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 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.

The Role of Excitotoxicity, Oxidative Stress and Bioenergetics Disruption in the Neuropathology of Nonketotic Hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the brain. Affected patients usually manifest with neurological symptoms including hypotonia, seizures, epilepsy, lethargy, and coma, the pathophysiology of which is still not completely understood. Treatment is limited and based on lowering Gly levels aiming to reduce overstimulation of N-methyl-D-aspartate (NMDA) receptors. Mounting in vitro and in vivo animal and human evidence have recently suggested that excitotoxicity, oxidative stress, and bioenergetics disruption induced by Gly are relevant mechanisms involved in the neuropathology of NKH. This brief review gives emphasis to the deleterious effects of Gly in the brain of patients and animal models of NKH that may offer perspectives for the development of novel adjuvant treatments for this disorder.

Biochemical and Oxidative Biomarkers in Preeclampsia.

OBJECTIVE: To determine the biochemical and oxidative stress parameters as biomarkers in preeclampsia. STUDY DESIGN: Cross-sectional analytical study. Place and Duration of the Study: Departments of Obstetrics / Gynaecology and Biochemistry, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from September 2022 to February 2023. METHODOLOGY: Women with preeclampsia were selected based on blood pressure exceeding 140/90 mmHg and proteinuria levels exceeding 300 mg/24 hours or showing a +1 on a dipstick test. Normotensive pregnant women were selected as controls. Venous blood was taken and centrifuged, and routine biochemical methods were used to estimate serum lipid profile levels and minerals. The estimation of oxidative stress enzymes was carried out manually using special chemicals. Student's t-test and Pearson's correlation were applied to analyse the result. RESULTS: The study included 228 subjects: 114 preeclampsia patients and 114 normal pregnant women as controls. The mean systolic blood pressure was measured at 166.25 mmHg and the diastolic blood pressure was 92.80 mmHg (p <0.001). All lipid profile estimations showed notable abnormalities, but the mean level of triglycerides (TGs) (214.90 ± 15.59 mg/dl) in preeclamptic patients was significantly elevated (p <0.05). In terms of minerals, all were deranged but magnesium (1.37 ± 0.35 mg/dl) and calcium (7.55 ± 0.45 mg/dl) were significantly decreased (p <0.05). All oxidative enzyme levels were increased (p <0.05) but malondialdehyde (MDA) with a mean level of 2.58 ± 0.40 nmol/ml was significantly elevated. The Pearson's correlation of these parameters with blood pressure also showed a positive association. CONCLUSION:  Total cholesterol triglyceride in the lipid profile, calcium and magnesium in minerals, and MDA in oxidative parameters were markedly deranged and exhibited significant associations with the severity of the disease, so could be used as disease biomarkers of preeclampsia. KEY WORDS: Preeclampsia, Gestational hypertension, Proteinuria, Lipid profile, Minerals, Oxidative stress.

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.

Breath of fresh air: Investigating the link between AGEs, sRAGE, and lung diseases.

Advanced glycation end products (AGEs) are compounds formed via non-enzymatic reactions between reducing sugars and amino acids or proteins. AGEs can accumulate in various tissues and organs and have been implicated in the development and progression of various diseases, including lung diseases. The receptor of advanced glycation end products (RAGE) is a receptor that can bind to advanced AGEs and induce several cellular processes such as inflammation and oxidative stress. Several studies have shown that both AGEs and RAGE play a role in the pathogenesis of lung diseases, such as chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, and acute lung injury. Moreover, the soluble form of the receptor for advanced glycation end products (sRAGE) has demonstrated its ability to function as a decoy receptor, possessing beneficial characteristics such as anti-inflammatory, antioxidant, and anti-fibrotic properties. These qualities make it an encouraging focus for therapeutic intervention in managing pulmonary disorders. This review highlights the current understanding of the roles of AGEs and (s)RAGE in pulmonary diseases and their potential as biomarkers and therapeutic targets for preventing and treating these pathologies.

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.

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.

Novel perspectives on autophagy-oxidative stress-inflammation axis in the orchestration of adipogenesis.

Adipose tissue, an indispensable organ, fulfils the pivotal role of energy storage and metabolism and is instrumental in maintaining the dynamic equilibrium of energy and health of the organism. Adipocyte hypertrophy and adipocyte hyperplasia (adipogenesis) are the two primary mechanisms of fat deposition. Mature adipocytes are obtained by differentiating mesenchymal stem cells into preadipocytes and redifferentiation. However, the mechanisms orchestrating adipogenesis remain unclear. Autophagy, an alternative cell death pathway that sustains intracellular energy homeostasis through the degradation of cellular components, is implicated in regulating adipogenesis. Furthermore, adipose tissue functions as an endocrine organ, producing various cytokines, and certain inflammatory factors, in turn, modulate autophagy and adipogenesis. Additionally, autophagy influences intracellular redox homeostasis by regulating reactive oxygen species, which play pivotal roles in adipogenesis. There is a growing interest in exploring the involvement of autophagy, inflammation, and oxidative stress in adipogenesis. The present manuscript reviews the impact of autophagy, oxidative stress, and inflammation on the regulation of adipogenesis and, for the first time, discusses their interactions during adipogenesis. An integrated analysis of the role of autophagy, inflammation and oxidative stress will contribute to elucidating the mechanisms of adipogenesis and expediting the exploration of molecular targets for treating obesity-related metabolic disorders.

