Oxidative stress biomarkers in pregnancy: a systematic review.

BACKGROUND: This systematic review explores the level of oxidative stress (OS) markers during pregnancy and their correlation with complications. Unlike previous studies, it refrains from directly investigating the role of OS but instead synthesises data on the levels of these markers and their implications for various pregnancy-related complications such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. METHOD: STUDY DESIGN: Utilizing a systematic review approach, we conducted a comprehensive search across databases, including MEDLINE, CINAHL (EBSCOhost), ScienceDirect, Web of Science, and SCOPUS. Our search encompassed all publication years in English. RESULTS: After evaluating 54,173 records, 45 studies with a low risk of bias were selected for inclusion. This systematic review has underscored the importance of these markers in both physiological and pathological pregnancy states such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. CONCLUSION: This systematic review provides valuable insights into the role of OS in pregnancy and their connection to complications. These selected studies delved deeply into OS markers during pregnancy and their implications for associated complications. The comprehensive findings highlighted the significance of OS markers in both normal and pathological pregnancy conditions, paving the way for further research in this field.

[Mechanisms of aging and age-related homeodynamics of bio-elementome.]

This article presents a data science review and our own evaluation on bio-element mediated aging of the human body from the point of view of homeodynamics of bioelementome. The study of bio-element basis of aging is currently one of the actively developing fields in gerontology. During postnatal ontogenesis, the bio-elementome shows no signs of stability. Being extremely dependent on endogenous and exogenous circumstances, the levels of macro- and microelements can either remain within the normal range or undergo significant changes, especially with the body aging. These bio-element developments appear to be very important in terms of a large number of currently known molecular, subcellular, cellular, and tissue mechanisms of aging (oxidative stress, loss of proteostasis, excessive telomere attrition, epigenetic landscape alterations, apoptosis, altered intercellular communication, and many others). Better understanding of metabolic pathways of essential bio-elements (intake in the gastrointestinal tract; absorption, including due to interaction with specific transporting proteins; spread through the circulatory system and the entire body; inclusion in specialized macromolecules and participation in their composition in biochemical processes; excretion from the body), as well as realizing their role in the mechanisms of senile tissue and organ involution, and features of age-related homeodynamics can significantly improve existing knowledge on the biology of aging.

Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank.

BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

LncRNA ILF3-AS1 mediates oxidative stress and inflammation through miR-504-3p/HMGB1 axis in a cellular model of temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE), a prevalent neurological disorder, is associated with hippocampal oxidative stress and inflammation. A recent study reveals that the long noncoding RNA ILF3 divergent transcript (ILF3-AS1) level is elevated in the hippocampus of TLE patients; however, the functional roles of ILF3-AS1 in TLE and underlying mechanisms deserve further investigation. Hence, this study aimed to elucidate whether ILF3-AS1 is involved in the pathogenesis of TLE by regulating oxidative stress and inflammation and to explore its underlying mechanism in vitro. METHODS: Human hippocampal neurons were subjected to a magnesium-free (Mg2+-free) solution to establish an in vitro model of TLE. The potential binding sites between ILF3-AS1 and miRNA were predicted by TargetScan/Starbase and confirmed by dual luciferase reporter assay. Cell viability and damage were assessed by cell counting kit-8 and lactate dehydrogenase assay kits, respectively. Levels of reactive oxygen species, malondialdehyde, and superoxide dismutase were determined by commercial kits. Levels of Interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-alpha were quantified by enzyme-linked immunosorbent assay. The expressions of gene and protein were determined by quantitative real-time polymerase chain reaction and Western blot analysis. RESULTS: In Mg2+-free-treated hippocampal neurons, both ILF3-AS1 and HMGB1 were highly up-regulated, whereas miR-504-3p was down-regulated. ILF3-AS1 knockdown ameliorated Mg2+-free-induced cellular damage, oxidative stress, and inflammatory response. Bioinformatics analysis revealed that miR-504-3p was a target of ILF3-AS1 and was negatively regulated by ILF3-AS1. MiR-504-3p inhibitor blocked the protection of ILF3-AS1 knockdown against Mg2+-free-induced neuronal injury. Further analysis presented that ILF3-AS1 regulated HMGB1 expression by sponging miR-504-3p. Moreover, HMGB1 overexpression reversed the protective functions of ILF3-AS1 knockdown. CONCLUSION: Our findings indicate that ILF3-AS1 contributes to Mg2+-free-induced hippocampal neuron injuries, oxidative stress, and inflammation by targeting the miR-504-3p/HMGB1 axis. These results provide a novel mechanistic understanding of ILF3-AS1 in TLE and suggest potential therapeutic targets for the treatment of epilepsy.

