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1.
Toxicol Lett ; 322: 66-76, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945382

RESUMO

Silent Information Regulator 1 (SIRT1), an NAD+-dependent deacetylase, contributes to the neuroprotective effect. However, intracellular signaling pathways that affect SIRT1 function remain unknown. It is well known that N-methyl-D-aspartate (NMDA) receptor activation induces calcium influx which then activates PKC, and SIRT1 is a mRNA target for HuR protein. We hypothesize that Ca2+-PKC-HuR-SIRT1 pathway modulates SIRT1 function. The present study is to investigate the potential pathway of SIRT1 in the SH-SY5Y cell line as an in vitro model of NMDA-induced neurotoxicity. The results showed that: (1) SIRT1 levels were downregulated in NMDA model; (2) NMDA induced an increase in serine phosphorylation of HuR, while inhibition of serine phosphorylation of HuR increased SIRT1 levels, promoting cell survival; (3) PKC inhibitor (Gö 6976) reversed NMDA insults and also suppressed serine phosphorylation of HuR; (4) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, fully reversed NMDA insults and also inhibited PKC activity evoked by NMDA. These results indicate that intracellular elevated Ca2+ activates PKC, which phosphorylates HuR and then promotes SIRT1 mRNA decay and subsequent neuronal death in NMDA model. Therefore, the study suggests that inhibition of Ca2+-PKC-HuR-SIRT1 pathway could be an effective strategy for preventing certain neurological diseases related to NMDA excitotoxicity.


Assuntos
Agonistas de Aminoácidos Excitatórios/toxicidade , N-Metilaspartato/toxicidade , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Sirtuína 1/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Humanos , Neurônios/enzimologia , Neurônios/patologia , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/patologia , Fosforilação , Proteína Quinase C/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina , Sirtuína 1/genética
2.
Redox Biol ; 29: 101404, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31926627

RESUMO

BACKGROUND: C-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels. AIMS: To explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP. METHODS: We included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP. RESULTS: The median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR < 0.001), whereas selenium was negatively associated with serum CRP (FDR = 0.01). Moreover, selenium and zinc attenuated the positive association between high plasma copper and CRP (P for interaction < 0.001). Participants with a higher GRS had a higher CRP level, with the increase in ln-transformed CRP per increment of 5 risk alleles were 0.64 for weighted GRS, and 0.54 for unweighted GRS (both P < 0.001). Furthermore, the genetic association with CRP was modified by copper concentration (P for interaction < 0.001). CONCLUSIONS: Our results suggest that serum CRP is positively associated with plasma concentration of copper, and inversely associated with selenium. Plasma zinc, selenium and CRP genetic predisposition would modify the associations between plasma copper and serum CRP.

3.
Biosens Bioelectron ; 151: 111966, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999576

RESUMO

Known for their capabilities in automated fluid manipulation, microfluidic devices integrated with pneumatic valves are broadly used for researches in life science and clinical practice. The application is, however, hindered by the high cost and overly complex fabrication procedure. Here, we present an approach for fabricating molds of active fluidic devices using a benchtop 3D printer and a simple 2-step protocol (i.e. 3D printing and polishing). The entire workflow can be completed within 6 h, costing less than US$ 5 to produce all necessary templates for PDMS replica molding, which have smooth surface and round-shaped pneumatic valve structures. Moreover, 3D printing can create unique bespoke on-off objects of a wide range of dimensions. The millimeter- and centimeter-sized features allow examination of large-scale biological samples. Our results demonstrate that the 3D-printed active fluidic device has valve control capacities on par with those made by photolithography. Controlled nutrients and ligands delivery by on-off active valves allows generation of dynamic signals mimicking the ever-changing environmental stimuli, and combinatorial/sequential drug inputs for therapeutic screening on liver tumor spheroid. We believe that the proposed methodology can pave the way for integration of active fluidic systems in research labs, clinical settings and even household appliances for a broad range of application.

