Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
Eur J Cancer Care (Engl) ; : e13225, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971652

RESUMO

OBJECTIVE: This study aims to investigate the impact of intervention of multidisciplinary team incorporating pharmacists for management of opioid-naïve patients with moderate to severe cancer pain. METHODS: A retrospective cohort study was conducted to compare pre- and post-multidisciplinary intervention groups in opioid-naïve patients with moderate to severe cancer pain. Primary outcome was the proportions of appropriate pain assessment and opioid titration. Secondary outcomes were pain intensity (PI), length of hospital stay, opioid escalation index percentage (OEI%) and incidences of opioid-related adverse events. RESULTS: A total of 400 patients were included in the study (pre-intervention, n = 200; post-intervention, n = 200). Continuous improvement in pain assessment and titration was recorded after intervention. Though no substantial differences existed between groups in PI on the day of discharge, post-intervention group was associated with reduced length of hospital stay as well as decreased proportion of subjects with OEI% >5%. As for safety, significant decreases in constipation and vomiting were seen. CONCLUSION: Findings suggest that interventions of multidisciplinary team incorporating pharmacists could improve cancer pain management for opioid-naïve patients. Pharmacists should be considered as an important member of a multidisciplinary team in good pain management.

3.
J Virol ; 94(4)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31748395

RESUMO

Fuselloviruses are among the most widespread and best-characterized archaeal viruses. They exhibit remarkable diversity, as the list of members of this family is rapidly growing. However, it has yet to be shown how a fuselloviral genome may undergo variation at the levels of both single nucleotides and sequence stretches. Here, we report the isolation and characterization of four novel spindle-shaped viruses, named Sulfolobus spindle-shaped viruses 19 to 22 (SSV19-22), from a hot spring in the Philippines. SSV19 is a member of the genus Alphafusellovirus, whereas SSV20-22 belong to the genus Betafusellovirus The genomes of SSV20-SSV22 are identical except for the presence of two large variable regions, as well as numerous sites of single-nucleotide polymorphisms (SNPs) unevenly distributed throughout the genomes and enriched in certain regions, including the gene encoding the putative end filament protein VP4. We show that coinfection of the host with SSV20 and SSV22 led to the formation of an SSV21-like virus, presumably through homologous recombination. In addition, large numbers of SNPs were identified in DNA sequences retrieved by PCR amplification targeting the SSV20-22 vp4 gene from the original enrichment culture, indicating the enormous diversity of SSV20-22-like viruses in the environment. The high variability of VP4 is consistent with its potential role in host recognition and binding by the virus.IMPORTANCE How a virus survives in the arms race with its host is an intriguing question. In this study, we isolated and characterized four novel fuselloviruses, named Sulfolobus spindle-shaped viruses 19 to 22 (SSV19-22). Interestingly, SSV20-22 differ primarily in two genomic regions and are apparently convertible through homologous recombination during coinfection. Moreover, sites of single-nucleotide polymorphism (SNP) were identified throughout the genomes of SSV20-22 and, notably, enriched in certain regions, including the gene encoding the putative end filament protein VP4, which is believed to be involved in host recognition and binding by the virus.

4.
J Food Sci ; 84(12): 3804-3814, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31750942

RESUMO

The human gastrointestinal tract represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation, as people from different regions have different gut microbiota structures. The Kazakh nomads in Xinjiang, China still retain their nomadic lifestyle and traditional diet. Their specific diet style and ancient genetic background shaped their gut microbiota to contain unique characteristics. In present study, the compositions of the gut microbiota and fermented dairy foods were assessed by high-throughput sequencing of the 16S rRNA gene. Twenty-nine Kazakh nomads were recruited, and 33 traditional fermented dairy foods were collected from five pasturing areas (Buerjin, Zhaosu, Nilka, Tekes, and Fuhai) in northern Xinjiang, China. The correlation of the physical index with the gut microbiota was also analyzed. The unique diet style of Kazakh may be a critical factor in keeping their gut microbiota in a balanced state and help them to remain in good health. PRACTICAL APPLICATION: This research shows that the consumption of spontaneous fermented dairy food plays an important role in increasing gut microbial diversity. Some probiotics in fermented dairy food, such as Bifidobacterium and Lactobacillus, have positive correlation with human body health index such as body mass index and blood glucose. These may provide some theoretical supports to adjuvant therapy of obesity and diabetes through scientific dietary intervention.

