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1.
Sci Total Environ ; : 174452, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964396

RESUMO

Airborne trace elements (TEs) present in atmospheric fine particulate matter (PM2.5) exert notable threats to human health and ecosystems. To explore the impact of meteorological conditions on shaping the pollution characteristics of TEs and the associated health risks, we quantified the variations in pollution characteristics and health risks of TEs due to meteorological impacts using weather normalization and health risk assessment models, and analyzed the source-specific contributions and potential sources of primary TEs affecting health risks using source apportionment approaches at four sites in Shandong Province from September to December 2021. Our results indicated that TEs experience dual effects from meteorological conditions, with a tendency towards higher TE concentrations and related health risks during polluted period, while the opposite occurred during clean period. The total non-carcinogenic and carcinogenic risks of TEs during polluted period increased approximately by factors of 0.53-1.74 and 0.44-1.92, respectively. Selenium (Se), manganese (Mn), and lead (Pb) were found to be the most meteorologically influenced TEs, while chromium (Cr) and manganese (Mn) were identified as the dominant TEs posing health risks. Enhanced emissions of multiple sources for Cr and Mn were found during polluted period. Depending on specific wind speeds, industrialized and urbanized centers, as well as nearby road dusts, could be key sources for TEs. This study suggested that attentions should be paid to not only the TEs from primary emissions but also the meteorology impact on TEs especially during pollution episodes to reduce health risks in the future.

2.
Sci Total Environ ; 946: 174108, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914328

RESUMO

Comprehensive volatile organic compounds (VOCs) emission control is imperative to decreasing occupational health risks and environmental impact of the packaging and printing industries. In this work, we investigated the VOCs emission characteristics and concentrations of individual contaminants generated by the packaging and printing industries, with regard to various categories, processes, and geographic regions. VOCs emissions, ozone formation potential (OFP), and associated health risks were assessed at 10 representative packaging and printing firms across several cities in Shandong Province, China. Plastic packaging enterprises had the greatest levels of unorganized VOCs emissions, consisting predominantly of oxygenated volatile organic compounds (OVOCs), followed by alkanes and halocarbons. From metal and paper packaging enterprises, OVOCs, alkanes, and aromatics were significant components of unorganized VOCs emissions. Aromatics, halocarbons, and OVOCs contributed significantly to OFP in workshops. The potential carcinogenic risk associated with VOCs in the packaging and printing industries was not significant. However, according to the findings in this study, the workshop environment may provide a comparatively elevated non-carcinogenic risk attributable to ethyl acetate, isopropanol, acrolein, 1,1,2-Trichloroethane, 1,2-Dichloropropane, and naphthalene exposure. In particular, the endocrine-disrupting and genetic toxic effects caused by benzene, toluene, styrene, and naphthalene should not be overlooked. Thus, it is essential to provide precedence to the working environment conditions of workshop laborers, while also undertaking scientific and systematic measures to mitigate the detrimental impacts of VOCs on the environment and human welfare.

3.
J Environ Manage ; 357: 120730, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574705

RESUMO

Volatile organic compounds (VOCs) significantly contribute to ozone pollution formation, and many VOCs are known to be harmful to human health. Plastic has become an indispensable material in various industries and daily use scenarios, yet the VOC emissions and associated health risks in the plastic manufacturing industry have received limited attention. In this study, we conducted sampling in three typical plastic manufacturing factories to analyze the emission characteristics of VOCs, ozone formation potential (OFP), and health risks for workers. Isopropanol was detected at relatively high concentrations in all three factories, with concentrations in organized emissions reaching 322.3 µg/m3, 344.8 µg/m3, and 22.6 µg/m3, respectively. Alkanes are the most emitted category of VOCs in plastic factories. However, alkenes and oxygenated volatile organic compounds (OVOCs) exhibit higher OFP. In organized emissions of different types of VOCs in the three factories, alkenes and OVOCs contributed 22.8%, 67%, and 37.8% to the OFP, respectively, highlighting the necessity of controlling them. The hazard index (HI) for all three factories was less than 1, indicating a low non-carcinogenic toxic risk; however, there is still a possibility of non-cancerous health risks in two of the factories, and a potential lifetime cancer risk in all of the three factories. For workers with job tenures exceeding 5 years, there may be potential health risks, hence wearing masks with protective capabilities is necessary. This study provides evidence for reducing VOC emissions and improving management measures to ensure the health protection of workers in the plastic manufacturing industry.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Humanos , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental , Medição de Risco , Indústria Manufatureira , Alcenos , China
4.
Hypertension ; 81(3): 658-667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38174564

