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1.
Adv Mater ; 36(7): e2309899, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37884393

ABSTRACT

Sugars are renewable resources essential to human life, but they are rarely used as raw materials for the industrial production of carbon-based materials, especially for the preparation of carbon fiber-reinforced carbon-matrix (C/C) composites, which are extremely useful for the semiconductor and aerospace sectors. Herein, a method utilizing sugar-derived carbon to replace petrochemicals as dense matrix to preparing C/C composites is reported. The matrix from sugar-derived C/C (S-C/C) composites has a nanocrystalline graphite structure that is highly thermally stable and effectively bonded to the carbon fibers. The mechanical properties of the S-C/C composite are comparable to those prepared from petrochemical sources; significantly, it exhibits a linear ablation rate of 0.03 mm s-1 after 200 s of ablation at 3000 °C in 10 MW m-2 heat flux. This new class of S-C/C is promising for use in a broad range of fields, ranging from semiconductor to aerospace.

2.
Invest New Drugs ; 41(4): 556-563, 2023 08.
Article in English | MEDLINE | ID: mdl-37318657

ABSTRACT

Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation.


Subject(s)
Adenocarcinoma of Lung , Antigens, Neoplasm , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Biomarkers , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Prospective Studies , Humans , Antigens, Neoplasm/genetics
3.
Invest New Drugs ; 41(3): 532-538, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37099161

ABSTRACT

Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell-Free Nucleic Acids , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell-Free Nucleic Acids/genetics , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Biomarkers, Tumor/genetics , Early Detection of Cancer/methods , Liquid Biopsy/methods
4.
Materials (Basel) ; 16(8)2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37109793

ABSTRACT

The mechanical properties of laser powder bed fused (LPBFed) Invar 36 alloy have been limited by the presence of manufacturing defects. It is imperative to investigate the influence of these defects on the mechanical behavior of LPBFed Invar 36 alloy. In this study, in-situ X-ray computed tomography (XCT) tests were conducted on LPBFed Invar 36 alloy fabricated at different scanning speeds to examine the relationship between manufacturing defects and mechanical behavior. For LPBFed Invar 36 alloy fabricated at a scanning speed of 400 mm/s, the manufacturing defects were randomly distributed and tended to be elliptical in shape. Plastic deformation behavior was observed, and failure initiated from defects inside the material resulting in ductile failure. Conversely, for LPBFed Invar 36 alloy fabricated at a scanning speed of 1000 mm/s, numerous lamellar defects were observed mainly located between deposition layers, and their quantity was significantly increased. Little plastic deformation behavior was observed, and failure initiated from defects on the shallow surface of the material resulting in brittle failure. The differences in manufacturing defects and mechanical behavior are attributed to changes in input energy during the laser powder bed fusion process.

5.
Anticancer Drugs ; 34(4): 595-598, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36730313

ABSTRACT

Metastatic urothelial carcinoma (mUC) is associated with poor prognosis. Cisplatin-based combination chemotherapy is the preferred initial regimen for patients with mUC. However, a substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. Currently, immune checkpoint inhibitors (ICI) showed to be effective in cisplatin-ineligible mUC patients on first-line treatment. Tislelizumab is an anti-human programmed death receptor-1 monoclonal IgG4 antibody, which was specifically engineered to minimize binding to FcɣR on macrophages to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as a first-line treatment for cisplatin-ineligible patients with mUC currently. Here, we report a cisplatin-ineligible mUC patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response receiving tislelizumab therapy after laparoscopic debulking surgery. Progression-free survival has exceeded 16 months since treatment with tislelizumab. To our knowledge, this is the first reported case of cisplatin-ineligible mUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as a first-line treatment. However, we still need more studies to assess the efficacy of tislelizumab as a first-line treatment in cisplatin-ineligible mUC patients and to confirm predictive values of TMB for efficacy of tislelizumab.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Urologic Neoplasms , Humans , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/surgery , Cisplatin/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urologic Neoplasms/drug therapy , Urologic Neoplasms/genetics , Urologic Neoplasms/surgery , B7-H1 Antigen/metabolism , Antibodies, Monoclonal/therapeutic use
6.
Invest New Drugs ; 40(4): 850-853, 2022 08.
Article in English | MEDLINE | ID: mdl-35441911

