In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity.Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia (“OSOS”); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in the OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

BACKGROUND: Stable-phase schizophrenia may comprise two distinct nosological entities namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with the deficit syndrome) and simple NP (SNP), which are defined by neuroimmune and neurocognitive abnormalities. Furthermore, cognitive impairments and PHEM (psychotic, hostility, excitation, mannerism) and negative symptoms load on the same dimension.METHODS: The current study aimed to investigate associations of psychomotor retardation (PMR) and clinical as well as biomarker characteristics of schizophrenia. We recruited 40 healthy controls and 79 schizophrenia patients and measured IgA responses to tryptophan catabolites (TRYCATs), IgM to malondialdehyde and nitroso (NO)-cysteinyl, macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, CCL-11 as well as PMR items of different rating scales and motor screening task (MOT). RESULTS: PMR differentiated schizophrenia from controls and MNP from SNP. In addition, PMR was strongly associated with executive functions, deficits in episodic and semantic memory, PHEM and negative (PHEMN) symptoms. Around 50% of the variance in PMR was predicted by the cumulative effects of immune activation, CCL-11, TRYCATs and NO-Cysteinyl levels, and lowered natural IgM. PRM may be reliably combined with PHEMN symptoms and memory and executive impairments into one latent vector reflecting overall psychopathology.CONCLUSIONS: Current findings indicate that PMR may be a key psychopathological feature of schizophrenia and mainly MNP. In addition, PMR and associated impairments in memory and executive functions, and PHEMN symptoms may be driven by deficits in the compensatory immune regulatory system (natural IgM) combined with increased production of neurotoxic immune products, namely TRYCATs and IgM to NO-cysteinyl, and an endogenous cognition deteriorating chemokine, namely CCL-11.

During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation, but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism, and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging.

Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects on dysmetabolism and neurodegeneration of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on the brains of high fat diet (HFD)-fed mice. A decreased expression of FACL-4, CerS-1 and CerS-4, reduced cholesterol concentration, increased IR expression and insulin signaling activation, were found in brains of NDS-treated HFD mice, suggesting that NDS is able to prevent brain lipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levels of RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP, IL-1β, IL-6, and CD4 positive cell infiltration were lower than in untreated HFD mice, suggesting antioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP in NDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptotic nuclei was found in cortical sections of NDS-treated HFD. All these data indicate that NDS exerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress and inflammation and improving brain insulin resistance.

Myeloperoxidase (MPO) belong to the family of heme containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kD) is the product of MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications like removal of introns and signal peptide and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing active proMPO by the insertion of heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into extracellular fluid after oxidative stress and different inflammatory responses. MPO is the only type of peroxidase using H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation that can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and pathogenesis of several other major chronic diseases like rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes and cancer have been reported to be linked with myeloperoxidase derived oxidants. So the enhanced level of MPO activity is one of the best diagnostic tool of inflammatory and oxidative stress biomarkers among these commonly occurring diseases.

The dietary proteins are one of the most important factors determining health conditions in human. The sufficient digestion and absorption of dietary proteins in the digestive tract have positive effects on performance and recovery in sportspeople or athletes. Improving of protein digestibility is a strategy for maintaining health status and optimal performance in sport or exercise activities. The hypothesis of the present study is that Weizmannia coagulans BC 99 (BC99) can increase muscle mass and strength. This randomized double-blind, controlled trial assigned 72 male college students to receive probiotics (n = 36, 20.25±1.03 years; 1.79±5.94 cm; 73.55±8.73 kg, protein powder with BC99) or placebo (n = 36, 20.19±0.79 years; 179.25±5.16 cm; 73.61±8.24 kg, protein powder) for 12-week. At the baseline and final stages of the study, strength tests and body composition assessment were performed; Blood and stool samples were taken at the end of the 12-week intervention, digestive enzymatic activity of stool samples, biochemical parameters, amino acids and hormone level of plasma were analyzed. BC99 administration significantly improved strength performance, skeletal muscle mass, activity of pepsin and trypsin, the concentrations of branched chain amino acids and essential amino acids, reduced activities of creatine kinase and lactic dehydrogenase and urea nitrogen (BUN) level, and increased testosterone and glucagon-like peptide-1 level in male college students. Therefore, BC99 supplementation can be an important nutritional strategy to improve strength performance, body composition, protein digestion and body metabolism in various groups of individuals.

Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves extracts contain high amounts of flavonoids and terpenoids, endowed with potential antioxidant, anti-inflammatory, anticancer, antidiabetic and antimicrobial effects. Re-cently, many in vitro and in vivo studies have assessed different potential health benefits of per-simmon leaves; however, its anticancer activity towards colorectal cancer (CRC), the second deadliest cancer in Western countries, has not been investigated in depth. Since CRC current therapies are associated with serious side effects and show no efficacy towards patients carrying RAS/BRAF mutations, the search for new and more effective therapies has turned to plant extracts, which could help reduce conventional drugs dosages and toxicity. The effect of Diospyros kaki al-coholic extract has been investigated on E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS activating mutation. This extract is effective in reducing tumor cells viability, without affecting the healthy mucosa cell line CCD 841, and it triggers apoptosis in CRC cells, by disrupting mitochondrial functionality and increasing oxidative stress.

Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main pathway for methylglyoxal (MGO) formation. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the RAGE pathway. This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.

