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1.
Macromol Rapid Commun ; : e1900406, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31557369

RESUMO

Thermal stability of polymer structure is a key to achieve stable energy density at elevated temperature for ferroelectric-polymer-based capacitors. Here, a poly (vinylidene fluoride) / polymethyl methacrylate (PMMA) blend with a stabilized spherulite structure displaying steady energy density around 7.8-9.8 J cm-3 across the temperature range up to 70 °C is reported, which outperforms most neat ferroelectric polymers at elevated temperature. The microstructure of the blend observed by atomic force microscopy exhibits an alternating lamellar structure (crystalline/mixed amorphous layers) within spherulites, which might be rationalized by PMMA being gradually expelled from the spherulite and finally staying between PVDF lamellae during crystallization. The structure with rigid amorphous layers can induce a spatial confinement effect of chain motion and structural change under thermal stress, which is evidenced by temperature-insensitive long period in small-angle X-ray scattering measurements. The enhanced thermal stability of energy storage can be attributed to the constraint on free volume and carrier transportation caused by the spatial confinement. Our findings provide a strategy to attain temperature-stable high-energy-density ferroelectric polymers for energy storage capacitors.

2.
Anal Biochem ; 587: 113460, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31563442

RESUMO

Betulin, as a new type of natural food preservative, is widely used in various kinds of meat products. However, its detailed mechanism of action and metabolism have not been clarified. In this study, for further gain insight of the mechanism of betulin as a preservative, an efficient method has been applied for measuring the antioxidant capacity of betulin, based on the absorbance of the DPPH• and ABTS• radical cation. When the concentration of betulin was more than 2.0 mg/mL, the scavenging rate of ABTS and DPPH radical reached over 90%, which was equivalent to the antioxidant capacity of Trolox. It is indicated that betulin has significant DPPH and ABTS free radical scavenging ability. This should be one of the important mechanisms for betulin as a preservative. A sensitive method using UHPLC-Q-TOF-MS/MS was established to determine the metabolite profile in vivo and in vitro of betulin. 32 phase I and 2 phase II metabolites were structurally characterized. This study will provide theoretical support for the safety and effectiveness of betulin in the field of preservatives and provide theoretical basis for the further study of betulin and the other natural preservatives. This research also contributes to the development of the food industry.

3.
J Am Chem Soc ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509393

RESUMO

Alloying is an important strategy for the design of catalytic materials beyond pure metals. The conventional alloy catalysts however lack precise control over the local atomic structures of active sites. Here we report on aninvestigation of the active site ensemble effect in bimetallic Pd-Au electrocatalysts for CO2 reduction. A series of Pd@Au electrocatalysts are synthesized by decorating Au nanoparticles with Pd of controlled doses, giving rise to bimetallic surfaces containing Pd ensembles of various sizes. Their catalytic activity for reduction of CO2 to CO exhibits a nonlinear behavior in dependence of the Pd content, which is attributed to the variation of Pd ensemble sizes and the corresponding tuning of adsorption properties. Density functional theory calculations reveal that the Pd@Au electrocatalysts with atomically dispersed Pd sites possess lower energy barriers for activation of CO2 than pure Au and are also less poisoned by strongly binding *CO intermediates than pure Pd, with an intermediate ensemble size of active sites, such as Pd dimers, giving rise to the balance between these two rate-limiting factors and achieving the highest activity for CO2 reduction.

4.
J Surg Res ; 245: 330-337, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425872

RESUMO

BACKGROUND: The goal of the present retrospective study was to elucidate the efficacy of conserving the celiac branch (CB), which can reduce the adverse reactions of Billroth-Ⅰ (B-Ⅰ) restoration after the laparoscopy-assisted distal gastrectomy (LADG). METHODS: Two hundred thirty-three patients with gastric cancer underwent B-Ⅰ reconstruction after LADG with dissection 2 lymphadenectomy from July 2005 to July 2012 and were monitored for 5 y. The patients were separated into 2 groups: celiac branch preserved (P-CB) group (n = 98) and celiac branch resected (R-CB) group (n = 135). In addition to patient information, tumor features, and surgical details, short-term and long-term variables such as bowel condition, surgical complications, and endoscopy findings were evaluated. RESULTS: In short-term efficacy, the time of first flatus and liquid ingestion were slightly shorter in the P-CB group than in the R-CB group (3.84 ± 0.74 versus 4.38 ± 0.71, P = 0.0001; 5.04 ± 1.07 versus 5.67 ± 1.10, P = 0.0001). For long-term efficacy, the incidences of chronic diarrhea, gastroparesis, residual food, bile reflux, and reflux esophagitis were less in the P-CB group compare with the R-CB group (6.1% versus 22.2%, P = 0.001; 5.1% versus 17.8%, P = 0.004; 4.1% versus 17.8%, P = 0.004; 8.2% versus 17.8%, P = 0.036; 8.2% versus 17.8%, P = 0.036). Other parameters such as postoperative ileus and gallstones had a better efficacy trend in the P-CB group but did not suggestively vary among the groups. CONCLUSIONS: The CB has an imperative part in the gastrointestinal motility, and celiac preservation mainly exerts long-term efficacy in patients who underwent B-I surgery with LADG.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31404699