5.
Vision Res ; 164: 44-52, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585388

RESUMO

In this study, we aimed to explore an objective, sensitive and quantitative measurement of interocular suppression in strabismic amblyopia. We compared 11 strabismic subjects with 12 normal vision subjects to explore the different response characterizations in normal eyes, nondominant and dominant eyes of strabismic subjects by using steady-state motion visual evoked potentials (SSMVEPs). Stimulation at different temporal frequencies was presented to two eyes by using an interocular dichoptic technique. Furthermore, canonical correlation analysis (CCA), signal-to-noise ratio (SNR) and some statistical methods, such as the paired t-test, analysis of variance (ANOVA) and correlation analysis, were used to analyze electroencephalography (EEG) signals. We proposed two indices-divergence J and suppression imbalance (SI) to describe the deficits in interocular suppression-and one index - mask attenuation coefficient (MAC)- to describe the influence of a dichoptic mask from the dominant eyes to nondominant eyes of strabismic subjects. A significant difference was found between nondominant and dominant eyes of strabismic subjects in SSMVEP response and SNR value while no apparent difference was observed between the two eyes in subjects with normal vision. There was a strong linear correlation between divergence J, SI and visual acuity difference of two eyes both in strabismic amblyopia and normal vision. A linear correlation was also found between visual acuity difference and MAC in patients with strabismic amblyopia. Our findings suggest that SSMVEPs can be an objective and quantitative method for measuring the interocular suppression in strabismus and assessing the deficits of strabismic amblyopia.

6.
Small ; : e1903739, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31565845

RESUMO

Single-cell analysis offers unprecedented resolution for the investigation of cellular heterogeneity and the capture of rare cells from large populations. Here, described is a simple method named interfacial nanoinjection (INJ), which can miniaturize various single-cell assays to be performed in nanoliter water-in-oil droplets on standard microwell plates. The INJ droplet handler can adjust droplet volumes for multistep reactions on demand with high precision and excellent monodispersity, and consequently enables a wide range of single-cell assays. Importantly, INJ can be coupled with fluorescence-activated cell sorting (FACS), which is currently the most effective and accurate single-cell sorting and isolation method. FACS-INJ pipelines for high-throughput plate well-based single-cell analyses, including single-cell proliferation, drug-resistance testing, polymerase chain reaction (PCR), reverse-transcription PCR, and whole-genome sequencing are introduced. This FACS-INJ pipeline is compatible with a wide range of samples and can be extended to various single-cell analysis applications in microbiology, cell biology, and biomedical diagnostics.

7.
Neurology ; 93(18): e1675-e1685, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31551260

RESUMO

OBJECTIVE: To prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured in 3,342 participants. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events. RESULTS: A total of 843 participants (25.2%) experienced major disability or died within 3 months. After adjustment for age, sex, admission NIH Stroke Scale score, and other important covariates, odds ratios or hazard ratios (95% confidence intervals) of 1-SD (0.17 ng/mL) higher log-TIMP-1 were 1.17 (1.06-1.29) for the primary outcome, 1.13 (1.02-1.25) for major disability, 1.49 (1.19-1.87) for death, and 1.34 (1.11-1.62) for the composite outcome of death and vascular events. The addition of serum TIMP-1 to conventional risk factors model significantly improved risk prediction of the primary outcome (net reclassification index 9.0%, p = 0.02; integrated discrimination improvement 0.2%, p = 0.03). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had the highest risk of all study outcomes. CONCLUSIONS: Higher TIMP-1 levels were associated with increased risk of mortality and major disability after acute ischemic stroke. Our findings provided evidence supporting the important prognostic role of extracellular matrix biomarkers after acute ischemic stroke.