Glutathione Levels and Lipid Oxidative Damage in Selected Organs of Obese Koletsky and Lean Spontaneously Hypertensive Rats.

Koletsky rats, the genetically obese strain of spontaneously hypertensive rats (SHROB), are the well-accepted animal model of human metabolic syndrome. They are characterized by early onset obesity, spontaneous hypertension, hyperinsulinemia, hyperlipidemia, proteinuria and shortened life-span. One of the factors in the pathogenesis of metabolic syndrome is oxidative stress. The aim of the present study was to compare two parameters related to oxidative stress: the levels of the main intracellular antioxidant, reduced glutathione as well as the indirect indicator of lipid peroxidation damage, thiobarbituric acid-reactive substances (TBARS) in heart, renal cortex and medulla and liver in male lean spontaneously hypertensive rats (SHR) and obese Koletsky rats. We did not find any significant differences in these markers in heart and kidneys. However, we found significantly lower glutathione level in Koletsky rat liver compared with SHR (5.03+/-0.23 vs. 5.83+/-0.14 µmol/g tissue, respectively). On the contrary, we observed significantly higher TBARS levels in Koletsky rat liver compared with SHR (28.56+/-2.15 vs. 21.83+/-1.60 nmol/mg protein, respectively). We conclude that the liver is the most sensitive tissue to oxidative damage with the significantly decreased concentration of glutathione and the significantly increased concentration of TBARS in obese Koletsky rats in comparison with lean control SHR.

True or false? Alzheimer's disease is type 3 diabetes: Evidences from bench to bedside.

Globally, Alzheimer's disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, as well as mental symptoms, like behavioral abnormalities, that place a heavy psychological and financial burden on the families of the afflicted. Unfortunately, no particular medications exist to treat AD, as the current treatments only impede its progression.The link between AD and type 2 diabetes (T2D) has been increasingly revealed by research; the danger of developing both AD and T2D rises exponentially with age, with T2D being especially prone to AD. This has propelled researchers to investigate the mechanism(s) underlying this connection. A critical review of the relationship between insulin resistance, Aß, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation of Tau protein, inflammatory response, high blood glucose levels, neurotransmitters and signaling pathways, vascular issues in AD and diabetes, and the similarities between the two diseases, is presented in this review. Grasping the essential mechanisms behind this detrimental interaction may offer chances to devise successful therapeutic strategies.

[Myalgic encephalomyelitis : etiopathogenesis, diagnosis and treatment]. / Encéphalomyélite myalgique : étiopathogénie, diagnostic et traitement.

Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a neurological disorder involving multiple pathophysiological mechanisms and etiologies. Symptoms include asthenia, myalgia, post-exertional malaise and neurocognitive disorders. While the numerous patient complaints pose a diagnostic challenge, the advent of new technologies paves the way for innovative methods to reveal ME. The heterogeneity of the disease's mechanisms complicates the search for effective treatments but also offers the prospect of numerous beneficial molecules. Combining treatments targeting mitochondrial dysfunction, oxidative stress, inflammation and immunological disorders appears to be the current optimal therapeutic approach.

L'encéphalomyélite myalgique (EM), aussi connue sous le nom de syndrome de fatigue chronique (SFC), est une maladie neurologique impliquant des mécanismes physiopathologiques et des étiologies multiples. Les symptômes comprennent une asthénie, des myalgies, un malaise après effort et des troubles neurocognitifs. Si les nombreuses plaintes des patients représentent un défi diagnostique, l'apparition de nouvelles technologies ouvre la voie à des méthodes novatrices pour révéler l'EM. L'hétérogénéité des mécanismes de la maladie complique la recherche de traitements efficaces mais offre également la perspective de nombreuses molécules bénéfiques. Associer des traitements ciblant le dysfonctionnement mitochondrial, le stress oxydatif, l'inflammation et les troubles immunologiques semble être la meilleure démarche thérapeutique actuelle.

Associations between the oxidative balance score and constipation: a cross-sectional study of the NHANES, 2005-2010.

OBJECTIVE: The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. METHODS: Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. RESULTS: After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95-0.97, p < 0.001). In the OBS subgroup, the risk of constipation significantly decreased compared to that in the lowest quartile (Q2: 0.72, P = 0.024; Q3: 0.59, P < 0.001; Q4: 0.54, P < 0.001). CONCLUSIONS: The present study demonstrated a significant association between constipation and the oxidative balance score (OBS), particularly dietary OBS, and that an increase in OBS may reduce the risk of developing constipation, in which oxidative stress may play an important role. This finding suggested that dietary modification could be an important approach for preventing constipation.