RESUMO

Methylmercury (MeHg) is a highly toxic contaminant in coastal environments and poses threats to marine fish in early life stages (ELSs). However, MeHg toxicity to fish embryos and larvae is not well investigated. This study investigated the antioxidant defenses and immune responses of flounder Paralichthys olivaceus larvae exposed to waterborne MeHg (0, 0.1, 1.0 and 10.0 µg L-1) for 35 days, from embryogenesis to settlement. The results revealed that metal accumulation in the larvae was positively correlated with MeHg concentration, reduced larval growth and survival. The activities of catalase and glutathione reductase were significantly increased at 10.0 µg L-1, while glutathione peroxidase activity and lipid peroxidation level were significantly increased at concentrations over 1.0 µg L-1. The corresponding antioxidant-related genes were upregulated under MeHg exposure (cat and gpx at 10.0 µg L-1; gr over 1.0 µg L-1). Lysozyme content was significantly increased, but immunoglobulin M content was significantly decreased at 10.0 µg L-1. The immune-related genes were significantly upregulated (hsp70 at 0.1 and 10.0 µg L-1; lzm and il-1ß over 1.0 µg L-1; tnf-α and il-6 at 10.0 µg L-1) or downregulated (igm, over 0.1 µg L-1). Overall, MeHg exposure induced oxidative stress and caused immunotoxicity at concentrations over 1.0 µg L-1 and 10.0 µg L-1, respectively. The transcription of selected genes correlated with the corresponding biochemical markers in response to MeHg toxicity. These findings improve our knowledge to better understand the mechanisms by which marine fish at ELSs cope with oxidative stress and immunotoxicity induced by MeHg.

6.
Int Immunopharmacol ; 75: 105819, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421546

RESUMO

Although several therapies are approved, none promote re-myelination in multiple sclerosis (MS) patients, limiting their ability for sustained recovery. Thus, treatment development in MS has the opportunity to tackle the challenges, including experimental therapies targeting neuroprotection and re-myelination. Here, we provide a novel therapeutic target for Ginkgolide K (GK) that is now becoming a very critical natural compound to treat demyelination and neurodegeneration. GK improves behavioral dysfunction and demyelination in cuprizone (CPZ) model, followed by the migration and enrichment of astrocytes in the corpus callosum. Both in vitro and in vivo experiments demonstrates that GK triggers the upregulation of Nrf2/HO-1 in astrocytes and inhibition of p-NF-kB/p65, which is associated with the outcome of anti-inflammation and anti-oxidation by suppressing the production of IL-6 and TNFα as well as nitric oxide and iNOS in astrocytes. Further findings suggest that IGF/PI3K, but not BDNF, was induced in the corpus callosum after GK treatment, revealing that Nrf2 activation inhibited caspase-3 and apoptosis in O4+ oligodendrocytes possibly through IGF/PI3K signaling molecules. Since the current immunomodulatory therapies for MS have failed to prevent patients from entering the progressive phase of the disease, thus targeting Nrf2 in astrocytes with GK would be an ideal strategy for myelin protection and regeneration.

