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1.
Stroke ; : STROKEAHA119027003, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31446884

RESUMO

Background and Purpose- We aimed to examine the relation of baseline plasma zinc with the risk of first stroke and investigate any possible effect modifiers in hypertensive patients. Methods- The study population was drawn from the CSPPT (China Stroke Primary Prevention Trial), using a nested case-control design, including 599 first stroke cases and 599 matched controls. Results- Compared with participants with baseline plasma zinc <106.9 µg/dL (median), a significantly lower risk of first hemorrhagic stroke was found in those with plasma zinc ≥106.9 µg/dL (multivariate-adjusted odds ratio, 0.45; 95% CI, 0.21-0.94). Furthermore, the inverse plasma zinc-first hemorrhagic stroke association was significantly stronger in participants with body mass index ≥25.0 kg/m2 or plasma copper <100.1 µg/dL at baseline (Pinteraction <0.05 for both variables). However, there was no significant association between plasma zinc and first ischemic stroke (<103.3 versus ≥103.3 µg/dL [median]; multivariate-adjusted odds ratio, 1.16; 95% CI, 0.83-1.61). Conclusions- In this sample of hypertensive patients, we found a significant, inverse association between plasma zinc and first hemorrhagic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.

2.
Sci Total Environ ; 694: 133698, 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31401504

RESUMO

Human behavior is affected not only by individuals' own psychological factors but also by the surrounding environment and the behaviors of others. Existing studies on tourists' responsible environmental behaviors tend to focus only on tourists' own psychological and environmental factors while ignoring the referential role of other people's behavior. The behavioral reference of others in tourist destinations is an important situational factor that affects tourists' responsible environmental behaviors and has important research value. Based on the theory of planned behavior and taking the Zhongshan Mausoleum Scenic Area as an example, this paper explores the influence of other people's behavioral reference on tourists' responsible environmental behaviors by using the multi-group analysis method of structural equation modelling. The results show the following: (1) Tourists' attitudes toward environmental behavior and subjective norms have a significant positive impact on their responsible environmental behavioral intention, perceived behavioral control has a significant positive impact on their responsible environmental behavioral intention and their responsible environmental behaviors, and responsible environmental behavioral intention has a significant positive impact on responsible environmental behaviors. (2) Tourist destination behavioral reference plays a positive regulatory role in the relationship between tourists' responsible environmental behavioral intention and responsible environmental behaviors. Accordingly, this paper proposes relevant countermeasures and suggestions for the high-quality management and development of tourist destinations.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31440983

RESUMO

Direct oral anticoagulants are increasingly used in clinical practice and have addressed many of the issues related to vitamin K antagonists. However, the lack of reversal in life-threatening situations raises concerns regarding patient safety. Thus, current research is aimed at developing reversal agents that can safely neutralize the effects of anticoagulants. We present the design and mechanisms of action of and the animal models, clinical trials, and current evidence supporting the use of these emerging reversal agents. Idarucizumab is approved in many countries, and andexanet alfa has been approved by the US FDA, whereas others are in clinical trials. In view of the results of clinical studies to date, the problems of safety, price and accessibility remain. Therefore, these antidotes are a significant step towards improving the field of urgent and emergency reversal. From a practical perspective, post-market surveillance will be crucial to monitor the safety and effectiveness of these agents.