Bipolar disorder and oxidative stress: A bibliometric perspective.

OBJECTIVE: Accumulating evidence indicates that oxidative stress and the disruption of antioxidant defenses play an important role in the neurobiology of bipolar disorder (BD). Studies have found that increased oxidative stress may be associated with cell apoptosis and neuronal damage in BD patients. Hence, this study explored the research field related to BD and oxidative stress from a bibliometrics perspective. METHODS: Literature search and relevant data retrieval based on the Web of Sciences Core Collection (WoSCC). R software (version 4.2.2), VOSviewer software (version 1.6.18), and CiteSpace (version 6.1.6) were used in this bibliometric analysis. RESULTS: A total of 2081 publications related to BD and oxidative stress were published between 1986 and 2024. Bipolar Disorders was the journal that had the most publications in this area (72; 3.46%; IF = 5.9), while the United States (1285; 61.7%) and the University of Toronto (377; 18.1%) were the most productive country and institution, respectively. Apart from "oxidative stress" and "bipolar disorder," the most frequently used keywords were "schizophrenia," "prefrontal cortex," and "nitric oxide." CONCLUSIONS: The growing number of publications related to BD and oxidative stress in recent years highlights the importance of this research field. Hot topics in research related to BD and oxidative stress included animal experiments and molecular mechanisms, psychiatric-related inflammation and biomarkers, neurodegenerative diseases, and metabolism. Furthermore, the biological mechanisms of BD, particularly biomarkers and inflammation, may be the emerging research priority area in the future.

Associations of oxidative stress markers with the prevalence of sarcopenia in the United States general population.

OBJECTIVE: The purpose of the present study was to examine the association of oxidative stress markers with sarcopenia in the general United States population under the age of 60. METHODS: We used the National Health and Nutrition Examination Survey data from 2011‒2014 and performed Restricted Cubic Spline (RCS) plots, weighted multivariable logistic regression analysis to calculate ratio ratios and 95% Confidence Intervals, and subgroup analysis based on age, sex, hypertension, diabetes mellitus, and body mass index stratification to determine the association of markers of oxidative stress with the prevalence of sarcopenia. RESULTS: The present analysis included a total of 8,782 participants. Firstly, the RCS plots showed a roughly L-shaped curve association of total bilirubin and serum iron with a prevalence of sarcopenia. Secondly, albumin was negatively and linearly associated with the risk of sarcopenia. Finally, with the increase in gamma-glutamyl transferase, the prevalence of sarcopenia showed a trend of first rising and then declining as a result of the iron increase. CONCLUSIONS: We demonstrated a nonlinear association between markers of oxidative stress and sarcopenia. The need to focus more on levels of oxidative stress in the body could provide better prevention strategies for sarcopenia.

Targeted saliva metabolomics in Sjögren's syndrome.

OBJECTIVE: Sjögren's Syndrome (SS) is a chronic inflammatory autoimmune exocrinopathy, and although, the role of metabolism in the autoimmune responses has been discussed in diseases such as lupus erythematosus, rheumatoid arthritis, psoriasis and scleroderma. There is a lack of information regarding the metabolic implications of SS. Considering that the disease affects primarily salivary glands; the aim of this study is to evaluate the metabolic changes in the salivary glands' microenvironment using a targeted metabolomics approach. METHODS: The saliva from 10 patients diagnosed with SS by the American-European consensus and 10 healthy volunteers was analyzed in an Ultra-high Performance Liquid Chromatograph Coupled Mass Spectrometry (UPLC-MS). RESULTS: The results showed an increased concentration in SS of metabolites involved in oxidative stress such as lactate, alanine and malate, and amino acids involved in the growth and proliferation of T-cells, such as arginine, leucine valine and isoleucine. CONCLUSIONS: These results revealed that is possible to differentiate the metabolic profile of SS and healthy individuals using a small amount of saliva, which in its turn may reflect the cellular changes observed in the microenvironments of damaged salivary glands from these patients.

