共查询到20条相似文献,搜索用时 15 毫秒
1.
Juho Pirhonen Johanna Arola Sanja S?devirta Panu Luukkonen Sanna-Maria Karppinen Taina Pihlajaniemi Antti Isom?ki Mika Hukkanen Hannele Yki-J?rvinen Elina Ikonen 《PloS one》2016,11(1)
Background and Aims
Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD.Methods
We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals.Results
We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III.Conclusions
This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. 相似文献2.
Karoline Kragelund Nielsen Peter Damm Anil Kapur Vijayam Balaji Madhuri S. Balaji Veerasamy Seshiah Ib C. Bygbjerg 《PloS one》2016,11(3)
Introduction
Hyperglycaemia in pregnancy (HIP), i.e. gestational diabetes mellitus (GDM) and diabetes in pregnancy (DIP), increases the risk of various short- and long-term adverse outcomes. However, much remains to be understood about the role of different risk factors in development of HIP.Objective
The aims of this observational study were to examine the role of potential risk factors for HIP, and to investigate whether any single or accumulated risk factor(s) could be used to predict HIP among women attending GDM screening at three centres in urban, semi-urban and rural Tamil Nadu, India.Methodology
Pregnant women underwent a 75 g oral glucose tolerance test. Data on potential risk factors was collected and analysed using logistical regression analysis. Receiver operating characteristic (ROC) curves, sensitivity, specificity and predictive values were calculated for significant risk factors and a risk factor scoring variable was constructed.Results
HIP was prevalent in 18.9% of the study population (16.3% GDM; 2.6% DIP). Increasing age and BMI as well as having a mother only or both parents with diabetes were significant independent risk factors for HIP. Among women attending the rural health centre a doubling of income corresponded to an 80% increased risk of HIP (OR 1.80, 95%CI 1.10–2.93; p = 0.019), whereas it was not significantly associated with HIP among women attending the other health centres. The performance of the individual risk factors and the constructed scoring variable differed substantially between the three health centres, but none of them were good enough to discriminate between those with and without HIP.Conclusions
The findings highlight the importance of socio-economic circumstances and intergenerational risk transmission in the occurrence of HIP as well as the need for universal screening. 相似文献3.
Chunyan Zhu Hongling Yang Qingshan Geng Qingling Ma Yan Long Cheng Zhou Ming Chen 《PloS one》2015,10(4)
Objective
The relationship between gestational diabetes mellitus (GDM) and oxidative stress has not been fully elucidated. This study examined the association between biomarkers of oxidative stress and GDM.Methods
We conducted a case-control study which included 36 women presenting with GDM and 36 asymptomatic matched control subjects who visited Guangzhou Women and Children’s Medical Centre, China, from June 2012 to December 2012. Pregnant women were prospectively recruited to the study, and blood samples were collected at the time of a routine oral glucose tolerance test. These samples were then analyzed for levels of endocrine and surrogate markers of oxidative stress.Results
Compared to control subjects, women with GDM exhibited elevated values for plasma glucose, insulin, and insulin resistance (IR), and showed reduced HOMA pancreatic β-cell function (HOMA-B), insulin sensitivity index (ISI), insulinogenic index, and corrected insulin response at 24–28 weeks gestation. A bivariate logistic regression analysis showed that levels of high-sensitivity C reactive protein (hs-CRP) and high fluorescence reticulocytes at fasting, and hs-CRP in a 1-h OGTT, were significantly associated with GDM. A linear regression analysis showed that levels of hs-CRP (P = 0.003) and reticulocytes (P = 0.029) at fasting were associated with IR, and levels of hs-CRP (P = 0.002) and monocytes (P = 0.006) in a 1-h OGTT were associated with ISI.Conclusions
Pregnant women with GDM developed a pathological IR and exhibited β-cell dysfunction. Their decreased ability to compensate for oxidative stress was associated with increased IR and a reduced ISI, which might be important factors in GDM. 相似文献4.