7.
J Immunother Cancer ; 7(1): 197, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345267

RESUMO

BACKGROUND: Strategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling by cediranib, a VEGFR1-3 inhibitor, would complement anti-tumor activity of durvalumab, a PD-L1 inhibitor, and the 3-drug combination would be tolerable. METHODS: This phase 1 study tested the 3-drug combination in a 3 + 3 dose escalation. Cediranib was taken intermittently (5 days on/2 days off) at 15 or 20 mg (dose levels 1 and 2, respectively) with durvalumab 1500 mg IV every 4 weeks, and olaparib tablets 300 mg twice daily. The primary end point was the recommended phase 2 dose (RP2D). Response rate, pharmacokinetic (PK), and correlative analyses were secondary endpoints. RESULTS: Nine patients (7 ovarian/1 endometrial/1 triple negative breast cancers, median 3 prior therapies [2-6]) were treated. Grade 3/4 adverse events include hypertension (1/9), anemia (1/9) and lymphopenia (3/9). No patients experienced dose limiting toxicities. The RP2D is cediranib, 20 mg (5 days on/2 days off) with full doses of durvalumab and olaparib. Four patients had partial responses (44%) and 3 had stable disease lasting ≥6 months, yielding a 67% clinical benefit rate. No significant effects on olaparib or cediranib PK parameters from the presence of durvalumab, or the co-administration of cediranib or olaparib were identified. Tumoral PD-L1 expression correlated with clinical benefit but cytokines and peripheral immune subsets did not. CONCLUSIONS: The RP2D is tolerable and has preliminary activity in recurrent women's cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02484404. Registered June 29, 2015.

8.
J Phys Chem Lett ; 10(15): 4422-4428, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318215

RESUMO

Fundamental understanding on the spin transport properties of semiconducting organic-inorganic hybrid perovskites (OIHP) is of great importance for advancing their applications for spin-optoelectronic devices. Herein, the study of spin-pumping induced inverse spin Hall effect in Ni80Fe20(Py)/CH3NH3PbCl3-xIx/Pt trilayers with different OIHP spacer thicknesses concludes the spin diffusion length in CH3NH3PbCl3-xIx as large as 61 ± 7 nm at room temperature. In addition, spin-valves with a structure of Ni80Fe20(Py)/CH3NH3PbCl3-xIx/AlOx/Co was fabricated as well. Using a ∼160 nm-thick CH3NH3PbCl3-xIx spacer, the present spin valve exhibits a positive magnetoresistance (MR) of 0.57% at 10 K. Thus, the present spin related results demonstrate that electrical spin-polarized carrier injection, transport, and detection, which are essential in spintronic devices, can be successfully established in OIHP films. The outstanding spin transport in the present CH3NH3PbCl3-xIx should be owing to its highly out-of-plane oriented crystalline texture and Rashba spin splitting at domain boundaries between crystallographic orientations. These results demonstrate OIHP as very attractive materials for spintronics.

9.
Virus Res ; 270: 197663, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301332

RESUMO

Porcine circovirus type 3 (PCV3) is an emerging circovirus species associated with several diseases. The study aimed to investigate the frequency of porcine circovirus 3 (PCV3) and its coinfection with canine parvovirus type 2 (CPV-2) in dogs in the Guangxi province from 2015 to 2017, China, and to examine the genome diversity of PCV3. Using polymerase chain reaction (PCR) amplification and sequencing, 96 of 406 (23.6%)samples were positive for PCV3, 38 out of 406 (9.4%) samples were coinfected with both PCV3 and CPV-2. The CPV-positive rate was significantly higher in the PCV3-positive samples than in the non-PCV3 samples, and the difference was extremely significant (P < 0.01). The complete genome (n=4) and ten capsid genes (n=10) of PCV3 were sequenced. Multiple sequence alignment results showed that these sequences shared 98.5-100% nucleotide similarity with the reference genome sequence and 97.5-100% nucleotide similarity with the reference capsid gene sequence. PCV3 was classified into two different genotypes, according to phylogenetic analysis based on the whole genome. These strains were clustered in PCV3a, showing a close relationship with PCV3-US/SD2016. Surprisingly, we separately analyzed these PCV3 strains from the Guangxi province and found that the dog and pig PCV3 are from different branches. In summary, this was the first seroprevalence and genetic investigation of PCV3 in dogs in the Guangxi province, China, and the first complete genome PCV3 from dogs obtained in the world. The results provide insights into the epidemiology and pathogenesis of this important virus.