ABSTRACT

Genomic fusions of anaplastic lymphoma kinase (ALK) are a well-established therapeutic target in non-small-cell lung cancer (NSCLC). Although various ALK fusion variants have been identified in NSCLC, their responses to ALK tyrosine-kinase inhibitors (TKIs) are heterogeneous. We report the case of a 71-year-old female patient diagnosed with lung adenocarcinoma with liver metastases. A novel CTNND1 (exon 14)-ALK (exon 20) fusion was identified from the biopsy sample by next-generation sequencing (NGS) and validated by immunohistochemistry (IHC) staining. Alectinib was administered, and the patient soon achieved partial response (PR). The progression-free survival (PFS) exceeded 15 months as of January 25, 2022. Our findings expand the spectrum of ALK rearrangements and provide a potential treatment option for lung adenocarcinoma patients with CTNND1-ALK fusions.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Aged , Anaplastic Lymphoma Kinase/genetics , Carbazoles , Carcinoma, Non-Small-Cell Lung/drug therapy , Crizotinib/therapeutic use , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Piperidines , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use
7.
ISA Trans ; 129(Pt A): 504-519, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35039152

ABSTRACT

Deep neural networks have been successfully utilized in the mechanical fault diagnosis, however, a large number of them have been based on the same assumption that training and test datasets followed the same distributions. Unfortunately, the mechanical systems are easily affected by environment noise interference, speed or load change. Consequently, the trained networks have poor generalization under various working conditions. Recently, unsupervised domain adaptation has been concentrated on more and more attention since it can handle different but related data. Sliced Wasserstein Distance has been successfully utilized in unsupervised domain adaptation and obtained excellent performances. However, most of the approaches have ignored the class conditional distribution. In this paper, a novel approach named Join Sliced Wasserstein Distance (JSWD) has been proposed to address the above issue. Four bearing datasets have been selected to validate the practicability and effectiveness of the JSWD framework. The experimental results have demonstrated that about 5% accuracy is improved by JSWD with consideration of the conditional probability than no the conditional probability, in addition, the other experimental results have indicated that JSWD could effectively capture the distinguishable and domain-invariant representations and have a has superior data distribution matching than the previous methods under various application scenarios.

8.
Environ Monit Assess ; 193(12): 852, 2021 Nov 30.
Article in English | MEDLINE | ID: mdl-34846562

ABSTRACT

As one of the most important industrial cities in Northwest China, Lanzhou currently suffers from serious air pollution. This study analyzed the formation mechanism and potential source areas of persistent air pollution in Lanzhou during the heating period from November 1, 2016 to March 31, 2017 based on the air pollutant concentrations and relevant meteorological data. Our findings indicate that particulate pollution was extremely severe during the study period. The daily PM2.5 and PM10 concentrations had significantly negative correlations with daily temperature, wind speed, maximum daily boundary layer height, while the daily PM2.5 and PM10 concentrations showed significantly positive correlations with daily relative humidity. Five persistent pollution episodes were identified and classified as either stagnant accumulation or explosive growth types according to the mechanism of pollution formation and evolution. The PM2.5 and PM10 concentrations and PM2.5/PM10 ratio followed a growing "saw-tooth cycle" pattern during the stagnant accumulation type event. Dust storms caused abrupt peaks in PM10 and a sharp decrease in the PM2.5/PM10 ratio in explosive growth type events. The potential sources of PM10 were mainly distributed in the Kumtag Desert in Xinjiang Uygur Autonomous Region, the Qaidam Basin and Hehuang Valley in Qinghai Province, and the western and eastern Hexi Corridor in Gansu Province. The contributions to PM10 were more than 120 µg/m3. The important potential sources of PM2.5 were located in Hehuang Valley in Qinghai and Linxia Hui Autonomous Prefecture in Gansu; the concentrations of PM2.5 were more than 60 µg/m3.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , China , Cities , Environmental Monitoring , Heating , Particulate Matter/analysis , Seasons
9.
Genet Test Mol Biomarkers ; 24(5): 230-238, 2020 May.
Article in English | MEDLINE | ID: mdl-32267777