RESUMO

BACKGROUND: It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. METHODS: The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. RESULTS: At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71-1.26), 1.08 (0.80-1.44), and 0.91 (0.69-1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (P=0.88 for interaction). CONCLUSIONS: Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Proteínas Supressoras de Tumor/farmacologia , Proteínas Supressoras de Tumor/uso terapêutico
5.
Expert Opin Drug Deliv ; 20(10): 1349-1369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450427

RESUMO

INTRODUCTION: Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins have multiple advantages, including high bioactivity and specificity with low toxicity. Developing oral dosage forms with active proteins is a route to improve patient compliance and significantly reduce production costs. However, the gastrointestinal environment remains a challenge to this delivery path due to enzymatic degradation, low permeability, and weak absorption, leading to reduced delivery efficiency and poor clinical outcomes. AREAS COVERED: This review describes the barriers to oral delivery of peptides and complex proteins, current oral delivery strategies utilized and the opportunities and challenges ahead to try and circumvent these barriers. Oral protein drugs on the market and clinical trials provide insights and approaches for advancing delivery strategies. EXPERT OPINION: Although most current studies on oral protein delivery rely on in vitro and in vivo animal data, the safety and limitations of the approach in humans remain uncertain. The shortage of clinical data limits the development of new or alternative strategies. Therefore, designing appropriate oral delivery strategies remains a significant challenge and requires new ideas, innovative design strategies and novel model systems.


Assuntos
Sistemas de Liberação de Medicamentos , Proteínas , Animais , Humanos , Administração Oral , Proteínas/efeitos adversos , Peptídeos
6.
Stroke ; 54(2): 509-517, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36511149

RESUMO

BACKGROUND: Osteoprotegerin was implicated in vascular injury and inflammatory responses, but its prognostic value in ischemic stroke remained unclear. We aimed to prospectively investigate the association between plasma osteoprotegerin and ischemic stroke prognosis combined with a Mendelian randomization analysis. METHODS: Our prospective study follows the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guideline. We measured baseline plasma osteoprotegerin levels for 3490 ischemic stroke patients recruited between August 2009 and May 2013 in 26 hospitals across China. The primary outcome was a composite outcome of death and major disability at 3 months after ischemic stroke. RESULTS: After adjustment for age, sex, admission National Institutes of Health Stroke Scale score, and other important covariates, elevated osteoprotegerin levels were associated with increased risks of primary outcome (odds ratio, 1.40 [95% CI, 1.05-1.88]), death (hazard ratio, 2.05 [95% CI, 1.04-4.08]), and composite outcome of death and vascular events (hazard ratio, 2.00 [95% CI, 1.15-3.48]) when 2 extreme quartiles were compared. Each 1-SD higher log-osteoprotegerin was associated with a 18% (95% CI, 6%-32%) increased risk of primary outcome, 69% (95% CI, 31%-118%) increased risk of death, and 53% (95% CI, 24%-89%) increased risk of composite outcome of death and vascular events, respectively. Multiple-adjusted spline regression model showed a linear association of osteoprotegerin with primary outcome (P for linearity <0.001). Adding osteoprotegerin to conventional risk factors did not significantly improve discriminatory power (C statistics, 0.817 versus 0.818; P=0.232) but did slightly improve the risk reclassification of primary outcome (net reclassification improvement: 13.68%, P<0.001; integrated discrimination improvement: 0.23%, P=0.039). In Mendelian randomization analysis, genetically determined high plasma osteoprotegerin was associated with increased risk of primary outcome (odds ratio, 5.74 [95% CI, 1.12-29.44]; P=0.036). CONCLUSIONS: Elevated plasma osteoprotegerin was associated with poor prognosis of ischemic stroke, and genetically determined high plasma osteoprotegerin was associated with an increased risk of primary outcome in Mendelian randomization analysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01840072.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/epidemiologia , Isquemia Encefálica/epidemiologia , Estudos Prospectivos , AVC Isquêmico/complicações , Biomarcadores , Osteoprotegerina , Análise da Randomização Mendeliana , Prognóstico , Fatores de Risco
7.
Eur J Pharm Biopharm ; 179: 206-220, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36150614