4.
Talanta ; 210: 120656, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987207

RESUMO

Given the great threat posed by clinical Carbapenemase-producing Enterobacteriaceae (CPE), its rapid and accurate detection is highly required to guide infection treatment and to prevent serious outbreaks. While the Carba NP test (CNPt) is a popular and methodologically simple colorimetric assay for detecting carbapenemase activity, its clinical application is limited by low throughput, poor sensitivity and obscure color interpretation due to the lack of quantitative information on time- and dose-dependent color changes. To address these limitations, we developed a multiplexed microfluidic device (1280 chambers) that is able to automatically generate 16 bacterial concentration gradients and uses green channel intensity to extract quantitative color changes as a function of time. Here we examined the dynamic color changing profiles of 3 reference and 8 clinical bacteria isolates. The results demonstrated linear correlations between color developments and time (within 0-120 min) or bacterial doses (within OD600 of 0.8-8.0), enabling accurate and reproducible detection of CPE with over 105 fold improved sensitivity for an NDM-producer (LOD of 2.4 × 103 cells) and over 104 fold improved sensitivity for an OXA-48-producer (LOD of 7.2 × 104 cells) as compared to the conventional CNPt method (LOD above 1.3 × 109 cells). As the first digital microfluidic platform for CPE, this on-chip CNPt compared favourably with the conventional bench-based method by significantly improved sensitivity, high throughput, low consumption and automatization, favouring its potential clinical applications for rapid screening of CPE with a low cost. Furthermore, the results also revealed dynamic signature associated with bacteria, which may hold promise for a new approach to study divergent bacterial responses to antibiotic treatments.

5.
Am J Cardiol ; 125(4): 528-533, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31864520

RESUMO

The aim of the cohort study was to investigate the relation between plasma lipoprotein(a) (Lp[a]) and long-term clinical outcomes in patients with three-vessel disease (TVD) after the following treatment strategies, including medical therapy alone, percutaneous coronary intervention, and coronary artery bypass grafting. A total of 6,175 consecutive patients with angiographically confirmed TVD and available baseline Lp(a) data were included in this study. Based on the median level of Lp(a) at admission, the patient was divided into 2 subgroups. Primary endpoint was major adverse cardiovascular events (MACE), of which all-cause death, myocardial infarction, and unplanned revascularization were all included. In general, the median value of Lp(a) reached 13.76 mg/dl for all patients. The median follow-up time of all patients was 6.2 years. For MACE, a total of 1,433 cases were generated, accounting for 23.2%, including 804 (13.0%) all-cause death, 302 (4.9 %) myocardial infarction, and 494 (8.0%) unplanned revascularization. For the incidence of MACE, the high Lp (a) and low Lp (a) groups were 24.3% to 22.1% (p = 0.015), respectively. When the risk factors were adjusted, the multivariate analysis showed that high Lp(a) levels was an independent predictor of primary outcome (adjusted hazard ratio 1.169, 95% confidence interval 1.046 to 1.306, p = 0.006). Except for gender group, there is a relatively consistent correlation in the various subgroups. In conclusion, plasma Lp(a) is a potential biomarker for risk stratification and prognosis in patients diagnosed with TVD.

6.
J Mol Neurosci ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828524

RESUMO

Forebrain ischemia induces delayed, selective neuronal death in hippocampal CA1. It has been established that BDNF (brain-derived neurotrophic factor) is an important factor in ischemic injury. However, the exact mechanism of BDNF expression in the hippocampus after ischemia is unclear. We found that the decrease of BDNF protein expression in hippocampal CA1 was associated with a decrease of Bdnf transcript IV expression in the same region of the rats after ischemia/reperfusion (I/R). In hippocampal CA3 and DG, the results showed increased expression of BDNF protein and transcripts I, IIc, III, IV, VI, and X1. Furthermore, at the Bdnf promoters, I/R led to decreased H3K27ac, increased H3K9ac, and H3K14ac in CA1; increased H3K9ac, H3K14ac, and H3K27ac in CA3; no significant change of H3K9ac, H3K14ac, and H3K27ac in DG. HDAC inhibitor SAHA increased the expression of Bdnf transcripts IV, VI, and X1 in CA1. These findings suggest a potential of modulation Bdnf transcript expression to resolve ischemic brain injury through histone acetylation patterns at the Bdnf promoters.