ABSTRACT

Background and Objective: Recently, AMP-activated protein kinase (AMPK) signaling was confirmed to be intimately associated with atherosclerosis. Evidence indicates that genetic susceptibility plays an important role in the etiology of symptomatic intracranial atherosclerotic stenosis (sICAS), however few genes have been pinpointed being etiologically associated. This study investigated possible links between single nucleotide polymorphisms (SNPs) of AMPK-related genes and sICAS in Han Chinese subjects. Methods: Target gene sequencing was carried out in 400 sICAS Han Chinese patients and 1007 healthy controls for 11 AMPK pathway-related genes. Chi-squared testing and multiple logistic regression in dominant, recessive, and additive models were used to evaluate the association between SNPs and risk of sICAS. Bonferroni corrections were performed with a p < (0.05/44 = 0.0011) as statistically significant. Further subgroup data analyses was conducted using chi-squared or t-tests. Results: There were 44 common variants of 11 candidate genes distributed differently between sICAS patients and healthy controls, among which the INSR rs78312382 SNP remained significant even after a Bonferroni correction. Logistic regression analysis showed that rs78312382 was significantly associated with the risk of sICAS in both dominant and additive models (pBonferroni = 7.874e-5 and 0.000506, respectively), with the A allele being much more prevalent in the sICAS group (p = 0.000404). Conclusions: Variants of the INSR rs7831282 locus may play an important role in the development of sICAS among the Han Chinese with the A allele being a risk factor and a potential biomarker for this illness.


Subject(s)
AMP-Activated Protein Kinases/genetics , Constriction, Pathologic/genetics , Intracranial Arteriosclerosis/genetics , Adult , Alleles , Asian People/genetics , Case-Control Studies , China/epidemiology , Ethnicity/genetics , Female , Gene Frequency/genetics , Genetic Association Studies , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Risk Factors
10.
Front Neurol ; 10: 1228, 2019.
Article in English | MEDLINE | ID: mdl-31803136

ABSTRACT

Background: Adipokines have been proven to be associated with atherosclerotic diseases such as ischemic stroke and coronary heart disease. The role of novel adipokines in the development of symptomatic intracranial atherosclerotic stenosis (sICAS) and extracranial atherosclerotic stenosis (sECAS) has not yet been investigated. This study aimed to evaluate the plasma levels of novel adipokines in patients with sICAS and sECAS and their associations with the prognosis of sICAS groups. Methods: A total of 134 patients with acute ischemic stroke attribute to large-artery atherosclerosis (LAA) and 66 age- and sex-matched controls without atherosclerotic stenosis (NCAS) were included in this study. The LAA group was further sub-classified as sICAS (n = 102) and sECAS (n = 32) according to the location of atherosclerosis. Demographics, clinical parameters, angiographical features and plasma levels of novel adipokines (apelin, visfatin, omentin, RBP-4) were assayed and compared among groups. Results: LAA patients had significantly lower levels of omentin [39.92 (30.74-52.61) ng/ml vs. 54.42 (34.73-79.91) ng/ml, P < 0.001] and visfatin [11.32 (7.62-16.44) ng/ml vs. 13.01 (9.46-27.54) ng/ml, P < 0.001] than those in the NCAS group. Multiple logistic regression analysis identified that the lowest tertile of omentin was independently associated with LAA (OR, 3.423; 95% CI, 1.267-9.244, when referenced to the third tertile). Levels of omentin, visfatin and RBP-4 showed no significant difference between sICAS and sECAS groups. However, median concentrations of apelin were lower in sECAS [84.94 (46.88-130.41) ng/mL) than in sICAS [118.64 (93.22-145.08) ng/mL, P = 0.002] and NCAS [114.38 (80.56-162.93) ng/mL, P = 0.004]. Logistic regression analysis showed that the lowermost tertile of apelin was independently associated with sECAS (OR, 5.121; 95% CI, 1.597-16.426) when adjusted for risk factors. As for sICAS patients, spearman coefficient analysis showed no significant correlation between these four adipokines and the severity of sICAS or the number of vessels with intracranial stenoses. Patients with severe stroke had lower levels of apelin (P = 0.005), while the other three adipokines showed no such difference. During follow up, no difference was found between these four novel adipokines and short- and long-term outcome of sICAS. Conclusions: Lower levels of omentin are independent biomarkers of LAA while low apelin plasma levels seem to be risk factors of sECAS.