Yang Li Yong Liu XiangPing Peng Wei Liu FeiYan Zhao DanDan Feng JianZhong Han YanHong Huang SiWei Luo Lian Li Shao Jie Yue QingMei Cheng XiaoTing Huang ZiQiang Luo 《PloS one》2015,10(5)
Background
Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice.Methods
C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation.Results
BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils.Conclusions
Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice. 相似文献5.
6.
Yang Jiao Sai Ma Yirong Wang Jing Li Lequn Shan Qian Liu Ying Liu Qian Song Fan Yu Haohan Yu Huan Liu Li Huang Jihua Chen 《PloS one》2016,11(1)
Purpose
To investigate the involvement of intrinsic mitochondrial apoptosis in dental monomer-induced cytotoxicity and the influences of N-acetyl cysteine (NAC) on this process.Methods
Human dental pulp cells (hDPCs) were exposed to several dental monomers in the absence or presence of NAC, and cell viability, intracellular redox balance, morphology and function of mitochondria and key indicators of intrinsic mitochondrial apoptosis were evaluated using various commercial kits.Results
Dental monomers exerted dose-dependent cytotoxic effects on hDPCs. Concomitant to the over-production of reactive oxygen species (ROS) and depletion of glutathione (GSH), differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase were detected. Apoptosis, as indicated by positive Annexin V/propidium iodide (PI) staining and activation of caspase-3, was observed after dental monomer treatment. Dental monomers impaired the morphology and function of mitochondria, and induced intrinsic mitochondrial apoptosis in hDPCs via up-regulation of p53, Bax and cleaved caspase-3, and down-regulation of Bcl-2. NAC restored cell viability, relieved oxidative stress and blocked the apoptotic effects of dental monomers.Conclusions
Dental monomers induced oxidative stress and mitochondrial intrinsic apoptosis in hDPCs. NAC could reduce the oxidative stress and thus protect hDPCs against dental monomer-induced apoptosis. 相似文献7.
Charlotte Rosso Christine Pires Jean-Christophe Corvol Flore Baronnet Sophie Crozier Anne Leger Sandrine Deltour Romain Valabregue Mélika Amor-Sahli Stéphane Lehéricy Didier Dormont Yves Samson 《PloS one》2015,10(3)
Background
Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.Methods
We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.Findings
Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.Conclusion
These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.Trial Registration
ClinicalTrials.gov NCT00472381 相似文献8.
Elizabeth A. McKie Juliet L. Reid Prafull C. Mistry Stephen L. DeWall Lee Abberley Philip D. Ambery Blas Gil-Extremera 《PloS one》2016,11(3)
Objective
Evidence suggests that chronic subclinical inflammation plays an important role in the pathogenesis of type 2 diabetes (T2DM). Circulating levels of interleukin (IL)-18 appear to be associated with a number of micro- and macrovascular comorbidities of obesity and T2DM. This study was designed to investigate whether inhibition of IL-18 had any therapeutic benefit in the treatment of T2DM. Preliminary efficacy, safety and tolerability, pharmacokinetics, and pharmacodynamics of the anti-IL-18 monoclonal antibody, GSK1070806, were assessed.Research Design and Methods
This was a multicentre, randomized, single-blind (sponsor-unblinded), placebo-controlled, parallel-group, phase IIa trial. Obese patients of either sex, aged 18–70 years, with poorly controlled T2DM on metformin monotherapy were recruited. Patients received two doses, of placebo (n = 12), GSK1070806 0.25 mg/kg (n = 13) or GSK1070806 5 mg/kg (n = 12). The primary end-point was the change from baseline in fasting plasma glucose and weighted mean glucose area under the curve (AUC)(0–4 hours) postmixed meal test on Days 29, 57, and 85.Results
Thirty-seven patients were randomized to one of the three treatment arms. There were no statistically significant effects of GSK1070806 doses on fasting plasma glucose levels, or weighted mean glucose AUC(0–4 hours) compared with placebo.Conclusions
GSK1070806 was well tolerated, and inhibition of IL-18 did not lead to any improvements in glucose control. However, because of study limitations, smaller, potentially clinically meaningful effects of IL-18 inhibition cannot be excluded.Trial Registration
ClinicalTrials.gov NCT01648153相似文献9.