During their life cycle, plants constantly respond to environmental changes. Abiotic stressors affect the photosynthetic and respiratory processes of plants. Reactive oxygen species (ROS) are produced during aerobic metabolism and play an important role as regulatory mediators in signaling processes, activating the plant's protective response to abiotic stress and restoring "oxidation-reduction homeostasis". Cells develop normally if the rates of ROS production and the ability to neutralize them are balanced. To implement oxidation-reduction signaling, this balance must be disrupted either by an increase in ROS concentration or a decrease in the activity of one or more antioxidant systems. Under abiotic stress, plants accumulate excessive amounts of ROS and if the ROS content exceeds the threshold amount dangerous for living organisms, it can lead to damage to all major cellular components. Adaptive resistance of plants to abiotic stressors depends on a set of mechanisms of adaptation to them. The accumulation of ROS in the cell depends on the type of abiotic stress, the strength of its impact on the plant, the duration of its impact and the recovery period. The aim of this review is to provide a general understanding of the processes occurring during ROS homeostasis in plants, oxidation-reduction processes in cellular compartments in response to abiotic stress and the participation of ROS in signaling processes activating adaptation processes to abiotic stress.

Owing to recent advancements in nanotechnology, magnetic iron oxide nanoparticles (MNPs), particularly magnetite (Fe3O4) and maghemite (γ-Fe2O3), are currently widely employed in the field of medicine. These MNPs, characterized by their large specific surface area, potential for diverse functionalization, and magnetic properties, have found application in various medical domains, including tumor imaging (MRI), radiolabelling, internal radiotherapy, hyperthermia, gene therapy, drug delivery, and theranostics. However, ensuring the non-toxicity of MNPs when employed in medical practices is paramount. Thus, ongoing research endeavors are essential to comprehensively understand and address potential toxicological implications associated with their usage. This review aims to present the latest research and findings on assessing the potential toxicity of magnetic nanoparticles. It meticulously delineates the primary mechanisms of MNPs toxicity at the cellular level, encompassing oxidative stress, genotoxic effects, disruption of the cytoskeleton, cell membrane perturbation, alterations in the cell cycle, dysregulation of gene expression, inflammatory response, disturbance in ion homeostasis, and interference with cell migration and mobility. Furthermore, the review expounds upon the potential impact of MNPs on various organs and systems, including the brain and nervous system, heart and circulatory system, liver, spleen, lymph nodes, skin, urinary, and reproductive systems.

Infective endocarditis (IE) results from infections by gram-positive bacteria, and, in this condition, the redox homeostasis is lost by overproduction of H2O2, leading to overstimulation of the immune system and up- regulation of the production of proinflammatory cytokines. The aim of this preliminary study of three cases with IE, was to evaluate the levels of oxidative biomarkers and of the enzymatic and non-enzymatic antioxidant systems, in subjects with IE. This is a preliminary retrospective analytical study of cases that had undergone aortic valve replacement surgery that was complicated by IE. We determined malondialdehyde (MDA), total antioxidant capacity (TAC), carbonyl groups, glutathione (GSH), thiols and the nitrate/nitrite ratio (NO3−/NO2−) in homogenized tissue of cardiac valves. We also measured the activities of GST, GPx, GR and TrxR. The super oxide dismutase (SOD) isoforms and peroxidase activities were determined using native gels. There were increases in the activities of antioxidant enzymes such as GST, SOD isoforms and peroxidases (p=0.01) and decreases in oxidative stress markers such as GSH, TAC, (p=0.01); however, MDA was increased (p=0.01). The results suggest that loss of the intricate redox homeostasis system in the aortic valve of patients with IE may favor the bacterial process and cause damage probably leading to a fatal outcome.

Nocardia cyriacigeorgica causes bovine mastitis, reduces milk quantity and quality, and is often re-sistant to antimicrobials. Selenomethionine (SeMet) is a form of selenium, an essential trace el-ement. Although SeMet reduced ROS-mediated apoptosis and intramammary infections. How-ever, protective effects of SeMet on N. cyriacigeorgica-infected bovine mammary epithelial cells (bMECs) are unclear. The objective was to evaluate whether SeMet mitigated N. cyriacigeorgi-ca-induced inflammatory injury, oxidative damage and apoptosis in bMECs. Cells were cultured with or without being pretreated 40 µM of SeMet for 12 h, then challenged N. cyriacigeorgica (MOI=5:1) for 6 h. Although N. cyriacigeorgica was resistant to lincomycin, erythromycin, en-rofloxacin, penicillin, amoxicillin, cephalonium, cephalexin, and ceftriaxone, 40 μM SeMet in-creased cell viability and inhibited LDH release in infected bMECs. Furthermore, N. cyriacigeor-gica significantly induced mRNA production and protein expression of TNF-α, IL-1β, IL-6, and IL-8 at 6 h. Cell membrane rupture, cristae degeneration and mitochondria swelling were evi-dent with transmission electron microscopy. SOD and GSH-px activities were down regulated after 3, 6 or 12 h, whereas MDA and ROS contents were significantly upregulated, with cell damage and apoptosis rapidly evident (the latter increased significantly in a time-dependent manner). In contrast, bMECs pretreated with 40 μM SeMet before infection, SOD and GSH-px ac-tivities were upregulated (P < 0.05), MDA and ROS concentrations were downregulated (P < 0.05), and apoptosis was reduced (P < 0.05). In conclusion, 40 μM SeMet alleviated inflammation, oxi-dative stress and apoptosis induced by N. cyriacigeorgica in bMECs cultured in vitro.

