravioleta
17.
Mar Pollut Bull ; 120(1-2): 184-191, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28511941

RESUMO

Ocean acidification (OA) resulting from increasing atmospheric CO2 strongly influences marine ecosystems, particularly in the polar ocean due to greater CO2 solubility. Here, we grew the Antarctic sea ice diatom Nitzschia sp. ICE-H in a semicontinuous culture under low (~400ppm) and high (1000ppm) CO2 levels. Elevated CO2 resulted in a stimulated physiological response including increased growth rates, chlorophyll a contents, and nitrogen and phosphorus uptake rates. Furthermore, high CO2 enhanced cellular particulate organic carbon production rates, indicating a greater shift from inorganic to organic carbon. However, the cultures grown in high CO2 conditions exhibited a decrease in both extracellular and intracellular carbonic anhydrase activity, suggesting that the carbon concentrating mechanisms of Nitzschia sp. ICE-H may be suppressed by elevated CO2. Our results revealed that OA would be beneficial to the survival of this sea ice diatom strain, with broad implications for global carbon cycles in the future ocean.


Assuntos
Carbono , Clorofila/análise , Diatomáceas , Camada de Gelo , Regiões Antárticas , Dióxido de Carbono , Clorofila A , Oceanos e Mares
18.
Oncotarget ; 8(12): 20213-20219, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28423627

RESUMO

BACKGROUND: Activated platelets promote tumor cell growth, aberrant angiogenesis, and invasion. However, the value of platelet indices for predicting survival in gastric cancer remains unknown. The goal of this study was to investigate the predictive significance of platelet indices in gastric cancer. RESULT: Reduced platelet distribution width (PDW) was significantly correlated with age, carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases stage. Moreover, decreased PDW correlated with a shorter overall survival in gastric cancer. Multivariate analysis identified PDW as an independent prognostic factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319-0.761, p = 0.001). METHOD: A total of 294 patients with gastric cancer were retrospectively analyzed between January 2009 and December 2009. The association between platelet indices and overall survival were evaluated. The prognostic analysis was carried out with Cox regression model. CONCLUSION: PDW is easily available with routine blood counts. Our data revealed that reduced PDW is unfavorable prognostic factor in gastric cancer. Further studies are warranted.


Assuntos
Plaquetas/patologia , Neoplasias Gástricas/patologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade
19.
Yao Xue Xue Bao ; 52(1): 86-90, 2017 01.
Artigo em Chinês | MEDLINE | ID: mdl-29911782

RESUMO

The study was designed to explore the effects of HS060098 on activation of peroxisome proliferator-activated receptors (PPARα, γ and δ) and in the down-regulation of hyperlipidemia in golden hamster. Luciferase gene reporters of PPARα, PPARγ and PPARδ were constructed in HepG2 cells and the green fluorescent protein (GFP) was used as an internal reference. Transfected cells were then cultured with various concentrations of HS060098 for 24 h. The peroxisome proliferator-response element luciferase activity was determined by the dual-luciferase reporter gene assay system. To investigate the lipid-lowering effect of HS060098, hyperlipidemic golden hamsters fed by high-diet were administered orally with HS060098 through prophylactic and therapeutic approaches respectively. The levels of blood lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fat index in hamsters were evaluated. The results showed that HS060098 was a potent activator of PPARδ with a good selectivity and the median effective concentration (EC(50)) is 0.01 µmol·L(-1), while no obvious PPARα and PPARγ activation was observed. In the golden hamster, oral administration of HS060098 (5, 10, 20 mg·kg(-1)·d(-1)) for 2 weeks, led to a significant decrease the concentrations of plasma TC, TG, LDL-C and fat index (P < 0.05 or P < 0.01), whereas the contents of plasma HDL-C were increased significantly (P < 0.05 or P < 0.01). The data suggest that HS060098 is a novel PPARδ agonist with a significant activity in the prevention and therapy of hyperlipemia in golden hamster.


Assuntos
Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , PPAR delta/agonistas , Animais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Células Hep G2 , Humanos , Mesocricetus , PPAR alfa , PPAR gama , Transfecção , Triglicerídeos/sangue
20.
Clin Exp Pharmacol Physiol ; 44(3): 413-420, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27896845

RESUMO

STAT3 is persistently activated in a wide variety of human tumours, and aberrant STAT3 activity promotes tumour growth, invasion and metastasis. To explore STAT3 down-regulation in human oesophageal cancer cells, cell proliferation, apoptosis and mitochondrial mechanisms were explored in oesophageal carcinoma TE1 cell cultures. We demonstrate for the first time that STAT3 down-regulation by RNAi is sufficient to inhibit oesophageal cancer cell proliferation inducing cell apoptosis. Further, we demonstrate that mitochondrial transmembrane potential is impaired thereby leading to collapsed mitochondrial membrane potential, abnormal mitochondrial membrane depolarization, nuclear DNA fragmentation and cell cycle G2/M arrest under the conditions of STAT3 down-regulation. Thus, our results suggest that STAT3 inhibition is a valid approach to induce oesophageal carcinoma cell mitochondrial-dependent apoptosis in therapeutic strategies against oesophageal cancers.


Assuntos
Apoptose , Neoplasias Esofágicas , Pontos de Checagem da Fase G2 do Ciclo Celular , Pontos de Checagem da Fase M do Ciclo Celular , Potencial da Membrana Mitocondrial/fisiologia , Fator de Transcrição STAT3/antagonistas & inibidores , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação para Baixo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Interferência de RNA , Fator de Transcrição STAT3/genética
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