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1.
Chem Commun (Camb) ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960842

RESUMO

Reversible single-crystal-to-single-crystal photocyclization-cycloreversion reaction of a stilbene-based coordination network exhibits a conspicuous fluorescence change. The controllable fluorescence and high fatigue resistance feature of this bistable material make it a single-crystalline device for applications in rewritable optical memory storage systems.

3.
FASEB J ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31909541

RESUMO

Allergic asthma with high plasma IgE levels is a significant risk factor of human abdominal aortic aneurysm (AAA). This study tests a direct role of IgE in angiotensin-II (Ang-II) perfusion- and peri-aortic CaCl2 injury-induced AAA in mice. In both models, IgE-deficiency in Apoe-/-Ige-/- mice blunts AAA growth and reduces lesion accumulation of macrophages, CD4+ and CD8+ T cells, and lesion MHC class-II expression, CD31+ microvessel growth, and media smooth muscle cell loss, compared with those from Apoe-/- control mice. Real time-PCR reveals significant reductions in expression of neutrophil chemoattractants MIP-2α and CXCL5 in AAA lesions or macrophages from Apoe-/-Ige-/- mice, along with reduced lesion Ly6G+ neutrophil accumulation. Consistent with reduced lesion inflammatory cell accumulation, we find significant reductions of plasma and AAA lesion IL6 expression in Apoe-/-Ige-/- mice. Immunofluorescent staining and FACS analysis show that AAA lesion neutrophils express FcεR1. Mechanistic study demonstrates that IgE induces neutrophil FcεR1 expression, activates MAPK signaling, and promotes IL6 production. This study supports a direct role of IgE in AAA by promoting lesion chemokine expression, inflammatory cell accumulation, MAPK signaling, and cytokine expression. IgE inhibition may represent a novel therapeutic approach in AAA management.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31907645

RESUMO

PURPOSE: This is the first study to compare the pharmacokinetics of QL1101, a proposed bevacizumab biosimilar, with Avastin® sourced from Roche Diagnostics GmbH. METHODS: In this double-blind, single-dose, parallel-group study, healthy male subjects were randomized 1:1 to receive QL1101 or Avastin® 3 mg/kg intravenously. Pharmacokinetic assessments were conducted for 85 days, with additional safety and immunogenicity assessments until day 90. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the C0-max, AUC0-last, and AUC0-∞ were within the predefined bioequivalence margin of 80-125.00%. RESULTS: A total of 82 subjects were randomized to the following groups: 42 to QL1101 and 40 to Avastin®. The 90% CIs of the GMRs of AUC0-∞, AUC0-last, and Cmax of QL1101 and Avastin® were (97.8%, 107.0%), (94.5%, 106.9%), and (94.1%, 107.3%), respectively, which were all within the bioequivalence margin. The incidence of adverse events was 90.5% and 95.0% in the QL1101 and Avastin® groups, respectively. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across the two treatment groups. CONCLUSIONS: The study demonstrated the pharmacokinetic equivalence of QL1101 to Avastin®. QL1101 (3 mg/kg, iv) is safe and tolerable in healthy Chinese subjects. These data support the further clinical evaluation of QL1101 as a bevacizumab biosimilar.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31926332

RESUMO

Cysteinyl cathepsins are lysosomal/endosomal proteases that mediate bulk protein degradation in these intracellular acidic compartments. Yet, studies indicate that these proteases also appear in the nucleus, nuclear membrane, cytosol, plasma membrane, and extracellular space. Patients with cardiovascular diseases (CVD) show increased levels of cathepsins in the heart, aorta, and plasma. Plasma cathepsins often serve as biomarkers or risk factors of CVD. In aortic diseases, such as atherosclerosis and abdominal aneurysms, cathepsins play pathogenic roles, but many of the same cathepsins are cardioprotective in hypertensive, hypertrophic, and infarcted hearts. During the development of CVD, cathepsins are regulated by inflammatory cytokines, growth factors, hypertensive stimuli, oxidative stress, and many others. Cathepsin activities in inflammatory molecule activation, immunity, cell migration, cholesterol metabolism, neovascularization, cell death, cell signaling, and tissue fibrosis all contribute to CVD and are reviewed in this article in memory of Dr. Nobuhiko Katunuma for his contribution to the field.