4.
Am J Clin Nutr ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31161196

RESUMO

BACKGROUND: Previous studies indicated that trace elements may play an important role in cardiovascular diseases. However, data concerning the association between blood copper and the risk of stroke are limited. OBJECTIVE: The aim of this study was to evaluate the association between plasma copper and the risk of first stroke, and examine any possible effect modifiers in hypertensive patients. METHODS: We conducted a nested case-control study, using data from the China Stroke Primary Prevention Trial. Hypertension is defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or taking antihypertensive medication. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. The crude and adjusted risks of first stroke were estimated by ORs and 95% CIs using conditional logistic regression, without or with adjusting for pertinent covariates, respectively. RESULTS: There were significant positive associations of plasma copper with risk of first stroke (per SD increment-OR: 1.20; 95% CI: 1.03, 1.39) and first ischemic stroke (OR: 1.26; 95% CI: 1.07, 1.50). When plasma copper was categorized in quartiles, significantly higher risks of first stroke (OR: 1.72; 95% CI: 1.12, 2.65) and first ischemic stroke (OR: 1.91; 95% CI: 1.18, 3.11) were found in participants in quartile 4 (≥ 117.0 µg/dL) than in those in quartile 1 (< 91.2 µg/dL). Furthermore, the plasma copper-first stroke association was significantly stronger in participants with higher BMI (< 25.0 compared with ≥ 25.0 kg/m2, P-interaction = 0.024). However, there was no significant association between plasma copper and first hemorrhagic stroke. CONCLUSIONS: In Chinese hypertensive patients, there was a significant positive association between baseline plasma copper and the risk of first stroke, especially among those with higher BMI.This trial was registered at clinicaltrials.gov as NCT00794885.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31236574

RESUMO

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.

6.
Plant Cell ; 31(9): 1990-2009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227559

RESUMO

Maize (Zea mays subsp mays) was domesticated from its wild ancestor, teosinte (Zea mays subsp parviglumis). Maize's distinct morphology and adaptation to diverse environments required coordinated changes in various metabolic pathways. However, how the metabolome was reshaped since domestication remains poorly understood. Here, we report a comprehensive assessment of divergence in the seedling metabolome between maize and teosinte. In total, 461 metabolites exhibited significant divergence due to selection. Interestingly, teosinte and tropical and temperate maize, representing major stages of maize evolution, targeted distinct sets of metabolites. Alkaloids, terpenoids, and lipids were specifically targeted in the divergence between teosinte and tropical maize, while benzoxazinoids were specifically targeted in the divergence between tropical and temperate maize. To identify genetic factors controlling metabolic divergence, we assayed the seedling metabolome of a large maize-by-teosinte cross population. We show that the recent metabolic divergence between tropical and temperate maize tended to have simpler genetic architecture than the divergence between teosinte and tropical maize. Through integrating transcriptome data, we identified candidate genes contributing to metabolic divergence, many of which were under selection at the nucleotide and transcript levels. Through overexpression or mutant analysis, we verified the roles of Flavanone 3-hydroxylase1, Purple aleurone1, and maize terpene synthase1 in the divergence of their related biosynthesis pathways. Our findings not only provide important insights into domestication-associated changes in the metabolism but also highlight the power of combining omics data for trait dissection.

7.
Adv Mater ; 31(32): e1902542, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183900

RESUMO

Current cancer immunotherapies including chimeric antigen receptor (CAR)-based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial-based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune-related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies. Herein, a rational design of immunomodulating nanoparticles is demonstrated that can in situ modify the tumor cell surface with natural killer cell (NK cell)-activating signals to achieve in situ activation of tumor-infiltrating NK cells, as well as direction of their antitumor immunity toward tumor cells. Using these immunomodulating nanoparticles, the remarkable inhibition of tumor growth is observed in mice without noticeable side effects. This study provides an accurate immunomodulation strategy that achieves safe and effective antitumor immunity through in situ NK cell activation in tumors. Further development by constructing interactions with various immune cells can potentially make this nanotechnology become a general platform for the design of advanced immunotherapies for cancer treatments.

