Background
To evaluate the relationship between leukocyte‐endothelial cell interactions and oxidative stress parameters in non‐diabetic patients with different grades of obesity.
Material and methods
...For this cross‐sectional study, 225 subjects were recruited from January 1, 2014 to December 31, 2016 and divided into groups according to BMI (<30 kg/m2, 30‐40 kg/m2 and >40 kg/m²). We determined clinical parameters, systemic inflammatory markers, soluble cellular adhesion molecules, leukocyte‐endothelium cell interactions—rolling flux, velocity and adhesion—, oxidative stress parameters—total ROS, total superoxide, glutathione—and mitochondrial membrane potential in leukocytes.
Results
We verified that HOMA‐IR and hsCRP increased progressively as obesity developed, whereas A1c, IL6 and TNFα were augmented in the BMI > 40 kg/m² group. The cellular adhesion molecule sP‐selectin was increased in patients with obesity, while sICAM, total ROS, total superoxide and mitochondrial membrane potential were selectively higher in the BMI > 40 kg/m² group. Obesity induced a progressive decrease in rolling velocity and an enhancement of rolling flux and leukocyte adhesion.
Conclusion
Our findings reveal that endothelial dysfunction markers are altered in human obesity and are associated with proinflammatory cytokines and increased oxidative stress parameters.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
The effect of dietary weight loss intervention on periodontal therapy is unknown. Therefore, we aimed to evaluate whether weight loss improves the response of obese subjects to non‐surgical ...periodontal treatment.
Materials and methods
This interventional study in obese patients was conducted at the University Hospital Dr. Peset (Valencia, Spain). Patients were divided into two groups with and without dietary therapy. All participants received non‐surgical periodontal treatment. Periodontal, anthropometric and biochemical parameters were assessed at baseline and 12 weeks.
Results
A total of 78 patients were re‐evaluated after intervention. All periodontal parameters improved in both groups after periodontal treatment, but the reductions in mean probing depth (PD) (0.23 mm vs. 0.12 mm) and in percentage of sites with PD 4–5 mm (10.4% vs. 5.89%) were significantly higher in the dietary group. Additionally, complement component 3 (C3) and tumour necrosis factor alpha (TNFα) decreased in the dietary group after intervention. Percentage of change in mean PD correlated with change in C3 (r = 0.233, p = 0.043), and percentage of change in sites with PD 4–5 mm correlated with change in TNFα (r = 0.414, p = 0.012).
Conclusions
This study suggests that dietary weight loss intervention causes a greater reduction in systemic inflammation, which may enhance the response to periodontal treatment.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
To evaluate the relationship between oxidative stress parameters in polymorphonuclear leucocytes (PMNs) and PMN–endothelial cell interactions in patients with chronic periodontitis (CP) according ...to different degrees of severity of the disease.
Materials and methods
For this cross‐sectional study, 182 subjects were divided into four groups according to degree of CP: without CP (n = 37), mild CP (n = 59), moderate CP (n = 51), and severe CP (n = 35). We determined anthropometric and biochemical variables, periodontal parameters, inflammatory markers, oxidative stress parameters (superoxide and mitochondrial membrane potential), and PMN–endothelium cell interactions (rolling flux, velocity, and adhesion).
Results
Systemic inflammatory markers—C‐reactive protein, leucocyte count, TNFα, and retinol‐binding protein 4—were altered in the group with CP. Total superoxide was augmented in patients with moderate and severe periodontitis, whereas mitochondrial membrane potential did not change. Furthermore, PMNs adhesion and rolling flux were increased in subjects with CP.
Conclusion
In a systemic proinflammatory environment, PMNs from patients with CP exhibit hyperactivity and produce higher amounts of superoxide. In parallel with this, an increase in PMNs rolling flux and cell adhesion to the endothelium suggests the presence of alterations of PMN–endothelium interactions in patients with CP that can lead to atherosclerosis and cardiovascular complications.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The relationship between caloric restriction-mediated weight loss and the generation of ROS and its effects on atherosclerotic markers in obesity is not fully understood. Therefore, we set out to ...investigate whether dietary weight loss intervention improves markers of oxidative stress in leukocytes and subclinical parameters of atherosclerosis.
This was an interventional study of 59 obese subjects (BMI > 35 kg/m
) who underwent 6 months of dietary therapy, including a 6-week very-low-calorie diet (VLCD) followed by an 18-week low-calorie diet (LCD). We determined clinical parameters, inflammatory markers-hsCRP, TNFα and NFκB -, oxidative stress parameters-total superoxide, glutathione, catalase activity and protein carbonyl groups-, soluble cellular adhesion molecules-sICAM, sP-selectin, sPSGL-1 -, myeloperoxidase (MPO), leukocyte-endothelium cell interactions-rolling flux, velocity and adhesion-and LDL subfractions, before and after the dietary intervention.
After losing weight, an improvement was observed in the patients' anthropometric, blood pressure and metabolic parameters, and was associated with reduced inflammatory response (hsCRP, TNFα and NFκB). Oxidative stress parameters improved, since superoxide production and protein carbonyl content were reduced and antioxidant systems were enhanced. In addition, a significant reduction of subclinical markers of atherosclerosis-small and dense LDL particles, MPO, sP-selectin and leukocyte adhesion-and an increase in soluble PSGL-1 were reported.
Our findings reveal that the improvement of subclinical atherosclerotic markers after dietary weight loss intervention is associated with a reduction of oxidative stress in leukocytes and inflammatory pathways, suggesting that these are the underlying mechanisms responsible for the reduced risk of cardiovascular disease in obese subjects after losing weight.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
We aimed to evaluate serum RBP4 levels before and after periodontal therapy in lean and obese subjects with chronic periodontitis (CP) in order to determine its possible association with ...periodontitis.
Materials and Methods
This is an interventional study for which a total of 112 lean and 119 obese subjects were recruited. Patients with CP were evaluated before and after three months of non‐surgical periodontal treatment. Periodontal, anthropometric, biochemical parameters and serum levels of TNF‐α, IL‐6, hs‐CRP and RBP4 were assessed.
Results
Serum RBP4 levels were associated with an increased probability of periodontitis (OR = 1.60; 95% CI: 1.02‐2.50), showing patients with CP to have higher RBP4 levels than those without CP in both lean and obese populations (3.35 vs 3.06 and 3.74 vs 3.21, respectively). Following periodontal treatment, RBP4 and TNF‐α decreased, and all periodontal parameters improved to the same extent in both groups, except for number of teeth with probing depth (PD) ≥4 mm, which improved to a less extent in obese than in lean subjects. In the multivariable regression model, the number of teeth with PD ≥4 mm was independently associated with RBP4 (β = 0.192).
Conclusion
RBP4 was associated with chronic periodontitis before and after non‐surgical periodontal treatment.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Type 2 diabetes is a chronic metabolic disease that affects mitochondrial function. In this context, the rescue mechanisms of mitochondrial health, such as mitophagy and mitochondrial biogenesis, are ...of crucial importance. The gold standard for the treatment of type 2 diabetes is metformin, which has a beneficial impact on the mitochondrial metabolism. In this study, we set out to describe the effect of metformin treatment on mitochondrial function and mitophagy in peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients. We performed a preliminary cross-sectional observational study complying with CONSORT requirements, for which we recruited 242 subjects, divided into 101 healthy volunteers, 93 metformin-treated type 2 diabetic patients and 48 non-metformin-treated type 2 diabetic patients. Mitochondria from the type 2 diabetic patients not treated with metformin displayed more reactive oxygen species (ROS) than those from healthy or metformin-treated subjects. Protein expression of the electron transport chain (ETC) complexes was lower in PBMCs from type 2 diabetic patients without metformin treatment than in those from the other two groups. Mitophagy was altered in type 2 diabetic patients, evident in a decrease in the protein levels of PINK1 and Parkin in parallel to that of the mitochondrial biogenesis protein PGC1α, both of which effects were reversed by metformin. Analysis of AMPK phosphorylation revealed that its activation was decreased in the PBMCs of type 2 diabetic patients, an effect which was reversed, once again, by metformin. In addition, there was an increase in the serum levels of TNFα and IL-6 in type 2 diabetic patients and this was reversed with metformin treatment. These results demonstrate that metformin improves mitochondrial function, restores the levels of ETC complexes, and enhances AMPK activation and mitophagy, suggesting beneficial clinical implications in the treatment of type 2 diabetes.
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•Metformin promoted electron transport chain expression on type 2 diabetic patients.•Metformin restored mitophagy levels via PINK1 and PARKIN on type 2 diabetic patients.•Mitochondrial biogenesis was enhanced by metformin on type 2 diabetic patients.•Metformin restored AMPK activation on type 2 diabetic patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the ...main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.
Mitochondrial dynamics, such as fusion and fission, play a critical role in maintaining cellular metabolic homeostasis. The molecular mechanisms underlying these processes include fusion proteins ...(Mitofusin 1 MFN1, Mitofusin 2 MFN2, and optic atrophy 1 OPA1) and fission mediators (mitochondrial fission 1 FIS1 and dynamin-related protein 1 DRP1), which interact with each other to ensure mitochondrial quality control. Interestingly, defects in these proteins can lead to the loss of mitochondrial DNA (mtDNA) integrity, impairment of mitochondrial function, a severe alteration of mitochondrial morphology, and eventually cell death. Emerging evidence has revealed a causal relationship between dysregulation of mitochondria dynamics and age-associated type 2 diabetes, a metabolic disease whose rates have reached an alarming epidemic-like level with the majority of cases (59%) recorded in men aged 65 and over. In this sense, fragmentation of mitochondrial networks is often associated with defects in cellular energy production and increased apoptosis, leading, in turn, to excessive reactive oxygen species release, mitochondrial dysfunction, and metabolic alterations, which can ultimately contribute to β-cell dysfunction and insulin resistance. The present review discusses the processes of mitochondrial fusion and fission and their dysfunction in type 2 diabetes, with special attention given to the therapeutic potential of targeting mitochondrial dynamics in this complex metabolic disorder.
The aim of this study was to evaluate markers of inflammation, oxidative stress and endothelial function in a disease-related malnutrition (DRM) outpatient population.
For this cross-sectional study, ...a total of 83 subjects were included and clustered in 3 groups: 34 with normonutrition (NN), 21 with DRM without inflammation (DRM-I) and 28 with DRM and inflammation (DRM + I). Nutritional diagnosis was conducted for all subjects according to ASPEN. Biochemical parameters, proinflammatory cytokines, reactive oxygen species production, glutathione, mitochondrial membrane potential, oxygen consumption, adhesion molecules and leukocyte-endothelium interactions were evaluated.
DRM + I patients showed lower albumin, prealbumin, transferrin, and retinol-binding protein levels with respect to the NN group (p < 0.05), differences that were less noticeable in the DRM-I group. DRM + I was associated with a significant increase in hsCRP and IL6 vs the NN and DRM-I groups, and TNFα was increased in both DRM vs NN. DRM was characterised by increased oxidative stress, which was marked by a significant increase in ROS levels and a decrease in mitochondrial membrane potential in the DRM + I group. An evident reduction in mitochondrial oxygen consumption and glutathione concentration was observed in both DRM groups, and was accompanied by increased leukocyte adhesion and adhesion molecules and decreased rolling velocity in the DRM + I group. Furthermore, percentage of weight loss was negatively correlated with albumin, prealbumin, transferrin, O
consumption, glutathione and leukocyte rolling velocity, and positively correlated with hsCRP, IL6, TNFα, ROS, leukocyte adhesion, and VCAM-1.
Our results show that DRM is associated with oxidative stress and an inflammatory state, with a deterioration of endothelial dysfunction in the DRM + I population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Type 2 diabetes is closely related to oxidative stress and cardiovascular diseases. In this study, we hypothesized that polymorphonuclear leukocytes (PMN)-endothelium interactions and autophagy are ...associated. We evaluated PMN-endothelial interactions, ROS production and autophagy parameters in 47 type 2 diabetic patients and 57 control subjects. PMNs from type 2 diabetic patients exhibited slower rolling velocity (p < 0.001), higher rolling flux (p < 0.001) and adhesion (p < 0.001) in parallel to higher levels of total (p < 0.05) and mitochondrial ROS (p < 0.05). When the protein expression of autophagy markers was analysed, an increase of Beclin-1 (p < 0.05), LC3I (p < 0.05), LC3II (p < 0.01) and LC3II/LC3I ratio (p < 0.05) was observed. Several correlations between ROS and leukocyte-endothelium parameters were found. Interestingly, in control subjects, an increase of Beclin-1 levels was accompanied by a decrease in the number of rolling (r = 0.561) and adhering PMNs (r = 0.560) and a rise in the velocity of the rolling PMNs (r = 0.593). In contrast, in the type 2 diabetic population, a rise in Beclin-1 levels was related to an increase in the number of rolling (r = 0.437), and adhering PMNs (r = 0.467).
These results support the hypothesis that PMN-endothelium interactions, ROS levels and formation of autophagosomes, especially Beclin-1 levels, are enhanced in type 2 diabetes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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