11.
World Neurosurg ; 129: e472-e477, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31150867

ABSTRACT

OBJECTIVE: The most potent vasoconstrictor, endothelin-1 and its receptors, endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) are involved in hypertension. Hypertension is a major risk factor of intracerebral hemorrhage (ICH). Recent studies have demonstrated increased plasma endothelin-1 level in ICH patients and relationships between EDNRA and EDNRB genetic variants and ischemic stroke. The aim of the current study was to investigate whether EDNRA and EDNRB polymorphisms are associated with ICH by interacting with blood pressure levels. METHODS: Five EDNRA and EDNRB polymorphisms were genotyped in this case-control study. RESULTS: We identified that EDNRA rs5333 T allele might be a protective factor of ICH (adjusted odds ratio [OR] = 0.638, 95% CI: 0.417-0.977, P = 0.038), while EDNRB rs5351 A allele could be a risk factor of ICH (adjusted OR = 1.476, 95% CI: 1.042-2.089, P = 0.028). Moreover, we only found that the GG genotype of EDNRA rs5335 had higher diastolic blood pressure than the GC + CC genotypes in ICH patients (91.69 ± 18.77 vs. 84.71 ± 21.48, P = 0.004). CONCLUSIONS: These findings support the important role of EDNRA and EDNRB polymorphisms in ICH, and suggest that they do not interact with blood pressure levels on altering ICH risk.


Subject(s)
Blood Pressure/genetics , Cerebral Hemorrhage/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Receptor, Endothelin A/genetics , Receptor, Endothelin B/genetics , Adult , Aged , Alleles , Case-Control Studies , Female , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Risk Factors
12.
Int J Neurosci ; 129(7): 635-641, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30251575

ABSTRACT

BACKGROUND: It is uncertain that the effect of free triiodothyronine (FT3) within normal ranges on initial severity and early functional outcomes in acute ischemic stroke (AIS) patients with Intracranial Atherosclerotic Stenosis (ICAS). The predictive values of white blood cell (WBC) and FT3 are also unclear in symptomatic ICAS (sICAS) patients. METHODS: We consecutively reviewed 848 ischemic stroke patients admitted into Xiangya Hospital within 72 h after symptom onset. sICAS was defined as AIS patient with degree of ICAS ≥50% proved by magnetic resonance angiography, computed tomography angiography or digital subtraction angiography. WBC and FT3 were assessed within 24 h after admission. Neurological severity was evaluated on admission using the National Institutes of Health Stroke Scale (NIHSS). Stroke outcomes were defined by the modified Rankin Scale (mRS) on the 14th day after admission. RESULTS: Logistic regression analysis showed that hypertension, lower FT3 and higher WBC concentrations independently associated with severe stroke [FT3 (odds ratio(OR) = 0.543, 95% confidence interval(95% CI): 0.383-0.769); hypertension (OR = 0.436, 95% CI: 0.238-0.800); WBC (OR = 1.17; 95% CI:1.041-1.316]. Besides, lower FT3, higher FT4, higher WBC and higher plasma glucose concentrations independently associated with unfavorable outcomes [FT3 (OR = 0.460; 95% CI: 0.306-0.690); FT4 (OR = 1.151; 95% CI: 1.055-1.255); WBC (OR = 1.178; 95% CI: 1.039-1.334); Plasma glucose (OR = 1.160; 95% CI: 1.002-1.342)]. CONCLUSIONS: Lower FT3 levels within normal ranges and higher WBC count are independently associated with the severity and early poor prognosis of sICAS simultaneously, FT3 and WBC count might be important biomarkers for sICAS patients.