8.
Mol Cell Proteomics ; 18(8): 1572-1587, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31182439

RESUMO

Proteins undergo acetylation at the Nε-amino group of lysine residues and the Nα-amino group of the N terminus in Archaea as in Bacteria and Eukarya. However, the extent, pattern and roles of the modifications in Archaea remain poorly understood. Here we report the proteomic analyses of a wild-type Sulfolobus islandicus strain and its mutant derivative strains lacking either a homolog of the protein acetyltransferase Pat (ΔSisPat) or a homolog of the Nt-acetyltransferase Ard1 (ΔSisArd1). A total of 1708 Nε-acetylated lysine residues in 684 proteins (26% of the total proteins), and 158 Nt-acetylated proteins (44% of the identified proteins) were found in S. islandicus ΔSisArd1 grew more slowly than the parental strain, whereas ΔSisPat showed no significant growth defects. Only 24 out of the 1503 quantifiable Nε-acetylated lysine residues were differentially acetylated, and all but one of the 24 residues were less acetylated by >1.3 fold in ΔSisPat than in the parental strain, indicating the narrow substrate specificity of the enzyme. Six acyl-CoA synthetases were the preferred substrates of SisPat in vivo, suggesting that Nε-acetylation by the acetyltransferase is involved in maintaining metabolic balance in the cell. Acetylation of acyl-CoA synthetases by SisPat occurred at a sequence motif conserved among all three domains of life. On the other hand, 92% of the acetylated N termini identified were acetylated by SisArd1 in the cell. The enzyme exhibited broad substrate specificity and could modify nearly all types of the target N termini of human NatA-NatF. The deletion of the SisArd1 gene altered the cellular levels of 18% of the quantifiable proteins (1518) by >1.5 fold. Consistent with the growth phenotype of ΔSisArd1, the cellular levels of proteins involved in cell division and cell cycle control, DNA replication, and purine synthesis were significantly lowered in the mutant than those in the parental strain.

9.
Hypertension ; 74(1): 102-110, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079533

RESUMO

The relationship of serum phosphate and new-onset hyperuricemia remains uncertain. We aimed to evaluate the relationship of serum phosphate with the risk of new-onset hyperuricemia, and to examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric Acid substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 10 612 participants with normal uric acid levels (<357 µmol/L [6 mg/dL]) at baseline were included in the current study. The primary outcome was new-onset hyperuricemia, which was defined as a uric acid concentration ≥417 µmol/L (7 mg/dL) in men or ≥357 µmol/L (6 mg/dL) in women. During a median follow-up of 4.4 years, 1663 (15.7%) participants developed new-onset hyperuricemia. Overall, there was a significant inverse association between serum phosphate and the risk of new-onset hyperuricemia (per SD increment; odds ratio, 0.71; 95% CI, 0.66-0.76). When serum phosphate was assessed as quartiles, a significantly lower risk of new-onset hyperuricemia was found in participants in quartile 4 (≥1.4 mmol/L; odds ratio, 0.48; 95% CI, 0.40-0.57) compared with those in quartile 1 (<1.2 mmol/L). Similar results were found in males and females. In summary, there was an inverse association between serum phosphate and the risk of new-onset hyperuricemia in hypertensive adults.

10.
Chem Biol Interact ; 307: 125-135, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31047916

RESUMO

(-)-Epigallocatechin-3-gallate (EGCG) found in tea is a natural activator of nuclear factor erythroid 2-related factor 2 (Nrf2), a primary regulator of the cellular defense system. The adverse health effects resulting from methylmercury (MeHg) exposure in humans are of worldwide concern. We hypothesized that EGCG could induce a Nrf2-mediated protective response to antagonize MeHg toxicity. Using the Caenorhabditis elegans (C. elegans) nematode model, we observed that EGCG activated SKN-1 (the functional ortholog of Nrf2 in C. elegans), as shown by the increased skn-1 mRNA level, induction of the gene gst-4, and enhanced SKN-1-mediated oxidative stress resistance that were indicated by elevation of total antioxidant ability and reductions in reactive oxygen species and malondialdehyde. Following exposure to MeHg, EGCG-treated C. elegans displayed increased survival rates, improved locomotion behaviors, decreased numbers of damaged neurons, and reduced oxidative damage compared to the controls. Moreover, the protective effects of EGCG against MeHg toxicity were counteracted by RNA-mediated interference of skn-1. These results demonstrated that EGCG could alleviate MeHg toxicity by upregulating the SKN-1-regulated protective response in C. elegans. Our study suggests a potentially beneficial effect of targeting Nrf2 by dietary EGCG in protecting humans against MeHg toxicity.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Catequina/análogos & derivados , Proteínas de Ligação a DNA/metabolismo , Compostos de Metilmercúrio/toxicidade , Substâncias Protetoras/farmacologia , Fatores de Transcrição/metabolismo , Animais , Antioxidantes/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Catequina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Larva/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

12.
Leukemia ; 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31028278

RESUMO

CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5-CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed 77 differentially expressed genes unique to CXCR5+CD8+ T cells. Among these, a signature comprised of 33 upregulated genes correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-ß, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T cell subset with ability to suppress TFH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.