RESUMO

Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The combination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvironment restrains the generation of ROS, leading to the decreased effects of SDT. To improve the clinical outcomes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/PFH@SP94-Lip). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/PFH@SP94-Lip combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Terapia por Ultrassom , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Lipossomos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Oxigênio , Peptídeos/uso terapêutico , Espécies Reativas de Oxigênio , Microambiente Tumoral
8.
J Inorg Biochem ; 224: 111591, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450410

RESUMO

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid ß peptide (Aß) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu2+ from Aß and become dimers upon Cu2+ coordination and show high efficiency for both Cu2+ elimination and Aß assembly inhibition. Besides, these designed complexes can inhibit the production of Aß-induced reactive oxygen species (ROS), protect mitochondria from damage, and improve the survival rate of neuron cells. Our work provides a new strategy to combine hydrophobic interaction and metal ion chelation to design amyloid inhibitors.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Quelantes/farmacologia , Complexos de Coordenação/química , Cobre/química , Rutênio/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Humanos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Oxiquinolina/farmacologia , Agregados Proteicos , Agregação Patológica de Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química
9.
Dalton Trans ; 50(26): 9068-9075, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34113944

RESUMO

Over the past few decades, the landscape of inorganic medicinal chemistry has been dominated by investigations on platinum or ruthenium, while the research based on other metal centers such as rhodium has been relatively insufficient. In this work, a series of cyclometalated rhodium(iii) complexes with imidazo[4,5-f][1,10]phenanthroline containing different aromatic rings were synthesized and characterized. Notably, all the complexes displayed stronger anticancer activity against various cancer cells compared with cisplatin. A mechanism study revealed that the rhodium complexes accumulated in the mitochondria, elevated the levels of mitochondrial reactive oxygen species (ROS) and released cytochrome c, indicating severe mitochondrial damage during the anticancer activity. Further studies illustrated that the rhodium complexes caused cell cycle arrest at the G2/M phase, upregulated the expression of p53 and reduced the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated x (Bax), which ultimately resulted in cellular apoptosis. Overall, through mitochondrial pathways, these Rh(iii) complexes could induce cellular apoptosis to a larger extent than cisplatin and should be paid close attention as promising chemotherapeutic drugs in anticancer research.


Assuntos
Ródio , Rutênio , Apoptose , Mitocôndrias , Espécies Reativas de Oxigênio
10.
J Inorg Biochem ; 218: 111400, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684684

RESUMO

Recently, rhodium complexes have received intensive attentions due to their tunable chemical and biological properties as well as attractive antitumor activity. In this work, two imidazole triphenylamino rhodium complexes [Rh(ppy)2L1]PF6 (Rh1) and [Rh(ppy)2L2]PF6 (Rh2) (ppy = 2-phenylpyridine, L1 = 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline, L2 = N-(4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl)-4-methyl-N-(p-tolyl)aniline) have been synthesized and characterized. Both complexes display stronger anticancer activity against a various of cancer cells than cisplatin and they can effectively localize to mitochondria. Further mechanism studies show that Rh1 induce caspase-dependent apoptosis through mitochondrial damage, down-regulate the expression of B-cell lymphoma-2 (Bcl-2)/Bcl2-associated x (Bax) and reactive oxygen species (ROS) elevation. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of rhodium complexes.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Complexos de Coordenação/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Ródio/química , Antineoplásicos/química , Proliferação de Células , Complexos de Coordenação/química , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estrutura Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
11.
Circ J ; 85(2): 213-219, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33208593

RESUMO

BACKGROUND: This study explored the value of cystatin C (CysC) in predicting stroke recurrence in patients with acute ischemic stroke.Methods and Results:This was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) on 3,474 acute ischemic stroke patients with documented serum CysC and high-sensitivity C-reactive protein (hsCRP) concentrations. Study outcomes included stroke recurrence and combined vascular events within 2 years after stroke. In stroke patients with higher (i.e., ≥4.8ng/mL), but not lower, hsCRP concentrations, a higher CysC concentration (i.e., ≥0.78 mg/L) was associated with a 2.48-fold increase in the risk of recurrent stroke (95% confidence interval [CI] 1.37-4.51; P=0.003) and a 2.04-fold increase in the risk of vascular events (95% CI 1.27-3.28; P=0.003). Serum hsCRP concentrations significantly modified the association of serum CysC with recurrent stroke (Pinteraction=0.001) and vascular events (Pinteraction=0.007). Moreover, CysC may improve reclassification of stroke recurrence (net reclassification improvement [NRI] 42.9%, P=0.001; integrated discrimination improvement [IDI] 1.2%, P=0.001) and vascular events (NRI 35.8%, P=0.001; IDI 1.1%, P=0.004). CONCLUSIONS: In ischemic stroke patients with high hsCRP concentrations, higher CysC concentrations increased the risk of stroke recurrence and vascular events. This indicates that the predictive value of CysC on stroke recurrence may depend on the inflammation status of patients.