Subject(s)
Brain Ischemia/blood , Brain Ischemia/diagnosis , Intracranial Arteriosclerosis/complications , Stroke/blood , Stroke/diagnosis , Triiodothyronine/blood , Brain Ischemia/complications , Female , Humans , Leukocyte Count , Male , Middle Aged , Risk Factors , Severity of Illness Index , Stroke/complications
13.
Mol Med Rep ; 17(1): 1173-1181, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29115485

ABSTRACT

Neurorehabilitation training is a therapeutic intervention for the loss of neural function induced by focal cerebral ischemia, however, the effect varies depending on the neurorehabilitation exercises. Willed movement (WM) training is defined as task­oriented training, which increases enthusiasm of patients to accomplish a specific task. The current study was performed to the evaluate effect of WM training on neurorehabilitation following focal cerebral ischemia, and further investigate the influence on neural plasticity­associated signaling pathway. Sprague­Dawley rats following temporary middle cerebral artery occlusion (tMCAO) were randomly divided into four groups: tMCAO (no rehabilitation training), CR (control rehabilitation), EM (environmental modification) and WM groups. Rats in the CR group were forced to exercise (running) in a rotating wheel. In the WM group, food was used to entice rats to climb on a herringbone ladder. Herringbone ladders were also put into the cages of the rats in the CR and EM groups, however without the food attraction. WM group exhibited an improvement in neurobehavioral performance compared with other groups. TTC staining indicated an evident reduction in brain damage in the WM group. There were increased synaptic junctions following WM training, based on the observations of transmission election microscopy. Investigation of the molecular mechanism suggested that WM training conferred the greatest effect on stimulating the extracellular signal­related kinase (ERK)/cyclic adenosine monophosphate response element­binding protein 1 (CREB) pathway and glutamate receptor 2 (GluR2)/glutamate receptor interacting protein 1­associated protein 1 (GRASP­1)/protein interacting with C­kinase 1 (PICK1) cascades among groups. Collectively, the improvement of neurobehavioral performance by WM training following tMCAO is suggested to involve the ERK/CREB pathway and GluR2/GRASP­1/PICK1 cascades. The present study provided a preliminary foundation for future research on the therapeutic effect of WM training against stroke­induced neuron damage.


Subject(s)
Brain Ischemia/metabolism , Brain Ischemia/rehabilitation , Neuronal Plasticity , Physical Conditioning, Animal , Signal Transduction , Animals , Brain/metabolism , Brain/pathology , Brain/ultrastructure , Brain Ischemia/etiology , Brain Ischemia/pathology , Fluorescent Antibody Technique , Immunohistochemistry , Male , Mortality , Muscle Strength , Rats
14.
Atherosclerosis ; 263: 237-243, 2017 08.
Article in English | MEDLINE | ID: mdl-28683362