13.
Nutr Cancer ; 71(1): 50-60, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30741002

RESUMO

Malnutrition is a problem affecting tumor patients greatly. This study aims to investigate whether demographic characteristics are related to the malnutrition of cancer patients. Twenty-three thousand nine hundred and four (23,904) patients with 16 common malignant tumors were enrolled in the study. Patient Generated Subjective Global Assessment (PG-SGA) was used as a screening tool to assess the nutritional risk of patients and analysis of variance was used to compare PG-SGA scores of patients. Correlations between PG-SGA scores and demographic characteristics were evaluated by correlation analysis. We observed that 57.88% tumor patients had some degree of malnutrition (score ≥4) and only 20.61% were well-nourished (score 0-1). Screening scores were higher among older patients for most of the tumors. PG-SGA scores showed the significant difference between females and males in some tumors. In addition, the PG-SGA scores of some tumors were significantly different in various types of medical insurances, education levels, occupations, regions, and nationalities. Correlation analysis indicated the existence of associations between PG-SGA scores and demographic characteristics. Understanding the distribution of nutritional risk of tumor patients and the correlations between the PG-SGA scores and demographic characteristics could help identify subgroups who may benefit from targeted interventions to improve the effect of clinical treatment and the quality of life for oncology patients.

14.
J Biomed Nanotechnol ; 15(2): 405-415, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30596562

RESUMO

Hydroxyapatite (HAP) plays an important role in skeleton formation and bone remodeling. Synthetic HAP is similar to naturally occurring HAP and has been widely used in orthopedic and dental implantation. While it is known nano-HAP easily aggregates at high concentrations, the intracellular fate and mechanisms-of-action of dispersed nano-HAP in osteoblast differentiation remain to be fully elucidated. In the present study, we treated the osteoblast cell line MC3T3E1 with autoclaved nano-HAP and added sodium hexametaphosphate to control nanoparticle agglomeration. Dispersed nano-HAP promoted osteoblast differentiation in a dose-dependent manner. Our findings further revealed that the internalized nano-HAP particles were located in typical autophagic vacuoles and increased the ratio of LC3II/LC3I, indicating nano-HAP induced cell autophagy. Moreover, the induction of autophagy by nano-HAP was via mTOR signaling pathway which also concentration dependent. Collectively, these results reveal nano-HAP modulates osteoblast differentiation by mediating autophagy in a dose-dependent manner.


Assuntos
Autofagia , Durapatita , Diferenciação Celular , Nanoestruturas , Osteoblastos , Transdução de Sinais , Serina-Treonina Quinases TOR
15.
Diabetes ; 68(4): 858-867, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30674623

RESUMO

Glycated hemoglobin (HbA1c) is an important measure of glycemia in diabetes. HbA1c is influenced by environmental and genetic factors both in people with and in people without diabetes. We performed a genome-wide association study (GWAS) for HbA1c in a Finnish type 1 diabetes (T1D) cohort, FinnDiane. Top results were examined for replication in T1D cohorts DCCT/EDIC, WESDR, CACTI, EDC, and RASS, and a meta-analysis was performed. Three SNPs in high linkage disequilibrium on chromosome 13 near relaxin family peptide receptor 2 (RXFP2) were associated with HbA1c in FinnDiane at genome-wide significance (P < 5 × 10-8). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA1c also in the meta-analysis with RASS (P < 5 × 10-8), where these variants had minor allele frequencies ≥1%. Furthermore, these SNPs were associated with HbA1c in an East Asian population without diabetes (P ≤ 0.013). A weighted genetic risk score created from 55 HbA1c-associated variants from the literature was associated with HbA1c in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA1c may lead to better prevention of diabetes complications.