Hyaluronic acid-mediated epithelial-mesenchymal transition of human lens epithelial cells via CD44 and TGF-ß2.

PURPOSE: The epithelial-mesenchymal transition of human lens epithelial cells plays a role in posterior capsule opacification, a fibrotic process that leads to a common type of cataract. Hyaluronic acid has been implicated in this fibrosis. Studies have investigated the role of transforming growth factor (TGF)-ß2 in epithelial-mesenchymal transition. However, the role of TGF-ß2 in hyaluronic acid-mediated fibrosis of lens epithelial cell remains unknown. We here examined the role of TGF-ß2 in the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells. METHODS: Cultured human lens epithelial cells (HLEB3) were infected with CD44-siRNA by using the Lipofectamine 3000 transfection reagent. The CCK-8 kit was used to measure cell viability, and the scratch assay was used to determine cell migration. Cell oxidative stress was analyzed in a dichloro-dihydro-fluorescein diacetate assay and by using a flow cytometer. The TGF-ß2 level in HLEB3 cells was examined through immunohistochemical staining. The TGF-ß2 protein level was determined through western blotting. mRNA expression levels were determined through quantitative real-time polymerase chain reaction. RESULTS: Treatment with hyaluronic acid (1.0 µM, 24 h) increased the epithelial-mesenchymal transition of HLEB3 cells. The increase in TGF-ß2 levels corresponded to an increase in CD44 levels in the culture medium. However, blocking the CD44 function significantly reduced the TGF-ß2-mediated epithelial-mesenchymal transition response of HLEB3 cells. CONCLUSIONS: Our study showed that both CD44 and TGF-ß2 are critical contributors to the hyaluronic acid-mediated epithelial-mesenchymal transition of lens epithelial cells, and that TGF-ß2 in epithelial-mesenchymal transition is regulated by CD44. These results suggest that CD44 could be used as a target for preventing hyaluronic acid-induced posterior capsule opacification. Our findings suggest that CD44/TGF-ß2 is crucial for the hyaluronic acid-induced epithelial-mesenchymal transition of lens epithelial cells.

Intracerebroventricular administration of the exercise hormone irisin or acute strenuous exercise alleviates epileptic seizure-induced neuroinflammation and improves memory dysfunction in rats.

BACKGROUND: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. RESULTS: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05). CONCLUSION: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.

From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men.

Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.

Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

The short-term effect of COVID-19 infection history on semen parameters in men referred to infertility centres.

Context In recent years, the COVID-19 pandemic became a threat to human health and induced global concern. The SARS-CoV-2 virus causes various disorders in the body's systems, and the reproductive system is no exception. Further, the rate of infertile couples is increasing and part of this is related to male infertility. Aims The aim of the present study was to investigate the impacts of COVID-19 infection history on semen quality in men referred to public and private infertility centres. Methods In this research, patients were divided into two groups: 88 men with a history of COVID-19 (Covid+) and 51 men without (Covid-). After semen collection, sperm parameters, fertilisation rate and oxidative stress were investigated. Key results Sperms with normal morphology and mature chromatin in patients with COVID-19 infection history decreased, and seminal oxidative stress and sperm DNA fragmentation were increased; moreover, the fertilisation rate in the Covid+ group decreased in compare to the Covid- group. Conclusion COVID-19 infection increases oxidative stress in the semen, so has a negative effect on some sperm parameters and fertilisation rate. Implications COVID-19 infection impairs semen quality by increasing in oxidative stress, thus reducing the fertility potential.

Insulin resistance in the retina: possible implications for certain ocular diseases.

Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.

The dynamic roles of advanced glycation end products.