Inflammation and immune cell dysfunction are critical facilitators of endometriosis pathophysiology. The diverse cellular fractions in the endometriotic microenvironment are represented mainly by glands and stroma, which are infiltrated by immune cells, including macrophages. Macrophages are renowned for stimulating lesion growth, vascularization, and innervation and contributing to pain in the disorder. By combining macrophages and endometriotic cells, we determined if resveratrol and its natural analogs can target the immune dysregulation and oxidative imbalance in endometriosis. We studied the effect of analyzed compounds on the expression of key inflammatory and oxidative stress markers, cytokines release, and ROS production by applying q-PCR, ELISA, Cytometric Beads Array, and multiplexed fluorogenic staining and flow cytometry analysis with bioimaging. The results showed that endometriosis-related macrophages treated with resveratrol or its derivatives have impaired expression of pro-inflammatory markers such as IL6, IL8, IL1B, TNF, CCL2, CXCL10, and PTGS2. This study also reported a pronounced antioxidant effect of the compounds by reducing the accumulation of free radicals in macrophages, which correlated with the transcript activation of detoxification enzymes (SOD, GPx). Considering the harmful macrophage action in endometriosis, we described the prospects for potential therapy based on regulating the immune microenvironment and reducing the accumulation of free radicals.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

Abstract: Ovarian cancer (OC) ranks as the fifth most common cancer among women in the United States and globally, posing a significant health threat. Reactive oxygen species (ROS) have emerged as critical factors in the pathophysiology of this malignancy. ROS, characterized by their instability due to an unpaired electron, are involved in essential cellular functions and play a crucial role in the immune response under normal physiological conditions. However, an imbalance in ROS homeostasis, leading to excessive ROS production, results in oxidative stress (OS), which can cause indiscriminate damage to cellular structures and contribute to the pathogenesis of specific diseases, including OC. OC is primarily classified based on the originating cell type into epithelial, stromal, and germinal tumors, with epithelial tumors being the most prevalent. Despite advancements in medical technology, early detection of OC remains challenging, often leading to delayed treatment initiation. Current therapeutic approaches include surgical excision of tumor tissue, radiotherapy and chemotherapy. While these treatments are effective in early-stage OC, high mortality rates and frequent relapse underscore the urgent need for novel diagnostic and therapeutic strategies. This review aims to elucidate the role of ROS in OC, emphasizing the potential for developing innovative diagnostic tools and treatments that target ROS-mediated pathways. Given the critical impact of early detection and effective treatment, advancing our understanding of ROS in the context of OC could significantly enhance patient outcomes.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network is constructed. Maximal subnetworks with dense connections are identified as functional clusters. Pathway enrichment analyses are conducted over mRNAs and lncRNAs in each cluster, which serve as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously build based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles by lncRNAs in activities related to stress response, reprogrammed metabolism, cell-polarity, and development. Our analyses have also revealed that lncRNAs have discerning power in distinguishing between AD samples of each stage and healthy controls. This study represents the first of its kind.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants – primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction, to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are in order, a viral infection, a metabolic disorder, an ischemic event, and a neurodegenerative disorder. OS may be an early initiator or a significant promotor of their progressive pathophysiologic processes. Consequently, addressing initial OS-related pathology may avoid subsequent severe and irreversible complications. Early intervention would modulate multiple factors, including cytokine stimulation, complement dysregulation, immuno-thrombosis, fibrosis, and autoimmunity. Past clinical studies that addressed OS have had equivocal results. It may be due to the use of ineffective antioxidants, an untimely delay in their use, or an inefficient delivery system. Experimental studies have used antioxidants that are not available for clinical trials. Although GSH can significantly reduce OS, its exogenous use is hampered by the lack of an effective delivery system. By incorporating GSH into cyclodextrin (CD) through nanotechnology, there is recent evidence that exogenous GSH can be delivered more effectively to prevent or mitigate injury from OS [1]. Future studies using the GSH/cyclodextrin (GC) complex will be needed to confirm its effectiveness and, hopefully, offer a path to treat many sub-optimally managed or currently untreatable illnesses.

The thymus, a central lymphoid organ in animals serves as the site for T cell development, differentiation and maturation, vital to adaptive immunity. Thymus is critical for maintaining tissue homeostasis to protect against tumors and tissue damage. Overactive or prolonged immune response can lead to oxidative stress from increased production of reactive oxygen species. Heat stress induces oxidative stress and overwhelms the natural antioxidant defense mechanisms. The study objectives were to investigate the protective properties of astaxanthin against heat-induced oxidative stress and apoptosis in the chicken thymus, by comparing the growth performance and gene signaling pathways among three groups- thermal neutral, heat stress and heat stress with astaxanthin. The thermal neutral temperature conditions were 21-22°C and heat stress temperature was 32-35°C. Both heat stress groups experienced reduced growth performance, while the astaxanthin treated group showed a slightly lesser decline. The inflammatory response and antioxidant defense system were activated by the upregulation of the NF-kB, NFE2L2, PPARα, cytoprotective capacity and apoptotic gene pathways in the heat stress compared to the thermal neutral group. Conversely, expression levels were without significance between the thermal neutral and heat stress with antioxidant groups, suggesting astaxanthin antioxidant effectiveness to mitigate inflammation and oxidative stress damage.

Helicobacter pylori infection affects over 50% of the world population and leads to chronic inflammation and gastric disorders, being the main pathogen correlated to gastric cancer development. The increasing on antibiotic resistance levels is a major global concern and alternative treatments are needed. Soybean peptides and other compounds might be an alternative in the treatment to avoid, eradicate and/or control symptoms of H. pylori infection. This study aimed to characterize a lunasin-enriched soybean extract (LSE) by proteomics tools and to evaluate its antioxidant, anti-inflammatory and antibacterial properties against H. pylori infection. By LC-MS/MS analysis, 124 proteins were identified, with the 2S albumin (lunasin and large chain subunits) being the fourth most abundant protein (8.9%). Lunasin consisted of 44 amino acid residues and an intramolecular disulfide bond. LSE at a low dose (0.0625 mg/mL) reduced ROS production in both H. pylori-infected and non-infected AGS gastric cells. This led to a significant reduction of 6.71% in the levels of pro-inflammatory interleukin (IL)-8. LSE also showed antibacterial activity against H. pylori which can be attributed to other soybean proteins and phenolic compounds. Our findings suggest that LSE might be a promising alternative in the management of H. pylori infection and associated symptoms.