ABSTRACT

BACKGROUND AND AIMS: microRNA223 (miR-223) plays an important role in the development of atherosclerosis and ischemic stroke. It is involved in regulation of multiple physiological and pathophysiological processes such as cholesterol metabolism, endothelial cell (EC) function, and thrombosis. Here we investigated the role of methylation regulation of MIR-223 promoter region in atherosclerotic cerebral infarction (ACI) patients. METHODS: A total of 23 patients with ACI and 32 healthy individuals were recruited. We performed bisulfite sequencing PCR and real-time PCR to detect methylation levels of MIR-223 promoter region and miR-223, respectively, in genomic DNA isolated from peripheral blood leukocytes. RESULTS: Mean methylation levels of a total of nine CpGs of MIR-223 promoter were significantly lower in ACI patients than in healthy individuals (p < 0.01), and were also significantly lower in individuals with carotid atherosclerosis than those without carotid atherosclerosis (p < 0.05). Meanwhile, miR-223 expression in leukocytes was significantly higher in ACI patients than in healthy individuals (p < 0.05). miR-223 level was negatively correlated with mean methylation levels of MIR-223 promoter (r = -0.4451, p < 0.01). The methylation level of MIR-223 promoter revealed a positive correlation with the circulating total cholesterol level (r = 0.318, p = 0.019). CONCLUSIONS: Hypomethylation of MIR-223 promoter is associated with atherosclerotic cerebral infarction.


Subject(s)
Carotid Artery Diseases/genetics , Cerebral Infarction/genetics , DNA Methylation , Intracranial Arteriosclerosis/genetics , MicroRNAs/genetics , Promoter Regions, Genetic , Carotid Artery Diseases/blood , Carotid Artery Diseases/diagnostic imaging , Case-Control Studies , Cerebral Infarction/blood , Cerebral Infarction/diagnostic imaging , Chi-Square Distribution , Down-Regulation , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Intracranial Arteriosclerosis/blood , Intracranial Arteriosclerosis/diagnostic imaging , Logistic Models , MicroRNAs/blood , Odds Ratio , Phenotype , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors
15.
J Stroke Cerebrovasc Dis ; 26(5): 1061-1070, 2017 May.
Article in English | MEDLINE | ID: mdl-28189572

ABSTRACT

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) are different in many aspects. Here, we explored the association between the location or severity of atherosclerotic stenosis and pro- or antiangiogenic factors, specifically vascular endothelial growth factor (VEGF) and endostatin (ES). METHODS: We evaluated 198 consecutive patients with acute ischemia stroke: 132 with large-artery atherosclerosis (LAA) and 66 with small-artery occlusion (small-vessel occlusion). The LAA group was subclassified into 102 patients with ICAS and 30 with ECAS. Independent associations of VEGF, ES levels, and VEGF/ES ratio with the location of cerebral stenosis and the severity or short-term prognosis (14th day modified Rankin Scale) of ICAS were evaluated. RESULTS: Plasma concentrations of VEGF and ES were lower (P < .05) in ICAS (38.07, 32.76-46.28 pg/mL and 58.95, 55.04-59.77 ng/mL) than those in ECAS (45.00, 34.30-83.34 pg/mL and 140.74, 85.63-231.21 ng/mL). Logistic regression analysis showed that VEGF concentrations and dyslipidemia were independently associated with ICAS, with odds ratios of .987 [95% CI = (.976, .998)] and .265 [95% CI = (.103, .792)], respectively. Moreover, plasmatic VEGF levels increased gradually along with the severity of ICAS (P = .003), and lower levels of ES (P = .040) or a higher VEGF/ES ratio (P = .048) were related to unfavorable short-term prognosis of ICAS. CONCLUSION: Lower VEGF levels are associated with the presence of symptomatic ICAS, but not with ECAS. Furthermore, the severity of ICAS is positively correlated with the levels of VEGF, and lower ES levels or a predominance of VEGF over ES are predictors of poor short-term prognosis of ICAS.


Subject(s)
Brain Ischemia/blood , Carotid Stenosis/blood , Cerebral Small Vessel Diseases/blood , Endostatins/blood , Intracranial Arteriosclerosis/blood , Stroke/blood , Vascular Endothelial Growth Factor A/blood , Adult , Aged , Aged, 80 and over , Area Under Curve , Asian People , Biomarkers/blood , Brain Ischemia/diagnosis , Brain Ischemia/ethnology , Carotid Stenosis/diagnosis , Carotid Stenosis/ethnology , Cerebral Small Vessel Diseases/diagnosis , Cerebral Small Vessel Diseases/ethnology , Chi-Square Distribution , China , Disability Evaluation , Female , Humans , Intracranial Arteriosclerosis/diagnosis , Intracranial Arteriosclerosis/ethnology , Logistic Models , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , Prognosis , ROC Curve , Severity of Illness Index , Stroke/diagnosis , Stroke/ethnology , Time Factors
16.
Brain Res ; 1663: 174-183, 2017 05 15.
Article in English | MEDLINE | ID: mdl-28130053