16.
Angiology ; 70(6): 515-522, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30651004

RESUMO

Arterial stiffness plays a key role in the pathogenesis of cardiovascular disease. However, the relationship between lipid levels and arterial stiffness is controversial. We aimed to investigate the association between lipid parameters and brachial-ankle pulse-wave velocity (baPWV) in Chinese patients with hypertension. A total of 14 071 participants with hypertension in the China Stroke Primary Prevention Trial (CSPPT) were enrolled in the present study. Patients were assigned to 4 equal groups according to their baPWV. Participants in the highest baPWV group were older with a higher prevalence of stroke and diabetes mellitus as well as higher body mass index (BMI), blood pressure, fasting plasma glucose, uric acid, total cholesterol (TC), triglycerides (TG), homocysteine (Hcy), and vitamin B12 levels ( P < .001). After adjusting for age, sex, BMI, and other cardiovascular risks, high-density lipoprotein cholesterol (HDL-C) was negatively related to baPWV (ß = -0.22, P = .012), TC (ß = 0.08, P = 0.001), TG (ß = 0.14, P = .001); non-HDL-C (ß = 0.12, P = .001) and positively related to baPWV. The effect was not observed for low-density lipoprotein cholesterol (LDL-C; ß = 0.12, P = .335).These results suggested that non-HDL-C, TG, and TC were associated with arterial stiffness in a Chinese population with hypertension. HDL-C was inversely associated with arterial stiffness.


Assuntos
Pressão Sanguínea , Dislipidemias/sangue , Hipertensão/fisiopatologia , Lipídeos/sangue , Doença Arterial Periférica/fisiopatologia , Rigidez Vascular , Idoso , Índice Tornozelo-Braço , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , China/epidemiologia , Comorbidade , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/etnologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etnologia , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Saúde da População Rural
17.
Molecules ; 24(1)2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30577688

RESUMO

In this study, we demonstrate a novel H2O2 activatable photosensitizer (compound 7) which contains a diiodo distyryl boron dipyrromethene (BODIPY) core and an arylboronate group that quenches the excited state of the BODIPY dye by photoinduced electron transfer (PET). The BODIPY-based photosensitizer is highly soluble and remains nonaggregated in dimethyl sulfoxide (DMSO) as shown by the intense and sharp Q-band absorption (707 nm). As expected, compound 7 exhibits negligible fluorescence emission and singlet oxygen generation efficiency. However, upon interaction with H2O2, both the fluorescence emission and singlet oxygen production of the photosensitizer can be restored in phosphate buffered saline (PBS) solution and PBS buffer solution containing 20% DMSO as a result of the cleavage of the arylboronate group. Due to the higher concentration of H2O2 in cancer cells, compound 7 even with low concentration is particularly sensitive to human cervical carcinoma (HeLa) cells (IC50 = 0.95 µM) but hardly damage human embryonic lung fibroblast (HELF) cells. The results above suggest that this novel BODIPY derivative is a promising candidate for fluorescence imaging-guided photodynamic cancer therapy.


Assuntos
Boro/química , Peróxido de Hidrogênio/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Porfobilinogênio/análogos & derivados , Transporte Biológico , Linhagem Celular , Humanos , Estrutura Molecular , Fotoquímica , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Porfobilinogênio/síntese química , Porfobilinogênio/química , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência
18.
J Environ Manage ; 231: 804-810, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30419435

RESUMO

Previous research on the environmentally responsible behaviour (ERB) of tourists has primarily focused on the personal psychological factors of tourists. However, the studies overlook the effect of contextual factors of a tourist site. According to the broken window theory, a disorderly, unkempt environment might lead more people to be involved in environmental destruction, which would form a vicious cycle. Therefore, it can be deduced that the environmental background (EB) of a tourist site is an important contextual factor. In this paper, the effect of the EB of a tourist site on the ERB was examined by the theory of planned behaviour (TPB) adopting structural equation model (SEM) multi-group analysis (MGA). The results show the following: first, both the attitude toward environmental behaviour (ATT) of tourists and their subjective norm (SN) have a positive impact on the environmentally responsible behavioural intention (ERBI) of tourists. In addition, perceived behavioural control (PBC) exerts a remarkable influence on the ERB of tourists and their behavioural intention. Second, the relationship between the ERBI and ERB of tourists is positively regulated by the EB of a tourist site. Additionally, this paper presents policy proposals for the environmental management of tourist sites.