8.
Mol Cancer Ther ; 18(12): 2457-2468, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31488699

RESUMO

MDR and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly upregulated in breast cancer tissues compared with adjacent nontumor tissues. A bioinformatics analysis indicated that Transgelin 2 was significantly related to clinicopathologic parameters and patient prognosis. Overexpression of Transgelin 2 enhanced the migration and invasion of human breast cancer cells and decreased the sensitivity of breast cancer cells to paclitaxel. Meanwhile, the tumorigenesis and metastasis of breast cancer cells were also enhanced by Transgelin 2 overexpression in vivo Moreover, Transgelin 2 overexpression activated the PI3K/Akt/GSK-3ß pathway by increasing the phosphorylation levels of Akt and GSK-3ß and decreasing the expression of PTEN. We also found that Transgelin 2 could directly interact with PTEN and was located upstream of PTEN. Furthermore, the PI3K/Akt pathway inhibitor MK-2206 reversed the resistance to paclitaxel and inhibited the migration and invasion of breast cancer cells. These findings indicate that Transgelin 2 promotes paclitaxel resistance and the migration and invasion of breast cancer by directly interacting with PTEN and activating the PI3K/Akt/GSK-3ß pathway. Transgelin 2 may therefore be useful as a novel biomarker and therapeutic target for breast cancer.

9.
Tumori ; 105(6): 494-500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31478461

RESUMO

BACKGROUND: An integral and well-functioning vascular system is essential for tumor progression and chemotherapy infusion. However, the lumen integrity of the microvessels and its significance in prognosis has not been studied. In this study, we found that the proportion of collapsed microvessels is suggested to be a novel biomarker for predicting prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, immunohistochemical CD31 staining was performed to identify the microvessels in tumor specimens. Proportions of collapsed vessels were estimated in CD31-stained tumor specimens from 100 patients with NSCLC. The correlation between collapsed microvessel proportion and survival time were evaluated by univariate and multivariate analysis. RESULTS: Data from 99 patients were analyzed and a wide range of collapse-microvessel fraction was observed in 96 patients (1.4%-70%). Elevated collapse proportion (⩾6.5%) indicated poor overall survival in both univariate analysis (p = 0.042) and multivariate analysis (p = 0.014). CONCLUSIONS: Elevated proportion of collapsed microvessels indicted poor survival outcome in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Microvasos/patologia , Neovascularização Patológica , Adulto , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
10.
J Cancer ; 10(15): 3397-3406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293643

RESUMO

Background: Sustained tumor growth and metastasis require sufficient blood supply, and microvessel area (MVA) has been reported that is related to prognosis of cancer patients. However, tumor cells may not be nourished enough by blood vessels when the cells are separated from vessels by thick stroma. Therefore we investigated whether stroma-area normalized MVA (SnMVA) is a more important prognostic factor than MVA. Materials and Methods: 100 NSCLC patients who underwent resection between July 2011 and October 2012 were randomly selected. We determined the MVA of the tumor tissues by anti-CD31 immunostaining of microvessels. Stroma-area normalized MVA (SnMVA) was a ratio of MVA to stromal area. Correlation of MVA and SnMVA with overall survival (OS) or progression-free survival (PFS) was assessed using multivariate analysis. Results: Median MVA was 0.0228 (range, 0.00393 to 0.172), and median SnMVA was 0.0441 × 10-6 (range, 0.00393 × 10-6 to 0.259 × 10-6). There was no significant difference in OS between groups of different MVA (HR 0.58, 95%CI 0.28 to 1.19, p = 0.148). In contrast, the risk of death was significantly decreased in high SnMVA group (at or below the median) than in group with low SnMVA (HR 0.47, 95%CI 0.23 to 0.97, p = 0.046). Furthermore, in multivariate analysis, high SnMVA, but not MVA, was an independent prognostic factor after adjusting for age, sex, tumor stage and other factors. OS was significantly associated with SnMVA in six of seven subgroup analysis, but with MVA in only three. Conclusions: Our study showed that the NSCLC patients with high SnMVA had higher OS. And SnMVA is a prognostic factor with greater accuracy than MVA. Since stroma exists widely in a variety of cancer tissues, we infer that SnMVA may also predict the prognostic of other types of cancers.