7.
Aging (Albany NY) ; 12(1): 611-627, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31905343

RESUMO

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of colon cancer. Nevertheless, the unavoidability of the notable toxicity and the development of the acquired resistance severely restricted its clinical application. Aspirin and some other non-steroidal anti-inflammatory drugs have been used to prevent colon tumorigenesis as chemopreventive agents. Here, we explored the possibility of aspirin as an adjuvant drug to boost the anti-cancer effect of cisplatin for colon cancer. We found that aspirin significantly enhanced the cisplatin-mediated inhibitions of cell proliferation, migration and invasion and the induction of apoptosis in colon cancer cells. The combined treatment of aspirin and cisplatin suppressed the expression of the anti-apoptotic protein Bcl-2 and the EMT-related proteins, up-regulated the levels of the cleaved PARP and Bax, and blocked the PI3K/AKT and RAF-MEK-ERK signaling pathway. In addition, we demonstrated that the enhanced effect of aspirin on the cisplatin-induced inhibition of tumor cell growth was also mediated through the suppression of the binding activity of NF-κB to the COX-2 promoter. The combination of aspirin and cisplatin effectively attenuated the translocation of NF-κB p65/p50 from the cytoplasm to the nucleus, and abrogated the binding of NF-κB p65/p50 to the COX-2 promoter, thereby down-regulating COX-2 expression and PGE2 synthesis. Moreover, the in vivo study also verified the enhanced anti-tumor activity of such combined therapy in colon cancer by targeting the NF-κB/COX-2 signaling. Our results provided new insights into understanding the molecular mechanisms of aspirin in sensitizing cisplatin-mediated chemotherapeutic effect in colon cancer and indicated a great potential of this combined therapy for cancer treatment.

8.
Environ Sci Technol ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976657

RESUMO

Extracellular DNA (eDNA), which is derived from lysis or secretion of cells, is ubiquitous in various environments and crucial for gene dissemination, bacterial metabolism, biofilm integrity, and aquatic monitoring. However, these processes are largely influenced by damage to eDNA. Photodamage to eDNA, one of the most important types of DNA damage in natural waters, thus far remains unclear. In particular, the roles of the ubiquitous dissolved organic matter (DOM) in this process have yet to be determined. In this study, eDNA photodamage, including both deoxynucleoside damage and strand breaks, proved to be significantly influenced by DOM. DOM competed with eDNA for photons to inhibit the direct photodamage of eDNA. Nevertheless, DOM was photosensitized to produce reactive oxygen species (ROS) (i.e., hydroxyl radicals (·OH) and singlet oxygen (1O2)) to enhance the indirect photodamage of eDNA. The ·OH induced damage to four deoxynucleosides and strand breaks, and the 1O2 substantially enhanced deoxyguanosine damage. The presence of DOM changed the main photodamage products of deoxynucleosides, additional oxidation products induced by ROS formed besides pyrimidine dimers caused by UV. Results indicate that DOM-mediated indirect photodamage contributed significantly to eDNA photodamage in most water bodies. This study revealed the previously unrecognized crucial role of DOM in the decay of eDNA in waters.

9.
Curr Top Med Chem ; 19(25): 2269-2270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31797756
10.
Eur Heart J ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31821481

RESUMO

AIMS: Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human and mouse AAA lesions, IL18 colocalizes to its receptors at regions rich in adipocytes, suggesting a role of adipocytes in promoting IL18 actions in AAA development. METHODS AND RESULTS: We localized both IL18r and NCC in human and mouse AAA lesions. Murine AAA development required both receptors. In mouse AAA lesions, IL18 binding to these receptors increased at regions enriched in adipocytes or adjacent to perivascular adipose tissue. 3T3-L1 adipocytes enhanced IL18 binding to macrophages, aortic smooth muscle cells (SMCs), and endothelial cells by inducing the expression of both IL18 receptors on these cells. Adipocytes also enhanced IL18r and IL18 expression from T cells and macrophages, AAA-pertinent protease expression from macrophages, and SMC apoptosis. Perivascular implantation of adipose tissue from either diet-induced obese mice or lean mice but not that from leptin-deficient ob/ob mice exacerbated AAA development in recipient mice. Further experiments established an essential role of adipocyte leptin and fatty acid-binding protein 4 (FABP4) in promoting IL18 binding to macrophages and possibly other inflammatory and vascular cells by inducing their expression of IL18, IL18r, and NCC. CONCLUSION: Interleukin-18 uses both IL18r and NCC to promote AAA formation. Lesion adipocyte and perivascular adipose tissue contribute to AAA pathogenesis by releasing leptin and FABP4 that induce IL18, IL18r, and NCC expression and promote IL18 actions.