A pathway frequently altered in cancer is glutaminolysis where glutaminase (GA) catalyses the main step: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 may function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We have reviewed the literature to highlight the critical roles of GLS and GLS2 to restrain ROS and regulate both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes and also by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy to dual activate ferroptosis and inhibit cancer cell growth in a ROS-mediated mechanism.

The present study aims to elucidate the effect of melatonin (MEL) on dexamethasone (DEX)-induced reproductive impairments in rats. Rats were procured and acclimatized with adequate food and water ad libitum. Twenty-four rats were divided into four groups (six in each) of Control, DEX (70µg/100g bw), DEX plus MEL, and MEL (200µg/100g bw) for 21 days. After completion, rats were sacrificed, and testes were dissected, weighed, and processed for biochemical, and receptor expression. Serum was collected for hormonal assay. DEX-treated rats showed a significant increase in lipid peroxidation (TBARS), a decrease in weight of the body and testes, and the level of antioxidative enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione oxidase (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH), glutathione S-transferase (GST)), total cellular protein content, serum testosterone, corticosterone, LH, FSH, melatonin levels, AR, MT1, and MT2 receptor expression. Marked cellular alterations were noted in the testis histology of the DEX group. Melatonin treated in DEX rats showed recovery and restoration in gravimetric, serum hormonal, biochemical parameters, receptor expression, and cellularity of testes. Therefore, findings suggest that melatonin improved defence against DEX-induced testicular damages suggesting its therapeutic potential for the management of male reproductive health.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

The increase in hypoxia events, a result of climate change in coastal and fjord ecosystems, impacts the health and survival of mussels. These organisms deploy physiological and molecular responses as an adaptive mechanism to maintain cellular homeostasis under environmental stress. However, the specific effects of hypoxia on mussels of socioeconomic interest, such as Mytilus chilensis, are unknown. Using RNA-seq, we investigated the transcriptomic profiles of the gills, digestive gland, and adductor muscle of M. chilensis under hypoxia (10 days at 2 mg L-1) and reoxygenation (10 days at 6 mg L-1). There were 15,056 differentially expressed transcripts identified in gills, 11,864 in the digestive gland, and 9,862 in the adductor muscle. The response varied among tissues, showing chromosomal changes in Chr1, Chr9, and Chr10 during hypoxia. Hypoxia regulated signaling genes in the Toll-Like, mTOR, citrate cycle, and apoptosis pathways in gills, indicating metabolic and immunological alterations. These changes suggest that hypoxia-induced a metabolic shift in mussels, reducing reliance on aerobic respiration and increasing reliance on anaerobic metabolism. Furthermore, hypoxia appeared to suppress the immune response, potentially increasing disease susceptibility, with negative implications for the mussel culture industry and natural bed populations. This study provides pivotal insights into metabolic and immunological adaptations to hypoxia in M. chilensis, offering candidate genes for adaptive traits.

This work aimed to elucidate how O3 pollution causes loss of regulation of the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 on the association between the antioxidant response of superoxide dismutase (SOD) levels and nuclear factor kappa light chains of activated B cells (NFκB) as a marker of inflammation. Method: 72 Wistar rats were used, divided into six groups that received the following treatments: Control, 7, 15, 30, 60, and 90 days at O3, respectively. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD, a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decrease. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to ozone alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This suggests that these responses are critical in the loss of regulation of the inflammatory response, and they respond to ozone pollution, which could be occurring in the progression of chronic degenerative diseases.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Myocardial ischemia/reperfusion injury (I/R) and the resulting heart failure is one of the main causes of mortality and morbidity worldwide. Camphene has been shown to have anti-inflammatory and hypolipidemic properties, however, its role in the protection of the heart from ischemia and reperfusion has not been investigated. The cardioprotective role of camphene and the mechanism that mediates its action against I/R injury was evaluated in the present study. A single dose of camphene was administered in adult rats prior to ex vivo I/R induction. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and cardiomyocyte injury was assessed by determining the release of lactate dehydrogenase (LDH) enzyme. Camphene pretreatment provided significant protection reducing myocardial infarct size and cell death after I/R. The effect was correlated with the activation of antioxidant defense mechanisms, namely CAT, MnSOD, GPx and GR, and reduction of oxidative stress as evidenced by determination of protein carbonylation and GSH/GSSG ratio in cardiomyocytes. The results suggest that camphene can protect the heart against I/R injury by maintaining redox homeostasis and can hold therapeutic potential for mitigating the detrimental effects of I/R in the heart.