Aim
To investigate the effects of rhubarb enema treatment using a 5/6 nephrectomized rat model and study its mechanisms.Methods
Twenty-eight Sprague Dawley rats were divided into three groups: sham operation group (n = 8), 5/6 nephrectomized (5/6Nx) (n = 10), and 5/6Nx with rhubarb enema treatment (n = 10). The rhubarb enema was continuous for 1.0 month. Serum creatinine, serum indoxyl sulfate (IS) level, renal pathology, tubulointerstitial fibrosis, and renal oxidative stress were assessed.Results
5/6Nx rats showed increasing levels of serum creatinine and severe pathological lesions. Their serum creatinine levels obviously decreased after rhubarb enema treatment (P < 0.05 vs 5/6Nx group). The administration of rhubarb enema attenuated the histopathological changes in 5/6Nx rats. In addition, 5/6Nx rats showed an enhanced extent of tubulointerstitial fibrosis compared with sham rats, and administration of rhubarb enema to 5/6Nx rats ameliorated tubulointerstitial fibrosis. 5/6Nx rats showed increased serum levels of IS, renal oxidative stress, and NF-κB compared with sham rats, whereas administration of rhubarb enema to 5/6Nx rats decreased serum levels of IS, renal oxidative stress, and NF-κB levels.Conclusion
Rhubarb enema treatment ameliorates tubulointerstitial fibrosis in the kidneys of 5/6Nx rats, most likely by alleviating IS overload and reducing kidney oxidative stress and inflammatory injury. 相似文献10.
Objective
The aim of this longitudinal study was to evaluate the association between occupational stress and metabolic syndrome (MetS) in a rapid response police unit.Method
Work-related stress was continuously monitored during the 5-year period with both the Demand-Control-Support (DCS) and the Effort-Reward Imbalance (ERI) models. Blood pressure, body mass index (BMI), waist circumference, triglycerides, HDL-cholesterol, and fasting blood glucose were measured at baseline in January 2009, and in January 2014. 234 out of 290 police officers (81%) completed the follow-up.Results
The majority of police officers had high stress levels. At follow-up, police officers in the highest quartile of stress had significantly higher mean levels of triglycerides, and lower levels of HDL-cholesterol than their colleagues in the lowest quartile. Police officers with high stress had an increased adjusted risk of developing MetS (aOR = 2.68; CI95% = 1.08–6.70), and hypertriglyceridemia (aOR = 7.86; CI95 = 1.29–48.04). Demand and Effort were significant predictors of MetS.Conclusion
Our study supports the hypothesis that work-related stress induces MetS, particularly through its effects on blood lipids. Future longitudinal studies with continuous monitoring of stress levels will definitively confirm this hypothesis. 相似文献11.
Objective
Stimulation with saturated fatty acids has been shown to induce oxidative stress and endoplasmic reticulum (ER) stress in β cells and has been recognized as an important component of the pathogenesis of type 2 diabetes (T2D). Interleukin-22 (IL-22) plays a critical role in preventing β cells from oxidative and ER stress, and autophagy is associated with the survival and function of β cells. However, whether IL-22 alleviates cellular stress through activation of autophagy is unclear. In this study, we investigated the effects of IL-22 on rat insulin-secreting cells and the mechanisms underlying IL-22 and lipotoxicity-induced oxidative and ER stress in vitro.Methods
The levels of reactive oxygen species (ROS) were detected by flow cytometry and fluorescence microscopy. The protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), microtubule-associated protein light chain 3B (LC3B) and Bcl-2-interacting myosin-like coiled-coil protein (Beclin-1) were evaluated by western blot. Transmission electron microscopy was utilized to observe the process of autophagy.Results
Palmitate induced increased levels of ROS and the overexpression of GRP78 and CHOP, whereas these effects were partly reversed by treatment with IL-22. Furthermore, IL-22 upregulated the protein expression of Beclin-1 and the conversion of LC3B-I to LC3B-II. Moreover, the aforementioned effects were partly suppressed by treating cells with 3-methyladenine (3-MA), an autophagy inhibitor.Conclusions
Our results suggest that IL-22 alleviated the oxidative and ER stress induced by palmitate, which was likely mediated by autophagy. These findings could facilitate the development of novel therapeutic strategies to suppress the progression of T2D. 相似文献12.