Assuntos
Isquemia Encefálica , Cistatina C/sangue , AVC Isquêmico , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Proteína C-Reativa/análise , Humanos , AVC Isquêmico/diagnóstico , Fatores de Risco
12.
Clin Chem ; 66(5): 706-717, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32285094

RESUMO

BACKGROUND: S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts. METHODS: Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events. RESULTS: Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66-2.68) for the primary outcome and 1.62 (95% CI, 1.27-2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10-8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38-3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%-39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations. CONCLUSIONS: High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.


Assuntos
Isquemia Encefálica/diagnóstico , Calgranulina A/sangue , Calgranulina B/sangue , Acidente Vascular Cerebral/diagnóstico , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade
13.
J Mater Sci Mater Med ; 30(7): 76, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218573

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.


Assuntos
Sistemas de Liberação de Medicamentos , Compostos Férricos/química , Nanopartículas de Magnetita/química , Fotoquimioterapia/métodos , Células A549 , Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/química , Movimento Celular , Daunorrubicina/química , Quadruplex G , Humanos , Hibridização de Ácido Nucleico , Oligonucleotídeos/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química
14.
Clin Chem ; 65(4): 569-578, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30679169

RESUMO

BACKGROUND: Growth differentiation factor 15 (GDF-15), a stress-responsive biomarker, is known to be independently associated with mortality and cardiovascular events in different disease settings, but data on the prognostic value of GDF-15 after stroke are limited. METHODS: Baseline serum GDF-15 was measured in 3066 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite of death and major disability within 3 months. Secondary outcomes included death, major disability, vascular events, and stroke recurrence. The associations between GDF-15 and clinical outcomes after stroke were assessed by multivariate logistic regression or Cox proportional hazards models. RESULTS: At 3 months' follow-up, 676 (22.05%), 86 (2.80%), 81 (2.64%), and 51 (1.66%) patients had experienced major disability, death, vascular events, or stroke recurrence, respectively. After adjusting for age, sex, current smoking, alcohol consumption, and baseline National Institutes of Health Stroke Scale score, the odds ratio/hazard ratio (95% CI) of 1 SD higher of base-10 log-transformed GDF-15 was 1.26 (1.15-1.39) for primary outcome, 1.13 (1.02-1.25) for major disability, 1.79 (1.48-2.16) for death, and 1.26 (1.00-1.58) for vascular events. The addition of GDF-15 to established risk factors improved risk prediction of the composite outcome of death and major disability (c-statistic, net reclassification index, and integrated discrimination improvement, all P < 0.05). CONCLUSIONS: High GDF-15 concentrations are independently associated with adverse clinical outcomes of acute ischemic stroke, suggesting that baseline serum GDF-15 could provide additional information to identify ischemic stroke patients at high risk of poor prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Isquemia Encefálica/diagnóstico , Fator 15 de Diferenciação de Crescimento/metabolismo , Acidente Vascular Cerebral/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Isquemia Encefálica/mortalidade , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/mortalidade
15.
Atherosclerosis ; 274: 146-151, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29778943