10.
PLoS One ; 14(7): e0219560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291362

RESUMO

Parvoviruses are a diverse group of viruses that infect a wide range of animals and humans. In recent years, advances in molecular techniques have resulted in the identification of several novel parvoviruses in swine. In this study, porcine parvovirus 7 (PPV7) isolates from clinical samples collected in Guangxi, China, were examined to understand their molecular epidemiology and co-infection with porcine circovirus type 2 (PCV2). In this study, among the 385 pig serum samples, 105 were positive for PPV7, representing a 27.3% positive detection rate. The co-infection rate of PPV7 and PCV2 was 17.4% (67/385). Compared with the reference strains, we noted 93.9%-97.9% similarity in the NS1 gene and 87.4%-95.0% similarity in the cap gene. Interestingly, compared with the reference strains, sixteen of the PPV7 strains in this study contained an additional 3 to 15 nucleotides in the middle of the cap gene. Therefore, the Cap protein of fourteen strains encoded 474 amino acids, and the Cap protein of the other two strains encoded 470 amino acids. However, the Cap protein of the reference strain PPV7 isolate 42 encodes 469 amino acids. This is the first report of sequence variation within the cap gene, confirming an increase in the number of amino acids in the Cap protein of PPV7. Our findings provide new insight into the prevalence of PPV7 in swine in Guangxi, China, as well as sequence data and phylogenetic analysis of these novel PPV7 isolates.

11.
PLoS One ; 14(6): e0218446, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31199846

RESUMO

Although the relationship between the incorporation of an element into otoliths and the concentration of the element in water has been extensively investigated in many fish species, the interactive effects of multiple elements in water on the otolith incorporation of an element are not adequately explored or well understood. In this study, 16 treatments in triplicate using strontium (Sr; 1, 2, 3 and 4 times the ambient baseline, 6.5 mg l-1) and barium (Ba; 1, 2, 4 and 6 times the ambient baseline, 40 µg l-1) as categorical variables in an orthogonal design were established to evaluate the relative or interactive effects of water elements on otolith elemental incorporation in juvenile flounder Paralichthys olivaceus (from 15 to 116 days post hatching). The results revealed that otolith incorporation (Me:CaOtolith) of Sr and Ba were positively dependent on the concentrations of the elements in water (Me:CaWater). Overall, Sr was incorporated into otoliths more efficiently than was Ba, and the partition efficiency (DMe) of both elements decreased with increasing water elemental concentrations. Increasing Sr concentrations in water appeared to negatively affect the uptake of Ba into otoliths rather than facilitate it, as previously reported in fish reared in freshwater and brackish water, or showed no effect on fish in seawater. Conversely, the Ba concentration in water did not influence the otolith uptake of Sr, which agrees with the findings for other fish species. When applying otolith microchemistry to fish ecology studies, it is essential to cautiously address the interactive effects of multiple elements in the environment on otolith elemental incorporation.

12.
Molecules ; 24(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035334

RESUMO

As part of our continual efforts to exploit 'Tujia Ethnomedicine' for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6α,9α,15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (-)-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4-7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 µM on isolated human polymorphonuclear cells or neutrophils.


Assuntos
Kadsura/química , Extratos Vegetais/química , Caules de Planta/química , Sesquiterpenos/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia
13.
Bull Environ Contam Toxicol ; 102(6): 770-777, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31011767

RESUMO

Methylmercury (MeHg) is a widespread pollutant in aquatic ecosystems, but its toxicity to the early life stages of marine fish has not been adequately investigated. This study used acute toxicity tests on embryonic-larval stages of a marine flounder Paralichthys olivaceus to determine the LC50 values for embryos and larvae and evaluate the responses of several biological endpoints to subacute MeHg exposure. Under exposures (0-15 µg L-1) below LC50 values ( < 15.3 µg L-1 for embryos and 16.3 µg L-1 for larvae), embryos were more sensitive to MeHg than were the larvae. MeHg exposures at ≥ 13 µg L-1 increased morphological deformities and mortality, reduced growth and yolk absorption rate of the embryonic-larval flounder. These endpoints were sensitive to MeHg and their responses were dose-dependent. They could be used as bioindicators for assessing MeHg toxicity to the ELS of the flounder. Embryonic-larval flounder could be a useful fish for ecotoxicological assessment of MeHg in marine ecosystems.


Assuntos
Linguado/fisiologia , Compostos de Metilmercúrio/toxicidade , Testes de Toxicidade Aguda/métodos , Poluentes Químicos da Água/toxicidade , Animais , Bioensaio , Ecotoxicologia , Linguado/embriologia , Larva/crescimento & desenvolvimento , Dose Letal Mediana
14.
Proc Natl Acad Sci U S A ; 116(17): 8206-8213, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30962380

