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1.
Aging (Albany NY) ; 122020 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-32602849

RESUMEN

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms. In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

2.
Biomed Chromatogr ; : e4946, 2020 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-32643816

RESUMEN

As a traditional Chinese medicine (TCM), Marsdenia tenacissima (Roxb.) Wight et Arn. plays an indispensable role in clinical practice due to its specific efficacy in treating malignant tumors, leukocythemia, cystitis and asthma. This study aimed to establish a novel and scientific LC-MS/MS approach to simultaneously determine tenacissoside B,H,G,I, caffeic acid, cryptochlorogenic acid, chlorogenic acid, and neochlorogenic acid from M. tenacissima extract within the rat plasma samples. Digoxin was used as the internal reference. All determinations were carried out using the Eclipse Plus C18 column, and water (containing 0.1% formic acid) was used as the mobile phase A, while acetonitrile as the mobile phase B for gradient elution. The UPLC methods, including calibration curves, accuracy, precision, stability and recovery of the total eight analytes were validated in accordance with the requirements for biopharmaceutical analysis. Moreover, the as-proposed approach was also used in the comprehensive pharmacokinetic research on those eight analytes within rats following M. tenacissima extract gavage. According to the pharmacokinetic parameters, tenacissoside B,I,H and G were the long-acting and primary bioactive constituents in M. tenacissima extract, which had long mean residence times and great concentrations. Our findings shed light on the absorption mechanism and provided significant information for the clinical application of M. tenacissima.

3.
Am Heart J ; 226: 198-205, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32615357

RESUMEN

BACKGROUND: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed. METHODS: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death. CURRENT STATUS: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018. CONCLUSION: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.

4.
Ecotoxicol Environ Saf ; 202: 110889, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32623235

RESUMEN

Coke oven emissions (COEs) can cause oxidative stress of the body, which in turn induces the occupational lung disease and also increases the risk of other diseases. COEs are the major occupational hazard factors for coke oven workers. The aim of the study is to explore the influences of COEs exposure on oxidative damage and estimate the benchmark dose (BMD) of COEs. A group of 542 workers exposed to COEs and 237 healthy controls from the same city were recruited in this study. The corresponding measuring kits were used to determine the plasma biomarkers of oxidative damage level. Generalized linear models and trend tests were used to analyze the relationship between COEs exposure and biomarkers. EPA Benchmark Dose Software was performed to calculate BMD and the lower confidence limit of the benchmark dose (BMDL) of COEs exposure. A significant association was observed between COEs exposure and oxidative damage with T-AOC as a biomarker. The BMD of COEs exposure were 2.83 mg/m3 and 1.39 mg/m3 for males and females, respectively, and the corresponding BMDL were 1.47 mg/m3 and 0.75 mg/m3, respectively. Our results suggested that the exposure level of COEs below the current national occupational exposure limits (OELs) would induce oxidative damage, and the OEL of COEs based on the T-AOC damage was suggested at 0.03 mg/m3 in this study.

6.
Artículo en Inglés | MEDLINE | ID: mdl-32640278

RESUMEN

OBJECTIVES: Children with cancer are exposed to repeated painful and invasive procedures. This study examines Chinese parents' stress and perception towards their children's procedural pain-control. METHODS: We recruited 265 parents of children (aged <18 years) diagnosed with hematological cancer (74.7%) and solid tumors (25.3%) from two major public hospitals. Parents used a scale (0-10) to rate perceived pain experienced by their child when undergoing lumbar puncture (LP), bone marrow aspirate or/and biopsy. They reported their stress level and attitudes towards analgesics using the adapted Pain Flexibility Scale for Parents and Parental Medication Attitude Questionnaire. General linear modelling was used to identify factors associated with perception outcomes. RESULTS: Parents (72.8% mothers, age 36.5[6.8] years) expressed that they were worried (31.7%) and had difficulty with concentration (57.7%) when the child was in pain. Among parents whose children had undergone LP (n=207), 39.1% perceived that their child still experienced severe pain (pain score>7) even with existing pain control measures. Parents reported concerns over side effects of analgesics (69.4%) and addiction (35.1%). Half of the parents (47.2%) perceived that analgesics should only be reserved for severe pain. Parents who were older (Estimate=2.07, SE=0.87; P=0.0054) and had lower education attainment (Estimate=-3.38, SE=1.09; P=0.0021) had a more negative attitude towards analgesics use. Higher parental distress was associated with avoidance of analgesics use (rs=0.17, P=0.0052). CONCLUSION: Our findings suggested that subgroups of Chinese parents demonstrated distress with their child's pain and harbored misconceptions over analgesics use. Future work includes devising targeted psychoeducation interventions for these parents.