Gina Cavaliere Giovanna Trinchese Paolo Bergamo Chiara De Filippo Giuseppina Mattace Raso Giorgio Gifuni Rosalba Putti Bottu Heleena Moni Roberto Berni Canani Rosaria Meli Maria Pina Mollica 《PloS one》2016,11(2)
Objectives
Omega (ω)-3 polyunsaturated fatty acids (PUFA) are dietary compounds able to attenuate insulin resistance. Anyway, the precise actions of ω-3PUFAs in skeletal muscle are overlooked. We hypothesized that PUFAs, modulating mitochondrial function and efficiency, would ameliorate pro-inflammatory and pro-oxidant signs of nutritionally induced obesity.Study Design
To this aim, rats were fed a control diet (CD) or isocaloric high fat diets containing either ω-3 PUFA (FD) or lard (LD) for 6 weeks.Results
FD rats showed lower weight, lipid gain and energy efficiency compared to LD-fed animals, showing higher energy expenditure and O2 consumption/CO2 production. Serum lipid profile and pro-inflammatory parameters in FD-fed animals were reduced compared to LD. Accordingly, FD rats exhibited a higher glucose tolerance revealed by an improved glucose and insulin tolerance tests compared to LD, accompanied by a restoration of insulin signalling in skeletal muscle. PUFAs increased lipid oxidation and reduced energy efficiency in subsarcolemmal mitochondria, and increase AMPK activation, reducing both endoplasmic reticulum and oxidative stress. Increased mitochondrial respiration was related to an increased mitochondriogenesis in FD skeletal muscle, as shown by the increase in PGC1-α and -β.Conclusions
our data strengthened the association of high dietary ω3-PUFA intake with reduced mitochondrial energy efficiency in the skeletal muscle. 相似文献13.
Ji-Hua Ren Xiang Chen Li Zhou Na-Na Tao Hong-Zhong Zhou Bo Liu Wan-Yu Li Ai-Long Huang Juan Chen 《PloS one》2016,11(3)
Background/Aim
The hepatitis B virus (HBV) infection is accompanied by the induction of oxidative stress, especially mediated by HBV X protein (HBx). Oxidative stress has been implicated in a series of pathological states, such as DNA damage, cell survival and apoptosis. However, the host factor by which cells protect themselves under this oxidative stress is poorly understood.Methodology/Principal Findings
In this study, we first confirmed that HBV infection significantly induced oxidative stress. Moreover, viral protein HBx plays a major role in the oxidative stress induced by HBV. Importantly, we found that mitochondrial protein SIRT3 overexpression could decrease reactive oxygen species (ROS) induced by HBx while SIRT3 knockdown increased HBx-induced ROS. Importantly, SIRT3 overexpression abolished oxidative damage of HBx-expressing cells as evidenced by γH2AX and AP sites measurements. In contrast, SIRT3 knockdown promoted HBx-induced oxidative damage. In addition, we also observed that oxidant H2O2 markedly promoted HBV replication while the antioxidant N-acetyl-L-cysteine (NAC) inhibited HBV replication. Significantly, SIRT3 overexpression inhibited HBV replication by reducing cellular ROS level.Conclusions/Significance
Collectively, these data suggest HBx expression induces oxidative stress, which promotes cellular oxidative damage and viral replication during HBV pathogenesis. Mitochondrial protein SIRT3 protected HBx expressing-cells from oxidative damage and inhibited HBV replication possibly by decreased cellular ROS level. These studies shed new light on the physiological significance of SIRT3 on HBx-induced oxidative stress, which can contribute to the liver pathogenesis. 相似文献14.