19.
Inflammopharmacology ; 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242748

RESUMO

BACKGROUND: This study aimed to explore the correlation of circulating inflammatory cytokines' levels with treatment response to etanercept (ETN) treatment in psoriasis patients. METHODS: 97 moderate-to-severe plaque-psoriasis patients were continuously recruited in this prospective cohort study, and all patients received ETN treatment. Serum samples were collected before and at 6 months (M6) after treatment, and nine inflammatory cytokines expressions were detected by enzyme-linked immuno sorbent assay. Psoriasis Area and Severity Index (PASI) score was evaluated at baseline (M0), 1 month (M1), 3 months (M3) and M6 after treatment, and the corresponding PASI 75/90 responses' rates were calculated. RESULTS: Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-22, IL-23, and IL-32 levels were reduced, while IL-10 level was elevated at M6 after ETN treatment compared to baseline. PASI 75/90 responses' rates to ETN were 69.1 and 38.1% at M6, respectively. IL-1ß and IL-17A levels were elevated in PASI 75-response patients compared to PASI 75 non-response patients, while IL-17A level was also increased in PASI 90-response patients compared to PASI 90 non-response patients. Multivariate logistic regression revealed that IL-1ß, IL-17A and combined phototherapy during study predicted higher, while previous systemic biologic treatment predicted lower PASI 75 response to ETN independently. In addition, IL-17A independently predicted higher PASI 90 response to ETN as well. CONCLUSIONS: IL-1ß, IL-17A, and combined phototherapy predicts higher while previous systemic biologic treatment predicts lower treatment response to ETN independently in psoriasis patients.

20.
Life Sci ; 209: 498-506, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30144452

RESUMO

AIM: Colorectal cancer (CRC) accounts for over 600,000 deaths annually worldwide. Euxanthone is a flavonoid compound extracted from Polygala caudata, with documented anti-neoplastic actions. The current study aimed to determine the therapeutic potential of euxanthone in CRC. METHODS AND MATERIALS: Cell Counting Kit-8 (CCK-8) assay was used to analyze the effect of euxanthone on the cell viability, and apoptosis was detected by the TUNEL assay. The in vitro migratory capacity was determined by wound healing and the invasiveness was assessed by Transwell assay. Western blotting was used to determine the level of relevant proteins. Furthermore, a CRC xenograft murine model was used to analyze the therapeutic efficacy of euxanthone in vivo. Isobaric tags for relative and absolute quantification (iTRAQ) was then performed to identify the potential targets of euxanthone. To validate the role of cancerous inhibitor of PP2A (CIP2A) in the anti-cancer effects of euxanthone, plasmid overexpressing CIP2A and shRNA targeting CIP2A were used in in vitro assays. KEY FINDINGS: Euxanthone decreased cell viability and increased apoptosis in CRC cells, in addition to restraining migration, invasion and EMT. Similarly, euxanthone also effectively suppressed tumor growth and pulmonary metastasis in vivo. iTRAQ analysis identified CIP2A as the primary target responsible for the anticancer effects of euxanthone. The mediatory role of CIP2A was validated when the anticancer activity of euxanthone was significantly blocked by CIP2A overexpression, while CIP2A knockdown sensitized the CRC cells to euxanthone. SIGNIFICANCE: Euxanthone exerts anti-cancer effects in vitro and in vivo in CRC by targeting CIP2A/PP2A signaling.


Assuntos
Autoantígenos/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/metabolismo , Proteína Fosfatase 2/metabolismo , Xantonas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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