7.
J Lipid Res ; 2020 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-32641433

RESUMEN

Triglyceride-rich lipoproteins (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particles cholesterol (RLP-C) and apolipoprotein C-III (apoC-III), have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous coronary artery disease (CAD). This study aimed to examine the associations of TRL-C, RLP-C and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C and total apoC-III were directly measured. A total of 4355 participants with angiographically confirmed CAD were followed-up for the occurrence of CVEs. During a median follow-up period of 5.1 (IQR: 3.9-6.4) years, 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C and apoC-III increased the risk of CVEs by 49% (95%CI: 1.16-1.93), 21% (95%CI: 1.09-1.35) and 40% (95%CI: 1.11-1.77), respectively. High TRL-C, RLP-C and apoC-III were also independent predictors of CVEs in individuals with low-density lipoprotein cholesterol levels ≤1.8 mmol/L (n=1068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.

8.
Neuroimage ; : 117107, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32622984

RESUMEN

This paper presents Contextual Fibre Growth (ConFiG), an approach to generate white matter numerical phantoms by mimicking natural fibre genesis. ConFiG grows fibres one-by-one, following simple rules motivated by real axonal guidance mechanisms. These simple rules enable ConFiG to generate phantoms with tuneable microstructural features by growing fibres while attempting to meet morphological targets such as user-specified density and orientation distribution. We compare ConFiG to the state-of-the-art approach based on packing fibres together by generating phantoms in a range of fibre configurations including crossing fibre bundles and orientation dispersion. Results demonstrate that ConFiG produces phantoms with up to 20% higher densities than the state-of-the-art, particularly in complex configurations with crossing fibres. We additionally show that the microstructural morphology of ConFiG phantoms is comparable to real tissue, producing diameter and orientation distributions close to electron microscopy estimates from real tissue as well as capturing complex fibre cross sections. Signals simulated from ConFiG phantoms match real diffusion MRI data well, showing that ConFiG phantoms can be used to generate realistic diffusion MRI data. This demonstrates the feasibility of ConFiG to generate realistic synthetic diffusion MRI data for developing and validating microstructure modelling approaches.

9.
Artículo en Inglés | MEDLINE | ID: mdl-32627045

RESUMEN

PURPOSE: The purpose of this study was to analyse the risk factors associated with residual graft laxity after medial patellofemoral ligament reconstruction (MPFL-R) in patients with recurrent patellar dislocation (RPD). METHODS: A total of 312 consecutive patients (354 knees) with clinically diagnosed RPD who underwent MPFL-R from 2011 to 2015 were retrospectively analysed. Postoperative MPFL graft stability was assessed with patellofemoral stress radiography, and if the patellar central ridge surpassed the apex of the lateral femoral trochlea, the reconstructed MPFL was defined as having residual graft laxity. Finally, 15 patients who exhibited MPFL residual graft laxity (study group) were matched in a 1:2 fashion to 30 control participants (control group), who showed a normal postoperative patellar stability on stress radiography. Preoperative three-dimensional computed tomography (3D-CT) was used to identify patients with a high-grade J-sign. Femoral tunnel position was assessed using 3D-CT to identify cases with femoral tunnel malposition. Potential predictors of MPFL residual graft laxity, including age, sex, a preoperative high-grade J-sign, femoral tunnel malposition, and several radiological parameters, were assessed by logistic regression analysis. RESULTS: A preoperative high-grade J-sign was identified in 66.7% of the study group, which was significantly higher than that the 13.3% in the control group (P = 0.001). In addition, the presence of a preoperative high-grade J-sign (odds ratio, 11.9 [95% CI, 1.7-82.8]; P = 0.012) and femoral tunnel malposition (odds ratio, 8.2 [95% CI, 1.2-58.0]; P = 0.036) were determined to be independent risk factors associated with residual graft laxity after MPFL-R. CONCLUSION: The presence of a preoperative high-grade J-sign and femoral tunnel malposition are associated with residual graft laxity after MPFL-R in patients with RPD. These results may provide additional information for counselling patients on residual graft laxity after MPFL-R. LEVEL OF EVIDENCE: Level III.