RESUMO

BACKGROUND AND AIMS: Serum cystatin C (CysC) is associated with the risk of ischemic stroke and may predict cardiovascular events and death after ischemic stroke onset. However, the association between serum CysC and functional outcome in ischemic stroke patients remains unclear, and whether lipid component level influences the relationship between them has not been studied. METHODS: A total of 3348 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included in the study. Serum CysC was used to calculate estimated glomerular filtration rate (eGFRCysC) at baseline. The primary outcome was poor functional outcome (modified Rankin Scale score ≥3) at one year after ischemic stroke. Secondary outcomes were death, stroke recurrence, vascular events and combination of the aforementioned outcomes. RESULTS: The association between eGFRCysC and primary outcome was appreciably modified by low-density lipoprotein cholesterol (LDL-C) (pinteraction = 0.048). Low eGFRCysC was associated with primary outcome only in ischemic stroke patients with LDL-C ≥4.14 mmol/l rather than all patients. The multivariable adjusted odds ratio (95% confidence interval) of poor functional outcome associated with low eGFRCysC was 3.94 (1.04-14.98) and a positive linear dose-response relationship between them was observed among patients with LDL-C ≥4.14 mmol/l (p for linearity = 0.021). Subgroup analyses further confirmed these associations. There was no association between eGFR based on serum creatinine and poor functional outcome of stroke. CONCLUSIONS: Low eGFRCysC may be an independent predictor for 1-year poor functional outcome in ischemic stroke patients with LDL-C ≥4.14 mmol/l. Further studies are needed to replicate our findings and to clarify the potential mechanisms.


Assuntos
Isquemia Encefálica/sangue , LDL-Colesterol/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Rim/fisiopatologia , Acidente Vascular Cerebral/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , China , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Resultado do Tratamento
16.
Neurology ; 89(8): 805-812, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28747453

RESUMO

OBJECTIVE: To examine the association between serum matrix metalloproteinases-9 (MMP-9) levels and prognosis of acute ischemic stroke. METHODS: We measured serum MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular disease were collected at 3 months after stroke onset. RESULTS: During 3 months of follow-up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus. For example, 1-SD (0.32 ng/mL) higher log-MMP-9 was associated with an odds ratio (95% confidence interval) of 1.16 (1.06-1.28) for the combined outcome of death and major disability, 1.12 (1.01-1.23) for major disability, and 1.29 (1.01-1.66) for death. The addition of serum MMP-9 to conventional risk factors improved risk prediction of the combined outcome of death or major disability (net reclassification index 9.1%, p = 0.033; integrated discrimination improvement 0.4%, p = 0.004). CONCLUSIONS: Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Metaloproteinase 9 da Matriz/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Biomarcadores/sangue , Isquemia Encefálica/terapia , China , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Análise de Regressão , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
17.
Chin Med J (Engl) ; 127(11): 2016-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24890144

RESUMO

BACKGROUND: Many studies have suggested that C-reactive protein (CRP) and blood lipids are associated with hypertension and cardiovascular disease (CVD). However, few studies discussed the combined action of CRP and blood lipids on the risk of hypertension and prehypertension. This study aimed to investigate the combined action of CRP and lipid profiles on the risk of hypertension and prehypertension in Mongolian adults from Inner Mongolia, China. METHODS: The systolic and diastolic blood pressure, height, weight and waist circumference were measured and factors such as smoking, alcohol intake, family history of hypertension, etc., were investigated and CRP, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) were tested for 2 534 Mongolian adults aged ≥ 20 years. The subjects were divided into four subgroups, namely CRP median subgroup, CRP >median and LDL-C (TG) median and LDL-C (TG) >median subgroup. The ORs (95% CIs) of hypertension and prehypertension for the subgroups were calculated by univariate and multivariate analysis. RESULTS: The multivariate adjusted ORs (95%CIs) of hypertension/prehypertension were 1.389 (0.979-1.970)/1.151(0.865-1.531), 1.666 (1.159-2.394)/1.431 (1.060-1.930), 1.756 (1.242-2.484)/ 1.770 (1.321-2.372), for CRP median subgroup, CRP >median and LDL-C median and LDL-C >median subgroup, respectively, compared with CRP median subgroup, CRP >median and TG median and TG >median subgroup, respectively, compared with CRP median and LDL-C (TG) >median subgroup among the four subgroups. CONCLUSIONS: Subjects with both CRP >median and LDL-C (TG) >median had highest risks of hypertension and prehypertension among all subjects. This study appeared to indicate that the combined action of elevated CRP and elevated LDL-C (TG) further increase the risks of hypertension and prehypertension among Mongolian population.


Assuntos
Proteína C-Reativa/metabolismo , Hipertensão/epidemiologia , Hipertensão/metabolismo , Lipídeos/sangue , Adulto , Estatura/fisiologia , Peso Corporal/fisiologia , China , Estudos Transversais , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Circunferência da Cintura/fisiologia
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