Serelaxin (RLX), the recombinant form of human Relaxin-2 hormone, protects the heart from the ischemia/reperfusion (I/R)-induced damage due to its anti-inflammatory, anti-apoptotic and antioxidant properties. RLX exerts its actions by binding to its specific RXFP1 receptor whereby it regulates multiple cellular transduction pathways. In this in vitro study we offer first evidence for the involvement of AMP kinase/Sirtuin1 (AMPK/SIRT1) pathway in the protection afforded by RLX against H/R-induced damage in H9c2 cells. Treatment of the H/R-exposed cells with RLX (17 nmol L−1) enhanced SIRT1 expression and activity. Inhibition of SIRT1 signaling with EX527 (10 µmol L-1) reduced the beneficial effect of the hormone on mitochondrial efficiency and cell apoptosis. Moreover, RLX upregulated AMPK pathway, as shown by the increase in the expression of phospho-AMPK active protein. Finally, AMPK pathway inhibition by Compound C (10 and 20 μmol L−1) abrogated the increase in SIRT1 expression induced by RLX, thus suggesting the involvement of AMPK pathway in this effect of RLX. The results of this study strengthen the concept that RLX exerts its cardioprotective effects against H/R-induced injury by multiple pathways which also include AMPK/SIRT1.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

The EPA has banned PFOA and PFOS as persistent organic pollutants, but their residues in environment should not be underestimated. Based on the demand for healthy aquaculture and safe aquatic products, it is necessary to explore alleviative methods for the toxicity of PFOA and PFOS to fish. This study is the first to investigate the protective effects of Lactobacillus rhamnosus against oxidative damage, neurotoxicity, and gut microbial dysbiosis induced by PFOA and PFOS in adult zebrafish. The results showed that L. rhamnosus effectively alleviated PFOA- and PFOS-induced oxidative stress by restoring superoxide dismutase (SOD), catalase (CAT), and lactate dehydrogenase (LDH) levels. Both PFOA and PFOS caused intestinal tissue damage, and the degree of damage is PFOA+PFOS>PFOS>PFOA. L. rhamnosus can restore damaged intestinal villi and lymphocyte numbers and also have a restorative effect on intestinal tissue damage. The up-regulated proportion of beneficial Firmicutes and Actinobacteria was also found after L. rhamnosus feeding. These findings provide new insights for L. rhamnosus to alleviate the toxicity of PFOA and PFOS to zebrafish and promote the progress of research on the successful use of probiotics in freshwater aquaculture.

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated by Western blot. Cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified by immunofluorescence and immunohistochemistry respectively. Our results indicate that DRF reduced malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nfr2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nfr2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization in DRF conditions. Also, SOD 2 immunoreactivity was increased in CA1 pyramidal neurons but not in CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE.

The study investigated the effect of a multi-strain probiotic compound containing Bacillus coagulans, Enterococcus faecalis, Clostridium butyricum and Bacillus mesentericus as in-feed zinc oxide (ZnO) alterna-tive on growth performance, diarrhea incidence, antioxidant status, lipid profile, stress and immunity in weaned piglets. A total of 72 piglets were randomly divided into 3 groups with four replicates of six piglets each. The details of the groups were as follows; (i) weaned control group (WC) received basal diet, (ii) weaned probiotic group (WB) received basal diet and probiotics and (iii) positive control (PC) group received basal diet with 2500 mg/kg ZnO. The experiment lasted for 28 days. Probiotic supple-mentation improved growth performance and reduced diarrhea rate. Probiotics supplementation im-proved lipid profile; significantly lower levels of total cholesterol and low-density lipoprotein cholesterol and higher level of high-density lipoprotein cholesterol in WB group as compared to those of the control group (WC) were recorded. Probiotic supplementation stimulated antioxidant defense system by in-creasing total antioxidant capacity and decreasing lipid peroxidation. Probiotic supplementation down-regulated the stress biomarkers like serum cortisol and serum heat shock proteins. WB group showed higher serum levels of IgG and IgM throughout the study period and higher IgA at day 28 as compared to WC. These data suggest that supplementation of the probiotic minimizes the weaning stress, thereby improves the growth performance, lipid profile, antioxidant status and systemic as well as mucosal immunity. Therefore, the multi-strain probiotic compound may be used to replace ZnO in weaned piglets.

Male infertility (MI) involves various endogenous and exogenous facts. These include oxidative stress (OS), which is known to alter several physiological pathways and it is estimated to be present at high levels in up to 80 % of infertile men. That is why since the late 20th Century, the relationship between OS and MI has been widely studied. New terms have emerged, such as Male Oxidative Stress Infertility (MOSI), which is proposed as a new category to define infertile men with high OS levels. Another important term is MOXI: Male, Antioxidants, and Infertility. Such term refers to the hypothesis that antioxidants could improve male fertility without the use of assisted reproductive technology. However, there is no evidence-based antioxidant treatments that directly improve seminal parameters or birth ratio. In this regard, there is controversy about their use. While certain scientists argue against their use due to the lack of results, others support this use because of their safety profile and low price. Some uncertainties related to the use of antioxidants for treating MI are their questionable efficacy or the difficulties to know their correct dosage. In addition, the lack of quality methods for OS detection can lead to an excessive antioxidant supplementation, resulting in “reductive stress”. Another important problem is that, although the inflammatory process is interdependent and closely linked to OS, it is usually ignored. To solve these uncertainties, new trends have recently emerged. These include the use of molecules with anti-inflammatory and antioxidant potential, and which are also able to specifically target the reproductive tissue; as well as the use of new methods that allow for reliable quantification of OS and a quality diagnosis. This review aims to elucidate the main uncertainties about MOXI and to outline the latest trends in research to achieve effective therapies with clinically relevant outcomes.