10.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2578-2585, 2020 Jun.
Artículo en Chino | MEDLINE | ID: mdl-32627492

RESUMEN

To explore whether paeonol can play an anti-atherosclerotic role by regulating the expression of aortic caveolin-1 and affecting NF-κB pathway, so as to inhibit the inflammatory response of vascular endothelium in atherosclerotic rats. The atherosclerotic model of rats was induced by high-fat diet and vitamin D_2. The primary culture of vascular endothelial cells(VECs) was carried out by tissue block pre-digestion and adherent method. The injury model of VECs was induced by lipopolysaccharide(LPS), and filipin, a small concave protein inhibitor, was added for control. HE staining was used to observe pathological changes of aorta. TNF-α, IL-6 and VCAM-1 were detected by ELISA. Western blot assay was used to detect the protein expression levels of caveolin-1 and p65 in aorta and VECs. The results showed that as compared with model group, paeonol significantly reduced aortic plaque area and lesion degree in rats, decreased the level of serum TNF-α, IL-6 and VCAM-1 in the rats and enhanced the relative expression level of caveolin-1, decreased p65 expression conversely(P<0.05 or P<0.01). In vitro, as compared to model group, paeonol obviously improved cell morphology, decreased the secretion of TNF-α, IL-6 and VCAM-1 in VECs, increased caveolin-1 expression, and decreased p65 protein expression(P<0.05 or P<0.01). Furthermore, filipin could reverse the effect of paeonol on expression of inflammatory factors and proteins(P<0.05 or P<0.01). According to the results, it was found that paeonol could play the role of anti-atherosclerosis by up-regulating the expression of caveolin-1 and inhibiting the activation of NF-κB pathway to reduce vascular inflammation in atherosclerotic rats.

11.
Endocrine ; 2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-32607763

RESUMEN

BACKGROUNDS: The thioredoxin-1 has atheroprotective effects via regulating oxidative stress and inflammation. In addition, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome also contributes to atherosclerosis development. However, whether the thioredoxin-1 suppresses atherosclerosis development by modulating the NLRP3 inflammasome remains unclear. METHODS: The regulation of NLRP3 inflammasome by thioredoxin-1 was determined in vitro on macrophage cells after ox-LDL (oxidized low-density lipoprotein) stimulation. The IL-1ß and caspase-1 p10 secretion were assessed by ELISA and western blot. Finally, the thioredoxin-1/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice. RESULTS: Thioredoxin-1 suppressed the expression of NLRP3, the secretion of IL-1ß and caspase-1 p10 in vitro. And ROS stimulation activated the NLRP3 inflammasome which was inhibited by thioredoxin-1. In the mouse model of atherosclerosis, thioredoxin-1 delivered by lentivirus vector inhibited atherosclerosis development. And the atheroprotective effects of thioredoxin-1 were attenuated by ROS stimulation. Furthermore, the regulation of NLRP3 inflammasome by thioredoxin-1 was also confirmed in vivo. CONCLUSIONS: We demonstrated here that the thioredoxin-1 had atheroprotective functions through thioredoxin-1/NLRP3 inflammasome pathway.

12.
Huan Jing Ke Xue ; 41(2): 849-855, 2020 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-32608746

RESUMEN

The use of an embedded broad-spectrum high-efficiency denitrification filler to treat secondary effluent from municipal wastewater treatment plants can effectively reduce total nitrogen (TN) concentration of the effluent. This study consists of two parts. The D1 stage studies the adaptability of the secondary effluent based on the embedded denitrification, removal effect of total nitrogen, stable working conditions, and backwashing conditions; In the D2 stage, the change in the nitrogen removal performance of the filler under the condition of a year-long stable operation was studied. The variation in the microbial population before and after the operation of the embedded packing was studied by high-throughput sequencing and real-time quantitative PCR detecting system real-time (qPCR). In this research, the embedded denitrification filler had a water temperature of (24±1)℃, pH:7.1, hydraulic retention time (HRT):1 h, and filling rate:10%. Sodium acetate was added to ensure stable operation for seven days. Under adequate carbon source conditions, the filler can adapt to the quality of secondary effluent water and achieve effluent TN<5mg·L-1. By comparing and studying the effect of different HRT on the removal of filler TN, it is concluded that HRT is 30 min and the filling rate is 10%. After a year of stable operation under 7.2 m3·d-1influent conditions, the TN removal rate can reach 90.42%, and the total nitrogen in the effluent can be stabilized below 5 mg·L-1. In comparison with the backwashing effect, the backwashing strength was 5.2 L·(m2·s)-1, and the cycle is three days long. High-throughput sequencing and real-time quantitative PCR analysis results show that the abundance and copy number of denitrifying functional genus in the filler before and after the operation exhibited significant changes, which indicated that the bacteria could achieve good self-growth under embedding conditions.