ABSTRACT

Alzheimer's disease (AD) is characterized by excessive amounts of senile plaques and neurofibrillary tangles in the brain, and cerebrovascular pathologies in AD are attracting increasingly more attention. Krüppel-like factor (KLF) 2, a transcription regulator expressed in the mouse embryonic vasculature and involved in the regulation of vascular gene expression, serves as a protective factor in endothelial cells. However, whether KLF2 is involved in neurodegenerative disease, and especially in AD, remains unknown. In the present study, the effects of KLF2 in Aß-induced neurotoxicity were investigated. Firstly, we found that KLF2 expression decreased at both the RNA and protein levels in AD cases. The following results show that KLF2 was found to be decreased in both a time- and dose-dependent manner in response to Aß1-42 treatment in primary mouse brain microvascular endothelial cells. Overexpression of KLF2 attenuated Aß-induced oxidative stress, improved mitochondrial function, and reduced the rate of apoptosis. Furthermore, inhibition of KLF2 promoted Aß1-42-induced oxidative stress, exacerbated mitochondrial dysfunction, and increased the rate of apoptosis. Our data imply that the promotion of KLF2 expression in cerebral endothelial cells has the potential to be developed as a novel therapeutic strategy for the treatment of cerebral vascular dysfunction in AD.


Subject(s)
Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/therapeutic use , Kruppel-Like Transcription Factors/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/physiology , Animals , Apoptosis/drug effects , Brain/drug effects , Brain/metabolism , Cells, Cultured , Endothelial Cells/drug effects , Gene Expression/drug effects , Gene Expression Regulation/drug effects , Humans , Kruppel-Like Transcription Factors/physiology , Kruppel-Like Transcription Factors/therapeutic use , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Peptide Fragments/pharmacology
17.
Cardiovasc Toxicol ; 17(1): 42-48, 2017 01.
Article in English | MEDLINE | ID: mdl-26717922

ABSTRACT

The aim of the study was to investigate the expression of miR-223 and FAM5C in the peripheral blood mononuclear cells (PBMCs) of cerebral infarction patients with or without diabetes. Sixteen cases with diabetes mellitus (DM), 14 cases with cerebral infarction (CI), 12 cases with cerebral infarction and diabetes mellitus (CIDM), and 18 healthy subjects were included in this study. Real-time PCR was used to quantify mRNA expression. Western blot was used to detect FAM5C protein level. Recombinant plasmids expressing miR-223-3p and 3' UTR of FAM5C were constructed. Dual-luciferase reporter system was used to analyze the binding of miR-223-3p to FAM5C 3' UTR. FAM5C mRNA and protein level were significantly higher in the PBMCs of CIDM patients compared with healthy controls (P < 0.05). miR-223-3p expression in PBMCs was significantly lower in DM patients than in healthy controls (P < 0.05). The expression of miR-223-3p was negatively correlated with FAM5C mRNA in all patients and healthy controls. Co-transfection of miR-223-3p plasmid with FAM5C 3'UTR dual-luciferase plasmid significantly inhibited the luciferase activity (P < 0.01). FAM5C, but not miR-223, is a risk factor for CI in type 2 DM patients.