Aim. To study the processes of lipid peroxidation and the activity of antioxidant defense enzymes depending on the chemiluminescent activity of neutrophilic granulocytes in patients with gastric cancer associated with H. pylori infection, depending on the stage. Materials and methods. 39 patients with stage I-II gastric cancer and 30 patients with stage III-IV gastric cancer were examined. The study of the chemiluminescent activity of neutrophilic granulocytes was carried out, the parameters of the lipid peroxidation system and antioxidant protection in plasma were determined using the spectrophotometric method. Statistical data processing was performed using the Statistica 7.0 software package (StatSoft, USA). Results. In patients with gastric cancer associated with H. pylori infection, regardless of stage, the proportion of neutrophilic granulocytes with normal activity does not exceed 1/3 of the total number of patients, the remaining 2/3 of patients have an altered chemiluminescent activity of neutrophilic granulocytes: in patients with gastric cancer by I -II stage of the disease, the majority revealed a reduced function of neutrophilic granulocytes, and in patients with gastric cancer stage III-IV of the disease, the majority showed increased chemiluminescent activity of neutrophilic granulocytes. In all patients with gastric cancer associated with H. pylori infection, regardless of the stage of the disease, an increase in lipid peroxidation processes with activation of antioxidant defense enzymes was detected. Conclusion. In all patients with gastric cancer associated with H. pylori infection, regardless of the stage of the disease, an increase in lipid peroxidation processes with activation of antioxidant defense enzymes was detected. At the same time, there are no statistically significant differences between the indicators of the system lipid peroxidation - antioxidant protection depending on the stage of gastric cancer and the chemiluminescent activity of neutrophilic granulocytes, which probably indicates that all reactive oxygen species produced by neutrophilic granulocytes in the respiratory burst are consumed locally, minimally affecting the development of oxidative stress in the blood plasma.

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

Neuroblastoma is the most common tumour in children under 1 year old, accounting for approximately 50% of infant cancer cases. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma accounts for 52% of brain tumours and has an extremely poor prognosis. Current chemotherapeutics include temozolomide, which has numerous negative side-effects and a low-effective rate. Previous studies have shown the manipulation of autophagy to be a promising method for targeting cancers, including glioblastoma. We sought to determine the effects of autophagic alterations in combination with current chemotherapies in both neuroblastoma and glioblastoma. Supplementing cisplatin or temozolomide with autophagy activator rapamycin stabilized cancer cell mitochondria, despite having little effect on apoptosis or oxidative stress. Autophagy inhibition via 3-methyladenine or hydroxychloroquine alongside standard chemotherapies enhanced apoptosis and oxidative stress, with 3-methyladenine also disrupting mitochondrial health. Importantly, combining hydroxychloroquine with 0.5 µM cisplatin or 50 µg/mL temozolomide was as or more effective than 2 µM cisplatin or 100 µg/mL temozolomide alone. Analyzing these interesting results, a combined treatment of autophagy inhibitor with a standard chemotherapeutic agent could help to improve patient prognosis and reduce chemotherapy doses and their associated side-effects.

Margarines are W/O emulsions with minimal fat and are heat treated when used for baking. Lipid oxi-dation has been identified as the major deterioration process of margarines and addition of antioxidants is necessary. Consumers are increasingly demanding that chemical antioxidants in foods be replaced by natural preservatives. A multivariate statistical study gave us oxidative stability depending on the com-position of 20 different commercial margarines and an analysis of the principal components allowed us to classify and select eight of them. This study analyzes the antioxidant capacity of six different natural ground herbs (Curcuma longa, Illicium verum, Rosmarinus officinalis, Taraxacum officinale, Thymus piperella and Thymus vulgaris) on the oxidative stability of eight selected margarines. In order to evalu-ate the oxidative stability, we determine the induction period (IP) with Rancimat assays at 120 ºC with 1.5 hours of suppression. As results, Rosmarinus officinalis increases the IP value by 73.17% with respect to its basal values, Curcuma longa, Thymus vulgaris and Thymus piperella increases it between 17% and 26% and Taraxacum officinale together with Illicium verum reduces it between 19% and 34% respec-tively. A multiple linear regression model approach shows that IP has a positive correlation with SFA, PUFA,  acids, MUFA/PUFA ratio and antioxidant activity.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases in elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca2+ dyshomeostasis play a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD. Because dysregulated Ca2+ metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca2+ homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca2+ homeostasis and signaling has been reported, including decreased Ca2+ uptake through voltage-operated Ca2+ channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca2+ homeostasis and trafficking, and their ability to regulate compromised mitochondrial function and associated free radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes.

Lifestyle has been associated with breast cancer risk through different pathways, including oxidative stress. Antioxidant enzymes are endogenous defense mechanisms against oxidative stress damage, and this response might be modulated by the genetic variation in these enzyme-codifying genes. This study aimed to analyze the synergistic effect of an antioxidant Healthy Lifestyle Index (HeLiX) composed of principal components of Western dietary pattern, alcohol consumption, smoking and physical activity, and genetic polymorphisms in the first-line antioxidant response family genes SOD, GPX, and CAT on breast cancer risk. We included 176 SNPs, and only CAT rs554576 remained significant after correction for multiple comparisons. Breast cancer odds were reduced at the highest (T3) and medium (T2) tertiles of the HeLiX. When stratified by HeLiX, we observed a reduced risk of breast cancer with at least one T-allele, and the effect increased in a dose-dependent manner. Compared to the reference category (HeLiX T1 and AA genotype), women at the HeLiX T3 with AT and TT genotypes in postmenopausal women showed an OR = 0.15 (95% CI 0.07–0.32). For HeLiX T2 and AT genotype OR = 0.26 (95% CI 0.13–0.54); for TT genotype OR = 0.24 (95% CI 0.12–0.45). For premenopausal women, at the HeLiX T3 and AT genotype OR = 0.29 (95% CI 0.13–0.62); for the TT genotype OR = 0.21 (95% CI 0.08–0.51). We also observed an inverse association for HeLiX T2 and TT genotype (OR 0.39 95% CI 0.17–0.87). Our study shows a significant synergistic gene-environment interaction on an additive scale, contributing to understanding pathways involved in breast cancer etiology and prevention.

Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.

A Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using Caenorhabditis elegans as a model system to study presenilin function, we found that loss of C. elegans presenilin orthologue, SEL-12, results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in sel-12 mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in sel-12 mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.

Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate belonging to the phylum of Tardigrada. At a length of 0.1-1.0 mm, tardigrades are small animals with an exceptional tolerance to extreme conditions such as high pressure, chemicals and irradia-tion. These properties have been attributed to the recently-discovered Dsup protein. Dsup is a nucleosome-binding protein that prevents DNA damage against X-ray and oxidative stress without impairing cell life, also in Dsup-transfected animal and plant cells. However, the precise “protective” role of this protein is still under study. We performed experiments on human cells and shows that, as compared to control cells, Dsup+ cells are more resistant to UV-C exposure and H2O2. Real-time PCR identified different expression patterns of endogenous genes involved in apoptosis, cell survival and DNA damage repair in Dsup+ cells in response to H2O2 and UV-C. While H2O2 treatment in Dsup+ cells only marginally involved the activation of pathways responsible for DNA repair reinforcing the idea of a direct protective effect of the protein on DNA, in UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes. In conclusion, our data may help to delineate the different mechanisms by which the Dsup protein operates in response to different insults.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H2O2), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H2O2 and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H₂O₂), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H₂O₂ and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

The approach towards myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) remains in a permanent state of crisis with fierce competition between the psychosocial school, which attributes ME/CFS to the perception of effort, and the medical approach (Maes and Twisk, BMC Med, 2010,8,35). The aim of this paper is to review how to construct a nomothetic model of ME/CFS using Partial Least Squares (PLS) path analysis and ensembling causome (bacterial translocation as assessed with IgM/IgA responses to LPS), protectome (lowered coenzyme Q10), adverse outcome pathways (AOP) including increased lysozyme, CD38+ T cell activation, cell-mediated immune activation (CMI), and IgM responses to oxidative specific epitopes and NO-adducts (IgM OSENO). Using PLS, we trained, tested and validated this knowledge- and data-driven causal ME/CFS model, which showed adequate convergence, construct and replicability validity. This bottom-up explicit data model of ME/CFS objectivates the descriptive narratives of the ME/CFS phenome, using causome-protectome-AOP data, whereby the abstract concept ME/CFS is translated into pathways, thereby securing the reification of the ME/CFS phenome. We found that 31.6% of the variance in the physiosomatic symptom dimension of ME/CFS was explained by the cumulative effects of CMI and CD38+ activation, IgM OSENO, IgA LPS, lysozyme (all positive) and coenzyme Q10 (inversely). Cluster analysis performed on the PLS-generated latent vector scores of all feature sets exposed three distinct immune groups of ME/CFS, namely one with increased lysozyme, one with increased CMI + CD38 activation + depressive symptoms, and another with increased bacterial translocation + autoimmune responses to OSENO.

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Pomegranate extract (PG-E) has been reported to exert a protective effect in skin due to its antioxidant activity. Ingredients rich in phenolic compounds are unstable in extract solutions and, therefore, the use of a suitable nanosystem to encapsulate this type of extract could be necessary in different biotechnological applications. Thus, we investigated the capacity of Brassica oleracea L. (cauliflower) inflorescence vesicles (CI-vesicles) to encapsulate PG-E and determined the stability and the antioxidant capacity of the system over time. In addition, the protective effect against UV radiation and heavy metals in HaCaT cells was also tested. The CI-vesicles had an entrapment efficiency around 50% and accelerated stability tests did not show significant changes in the parameters tested. The results for the HaCaT cells show the non-cytotoxicity of the CI-vesicles containing PG-E and their protection against heavy metals (lead acetate and mercuric chloride) and UV-B radiation through a reduction of oxidative stress. The reduction of the percentage of deleted mtDNA (mtDNA4977, “common deletion”) in UV-treated HaCaT cells due to the presence of CI-vesicles containing PG-E indicates the mechanism of protection. Therefore, the effects of CI-vesicles loaded with PG-E against oxidative stress support their utilization as natural cosmeceuticals to protect skin health against external damage from environmental pollution and UV radiation.

Glyceraldehyde 3–phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme, which is crucial for the breakdown of glucose to provide cellular energy. Over the past decade, GAPDH has been reported to be one of the most prominent cellular targets of post-translational modifications (PTMs), which divert GAPDH towards different non-glycolytic functions. Hence, it is termed a moonlighting protein. During metabolic and oxidative stress, GAPDH is a target of different oxidative PTMs (oxPTM), e.g. sulfenylation, S-thiolation, nitrosylation and sulfhydration. These modifications alter the enzyme’s conformation, subcellular localization and regulatory interactions with downstream partners, which impact its glycolytic and non-glycolytic functions. In this review, we discuss the redox regulation of GAPDH by different redox writers, which introduce the oxPTM code on GAPDH to instruct a redox response; the GAPDH readers, which decipher the oxPTM code through regulatory interactions and coordinate cellular response via the formation of multi-enzyme signaling complexes; and the redox erasers, which are the reducing systems that regenerate the GAPDH catalytic activity. Human pathologies associated with the oxidation-induced dysregulation of GAPDH are also discussed, featuring the importance of the redox regulation of GAPDH in neurodegeneration and metabolic disorders.