Advanced glycation end products (AGEs) are a heterogeneous group of potentially harmful molecules that can form as a result of a non-enzymatic reaction between reducing sugars and proteins, lipids, or nucleic acids. The total body pool of AGEs reflects endogenously produced AGEs as well as exogeneous AGEs that come from sources such as diet and the environment. Engagement of AGEs with their cellular receptor, the receptor for advanced glycation end products (RAGE), which is expressed on the surface of various cell types, converts a brief pulse of cellular activation to sustained cellular dysfunction and tissue destruction. The AGEs/RAGE interaction triggers a cascade of intracellular signaling pathways such as mitogen-activated protein kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinases, transforming growth factor beta, c-Jun N-terminal kinases (JNK), and nuclear factor kappa B, which leads to the production of pro-inflammatory cytokines, chemokines, adhesion molecules, and oxidative stress. All these events contribute to the progression of several chronic diseases. This chapter will provide a comprehensive understanding of the dynamic roles of AGEs in health and disease which is crucial to develop interventions that prevent and mitigate the deleterious effects of AGEs accumulation.

Advanced glycation end products and insulin resistance in diabetic nephropathy.

Insulin resistance is a central hallmark that connects the metabolic syndrome and diabetes to the resultant formation of advanced glycation end products (AGEs), which further results in the complications of diabetes, including diabetic nephropathy. Several factors play an important role as an inducer to diabetic nephropathy, and AGEs elicit their harmful effects via interacting with the receptor for AGEs Receptor for AGEs, by induction of pro-inflammatory cytokines, oxidative stress, endoplasmic reticulum stress and fibrosis in the kidney tissues leading to the loss of renal function. Insulin resistance results in the activation of other alternate pathways governed by insulin, which results in the hypertrophy of the renal cells and tissue remodeling. Apart from the glucose uptake and disposal, insulin dependent PI3K and Akt also upregulate the expression of endothelial nitric oxide synthase, that results in increasing the bioavailability of nitric oxide in the vascular endothelium, which further results in tissue fibrosis. Considering the global prevalence of diabetic nephropathy, and the impact of protein glycation, various inhibitors and treatment avenues are being developed, to prevent the progression of diabetic complications. In this chapter, we discuss the role of glycation in insulin resistance and further its impact on the kidney.

Non-enzymatic glycation and diabetic kidney disease.

Chronic diabetes leads to various complications including diabetic kidney disease (DKD). DKD is a major microvascular complication and the leading cause of morbidity and mortality in diabetic patients. Varying degrees of proteinuria and reduced glomerular filtration rate are the cardinal clinical manifestations of DKD that eventually progress into end-stage renal disease. Histopathologically, DKD is characterized by renal hypertrophy, mesangial expansion, podocyte injury, glomerulosclerosis, and tubulointerstitial fibrosis, ultimately leading to renal replacement therapy. Amongst the many mechanisms, hyperglycemia contributes to the pathogenesis of DKD via a mechanism known as non-enzymatic glycation (NEG). NEG is the irreversible conjugation of reducing sugars onto a free amino group of proteins by a series of events, resulting in the formation of initial Schiff's base and an Amadori product and to a variety of advanced glycation end products (AGEs). AGEs interact with cognate receptors and evoke aberrant signaling cascades that execute adverse events such as oxidative stress, inflammation, phenotypic switch, complement activation, and cell death in different kidney cells. Elevated levels of AGEs and their receptors were associated with clinical and morphological manifestations of DKD. In this chapter, we discussed the mechanism of AGEs accumulation, AGEs-induced cellular and molecular events in the kidney and their impact on the pathogenesis of DKD. We have also reflected upon the possible options to curtail the AGEs accumulation and approaches to prevent AGEs mediated adverse renal outcomes.

FABP3 Induces Mitochondrial Autophagy to Promote Neuronal Cell Apoptosis in Brain Ischemia-Reperfusion Injury.

This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury.

Role of AMPK-regulated autophagy in retinal pigment epithelial cell homeostasis: A review.

The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed.

Evaluation of Oxidative Stress and Endothelial Dysfunction in COVID-19 Patients.