13.
Huan Jing Ke Xue ; 41(6): 2812-2821, 2020 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-32608798

RESUMEN

To investigate the potential interference of dead bacteria DNA on the analysis of antibiotic resistance genes (ARGs) and microbial communities in anaerobic digestion sludge, three different types of anaerobic digestion sludge were treated with propidium monoazide (PMA) in this study, and the results of subsequent ARGs and microbial community analysis with the interference of dead cell DNA blocked by PMA was compared to that without PMA treatment. It was found that after PMA treatment, the absolute abundance of the ARGs in the anaerobic digestion sludge from self-anaerobic digestion system of excess sludge and from high solid sludge anaerobic digestion system decreased by 41%-86%, and 74%-98%, respectively. ARGs abundance in the sludge from the anaerobic digestion system with sludge hydrolyzate as a substrate and anaerobic granular sludge as inoculum after 15 days of digestion considerably decreased with PMA treatment. However, its ARGs abundance still declined by up to 34%. PMA treatment influenced the analysis of microbial community of the three types of anaerobic digestion sludge to different degrees, in which the influence was the highest on the community structure analysis of the sludge from high solid anaerobic digestion system. The results of the correlation analysis between the ARGs abundance and the microbial community composition were completely different in the case with PMA treatment and without PMA treatment. This study proved the potential interference of dead cell DNA on the analysis of ARGs and microbial community in anaerobic digestion sludge. PMA pretreatment could achieve a more accurate analysis of the microbial community and ARGs characteristics in anaerobic digestion sludge.

14.
Huan Jing Ke Xue ; 41(7): 3204-3211, 2020 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-32608893

RESUMEN

Transformation of perfluoroalkyl substance (PFASs) precursors and their contribution to PFASs pollution have become a subject of great research interest. The concentration of PFASs and their precursors and the transformation of precursors in the water samples collected from Le'an River and the effluents of sewage treatment plants (STPs) were investigated based on methods including hydroxyl radical (·OH) oxidation, extraction by solid phase, and ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The results of the study revealed that the PFAS concentrations were in the range of 14.89-40.84 ng·L-1and 58.63-114.87 ng·L-1, and averaged 28.76 ng·L-1 and 86.75 ng·L-1 in the water of the Le'an River and the STP effluents, respectively. The compound with the highest concentration for the two kinds of waterbodies was perfluorooctanesulfonic acid (PFOS). The PFAS concentrations showed obvious spatial differences in the water of the Le'an River. After the oxidation treatment, the PFAS concentrations clearly increased in the two kinds of waterbodies. The increased concentrations of short-chain perfluorocarboxylic acids with carbon atom numbers of 4-8 (ΣΔï¼»PFCAC4-C8ï¼½oxidation conversion) were higher than those of compounds with long carbon chains. However, the increased concentrations of PFCAs for the STP effluents were higher than those for the river water. The transformation ratio obtained from the increased concentration of PFCAs led by the oxidation treatment against the PFCA concentration before oxidation (ΔPFCAoxidation conversion/PFCAbefore oxidation) was lower for the STP effluents than those for the water of Le'an River, which might be induced by the precursors' degradation during the sewage treatment process.

15.
Food Chem ; 332: 127408, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32619944

RESUMEN

A research was performed to determine and compare the physicochemical properties, chemical compositions and in vitro antioxidant activities of Paeonia lactiflora Pall seed oils with ultrasonic-assisted solvent extraction, pressing and supercritical fluid extraction. Paeonia lactiflora Pall seed oil contained a high percentage of polyunsaturated fatty acids and monounsaturated fatty acids, especially oleic (31.62-32.88%) and α-linolenic acids (37.55-39.95%). The beneficial multiple dietary phytochemicals (tocopherol, phytosterols and squalene) and in vitro antioxidant activity were significantly influenced by the hull and processing method (P<0.05). However, higher tocopherol (596.67-738.76 mg/kg) and phytosterols (5775.01-6055.62 mg/kg) contents were found in supercritical fluid extraction oils. Additionally, ten individual polyphenols were quantified, and significantly influenced by the hull and processing method (P<0.05), with the content of benzoic acid and several individual flavonoids being the higher. According to the results, pressing might be the best process for extracting oil with a high number of polyphenols.

16.
Food Chem Toxicol ; 143: 111513, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32621845

RESUMEN

Development of reliable and efficient alternative in vivo methods for evaluation of the chemicals with potential neurotoxicity is an urgent need in the early stages of drug design. In this investigation, the computational prediction models for drug-induced neurotoxicity were developed by using the classical naïve Bayes classifier. Eight molecular properties closely relevant to neurotoxicity were selected. Then, 110 classification models were developed with using the eight important molecular descriptors and 10 types of fingerprints with 11 different maximum diameters. Among these 110 prediction models, the prediction model (NB-03) based on eight molecular descriptors combined with ECFP_10 fingerprints showed the best prediction performance, which gave 90.5% overall prediction accuracy for the training set and 82.1% concordance for the external test set. In addition, compared to naïve Bayes classifier, the recursive partitioning classifier displayed worse predictive performance for neurotoxicity. Therefore, the established NB-03 prediction model can be used as a reliable virtual screening tool to predict neurotoxicity in the early stages of drug design. Moreover, some structure alerts for characterizing neurotoxicity were identified in this research, which could give an important guidance for the chemists in structural modification and optimization to reduce the chemicals with potential neurotoxicity.