7.
Orphanet J Rare Dis ; 14(1): 252, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722741

RESUMO

BACKGROUND: Animal studies suggested that blocking the activation of the mammalian target of rapamycin (mTOR) pathway might be effective to treat cardiac hypertrophy in LEOPARD syndrome (LS) caused by PTPN11 mutations. RESULTS: In the present study, mTOR pathway activity was examined in human myocardial samples from two patients with LS, four patients with hypertrophic cardiomyopathy (HCM), and four normal controls. The two patients with LS had p.Y279C and p.T468 M mutations of the PTPN11 gene, respectively. Although PTPN11 mutation showed initially positive regulation on phosphoinositide 3-kinase, overall the mTOR complex 1 pathway showed widely attenuated activity in LS. This included mildly hypophosphorylated mTOR and ribosomal protein S6 kinase and significantly hypophosphorylated Akt308 and ribosomal protein S6, which is similar to HCM. Akt473 is a basal molecule of the mTOR complex 2 pathway. Akt473 was less affected and showed hyperactivity in LS compared with HCM and normal controls. Additionally, MAPK/ERK kinase and ERK1/2 were significantly more phosphorylated in both HCM and LS than normal controls. CONCLUSIONS: In LS, the mTOR signaling pathway shows similar activity to HCM and is attenuated compared with normal controls. Thus, caution should be applied when using rapamycin to treat heart hypertrophy in LS.

8.
Biomed Microdevices ; 21(4): 89, 2019 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655887

RESUMO

In this paper, petaling hydroxyapatite (HA)/TiO2 composite coatings were firstly prepared on titanium (Ti) surface by one-step micro-arc oxidation (MAO), and then pure chitosan (CS) and bone morphogenic protein-2 (BMP-2)-encapsulated CS coatings were respectively loaded on the HA/TiO2 surfaces by dip-coating method to endow Ti with good antibacterial and biological properties. The bonding strength between coatings was studied by scratch method. The degradability of CS, BMP-2 release behavior, bioactivity, biocompatibility and antibacterial activity of the obtained (BMP-2)/CS/HA/TiO2 coatings were examined by in vitro tests. The results showed that, the thicker the HA layer, the larger the loaded BMP-2 and CS amount, resulting in better bonding strength between coatings, antibacterial activity and biocompatibility. In addition, with the increase of CS concentration, more CS was loaded on HA coatings, which benefited the increase of CS degrading amount, the prolonged CS degradation time and BMP-2 release time, resulting in improved antibacterial and biological property. All CS/HA/TiO2 coatings accelerated cell adhesion, spreading and proliferation, and promoted HA formation in simulated body fluids (SBF). After loading BMP-2 in CS, the BMP-2 can significantly improve cell adhesion, spreading and proliferation, and the loaded amount can also be controlled by the concentration of BMP-2 solution. The present study indicates that, by controlling the thickness of HA layers and concentrations of CS and BMP-2 solutions, the Ti implant material with excellent biological and antibacterial properties can be achieved.

9.
Sheng Li Xue Bao ; 71(5): 749-759, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646329

RESUMO

With the evolution of medical techniques and technology, an increasing number of infants, neonates, and fetuses are exposed to general anesthesia for clinical diagnostic and therapeutic process. The neurotoxic effects of general anesthetics on developing brain have been a subject of concern and considerable research interest. Population-based study confirmed that single short-term general anesthetic exposure does not affect nervous system function, but multiple exposures to general anesthesia could damage cognitive function. Animal studies further discovered the underlying mechanisms. Nervous system is most susceptible to general anesthetics during the brain growth spurt. The time-point is more critical than the duration of exposure to general anesthetics. General anesthetics can induce intracellular calcium overload, disturb energy metabolism, promote cell apoptosis and lead to cell loss. General anesthetics can damage synaptic structure, transmission and plasticity, and impair brain function. High throughput omics technologies have been used to screen the differentially expressed genes induced by general anesthetics, which provide further understanding of the mechanism of general anesthetics affecting cognitive function. This review provides an update on the pathophysiologic mechanisms underlying the anesthesia-neurotoxicity, which will be helpful to provide instructions for the clinical use of general anesthesia in children.


Assuntos
Anestésicos Gerais/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Cognição , Anestesia Geral/efeitos adversos , Animais , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
10.
Life Sci ; 239: 116871, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31521692

RESUMO

Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.


Assuntos
Neoplasias Pancreáticas/genética , Receptores de LDL/genética , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Citocinas/metabolismo , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Pâncreas/metabolismo , RNA/metabolismo , Receptores de LDL/metabolismo
11.
Biochem J ; 476(16): 2355-2369, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31395734

RESUMO

Hepsin is a transmembrane serine protease implicated in many biological processes, including hepatocyte growth, urinary protein secretion, auditory nerve development, and cancer metastasis. Zymogen activation is critical for hepsin function. To date, how hepsin is activated and regulated in cells remains an enigma. In this study, we conducted site-directed mutagenesis, cell expression, plasma membrane protein labeling, trypsin digestion, Western blotting, and flow cytometry experiments in human hepatoma HepG2 cells, where hepsin was originally discovered, and SMMC-7721 cells. Our results show that hepsin is activated by autocatalysis on the cell surface but not intracellularly. Moreover, we show that hepsin undergoes ectodomain shedding. In the conditioned medium from HepG2 and SMMC-7721 cells, we detected a soluble fragment comprising nearly the entire extracellular region of hepsin. By testing protease inhibitors, gene knockdown, and site-directed mutagenesis, we identified calpain-1 as a primary protease that acted extracellularly to cleave Tyr52 in the juxtamembrane space of hepsin. These results provide new insights into the biochemical and cellular mechanisms that regulate hepsin expression and activity.