Wan Nor Hanis Wan Ahmad Farah Sakri Atiqah Mokhsin Thuhairah Rahman Nadzimah Mohd Nasir Suraya Abdul-Razak Mazapuspavina Md Yasin Aletza Mohd Ismail Zaliha Ismail Hapizah Nawawi 《PloS one》2015,10(1)
Background
Inflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established.Objectives
(1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.Methods
422 subjects (mean age±SD = 43.2±11.9years) of whom 207 had low HDL-c concentrations (HDL-c <1.0mmol/L and <1.3mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].Results
Subjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.Conclusion
Low serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications. 相似文献15.
Rakesh K. Bijarnia Matthias Bachtler Prakash G. Chandak Harry van Goor Andreas Pasch 《PloS one》2015,10(4)
Background
Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na2S2O3) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known.Methods
Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na2SO4 were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells.Results
Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments.Conclusions
STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered. 相似文献16.
Background
The chemokine receptor CXCR4 is a multifunctional receptor which is activated by its natural ligand C-X-C motif chemokine 12 (CXCL12). As CXCR4 is part of the lipopolysaccharide sensing complex and CXCL12 analogs are not well characterized in inflammation, we aimed to uncover the systemic effects of a CXCL12 analog in severe systemic inflammation and to evaluate its impact on endotoxin induced organ damages by using a sublethal LPS dose.Methods
The plasma stable CXCL12 analog CTCE-0214D was synthesized and administered subcutaneously shortly before LPS treatment. After 24 hours, mice were sacrificed and blood was obtained for TNF alpha, IFN gamma and blood glucose evaluation. Oxidative stress in the liver and spleen was assessed and liver biotransformation capacity was determined. Finally, CXCR4, CXCL12 and TLR4 expression patterns in liver, spleen and thymus tissue as well as the presence of different markers for apoptosis and oxidative stress were determined by means of immunohistochemistry.Results
CTCE-0214D distinctly reduced the LPS mediated effects on TNF alpha, IFN gamma, ALAT and blood glucose levels. It attenuated oxidative stress in the liver and spleen tissue and enhanced liver biotransformation capacity unambiguously. Furthermore, in all three organs investigated, CTCE-0214D diminished the LPS induced expression of CXCR4, CXCL12, TLR4, NF-κB, cleaved caspase-3 and gp91 phox, whereas heme oxygenase 1 expression and activity was induced above average. Additionally, TUNEL staining revealed anti-apoptotic effects of CTCE-0214D.Conclusions
In summary, CTCE-0214D displayed anti-inflammatory, anti-oxidative and cytoprotective features. It attenuated reactive oxygen species, induced heme oxygenase 1 activity and mitigated apoptosis. Thus, the CXCR4/CXCL12 axis seems to be a promising target in the treatment of acute systemic inflammation, especially when accompanied by a hepatic dysfunction and an excessive production of free radicals. 相似文献17.