Subject(s)
Cerebral Infarction/blood , DNA-Binding Proteins/blood , Diabetes Mellitus, Type 2/blood , Leukocytes, Mononuclear/metabolism , MicroRNAs/blood , 3' Untranslated Regions , Adult , Aged , Binding Sites , Case-Control Studies , Cerebral Infarction/diagnosis , Cerebral Infarction/etiology , Cerebral Infarction/genetics , DNA-Binding Proteins/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Female , Gene Expression Regulation , HEK293 Cells , Humans , Male , MicroRNAs/genetics , Middle Aged , RNA, Messenger/blood , RNA, Messenger/genetics , Risk Factors , Transfection
18.
J Genet ; 95(2): 383-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27350683

ABSTRACT

Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case-control study and in a family-based association study. Case-control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the 'G' allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the 'A' allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z= -1.882, P = 0.049; Z= -2.000, P = 0.045; Z= -2.319, P = 0.020; Z= -2.002, P = 0.045; Z= -2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.


Subject(s)
Blood Proteins/genetics , Cerebral Hemorrhage/genetics , Factor VII/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Asian People , Case-Control Studies , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/ethnology , Cerebral Hemorrhage/pathology , Female , Gene Expression , Gene Frequency , Genetic Association Studies , Haplotypes , Humans , Male , Pedigree , Risk
19.
J Int Med Res ; 44(3): 444-52, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27036146

ABSTRACT

OBJECTIVE: To determine whether endothelin converting enzyme-1 (ECE1) gene polymorphisms contribute to susceptibility to intracerebral haemorrhage (ICH) by influencing blood pressure. METHODS: This case-control study enrolled patients with ICH and healthy control subjects from a Southern Han Chinese population. The ECE1 gene polymorphisms rs212528 and rs213045 were genotyped. The association between the genotypes and the risk of ICH was assessed. The effects of these two ECE1 gene polymorphisms on blood pressure were also analysed. RESULTS: A total of 389 patients with ICH and 404 healthy control subjects participated in the study. There was no significant association between the ECE1 rs212528 and rs213045 polymorphisms and ICH even after adjusting for different confounding variables. In patients with ICH, the systolic blood pressure of patients with the rs212528 AA genotype was significantly lower than that of patients with the AG/GG genotypes. CONCLUSIONS: These results indicated that the ECE1 rs212528 and rs213045 polymorphisms had no major role to play in the genetic susceptibility to ICH, although rs212528 might influence blood pressure in patients with ICH.


Subject(s)
Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/physiopathology , Endothelin-Converting Enzymes/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Case-Control Studies , Demography , Female , Humans , Male , Middle Aged , Risk Factors
20.
PLoS One ; 11(3): e0151576, 2016.
Article in English | MEDLINE | ID: mdl-26991786

ABSTRACT

Improving the capability of land-surface process models to simulate soil moisture assists in better understanding the atmosphere-land interaction. In semi-arid regions, due to limited near-surface observational data and large errors in large-scale parameters obtained by the remote sensing method, there exist uncertainties in land surface parameters, which can cause large offsets between the simulated results of land-surface process models and the observational data for the soil moisture. In this study, observational data from the Semi-Arid Climate Observatory and Laboratory (SACOL) station in the semi-arid loess plateau of China were divided into three datasets: summer, autumn, and summer-autumn. By combing the particle swarm optimization (PSO) algorithm and the land-surface process model SHAW (Simultaneous Heat and Water), the soil and vegetation parameters that are related to the soil moisture but difficult to obtain by observations are optimized using three datasets. On this basis, the SHAW model was run with the optimized parameters to simulate the characteristics of the land-surface process in the semi-arid loess plateau. Simultaneously, the default SHAW model was run with the same atmospheric forcing as a comparison test. Simulation results revealed the following: parameters optimized by the particle swarm optimization algorithm in all simulation tests improved simulations of the soil moisture and latent heat flux; differences between simulated results and observational data are clearly reduced, but simulation tests involving the adoption of optimized parameters cannot simultaneously improve the simulation results for the net radiation, sensible heat flux, and soil temperature. Optimized soil and vegetation parameters based on different datasets have the same order of magnitude but are not identical; soil parameters only vary to a small degree, but the variation range of vegetation parameters is large.


Subject(s)
Desert Climate , Models, Theoretical , Plant Physiological Phenomena , Soil/chemistry , Water , Algorithms , China , Ecosystem , Plants
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