11.
Aging Clin Exp Res ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786744

RESUMO

BACKGROUND AND AIMS: This study aimed at investigating whether depression symptoms are associated with prevalent and incident physical frailty in Chinese older population. METHODS: We analyzed data of 1168 older Chinese adults aged 70 and above in the aging arm of the Rugao Longevity and Aging Study (RuLAS). Depressive symptoms (Geriatric Depression Scale ≥ 6) were assessed by the Geriatric Depression Scale. Frailty was defined using Fried phenotype criteria at baseline and 3-year survey. RESULTS: At baseline, 8.9% of the participants had depression symptoms. The prevalence of pre-frailty and frailty were 34.5% and 5.9%, respectively. The percentages of depressive symptoms increase from robust (5.3%) to pre-frail (11.2%), and then to frail (31.9%) groups. After adjustments of multiple covariates, depressive symptoms were associated with both prevalent pre-frailty (OR = 1.75, 95% CI 1.08-2.84) and prevalent frailty (OR = 5.64, 95% CI 2.85-11.14) at baseline. At 3-year survey, 9.3% participants reported the development of frailty. After multiple adjustments, depressive symptoms were associated with a 2.79-fold (95% CI 1.09-7.10) increased risk of 3-year incident frailty. CONCLUSION: Depressive symptoms are associated with prevalent and incident frailty in Chinese older population. Together with the observations of the European populations, depressive symptoms may be a candidate risk factor of frailty.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31793764

RESUMO

Herein, a new porous Zn(II)-based metal-organic framework (MOF 1) has been prepared, the structure of which featured a twofold entangled motif based on two typical secondary building units (SBUs). The gas sorption studies indicated that MOF 1 may be explored as a useful platform to encapsulate metallic nanoparticles. Then the Au@1 composite has been prepared via a facile incorporation method without extra reducing agents. The Au@1 composite has been fully characterized by HRTEM, SEM-EDX, PXRD, gas sorption, XPS, ICP, etc. Catalytic experiments showed that the Au@1 composite had a perfect catalytic performance in CO2 fixation for epoxides with different substituents under mild conditions.

14.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3635-3645, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31833675

RESUMO

We carried out niche monitoring and analysis of plant populations under the forest community in the talus slope ecotone of a typical moderate-degraded Bajiaxiantang tiankeng to provide scientific references for biodiversity conservation and vegetation restoration in degraded tiankeng area. The results showed that soil ammonium, available potassium, and available phosphorus signifi-cantly affected species distribution, which explained 37.4%, 32.8%, 29.3% of the total variation, respectively. With the change of talus slope of tiankeng (pit, uphill, mid-slope, downhill and pit bottom), life form of understory plants changed from evergreen and xerophytes to evergreen and hygro-mesophytes, with the niche overlap of herbs being larger than that of shrubs. Shrubs of Viburnum congestum and Campylotropis polyantha, and herbs of Arisaema erubescens and Arthraxon hispidus had wide ecological amplitude and strong resistance, which occupied the upper layer of the shrub and herb layers. Shrub Cornus oblonga and herb Geranium nepalense, Agrimonia pilosa lost the competitiveness with increasing soil alkalinity. Niche characteristics of understory dominant species in Bajiaxiantang were closely related to the canopy structure of mixed trees, ecological strategies of shrub and herb species, unique habitat of tiankeng, and the importance value of dominant species.

15.
Environ Int ; 135: 105383, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835022

RESUMO

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related enzymes/proteins, interfering with the production and signal regulation of thyroid hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

16.
J Am Heart Assoc ; 8(24): e005886, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31838975

RESUMO

Background Although apoptosis and cell proliferation have been extensively investigated in atherosclerosis and restenosis postinjury, the communication between these 2 cellular events has not been evaluated. Here, we report an inextricable communicative link between apoptosis and smooth muscle cell proliferation in the promotion of vascular remodeling postinjury. Methods and Results Cathepsin K-mediated caspase-8 maturation is a key initial step for oxidative stress-induced smooth muscle cell apoptosis. Apoptotic cells generate a potential growth-stimulating signal to facilitate cellular mass changes in response to injury. One downstream mediator that cathepsin K regulates is PLF-1 (proliferin-1), which can potently stimulate growth of surviving neighboring smooth muscle cells through activation of PI3K/Akt/p38MAPK (phosphatidylinositol 3-kinase/protein kinase B/p38 mitogen-activated protein kinase)-dependent and -independent mTOR (mammalian target of rapamycin) signaling cascades. We observed that cathepsin K deficiency substantially mitigated neointimal hyperplasia by reduction of Toll-like receptor-2/caspase-8-mediated PLF-1 expression. Interestingly, PLF-1 blocking, with its neutralizing antibody, suppressed neointima formation and remodeling in response to injury in wild-type mice. Contrarily, administration of recombinant mouse PLF-1 accelerated injury-induced vascular actions. Conclusions This is the first study detailing PLF-1 as a communicator between apoptosis and proliferation during injury-related vascular remodeling and neointimal hyperplasia. These data suggested that apoptosis-driven expression of PLF-1 is thus a novel target for treatment of apoptosis-based hyperproliferative disorders.