17.
Mol Med Rep ; 22(2): 1647-1655, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32627032

RESUMEN

Melatonin, which is mainly secreted by the pineal gland, appears to have anti­inflammatory activities. Acute pancreatitis (AP) is characterized by inflammation and acinar cell death, and is associated with a high mortality rate. It has been reported that melatonin can alleviate cerulein (Cer) or Cer + lipopolysaccharide (LPS)­induced inflammatory responses in AR42J rat pancreatic acinar cells (AR42J cells). CCAAT/enhancer binding protein homologous protein (CHOP) is a specific transcription factor involved in endoplasmic reticulum (ER) stress­induced apoptosis, and regulates ER stress responses. However, the mechanisms of the anti­inflammatory effects of melatonin' are unknown, particularly the relationship between melatonin and ER stress. Therefore, the present study aimed to investigate the anti­inflammatory activity of melatonin in AR42J cells and analyze its molecular mechanisms during ER stress. The RNA interference method was used to determine the potential role of CHOP in AR42J cells during AP. In vitro models of AP were induced by treating AR42J cells with Cer + LPS, and pre­treatment with melatonin was used to identify the potential anti­inflammatory mechanisms. The cells also underwent Cell Counting Kit­8, western blotting and reverse transcription­quantitative PCR analyses. The expression levels of ER stress­related molecules were rapidly activated in the early stage and increased over time in the AR42J AP models, with significant pancreatic inflammation and apoptosis. However, knockdown of CHOP expression significantly reduced apoptosis, the activation of NF­κB and the downstream signal pathway. Moreover, cells treated with melatonin exhibited attenuated inflammation, decreased expression levels of ER stress­associated proteins and inhibition of apoptosis. Thus, the present results suggested that melatonin may attenuate the inflammatory response by inhibiting the activation of the CHOP­mediated pathway in AR42J cells.

18.
Cardiovasc Diabetol ; 19(1): 104, 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32631321

RESUMEN

BACKGROUND: The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status. METHODS: Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. RESULTS: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. . CONCLUSIONS: In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.

19.
Cardiovasc Diabetol ; 19(1): 111, 2020 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-32646432

RESUMEN

BACKGROUND: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. METHODS: From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. RESULTS: During 7613 patient-years' follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051-3.840); ≥ 7.0%, 2.162 (1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. CONCLUSIONS: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.

20.
Cell Commun Signal ; 18(1): 107, 2020 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-32646440

RESUMEN

BACKGROUND: Foxp3+CD4+ regulatory T cells (Treg) constitutes a key event in autoimmune diseases. STAT5b is the critical link between the IL-2/15 and FOXP3, the master regulator of Treg cells. METHODS: The CD3+T cell and Foxp3+CD4+ regulatory T cells were overexpressioned or knockdown MKL-1 and STAT5a and tested for Treg cell development and function. Direct interaction of MKL-1 and STAT5a were analyzed by coimmunoprecipitation assays, Luciferase assay, Immunofluoresence Staining and Yeast two-hybrid screening. The effect of MKL-1 and STAT5a on the Treg genes expression was analyzed by qPCR and western blotting and Flow cytometry. RESULTS: However, the molecular mechanisms mediating STAT5b-dependent Treg genes expression and Treg cell phenotype and function in autoimmune diseases are not well defined. Here, we report that the MKL-1 is a coactivator for the major Treg genes transcription factor STAT5b, which is required for human Treg cell phenotype and function. The N terminus of STAT5b, which contains a basic coiled-coil protein-protein interaction domain, binds the C-terminal activation domain of MKL-1 and enhances MKL-1 mediated transcriptional activation of Treg-specific, CArG containing promoters, including the Treg-specific genes Foxp3. Suppression of endogenous STAT5b expression by specific small interfering RNA attenuates MKL-1 transcriptional activation in cultured human cells. The STAT5b-MKL-1 interaction identifies a role of Treg-specific gene regulation and regulated mouse Treg cell development and function and suggests a possible mechanism for the protective effects of autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP). CONCLUSIONS: Our studies demonstrate for the first time that MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function. Video abstract.

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