11.
Mol Cell Proteomics ; 18(8): 1572-1587, 2019 08.
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.

12.
Comput Intell Neurosci ; 2019: 9439407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239837

RESUMO

The steady-state motion visual evoked potential (SSMVEP) collected from the scalp suffers from strong noise and is contaminated by artifacts such as the electrooculogram (EOG) and the electromyogram (EMG). Spatial filtering methods can fuse the information of different brain regions, which is beneficial for the enhancement of the active components of the SSMVEP. Traditional spatial filtering methods fuse electroencephalogram (EEG) in the time domain. Based on the idea of image fusion, this study proposed an SSMVEP enhancement method based on time-frequency (T-F) image fusion. The purpose is to fuse SSMVEP in the T-F domain and improve the enhancement effect of the traditional spatial filtering method on SSMVEP active components. Firstly, two electrode signals were transformed from the time domain to the T-F domain via short-time Fourier transform (STFT). The transformed T-F signals can be regarded as T-F images. Then, two T-F images were decomposed via two-dimensional multiscale wavelet decomposition, and both the high-frequency coefficients and low-frequency coefficients of the wavelet were fused by specific fusion rules. The two images were fused into one image via two-dimensional wavelet reconstruction. The fused image was subjected to mean filtering, and finally, the fused time-domain signal was obtained by inverse STFT (ISTFT). The experimental results show that the proposed method has better enhancement effect on SSMVEP active components than the traditional spatial filtering methods. This study indicates that it is feasible to fuse SSMVEP in the T-F domain, which provides a new idea for SSMVEP analysis.


Assuntos
Algoritmos , Eletroencefalografia , Potenciais Evocados Visuais , Processamento de Sinais Assistido por Computador , Adulto , Feminino , Humanos , Masculino , Análise de Ondaletas , Adulto Jovem
13.
J Diabetes Res ; 2019: 2936962, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214621

RESUMO

Objective: Hypoxia is central in the pathogenesis of diabetic retinopathy (DR). Hypoxia-inducible factor-1 (HIF-1) is the key mediator in cellular oxygen homeostasis that facilitates the adaptation to hypoxia. HIF-1 is repressed by hyperglycemia contributing by this to the development of complications in diabetes. Recent work has shown that the HIF-1A Pro582Ser polymorphism is more resistant to hyperglycemia-mediated repression, thus protecting against the development of diabetic nephropathy. In this study, we have investigated the effect of the HIF-1A Pro582Ser polymorphism on the development of DR and further dissected the mechanisms by which the polymorphism confers a relative resistance to the repressive effect of hyperglycemia. Research Design and Method: 703 patients with type 1 diabetes mellitus from one endocrine department were included in the study. The degree of retinopathy was correlated to the HIF-1A Pro582Ser polymorphism. The effect of glucose on a stable HIF-1A construct with a Pro582Ser mutation was evaluated in vitro. Results: We identified a protective effect of HIF-1A Pro582Ser against developing severe DR with a risk reduction of 95%, even when adjusting for known risk factors for DR such as diabetes duration, hyperglycemia, and hypertension. The Pro582Ser mutation does not cancel the destabilizing effect of glucose but is followed by an increased transactivation activity even in high glucose concentrations. Conclusion: The HIF-1A genetic polymorphism has a protective effect on the development of severe DR. Moreover, the relative resistance of the HIF-1A Pro582Ser polymorphism to the repressive effect of hyperglycemia is due to the transactivation activity rather than the protein stability of HIF-1α.


Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Nefropatias Diabéticas/genética , Feminino , Genótipo , Glucose/análise , Células HEK293 , Humanos , Hiperglicemia/genética , Hiperglicemia/fisiopatologia , Hipóxia , Masculino , Pessoa de Meia-Idade , Mutação , Prolina/genética , Fatores de Risco , Serina/genética , Ativação Transcricional , Adulto Jovem
14.
Doc Ophthalmol ; 139(2): 123-136, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31214918

RESUMO

PURPOSE: The traditional assessment of visual acuity and contrast sensitivity depends more on subjective judgments. Steady-state motion visual evoked potentials (SSMVEPs) can provide an objective and quantitative method to evaluate visual functions such as visual acuity and contrast sensitivity. Here, we explored the possibility of objective SSMVEP visual acuity and contrast sensitivity testing, and compared its performance with that of psychophysical methods. METHODS: In this study, we designed a specific concentric ring with oscillating expansion and contraction SSMVEP paradigm to assess visual acuity and contrast sensitivity. By changing the parameters of the paradigm, the SSMVEP paradigm with different contrasts and spatial frequencies corresponding to different visual acuity and contrast sensitivity was designed. Moreover, we proposed a threshold determination criterion to define the corresponding objective SSMVEP visual acuity and contrast sensitivity. RESULTS: We tested visual acuity and contrast sensitivity of sixteen healthy adults utilizing this paradigm with an electroencephalography system. Our data suggested that there was no significant difference between objective visual acuity and contrast sensitivity measurements based on the SSMVEPs and subjective psychophysical ones. CONCLUSION: Our study proved that SSMVEPs can be an objective and quantitative method to measure visual acuity and contrast sensitivity.


Assuntos
Sensibilidades de Contraste/fisiologia , Potenciais Evocados Visuais/fisiologia , Percepção de Movimento/fisiologia , Acuidade Visual/fisiologia , Adulto , Eletroencefalografia , Eletrorretinografia , Feminino , Humanos , Masculino , Psicofísica , Limiar Sensorial , Testes Visuais , Adulto Jovem
15.
EBioMedicine ; 44: 489-501, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31221584

RESUMO

BACKGROUND: A positive energy balance promotes white adipose tissue (WAT) expansion which is characterized by activation of a repertoire of events including hypoxia, inflammation and extracellular matrix remodelling. The transmembrane glycoprotein CD248 has been implicated in all these processes in different malignant and inflammatory diseases but its potential impact in WAT and metabolic disease has not been explored. METHODS: The role of CD248 in adipocyte function and glucose metabolism was evaluated by omics analyses in human WAT, gene knockdowns in human in vitro differentiated adipocytes and by adipocyte-specific and inducible Cd248 gene knockout studies in mice. FINDINGS: CD248 is upregulated in white but not brown adipose tissue of obese and insulin-resistant individuals. Gene ontology analyses showed that CD248 expression associated positively with pro-inflammatory/pro-fibrotic pathways. By combining data from several human cohorts with gene knockdown experiments in human adipocytes, our results indicate that CD248 acts as a microenvironmental sensor which mediates part of the adipose tissue response to hypoxia and is specifically perturbed in white adipocytes in the obese state. Adipocyte-specific and inducible Cd248 knockouts in mice, both before and after diet-induced obesity and insulin resistance/glucose intolerance, resulted in increased microvascular density as well as attenuated hypoxia, inflammation and fibrosis without affecting fat cell volume. This was accompanied by significant improvements in insulin sensitivity and glucose tolerance. INTERPRETATION: CD248 exerts detrimental effects on WAT phenotype and systemic glucose homeostasis which may be reversed by suppression of adipocyte CD248. Therefore, CD248 may constitute a target to treat obesity-associated co-morbidities.