RESUMO

Realizing the goal of the Paris Agreement to limit global warming to 2 °C by the end of this century will most likely require deployment of carbon-negative technologies. It is particularly important that China, as the world's top carbon emitter, avoids being locked into carbon-intensive, coal-fired power-generation technologies and undertakes a smooth transition from high- to negative-carbon electricity production. We focus here on deploying a combination of coal and biomass energy to produce electricity in China using an integrated gasification cycle system combined with carbon capture and storage (CBECCS). Such a system will also reduce air pollutant emissions, thus contributing to China's near-term goal of improving air quality. We evaluate the bus-bar electricity-generation prices for CBECCS with mixing ratios of crop residues varying from 0 to 100%, as well as associated costs for carbon mitigation and cobenefits for air quality. We find that CBECCS systems employing a crop residue ratio of 35% could produce electricity with net-zero life-cycle emissions of greenhouse gases, with a levelized cost of electricity of no more than 9.2 US cents per kilowatt hour. A carbon price of approximately $52.0 per ton would make CBECCS cost-competitive with pulverized coal power plants. Therefore, our results provide critical insights for designing a CBECCS strategy in China to harness near-term air-quality cobenefits while laying the foundation for achieving negative carbon emissions in the long run.

15.
Zhongguo Zhong Yao Za Zhi ; 44(2): 298-307, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30989949

RESUMO

The study aims to qualitatively analyze the chemical composition of compound Nanxing acesodyne plaster by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C_(18)( 4. 6 mm×250 mm,5 µm) column. The mobile phase consisted of methanol and 0. 2% formic acid-water was used as gradient elution. The flow rate was 1 mL·min~(-1) and column temperature was 30 ℃. The Mass spectrometry was acquired in both positive and negative ion modes using ESI. The components were identified by the precise mass-to-charge ratio,secondary fragmentation and other information combined with reference substance and literature data. As a result,58 compounds were identified and predicted,including alkaloids,flavonoids,coumarins,organic acids and lactone compounds,of which 12 compounds were verified by the reference substances. The results provide reference for the quality control of compound Nanxing acesodyne plaster,and lay the foundation for elucidating the active components mechanism.


Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/análise , Espectrometria de Massas em Tandem
16.
J Thorac Oncol ; 14(7): 1192-1203, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953795

RESUMO

INTRODUCTION: Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States. We and others have previously shown a relationship between immune and inflammation proteins with lung cancer in EAs. Our aim was to investigate the etiologic relationship between inflammation and lung cancer in AAs. METHODS: We adopted a two-stage, independent study design (discovery cases, n = 316; control cases, n = 509) (validation cases, n = 399; control cases, n = 400 controls) and measured 30 inflammation proteins in blood using Meso Scale Discovery V- PLEX multiplex assays. RESULTS: We identified and validated 10 proteins associated with lung cancer in AAS, some that were common between EAs and AAs (C-reactive proteins [OR: 2.90; 95% confidence interval (CI): 1.99-4.22], interferon γ [OR: 1.55; 95% CI: 1.10-2.19], interleukin 6 [OR: 6.28; 95% CI: 4.10-9.63], interleukin 8 [OR: 2.76; 95% CI: 1.92-3.98]) and some that are only observed among AAs (interleukin 10 [OR: 1.69; 95% CI: 1.20-2.38], interleukin 15 [OR: 2.83; 95% CI: 1.96-4.07], interferon gamma-induced protein 10 [OR: 1.54; 95% CI: 1.09-2.18], monocyte chemotactic protein-4 [OR: 0.54; 95% CI: 0.38-0.76], macrophage inflammatory protein-1 alpha [OR: 1.57; 95% CI: 1.12-2.21], and tumor necrosis factor ß [OR: 0.52; 95% CI: 0.37-0.74]). We did not find evidence that either menthol cigarette smoking or global genetic ancestry drove these population differences. CONCLUSIONS: Our results highlight a distinct inflammation profile associated with lung cancer in AAs compared with EAs. These data provide new insight into the etiology of lung cancer in AAs. Further work is needed to understand what drives this relationship with lung cancer and whether these proteins have utility in the setting of early diagnosis.

17.
Anticancer Drugs ; 30(4): 347-355, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30875347

RESUMO

Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR). This study investigated the impacts of caffeine and theophylline on gastric cancer cell apoptosis and autophagy using a gastric cancer cell line (MGC-803) and a nude mouse model. Peritumoural and tumour tissues were collected from five patients diagnosed with gastric carcinoma who underwent laparoscopic radical gastrectomy at our hospital. Autophagy was suppressed in gastric cancer tumour tissue compared with peritumoural tissue. In vitro, both caffeine and theophylline effectively suppressed MGC-803 cell proliferation and migration and induced autophagy. To assess the involvement of PTEN in caffeine-mediated and theophylline-mediated gastric cancer cell death, we transiently transfected MGC-803 cells with an siRNA targeting PTEN. PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling. In nude mice treated with caffeine or theophylline, MGC-803 cell tumours injected with siPTEN were larger than those injected with negative control siRNA. These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.