Altered hypoxia-induced cellular responses and inflammatory profile in lung fibroblasts from COPD patients compared to control subjects.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators. METHODS: In this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-ß1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA. RESULTS: Hypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-ß significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFß1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects. CONCLUSION: These results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.

The relationship between lung function, exercise capacity, oxidant and antioxidant response in primary ciliary dyskinesia and cystic fibrosis.

BACKGROUND: There is a need to identify the complex interplay between various physiological mechanisms in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). The study investigated the interaction between respiratory function, exercise capacity, muscle strength, and inflammatory and oxidant/antioxidant responses in patients with PCD and CF. METHODS: The study included 30 PCD patients, 30 CF patients, and 29 age and sex-matched healthy subjects. Exercise capacity was assessed using the modified shuttle walk test (MSWT). Handgrip strength (HGS) was used to evaluate general muscle strength. Oxidative stress-inflammatory parameters were also assessed. Pulmonary function test was performed by spirometry. Regarding the forced expiratory volume in 1 second (FEV1) z-score, patients with PCD and CF were subdivided into normal, mild, and severe/moderate groups. RESULTS: Forced vital capacity (FVC) z-scores were lower in PCD and CF patients than controls. FEV1, FEV1/FVC, peak expiratory flow (PEF), and forced mid expiratory flow (FEF25-75%) z-scores were lower in PCD than in the other groups. HGS was lower in both mild PCD and normal CF patients relative to the controls. MSWT distance was lower in severe/moderate PCD patients than controls. Catalase (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels did not differ significantly among the study groups, but superoxide dismutase (SOD) level in severe/moderate PCD, and glutathione (GSH) level in normal CF were higher than in controls. Interleukin-6 (IL-6) level was higher in patients with normal PCD and CF compared to the controls. IL-1ß level was higher in PCD compared to controls. Additionally, correlations among these parameters were also determined in some patient groups. CONCLUSION: Homeostasis related to respiratory function, aerobic performance, muscle strength, inflammatory response, and oxidant/antioxidant balance were affected in PCD and CF. Evaluating these mechanisms together may contribute to elucidating the pathophysiology of these rare diseases.

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.

Epidermal factor Foxn1 as a regulator of antioxidant defense in the skin / Naskórkowy czynnik Foxn1 regulatorem obrony antyoksydacyjnej skóry.

The skin, as the largest organ of the body, is constantly exposed to environmental threats, including: injuries and oxidative stress. The thioredoxin system is one of the skin antioxidant systems , which protects cells against oxidative stress, regulates cell migration, proliferation and apoptosis, and also participates in signal transmission by regulating the activity of transcription factors. Recent studies have shown a correlation between the epidermal transcription factor Foxn1 and the thioredoxin system in mouse skin. Mass spectrometry analysis, followed by in vitro and in vivo experiments, showed that Foxn1 in keratinocytes regulates elements of the electron transport chain as well as the thioredoxin system (Txn2, Txnrd3), especially under hypoxic condition. High levels of Txnrd3 mRNA were detected for the first time in the injured skin of Foxn1+/+ mice compared to Foxn1-/- mice, and also showed that Foxn1 in keratinocytes upregulates Txnrd3 protein expression. Moreover, in silico analyzes indicated possible binding sites of the transcription factor Foxn1 in the Txn system. In conclusion, the data presented in this review identify Foxn1 as a novel component of the skin antioxidant system.

GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat.

AIM: Glucose-dependent insulinotropic polypeptide (GIP) is a ligand of glucose-dependent insulinotropic polypeptide receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as a hormone-like peptide to regulate the local metabolic environment. In this study, we investigated the antioxidant role of GIP on the neuron and explored the possible mechanism. METHODS: Cell counting Kit-8 (CCK-8) was used to measure cell survival. TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect apoptosis in vitro and in vivo. Reactive oxygen species (ROS) levels were probed with 2', 7'-Dichloro dihydrofluorescein diacetate (DCFH-DA), and glucose intake was detected with 2-NBDG. Immunofluorescence staining and western blot were used to evaluate the protein level in cells and tissues. Hematoxylin-eosin (HE) staining, immunofluorescence staining and tract-tracing were used to observe the morphology of the injured spinal cord. Basso-Beattie-Bresnahan (BBB) assay was used to evaluate functional recovery after spinal cord injury. RESULTS: GIP reduced the ROS level and protected cells from apoptosis in cultured neurons and injured spinal cord. GIP facilitated wound healing and functional recovery of the injured spinal cord. GIP significantly improved the glucose uptake of cultured neurons. Meanwhile, inhibition of glucose uptake significantly attenuated the antioxidant effect of GIP. GIP increased glucose transporter 3 (GLUT3) expression via up-regulating the level of hypoxia-inducible factor 1α (HIF-1α) in an Akt-dependent manner. CONCLUSION: GIP increases GLUT3 expression and promotes glucose intake in neurons, which exerts an antioxidant effect and protects neuronal cells from oxidative stress both in vitro and in vivo.