Background and Objectives: Heat shock proteins (HSPs) are stress proteins. The endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethyl arginine (ADMA) is a mediator of endothelial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes endothelial dysfunction and coagulopathy through severe inflammation and oxidative stress. Using these markers, we analyzed the prognostic value of serum ADMA and HSP-90 levels for early prediction of severe coronavirus disease (COVID-19) patients. Materials and Methods: A total of 76 COVID-19 patients and 35 healthy control subjects were included in this case-control study. COVID-19 patients were divided into two groups: mild and severe. Results: Serum ADMA and HSP-90 levels were significantly higher in the COVID-19 patients compared to the control subjects (p < 0.001). Additionally, serum ADMA and HSP-90 levels were determined to be higher in a statistically significant way in severe COVID-19 compared to mild COVID-19 (p < 0.001). Univariable logistic regression analysis revealed that ADMA and HSP-90, respectively, were independent predictors of severe disease in COVID-19 patients (ADMA (OR = 1.099, 95% CI = 1.048-1.152, p < 0.001) and HSP-90 (OR = 5.296, 95% CI = 1.719-16.316, p = 0.004)). When the cut-off value for ADMA was determined as 208.94 for the prediction of the severity of COVID-19 patients, the sensitivity was 72.9% and the specificity was 100% (AUC = 0.938, 95%CI = 0.858-0.981, p < 0.001). When the cut-off value for HSP-90 was determined as 12.68 for the prediction of the severity of COVID-19 patients, the sensitivity was 88.1% and the specificity was 100% (AUC = 0.975, 95% CI= 0.910-0.997, p < 0.001). Conclusions: Increased levels of Heat shock proteins-90 (HSP-90) and ADMA were positively correlated with increased endothelial damage in COVID-19 patients, suggesting that treatments focused on preventing and improving endothelial dysfunction could significantly improve the outcomes and reduce the mortality rate of COVID-19. ADMA and HSP-90 might be simple, useful, and prognostic biomarkers that can be utilized to predict patients who are at high risk of severe disease due to COVID-19.

Antioxidant Status in Patients after Breast Mastopexy and Augmentation.

Background and Objectives: Mammary gland surgery has become very common, but there are complications of these operations, including the concept of breast implant illness (BII) in women with silicone gel breast implants (SBI), who suffer from various symptoms such as myalgia, arthralgia, fatigue, fever, dry eyes, or dry mouth. Silicone biomaterials are synthetic polymers that have their own physical and chemical properties and can exert their effect at the site of use and possibly on the general status of the body, causing inflammation and oxidative stress signs. The aim of the study was to examine components of the blood antioxidant system (AOS) of the mastopexy and breast augmentation patients before the operation, on the first post-op day, and 6 months after surgery. Materials and Methods: Healthy breast surgery patients (women aged 31 to 60 years without visible pathologies) were selected for the study and formed 2 groups: breast lift-mastopexy without silicone biomaterials (I group, 30 patients) and breast augmentation using silicone biomaterials (II group, 28 patients). All patients underwent standard preoperative tests. Glutathione peroxidase (GPxSe) and gamma-glutamyl transferase (GGT) in blood, selenium (Se), selenium protein P (SelPP), and total antioxidant status (TAS) in plasma were measured as AOS parameters. The concentration of vitamin D was also determined. A total of 174 blood tests were performed. Results: Overall, there were no differences in both groups in measured antioxidant system indicators over time; neither changes in objective nor subjective status were observed. However, baseline activity of GPxSe was relatively high but restored to normal values 6 months after surgery. In the mastopexy group, GPxSe decreased from 12,961.7 U/L by 18.9% to 10,513.4 U/L, and in the breast augmentation group, from 15,505.0 U/L by 25.1% to 11,265.5 U/L, which is a decrease of 18.9% and 25.1%, respectively. The patients did not note any complaints; other indicators of standard biochemical tests were within normal limits. Conclusions: The two types of surgical interventions, breast mastopexy and augmentation of the mammary glands, do not significantly impact blood AOS and are physiological in nature.