17.
Ying Yong Sheng Tai Xue Bao ; 30(12): 4344-4352, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31840481

RESUMO

Behavioral and physiological ecology are two important research aspects of ecological field. Related studies help us better understand the marine animal's habit and adaptability to environment. Antarctic krill (Euphausia superba, thereafter krill) is a key-stone species in the Southern Ocean. Understanding its behavioral and physiological ecology can understand the ability of marine organisms such as krill to cope with extreme environment. We summarized the typical ecological characteristics of krill from both aspects of behavioral ecology and physiological ecology. Behavioral ecology included its swarming (size and behavior) and swimming (angle, beat of pleopod), while physiological ecology included respiration, excretion, metabolism, molting and growth. Generally, the studies on behavioral and physiological ecology of krill were very limited, and many studies were based on land-based krill aquarium. In view of the large difference between land-based aquarium and natural environment of krill, it's extremely urgent to develop the in-situ experimental ecology of krill in the sea.

18.
Drug Des Devel Ther ; 13: 4135-4144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827320

RESUMO

Purpose: To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection. Patients and methods: A randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Results: After administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, P<0.001). Further analysis showed that gender did not affect the pharmacokinetics of esketamine and racemate ketamine. Regarding the safety of esketamine and racemate ketamine, no serious adverse events were observed during treatment, and the incidences of adverse events were 75.0% (esketamine) and 87.5% (racemate ketamine). The main adverse reactions were dizziness, agitation, nausea, vomiting, headache, and fatigue. However, compared with racemic ketamine, esketamine offers a shorter recovery time (9 mins vs. 13 mins, P<0.05) and orientation recovery time (11.5 mins vs. 17 mins, P<0.05) after short anesthesia. Conclusion: Esketamine administration as a single dose of 0.5 mg/kg was generally safe and tolerated in patients undergoing painless gastroscopy. In terms of anesthesia, a relatively small dose of esketamine can be used instead of racemate ketamine for routine treatment without consideration of gender differences.

19.
Bioanalysis ; 11(22): 2049-2060, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31829738

RESUMO

Aim: To develop and validate a simple method using UPLC-MS/MS for determination of apatinib and its three active metabolites in a Phase IV clinical trial. Materials & methods: All compounds were separated on a Hypersil GOLD™ aQ C18 Polar Endcapped LC column (50 × 2.1 mm, 1.9 µm, Thermo) using 5 mmol/l ammonium acetate with 0.1% formic acid:acetonitrile (20:80, v/v) as the mobile phase after a rapid liquid-liquid extraction. This method was validated over the linear concentration range of 1.00-1000 ng/ml for each compound. Results: The interassay precision and accuracy were less than ±15%. The validated method was successfully applied to determine concentrations of clinical samples in non-small-cell lung cancer patients.

20.
J Hazard Mater ; 386: 121972, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31887564

RESUMO

Ionic liquids, a kind of emerging and persistent organic contaminants, always coexist with heavy metals in aquatic and terrestrial environments. However, the feasibility of phytoremediation to remove ionic liquids and heavy metals co-contaminants is still unclear. Thus, in this study, the hydroponic experiment was conducted to investigate the combined effect of 1-butyl-3-methylimidazolium bromide ([C4mim]+Br-) and cadmium (Cd2+) on growth and physiological indictors of perennial ryegrass, together with their uptake and translocation by plants. Results show that the exposure of ryegrass to [C4mim]+ and Cd2+ mixture significantly inhibited the biomass growth and affected the photosynthetic pigments contents in leaves. The increases of lipid peroxidation and catalase, peroxidase activity were also observed under the co-exposure experiments. The mixture toxicity of [C4mim]+ and Cd2+ to ryegrass growth showed an additive effect predicted by concentration addition and independent action. [C4mim]+ uptake and acropetal translocation by ryegrass were significantly inhibited with dosing Cd2+. In contrast, [C4mim]+ had no obvious effect on Cd2+ uptake by ryegrass, while enhanced Cd2+ translocation from roots to shoots occurred with increasing [C4mim]+ dosages. These results indicate that the co-contamination of ionic liquids and heavy metals would affect their fates during phytoremediation.

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