Ramu Adela Susheel Kumar Nethi Pankaj K. Bagul Ayan K. Barui Saidulu Mattapally Madhusudan Kuncha Chitta R. Patra P. Naveen Chander Reddy Sanjay K. Banerjee 《PloS one》2015,10(4)
Background
We have previously reported that increased glucose levels were associated with higher serum nitric oxide (NO) levels in fructose-fed insulin resistant rats. However, the relationship between hyperglycemia and serum NO level was not clear. Therefore, the present study was designed to find the association between hyperglycemia and serum NO levels in Type 2 diabetic (T2DM) patients and T2DM with cardiovascular complication.Methods
Endothelial cells (HUVEC) were treated with of D-glucose (10-100mM), and NO levels and NOS gene expression was measured. Hyperglycaemia was induced in Sprague-Dawley rats, and serum NO levels were measured after 8 weeks. For clinical evaluation, five groups of patients were recruited: Control (CT, n=48), Type 2 diabetes (T2DM, n=26), T2DM with hypertension (DMHT, n=46), Coronary artery diseases (CAD, n=29) and T2DM with coronary artery diseases (DMCD, n=38). NO (nitrite + nitrate) levels were measured from human serum.Results
We found a significant (p<0.05) and dose-dependent increase in NO levels in HUVEC cells after 4 hours of high glucose exposure. eNOS and iNOS gene expression was increased in HUVEC cells after different concentrations and time periods of glucose treatment. We also observed significant (149.1±25μM, p<0.01) increase in serum NO levels in hyperglycaemic rats compared to control (76.6±13.2μM). Serum NO level was significantly higher in T2DM (111.8 μM (81.7-122.4), p<0.001) and DMCD patients ((129.4 μM (121.2-143.5), p <0.001) but not in CAD patients (76.4 μM (70.5-87)), as compared to control (68.2 μM (56.4-82.3)). We found significantly lower NO levels (83.5 μM (60.5-122.9)) in subjects suffering from diabetes since more than 5 years, compared to subjects (115.3 μM (75.2-127.1), p<0.001) with less than 5 years.Conclusion
In conclusion, high NO levels were observed in South Indian diabetic patients. Higher glucose levels in serum might be responsible for activation of endothelial cells to enhance NO levels. 相似文献18.
Mario Siervo Heather L. Riley Bernadette O. Fernandez Carl A. Leckstrom Daniel S. Martin Kay Mitchell Denny Z. H. Levett Hugh E. Montgomery Monty G. Mythen Michael P. W. Grocott Martin Feelisch for the Caudwell Xtreme Everest Research Group 《PloS one》2014,9(4)
Objectives
The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses.Methods
After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC;5,300 m) over 13 days. Of these, 14 ascended higher, with 8 reaching the summit (8,848 m). Assessments were conducted at baseline, during ascent to EBC, and 1, 6 and 8 week(s) thereafter. Changes in body weight and indices of gluco-insular control were measured (glucose, insulin, C-Peptide, homeostasis model assessment of insulin resistance [HOMA-IR]) along with biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE), inflammation (Interleukin-6 [IL-6]) and counter-regulatory hormones (glucagon, adrenalin, noradrenalin). In addition, peripheral oxygen saturation (SpO2) and venous blood lactate concentrations were determined.Results
SpO2 fell significantly from 98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained stable, insulin and C-Peptide concentrations increased by >200% during the last 2 weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with increases in markers of oxidative stress (4-HNE) and inflammation (IL-6). Lactate levels progressively increased during ascent and remained significantly elevated until week 8. Subjects lost on average 7.3 kg in body weight.Conclusions
Sustained hypoxemia is associated with insulin resistance, whose magnitude correlates with the degree of oxidative stress and inflammation. The role of 4-HNE and IL-6 as key players in modifying the association between sustained hypoxia and insulin resistance merits further investigation. 相似文献19.
Objective
To measure the elongation and compliance of endothelial cells subjected to different patterns of shear stress in vitro, and to compare these parameters with the elongation and compliance of endothelial cells from different regions of the intact aorta.Materials and Methods
Porcine aortic endothelial cells were cultured for 6 days under static conditions or on an orbital shaker. The shaker generated a wave of medium, inducing pulsatile shear stress with a preferred orientation at the edge of the well or steadier shear stress with changing orientation at its centre. The topography and compliance of these cells and cells from the inner and outer curvature of ex vivo porcine aortic arches were measured by scanning ion conductance microscopy (SICM).Results
Cells cultured under oriented shear stress were more elongated and less compliant than cells grown under static conditions or under shear stress with no preferred orientation. Cells from the outer curvature of the aorta were more elongated and less compliant than cells from the inner curvature.Conclusion
The elongation and compliance of cultured endothelial cells vary according to the pattern of applied shear stress, and are inversely correlated. A similar inverse correlation occurs in the aortic arch, with variation between regions thought to experience different haemodynamic stresses. 相似文献20.
Mariana Romero Carolina Caniffi Gonzalo Bouchet María A. Costa Rosana Elesgaray Cristina Arranz Analía L. Tomat 《PloS one》2015,10(3)