Assuntos
Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Antígenos CD/genética , Antígenos de Neoplasias/genética , Metabolismo Energético/genética , Hipóxia/metabolismo , Paniculite/genética , Paniculite/metabolismo , Adulto , Animais , Modelos Animais de Doenças , Matriz Extracelular , Feminino , Fibrose , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Paniculite/patologia , Transdução de Sinais
16.
Atherosclerosis ; 285: 163-169, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31071503

RESUMO

BACKGROUND AND AIMS: The association between homocysteine and prognosis of ischemic stroke remains controversial, and the role of platelet count on the effects of homocysteine in the prognosis of ischemic stroke is still not elucidated. METHODS: A total of 3229 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) with homocysteine and platelet measurements were included in this analysis. They were prospectively followed up for death, recurrent stroke and vascular events within 1 year after acute ischemic stroke. RESULTS: There was a significant interaction effect between platelet count and homocysteine level on death (p for interaction < 0.05) within 1 year after ischemic stroke. After multivariate adjustment, high homocysteine level was associated with increased risk of 1-year mortality in patients with low platelet level (hazard ratio, 1.70; 95% confidence interval, 1.01-2.88) but not in those with high platelet level (hazard ratio, 1.08; 95% confidence interval, 0.65-1.75). The addition of homocysteine to a model containing conventional risk factors improved risk prediction of 1-year death (net reclassification index 0.53%, p < 0.001; integrated discrimination improvement 0.07%, p < 0.001). CONCLUSIONS: High homocysteine may be merely an independent risk factor of death in ischemic stroke patients with low platelet levels. Further prospective studies from other populations and randomized clinical trials are needed to verify our findings and clarify the potential mechanisms.

17.
J Stroke Cerebrovasc Dis ; 28(7): 1879-1885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31085131

RESUMO

GOAL: The association of combined galectin-3 and high-density lipoprotein cholesterol (HDL-C) with prognosis of acute ischemic stroke remains unknown. This study aimed to evaluate the coeffect of galectin-3 and HDL-C on death and vascular events within 1 year after ischemic stroke. MATERIALS AND METHODS: Based on China Antihypertensive Trial in Acute Ischemic Stroke, a prospective study was conducted among 2970 patients with acute ischemic stroke. The primary outcome was a combination of death and vascular events within 1 year after ischemic stroke. The secondary outcomes were separately those of recurrent stroke, vascular events, and death. FINDINGS: The multivariate adjusted hazard ratios (95% confidence intervals) of primary outcome, recurrent stroke, and vascular events were 1.54 (1.07-2.20), 1.78 (1.08-2.95), and 1.92 (1.26-2.94), respectively, in patients with both high galectin-3 and low HDL-C compared to those with both low galectin-3 and high HDL-C. The addition of galectin-3 and HDL-C to conventional factors significantly improved predictive value. Net reclassification index was 15.7% for primary outcome, 18.3% for recurrent stroke, and 20.5% for vascular events. CONCLUSION: Combination of high galectin-3 and low HDL-C was associated with primary outcome, recurrent stroke, and vascular events within 1 year after ischemic stroke, suggesting that the combination of galectin-3 and HDL-C may be used to identify the individuals at risk of poor prognosis after ischemic stroke.


Assuntos
Isquemia Encefálica/sangue , HDL-Colesterol/sangue , Galectina 3/sangue , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Método Simples-Cego , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Adulto Jovem
18.
Proc Natl Acad Sci U S A ; 116(14): 6985-6994, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30886104