18.
Sci Total Environ ; 670: 508-522, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30909029

RESUMO

This study investigated the trophic transfer of four common toxic metals (Cd, Cr, Cu and Hg) in the food web and assessed their potential ecological risks in Laizhou Bay, a spawning area for fishery populations in the Bohai Sea, North China. Based on the predation relations of 43 species that were representatives of the main trophic levels (TLs), a simplified food web was constructed using stomach content analysis and stable nitrogen isotope ratio (δ15N) analysis. Using copepods as the baseline species (TL = 2.00), the TLs of the organisms ranged from 1.96 (Polychaeta) to 4.47 (Japanese flounder) and showed the following ranking order: predatory pelagic or demersal fish > medium demersal fish > crustacean, cephalopod, small pelagic or demersal fish > zooplankton and Polychaeta. The metals showed different trophic transfer behaviors in the food web. Hg and Cr tended to be efficiently biomagnified between TLs, along the main food chains and in the food web. Cu biodiluted significantly with increasing TLs, while Cd showed no biomagnification or biodilution trends in the food web. At low or moderate levels of Cd and Hg, potential ecological risks were detected in the water and sediments at only a few sites, indicating their overall low ecological risks in the environment. The metals in the important fishery species (four top predatory fish, two cephalopods and eight crustaceans) were below the permissible limits, except for Cd in octopus and paddle crab, which reached or exceeded the most restrictive criteria. Based on the provisional tolerable weekly intake (PTWI) criteria, the safe weekly human consumption levels by humans of the predatory fish, cephalopods and crustaceans were species-specific (0.20-4.44 kg) and should be cautiously assessed.


Assuntos
Monitoramento Ambiental , Cadeia Alimentar , Metais Pesados/análise , Poluentes Químicos da Água/análise , Baías , China , Medição de Risco
19.
Virus Res ; 265: 127-131, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30914299

RESUMO

Bufaviruses are small, nonenveloped, single-stranded DNA viruses belonging to the subfamily Parvovirinae. Human bufaviruses were first identified in 2012 in fecal samples from children with diarrhea. A new parvovirus of canines that was first detected in various samples from dogs with enteric and respiratory symptoms in Italy between 2014 and 2018 is closely related to the newly described human bufavirus. To explore the prevalence and genetic diversity of CBuV in Chinese dogs, 540 canine parvovirus (CPV)-positive serum and diarrhea samples were collected in Guangxi Province between 2016 and 2018. Among the samples, 6.25% (5/80) of rectal swabs and 2.5% (5/200) of CPV PCR-positive samples were positive for CBuV. However, the virus was not detected in CPV PCR-negative samples or nasal swabs. Two CBuV isolates were identified from CPV-positive fecal and serum samples by complete sequence analysis, with 99.8%-99.9% NS1 and VP2 protein identity to each another. Sequence analysis indicated that the CBuV GXNN01-2018 isolate VP2 protein shares 99.6% identity with the Italian CBuV ITA/2015/297 isolate and 62.3%-65.5% identity with human bufavirus. Phylogenetic analysis showed that CBuV was significantly distinct from other known bufaviruses and was most closely related to CBuV ITA/2015/297. This is the first report of the existence of CBuV in China, and our findings will strengthen the understanding of the epidemiology of bufaviruses in different animals.


Assuntos
Diarreia/virologia , Evolução Molecular , Variação Genética , Infecções por Parvoviridae/veterinária , Parvovirus Canino/classificação , Animais , Animais Domésticos/virologia , China/epidemiologia , Diarreia/epidemiologia , Diarreia/veterinária , Doenças do Cão/virologia , Cães , Fezes/virologia , Humanos , Infecções por Parvoviridae/epidemiologia , Parvovirus Canino/isolamento & purificação , Prevalência
20.
Int Immunopharmacol ; 70: 284-294, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30851709

RESUMO

Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Encefalomielite Autoimune Experimental/dietoterapia , Ginkgolídeos/uso terapêutico , Lactonas/uso terapêutico , Microglia/fisiologia , Esclerose Múltipla/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Diferenciação Celular , Células Cultivadas , Microambiente Celular , Quimiotaxia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fator de Ativação de Plaquetas/antagonistas & inibidores , Equilíbrio Th1-Th2/efeitos dos fármacos
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