12.
Mol Genet Genomic Med ; 7(9): e874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397097

RESUMO

BACKGROUND: Robust data regarding genotype-phenotype correlations in left ventricular noncompaction cardiomyopathy (LVNC) are lacking. METHODS: About 72 cardiomyopathy-related genes were comprehensively screened in a cohort of LVNC patients using targeted sequencing. Baseline and follow-up data were collected. The primary endpoint was a composite of death and heart transplantation. RESULTS: A total of 83 unrelated adult patients were included in analyses. Following stringent classification according to the American College of Medical Genetics and Genomics (ACMG) guidelines, 36 pathogenic variants of 14 genes were detected in 32 patients. Among them, 12 patients carried at least one nonsarcomere variant (NSV). At baseline, NSV carriers had a higher frequency of atrial fibrillation, but lower left ventricular ejection fraction, than did noncarriers. During a median follow-up of 4.2 years, NSV carriers experienced a higher rate of the primary endpoint compared with noncarriers. There was no significant difference in the rate between carriers of sarcomere variant (SV) and noncarriers, as well as between carriers of SV and NSV. The presence of NSV was associated with an increased risk of the primary endpoint independent of age, sex, and cardiac function (hazard ratio: 3.61, 95% confidence interval: 1.42-9.19, p = .002). CONCLUSION: NSV may act as a genetic modifier and worsen the clinical phenotype in patients with LVNC.

13.
Hypertens Res ; 42(10): 1536-1543, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31388123

RESUMO

The genetic factors related to early-onset hypertension are largely unknown. This study aimed to determine the spectrum of steroid metabolism gene variants and the clinical relationships of these variants to phenotypes in Chinese patients with early-onset hypertension. A total of 306 consecutive early-onset hypertensive patients were recruited. All coding exons and flanking intronic regions of KCNJ5, CYP11B1, and CYP17A1 were sequenced. Long-distance polymerase chain reaction was used to search for a CYP11B1/CYP11B2 chimeric gene. Pedigree investigations and genotype-phenotype analyses were performed for patients with rare variants. Nine rare variants were detected in eight patients (2.6%), but no CYP11B1/CYP11B2 chimeric gene was identified. One patient and two of her siblings were found to carry compound heterozygous mutations (C183Y and T390R) in CYP17A1 and were eventually diagnosed with atypical congenital adrenal hyperplasia. Patients with rare variants had younger ages of onset [17 (16, 20) vs. 30 (23, 35) years old, p = 0.010] and higher systolic blood pressure (148.5 ± 9.6 vs. 137.9 ± 17.8 mmHg, p = 0.021) than those without rare variants. Additionally, the patients and their relatives carrying rare variants exhibited increased serum free corticosterone [230.4 (7.4, 533.0) vs. 1.9 (0.9, 6.7)ng/ml, p = 0.001] and 11-deoxycorticosterone [16.16 (0.59, 33.23) vs. 0.77 (0.41, 0.96)ng/ml, p = 0.038] levels. Genetic testing is useful for the etiologic diagnosis of early-onset hypertension. Rare variants in steroid metabolism genes were associated with more severe clinical expression and abnormal circulating steroid metabolites in patients with early-onset hypertension.

14.
PLoS One ; 14(8): e0221704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437263

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0212648.].

15.
J Proteome Res ; 18(9): 3353-3359, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31407580

RESUMO

The processing of peptide tandem mass spectrometry data involves matching observed spectra against a sequence database. The ranking and calibration of these peptide-spectrum matches can be improved substantially using a machine learning postprocessor. Here, we describe our efforts to speed up one widely used postprocessor, Percolator. The improved software is dramatically faster than the previous version of Percolator, even when using relatively few processors. We tested the new version of Percolator on a data set containing over 215 million spectra and recorded an overall reduction to 23% of the running time as compared to the unoptimized code. We also show that the memory footprint required by these speedups is modest relative to that of the original version of Percolator.