RESUMO

Diabetic foot ulcerations (DFUs) represent a major medical, social, and economic problem. Therapeutic options are restricted due to a poor understanding of the pathogenic mechanisms. The Notch pathway plays a pivotal role in cell differentiation, proliferation, and angiogenesis, processes that are profoundly disturbed in diabetic wounds. Notch signaling is activated upon interactions between membrane-bound Notch receptors (Notch 1-4) and ligands (Jagged 1-2 and Delta-like 1, 3, 4), resulting in cell-context-dependent outputs. Here, we report that Notch1 signaling is activated by hyperglycemia in diabetic skin and specifically impairs wound healing in diabetes. Local inhibition of Notch1 signaling in experimental wounds markedly improves healing exclusively in diabetic, but not in nondiabetic, animals. Mechanistically, high glucose levels activate a specific positive Delta-like 4 (Dll4)-Notch1 feedback loop. Using loss-of-function genetic approaches, we demonstrate that Notch1 inactivation in keratinocytes is sufficient to cancel the repressive effects of the Dll4-Notch1 loop on wound healing in diabetes, thus making Notch1 signaling an attractive locally therapeutic target for the treatment of DFUs.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Pé Diabético/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Cicatrização , Idoso , Animais , Proteínas de Ligação ao Cálcio , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Pé Diabético/genética , Pé Diabético/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Receptor Notch1/genética
19.
Neurol Res ; 41(5): 466-472, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30829563

RESUMO

BACKGROUND AND AIMS: The association between family history of stroke and clinical outcomes after ischemic stroke remains unclear. METHODS: A total of 3878 acute ischemic stroke patients from CATIS were included. The participants with ischemic stroke were divided into groups according to types of family history of stroke, stroke onset age and stroke subtypes. The primary outcome was a composite outcome of death and vascular events within 1 year after stroke. Multivariable Cox proportional hazard models were used to analyze the association between family history of stroke and other variables and clinical outcomes. RESULTS: Among 3878 ischemic stroke patients, 708 (18.26%) had a history of stroke in their first-degree relatives and 399 experienced a composite outcome (172 patients died and 227 experienced vascular events) within 1 year after stroke. Overall family history was not associated with the primary outcome (HR, 1.08; 95% CI, 0.37-3.19). However, the patients with maternal stroke history (HR, 1.87; 95% CI, 1.31-2.97), stroke onset age<55 years with family history (HR, 2.02; 95% CI, 1.08-3.80) and thrombotic stroke in the patients with family history (HR, 1.46; 95% CI, 1.00-2.12) were associated with primary outcome, death and vascular events, respectively. CONCLUSION: This study suggests that maternal stroke history, age<55 years at stroke onset and thrombotic stroke in the patients with a family history are associated with poor outcomes after stroke. Further studies from other samples are needed to replicate our findings due to a reason for excluding some severe stroke patients in this study.


Assuntos
Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idade de Início , Isquemia Encefálica/genética , Família , Feminino , Predisposição Genética para Doença , Humanos , Trombose Intracraniana/epidemiologia , Trombose Intracraniana/genética , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Acidente Vascular Cerebral/genética , Fatores de Tempo
20.
J Cell Mol Med ; 23(4): 2901-2906, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729666

RESUMO

Semaphorin 7A (Sema7A), a neural guidance cue, was recently identified to regulate atherosclerosis in mice. However, the clinical relevance of Sema7A with atherosclerotic diseases remains unknown. The aim of this study was to investigate the association between serum Sema7A and the risk of acute atherothrombotic stroke (AAS). We measured serum concentrations of Sema7A in 105 newly onset AAS cases and 105 age- and sex-matched controls, showing that median Sema7A level in AAS cases was over three times of that in controls (5.86 vs 1.66 ng/mL). Adjusted for hypertension, body mass index, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, current smoking and alcohol consumption, multivariate logistic regression showed that higher Sema7A was independently associated with the odds of AAS (OR = 6.40, 95% CI: 2.88-14.25). Each 1-standard deviation increase in Sema7A was associated with a threefold higher odds of AAS (OR = 3.42, 95% CI: 1.84-6.35). Importantly, adding Sema7A to a multivariate logistic model containing conventional cardiovascular risk factors improved the area under receiver operating characteristic curves from 0.831 to 0.891 for the association with AAS. In conclusion, elevated serum Sema7A is independently associated with the risk of AAS, suggesting that it may play a potential role in AAS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA