Systemic Oxidative Stress Research Articles

Sheep (Ovis aries) Milk Exosomal miRNAs Attenuate Dextran Sulfate Sodium-Induced Colitis in Mice via TLR4 and TRAF-1 Inhibition.

Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Unravelling the interplay between Harmattan wind and baroreflex functions: implications on environmental health and cardiovascular pathophysiology

Harmattan is a season characterized by dust, cold, and sub-humid trade winds in Sub-Saharan countries. It’s similar to meteorological phenomena like Asian dust storms, Santa Ana winds, Australian bushfires, and Saharan dust in the Caribbean. It causes profound changes in the cardiorespiratory system in apparently healthy individuals and increases the risk of hospitalization in susceptible individuals. Exposure to these extreme conditions has been associated with alterations in autonomic function and baroreceptor sensitivity thus resulting in dysregulation of blood pressure control mechanisms. Baroreceptors are critical regulators of hemodynamics and cardiovascular function. They play a vital role in the short-term responses to blood pressure perturbation and are essential for acute restoration of blood pressure following cold exposure. Harmattan wind contains a barrage of chemicals, dust, and particulate matters depending on industrialization, natural and human activities. Particulate matter from Harmattan dust can trigger systemic inflammation and oxidative stress, exacerbating endothelial dysfunction and impairing vascular reactivity thus contributing to the pathogenesis of alterations in baroreceptor insensitivity, and cardiovascular diseases, including hypertension and atherosclerosis. Furthermore, fine particulate matter from dust may penetrate deep into the respiratory tract, activating pulmonary sensory receptors and eliciting reflex responses that influence autonomic tone. The presence of rich acrolein smokes and non-essential heavy metals such as cadmium, lead, and mercury in Harmattan wind also reduces baroreflex sensitivity, culminating in a sustained increase in diastolic and systolic blood pressure. This integrated review aims to provide valuable insights into how changes in each of these environmental constituents alter vital pathophysiologic and immunologic mechanisms of the body leading to baroreceptor instability and ultimately hemodynamic imbalance using available primary studies. Understanding this intricate interplay is crucial for implementing targeted interventions and informed public health strategies to mitigate the adverse effects of extreme environmental exposure and ultimately reduce poor health outcomes in the affected regions.

Childhood Cardiovascular Health, Obesity, and Some Related Disorders: Insights into Chronic Inflammation and Oxidative Stress.

Childhood obesity and associated metabolic abnormalities have become pressing public health concerns worldwide, significantly impacting cardiovascular health. Metabolic syndrome, characterized by a cluster of metabolic abnormalities including central obesity, altered glucose metabolism, dyslipidemia, and arterial hypertension, has emerged as a critical precursor to cardiovascular disease. Chronic systemic inflammation and oxidative stress seem to play pivotal roles in the pathogenesis of childhood obesity-related disorders such as early atherosclerosis. A significant distinction between the objective components of cardiovascular health metrics, including body mass index, blood pressure, cholesterol, and fasting glucose levels, and the definition of metabolic syndrome is evident in the identification of obesity. Whereas cardiovascular health metrics predominantly rely on body mass index percentiles to assess obesity, metabolic syndrome criteria prioritize waist circumference, specifically targeting individuals with a measurement ≥90th percentile. This discrepancy emphasizes the need for a nuanced approach in assessing the risks associated with obesity and underscores the importance of considering multiple factors when evaluating cardiovascular risk in children. By recognizing the complex interplay between various health metrics, obesity and metabolic syndrome criteria, clinicians can more accurately identify individuals at risk and tailor interventions accordingly to mitigate cardiovascular disease in children with obesity.

Effectiveness of remote ischaemic conditioning is not affected by hyper-inflammation in a rat model of stroke

The inflammation and coagulopathy during coronavirus disease (COVID-19) impairs the efficiency of the current stroke treatments. Remote ischaemic conditioning (RIC) has shown potential in recent years to protect the brain and other organs against pathological conditions. This study aimed to evaluate the efficiency of RIC in brain infarct size using TTC staining and lung injury reduction by H&E staining during the hyper-inflammatory response in rats. The inflammation and coagulopathy were assessed by sedimentation rate, haematocrit, systemic oxidative stress and clotting time. Moreover, we observed changes in the cytokine profile. The results of the first part of the experiment showed that the inflammation and lung injury are fully developed after 24 h of intratracheal LPS administration. At this time, we induced focal brain ischaemia and examined the effect of RIC pre- and post-treatment. Our results showed that RIPre-C reduced the infarct size by about 23%, while RIPost-C by about 30%. The lung injury was also reduced following both treatments. Moreover, RIC modulated systemic inflammation. The level of chemokines CINC-1, LIX and RANTES decreased after 24 h of post-ischaemic reperfusion in treated animals compared to non-treated. The RIC-mediated decrease of inflammation was reflected in improved sedimentation rate and hematocrit, as well as reduced systemic oxidative stress. The results of this work showed neuroprotective and lung protective effects of RIC with a decrease in inflammation response. On the basis of our results, we assume that immunomodulation through the chemokines CINC-1, LIX, and RANTES play a role in RIC-mediated protection.

The brain and systemic oxidative stress and memory changes induced by inhaled paraquat in rat improved by Crocus sativus

The present study aimed to investigate the effect of Crocus sativus (Cs) on paraquat (PQ)-induced learning and memory deficits as well as brain and lung oxidative stress and systemic inflammation, and oxidative stress in rats.Rats were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ groups were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day Cs-L and Cs-H, 5 mg/kg/day pioglitazone (Pio), and Cs-L+Pio for 16 days during PQ exposure period. Learning and memory abilities were assessed by Morris water maze (MWM) and passive avoidance tests.PQ group showed increased numbers of total and differential WBCs in blood, and increased malondialdehyde (MDA), in the serum, brain, and lung but reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the MWM test and the latency to enter the dark room were reduced after receiving an electrical shock (p < 0.05 to P<0.001). In all treated groups, measured values were improved compared to PQ group (p < 0.05 to p < 0.001). The combination of Cs-L+Pio showed more pronounced effects compared to either treatment alone (p < 0.05 to p < 0.001).These findings suggest that Cs has neuroprotective properties and may be beneficial in the treatment of neurodegenerative diseases induced by noxious agents such as PQ.

Association between the oxidative balance score and all-cause and cardiovascular mortality in patients with diabetes and prediabetes

BackgroundFew studies have examined the link between systemic oxidative stress and mortality risk in diabetes and prediabetes patients. The Oxidative Balance Score (OBS) is a novel measure of systemic oxidative stress, with higher scores indicating greater antioxidant exposure. This study investigates the relationship between OBS and all-cause and cardiovascular mortality in these patients. MethodsThis study analyzed 10,591 diabetes and prediabetes patients from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). The endpoints were all-cause and cardiovascular mortality, determined from the National Death Index (NDI). OBS was calculated using 20 dietary and lifestyle factors. Kaplan-Meier survival analysis, multivariable Cox regression models, restricted cubic splines (RCS), and subgroup analyses were used to assess the relationship between OBS and mortality risks. ResultsOver an average follow-up of 99.8 months, 2900 (26.4 %) participants died, including 765 (8.9 %) from cardiovascular diseases. Kaplan-Meier analysis showed the lowest all-cause and cardiovascular mortality in the highest OBS quartile (Q4) and the highest mortality in the lowest quartile (Q1) (p < 0.001). In the fully adjusted model, multivariable Cox regression revealed that each unit increase in OBS was linked to a 1.8 % decrease in all-cause mortality risk (HR 0.982, 95 % CI 0.976–0.987, p < 0.0001) and a 4 % decrease in cardiovascular mortality risk (HR 0.960, 95 % CI 0.949–0.970, p < 0.0001). Compared to Q1, those in Q4 had significantly lower all-cause mortality (HR 0.719, 95 % CI 0.643–0.804, p < 0.0001, p for trend <0.0001) and cardiovascular mortality (HR 0.567, 95 % CI 0.455–0.705, p < 0.0001, p for trend <0.0001). These findings were consistent across subgroups. RCS curves showed a negative correlation between OBS and both mortality types. ConclusionHigher OBS is linked to reduced all-cause and cardiovascular mortality in diabetes and prediabetes patients.

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

Associations of oxidative balance score with lumbar spine osteopenia in 20-40 years adults: NHANES 2011-2018.

Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.

Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals

BackgroundPost-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R–SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R–SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19. MethodsBaseline serum R–SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R–SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS. ResultsBaseline albumin-adjusted serum R–SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R–SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = −9.48, p = 0.023). ConclusionNon-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R–SH as a monitoring biomarker and a potential therapeutic target in the development of PCS.

Western diet-induced cognitive and metabolic dysfunctions in aged mice are prevented by rosmarinic acid in a sex-dependent fashion

Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain. Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis. RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways. Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements.

“The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study”

BackgroundPeriodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood.MethodsA quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed.ResultsIn this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT.ConclusionThe use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity.Trial Registrationhttps://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.Graphical

Hypersensitivity to man-made electromagnetic fields (EHS) correlates with immune responsivity to oxidative stress: a case report

ABSTRACT There is increasing evidence that exposure to weak electromagnetic fields (EMFs) generated by modern telecommunications or household appliances has physiological consequences, including reports of electromagnetic field hypersensitivity (EHS) leading to adverse health effects. Although symptoms can be serious, no underlying mechanism for EHS is known and there is no general cure or effective therapy. Here, we present the case study of a self-reported EHS patient whose symptoms include severe headaches, generalized fatigue, cardiac arrhythmia, attention and memory deficit, and generalized systemic pain within minutes of exposure to telecommunications (Wifi, cellular phones), high tension lines and electronic devices. Tests for cerebral, cardiovascular, and other physiological anomalies proved negative, as did serological tests for inflammation, allergies, infections, auto-immune conditions, and hormonal imbalance. However, further investigation revealed deficits in cellular anti-oxidants and increased radical scavenging enzymes, indicative of systemic oxidative stress. Significantly, there was a large increase in circulating antibodies for oxidized Low-Density Lipoprotein (LDLox), byproducts of oxidative stress accumulating in membranes of vascular cells. Because a known primary effect of EMF exposure is to increase the concentration of cellular oxidants, we propose that pathology in this patient may be causally related to a resulting increase in LDLox synthesis. This in turn could trigger an exaggerated auto-immune response consistent with EHS symptoms. This case report thereby provides a testable mechanistic framework for EHS pathology with therapeutic implications for this debilitating and poorly understood condition.

Impact of Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i) Therapy on Dementia and Cognitive Decline.

Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes is often associated with cognitive decline and shares similar pathophysiological mechanisms with dementia, such as systemic inflammation, oxidative stress, insulin resistance, and advanced glycation end-products formation. Therefore, adequate diabetes management may reduce the risk of cognitive decline, especially in patients with other comorbidities and risk factors. The sodium glucose cotransporter inhibitors (SGLT2i) regulate renal glucose reabsorption by blocking the SGLT2 cotransporters located in the proximal tubules, causing glycosuria and intraglomerular pressure reduction. Their use helps to lower blood pressure by modifying sodium and water homeostasis; these drugs are also commonly used in the treatment of heart failure and chronic kidney disease, while recently, a potential neuroprotective role in the central nervous system has been suggested. The aim of our scoping review is to analyze current evidence about the potential neuroprotective effects of SGLT2i in adult patients. We performed a scoping literature review to evaluate the effect of SGLT2i on dementia, mild cognitive impairment (MCI) and Alzheimer's disease incidence and progression. The screening process was performed through different searches on PubMed and EMBASE, evaluating original works published up to January 2024. In conclusion, the use of SGLT2i could be associated with a neuroprotective effect in patients with diabetes, reducing the incidence or the progression of MCI and dementia. Further prospective studies are needed to validate this hypothesis and to evaluate the effectiveness of this class of drugs in normal glycemic profile patients.

Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999–2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

The impact of subdermal adipose derived stem cell injections and early excision on systemic oxidative stress and wound healing in rats with severe scald burns

AimThis study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. MethodsFive rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. ResultsOn the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6–8.8]), control (6.7 [5.9–7.6]), and early excision (7.5 [6.6–8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5–16.9]) had the highest TOC levels. The PLM group (9.7 [8.6–10.7]) had lower TOC levels than the burn group but higher levels than the other groups.Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10–30]), early excision group (25 [15–50]), PLM group (70 [50–100]), control group (0), and burn group (80 [60–120]). Other oxidative stress and end-organ damage outcomes were consistent with these results.All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. ConclusionStem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.

Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction.

We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI). To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril. Male rats were assigned to either sham or MI operation. In the MI group, rats with an ejection Fraction less than 50% were included, and then they received one of the following treatments for 5 weeks: vehicle, enalapril, Mdivi-1, or M1. Cognitive function was tested, and the brains were used for molecular study. MI rats exhibited cardiac dysfunction with systemic oxidative stress. Cognitive impairment was found in MI rats, along with dendritic spine loss, blood-brain barrier (BBB) breakdown, brain mitochondrial dysfunction, and decreased mitochondrial and increased glycolysis metabolism, without the alteration of APP, BACE-1, Tau and p-Tau proteins. Treatment with Mdivi-1, M1, and enalapril equally improved cognitive function in MI rats. All treatments decreased dendritic spine loss, brain mitochondrial oxidative stress, and restored mitochondrial metabolism. Brain mitochondrial fusion was recovered only in the Mdivi-1-treated group. Mitochondrial dynamics modulators improved cognitive function in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction and the enhancement of mitochondrial metabolism. In addition, this mitochondrial fission inhibitor increased mitochondrial fusion in MI rats.

Impaired Cholesterol Efflux Capacity rather than Low HDL-C Reflects Oxidative Stress under Acute Myocardial Infarction.

Acute myocardial infarction (AMI) causes irreversible damage to cardiomyocytes due to the discontinuation of oxygen supply and leads to systemic oxidative stress. It has been reported that high-density lipoprotein (HDL) particles have antioxidant capacity, and reduced antioxidant capacity is associated with decreased cholesterol efflux capacity (CEC). The purpose of this study was to clarify the usefulness of CEC measurement in patients with AMI. We investigated the association between CEC and oxidative stress status in a case-control study. This study included 193 AMI cases and 445 age- and sex-matched controls. We examined the associations of CEC with HDL-cholesterol (HDL-C) and oxidized human serum albumin (HSA), an index of systemic oxidative stress status, and the effect of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which has been reported to affect HDL-C level and risk for MI, on these associations. Both bivariable and multivariable analyses showed that CEC was positively correlated with HDL-C levels in both AMI cases and controls, with a weaker correlation in AMI cases than in controls. In AMI cases, oxidized HSA levels were associated with CEC in both bivariable and multivariable analyses, but not with HDL-C. These associations did not differ among the ALDH2 genotypes. CEC, but not HDL-C level, reflects systemic oxidative stress status in patients with AMI. CEC measurement for patients with AMI may be useful in that it provides information on systemic oxidative stress status as well as atherosclerosis risk.

Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk

BackgroundCardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood. ObjectivesIn order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients. MethodsA case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls. ResultsPatients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate. ConclusionROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.

Melatonin and Metformin Mitigate Doxorubicin-Induced Alveolar Bone Toxicity

Evidence concerning the osteotoxic effects of chemotherapy (doxorubicin) has been previously described. Periodontitis also progressively increases in patients receiving chemotherapy; however, the beneficial effects of melatonin and metformin on the alleviation of doxorubicin-induced osteotoxicity have never been investigated. Therefore, we investigated the negative impact of doxorubicin on alveolar bone homeostasis and the benefits of melatonin and metformin on the attenuation of doxorubicin-induced alveolar bone toxicity. Male Wistar rats were divided into 4 groups to receive either 1 mL of normal saline solution as a control group, 3 mg/kg of doxorubicin, 3 mg/kg of doxorubicin plus 10 mg/kg of melatonin, or 3 mg/kg of doxorubicin plus 250 mg/kg of metformin. Doxorubicin treatment was given on days 0, 4, 8, 15, 22, and 29, while interventions were given daily on days 0 to 29. Following euthanasia, blood and alveolar bones were collected for evaluation of oxidative stress, bone remodeling, inflammation, microarchitecture, and periodontal condition. We found that doxorubicin increased systemic oxidative stress, decreased antioxidative capacity, increased inflammation, decreased bone formation, increased bone reabsorption, impaired microarchitecture, and impaired periodontal condition of the alveolar bone. Although cotreatment with melatonin or metformin resulted in some improvement in these parameters, cotreatment with melatonin was more effective than cotreatment with metformin in terms of decreasing oxidative stress, reducing bone resorption, and improving microarchitecture and periodontal condition. All of these findings highlight the potential for antioxidants, especially melatonin, to ameliorate doxorubicin-induced alveolar bone toxicity.