16.
Biomed Environ Sci ; 32(4): 250-259, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31217061

RESUMO

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.


Assuntos
Cloretos/sangue , Doença da Artéria Coronariana/sangue , Sódio/sangue , Idoso , China/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
17.
Eur Heart J ; 40(41): 3397-3405, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236563

RESUMO

AIMS: Risk assessment and treatment stratification for three-vessel disease (3VD) remain challenging. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an established biomarker for prognostication and treatment in heart failure. The present study aimed to evaluate the prognostic value of NT-proBNP beyond the SYNTAX score II (SSII), and its association with long-term outcome after three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and medical therapy (MT)] in a cohort of patients with 3VD. METHODS AND RESULTS: A total of 6597 patients with available baseline NT-proBNP data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, and stroke. During a median follow-up of 7.0 years, higher NT-proBNP levels were strongly associated with increased risks of all-cause death, cardiac death, and MACCE (all adjusted P < 0.01). Moreover, NT-proBNP significantly improved discrimination and reclassification of the SSII. Notably, there was a significant interaction between NT-proBNP quartiles and treatment strategies for MACCE (P = 0.004). Revascularization was associated with lower risks of MACCE than MT, except for patients in the lowest quartile wherein no such association was observed. Among patients in the highest quartile, PCI was associated with an increased risk of MACCE compared with CABG (hazard ratio 1.43, 95% confidence interval 1.09-1.87). CONCLUSION: N-terminal pro-BNP is a potential biomarker for risk stratification and therapeutic decision-making in patients with 3VD. Further randomized studies are needed to confirm these findings.

18.
Endocr J ; 66(8): 731-737, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31118347

RESUMO

This study aimed to investigate if hyperinsulinemia and/or insulin resistance was correlated with the occurrence of papillary thyroid cancer (PTC) in a group of Chinese patients. 258 inpatients were included in the study. According to the postoperative pathology results, all subjects were divided into PTC (n = 153) and control groups (with benign thyroid nodules, n = 105). Body mass index (BMI), fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid-stimulating hormone (TSH), FT4, FT3, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), serum uric acid (UA), and lipid levels. Fasting insulin levels, HOMA-IR values, TPOAb levels, serum TSH levels, and serum uric acid levels in the PTC group were higher than those in the control group (p < 0.05). However, no significant differences in age, gender, BMI, history of hypertension, and the levels of fasting plasma glucose, FT3, FT4, TGAb, total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were observed between the two groups (p > 0.05). After the multiple logistic regression analysis, the occurrence of PTC was positively associated with fasting insulin (odds ratio [OR] = 1.048, 95% confidence interval [CI]: 1.003-1.096, p = 0.037) and TPOAb levels (OR = 1.001, 95% CI: 1.000-1.002, p = 0.032). Moreover, TPOAb level was positively correlated with vague margin (r = 0.126, p = 0.045) and negatively correlated with homogeneous echo (r = -0.179, p = 0.004). However, fasting insulin levels were not correlated with pathological characteristics of PTC. Hyperinsulinemia and higher TPOAb levels might be the risk factors of PTC, but not disease severity in Chinese patients.


Assuntos
Autoanticorpos/sangue , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/complicações , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/complicações , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Hiperinsulinismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Câncer Papilífero da Tireoide/epidemiologia , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/epidemiologia , Tireotropina/sangue , Tri-Iodotironina/sangue
19.
Nano Lett ; 19(6): 4118-4125, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31140281

RESUMO

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded Fe3O4 nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

20.
Sci Adv ; 5(4): eaav7959, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30949582

RESUMO

Dynamical control of cellular microenvironments is highly desirable to study complex processes such as stem cell differentiation and immune signaling. We present an ultra-multiplexed microfluidic system for high-throughput single-cell analysis in precisely defined dynamic signaling environments. Our system delivers combinatorial and time-varying signals to 1500 independently programmable culture chambers in week-long live-cell experiments by performing nearly 106 pipetting steps, where single cells, two-dimensional (2D) populations, or 3D neurospheres are chemically stimulated and tracked. Using our system and statistical analysis, we investigated the signaling landscape of neural stem cell differentiation and discovered "cellular logic rules" that revealed the critical role of signal timing and sequence in cell fate decisions. We find synergistic and antagonistic signal interactions and show that differentiation pathways are highly redundant. Our system allows dissection of hidden aspects of cellular dynamics and enables accelerated biological discovery.

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