Inorganic polyphosphate (polyP) is an important factor of stress tolerance in microbial cells. In yeast, the major enzyme of polyP biosynthesis is Vtc4, a subunit of the vacuole transporter chaperone (VTC) complex. In this study, we demonstrated that Vtc4 knockout in Saccharomyces cerevisiae not only decreased polyP content but also caused shifts in the composition of the intracellular polyP pool and changed the stress tolerance profile. In the mutant S. cerevisiae, the level of short-chain acid-soluble polyPs was decreased nearly 10-fold, whereas that of longer acid-insoluble polyPs was decreased only 2-fold, suggesting the existence of other enzymes compensating the production of long-chain polyPs. The Δvtc4 mutant showed inhibition of Mg2+-dependent phosphate uptake and decreased resistance to alkaline stress but increased tolerance to oxidation and heavy metal ions, especially Mn2+. Quantitative PCR revealed the upregulation of the DDR2 gene implicated in multiple stress responses and downregulation of PHO84 encoding a phosphate and Mn2+ transporter, which could account for the effects on phosphate uptake and Mn2+-related stress response in the Δvtc4 mutant. Our study indicates that short-chain polyPs, plays an important role in the regulation of stress response in yeast.

Both tissue repair and regeneration are a priority in regenerative medicine. Retinitis pigmentosa (RP), a complex retinal disease characterized by the progressive loss of impaired photoreceptors, is currently lacking effective therapies: this represents one of the greatest challenge in the ophthalmological research field. Although this inherited retinal dystrophie is still incurable genetic disease, the oxidative damage is an important pathogenetic element that may represent a viable target of therapy. In this review, we summarize the current neuroscientific evidences about the cell therapies effectiveness, especially based on mesenchymal cells, in RP and focus on their therapeutic actions: limitation of both oxidative stress and apoptotic processes triggered by the disease, promoting cell survival. Cell therapy could therefore represent a feasible therapeutic option in RP.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic network reflecting the direct effects of risk resilience (RR) factors, and direct and mediated effects of both RR and adverse outcome pathways (AOPs) on the schizophrenia phenome. This study was conducted using data of 40 healthy controls and 80 patients with schizophrenia. Using partial least Squares (PLS) analysis, we found that 39.7% of the variance in the phenomenome (lowered self-reported quality of life) was explained by the unified effects of AOPs (IgA to tryptophan catabolites, LPS, and the paracellular pathway, cytokines, and oxidative stress biomarkers), the cognitome (memory and executive deficits), and symptomatome (negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, formal thought disorders); 55.8% of the variance in the symptomatome was explained by a single trait extracted from AOPs and the cognitome; and 22.0% of the variance in the latter was explained by the RR (Q192R polymorphism and CMPAaase activity, natural IgM, and IgM levels to zonulin). There were significant total effects (direct + mediated) of RR and AOPs on the symptomatome and phenomenome. In the current study, we built a reliable nomothetic network that reflects the associations between RR, AOPs, and the phenome of schizophrenia and discovered new diagnostic subclasses of schizophrenia based on unified RR, AOPs, and phenome scores.

The mass concentration of particulate matter (PM) has been systematically used in epidemiological studies as exposure indicator, to relate airborne concentrations with a wide variety of human health effects, which can be hardly explained by using this single parameter. In fact, PM is a “particle cocktail” that includes a complex mixture of compounds with a wide range of sizes, chemical compositions and emission sources. Current research hypothesizes that many of the adverse health effects are derived from oxidative stress in biological systems caused by the deposition of PM into the lungs. This emerging hypothesis is called the oxidative stress paradigm. In this commentary article we analize how this new paradigm could help to answer the as-of-yet unanswered questions related to the mechanism of action of PM pollution on human health. Acellular oxidative potential (OP) assays have been emerged as a promising approach to quantify the PM potential to induce oxidative stress and to relate it with the chemical composition and size distribution of PM. Recent researches have shown that the OP is related to the presence of metals, organic carbon, polyaromatic hydrocarbons and quinones. However, the association between PM and particle-induced toxicity is still largely unknown. Therefore, additional research is needed to identify the specific PM characteristic(s), such as its specific size, emission source or chemical content, which contribute the most to its redox activity. Thus, the OP measurements provide information that allows us to evaluate and integrate the toxic potential of PM in a unique parameter, whose relationships with emission sources, size distribution and/or chemical composition should be faced in the near future.

Transfusion dependent thalassemia (TDT) patients are treated with continued blood transfusions and show a higher prevalence of depression. TDT with consequent iron overload and inflammation is associated with increased severity of depressive symptoms in TDT children.Aim of the study: To construct a pathway-phenotype which combines iron overload and neuro-immune biomarkers with depressive symptom subdomains in TDT children.Methods: We measured iron status parameters (iron, ferritin, transferrin saturation percentage) and inflammatory (interleukin-1β and tumour necrosis factor-α) biomarkers in TDT (n=111) and healthy (n=53) children and analyzed the results using machine learning.Results: Cluster analysis separated TDT children with depression from those without depression and revealed two depressive subgroups one with low self-esteem and another with increased social-irritability scores. Exploratory factor analysis validated four depressive symptom dimensions as reliable constructs, namely key depressive, physiosomatic, lowered self-esteem and social-irritability dimensions. Partial Least Squares showed that 73.0% of the variance in a latent vector extracted from those four clinical subdomains, immune-inflammatory and iron overload biomarkers was explained by exposure variables including the number of blood transfusions and hospitalizations and use of deferoxamine. The exposure data, iron and immune biomarkers, and symptom subdomains are reflective manifestations of a single latent trait, which shows internal consistency reliability and predictive relevance.Conclusions: The nomological network combining exposure, pathways and behavioral phenome manifestations provides an index of overall severity and disease risk and, therefore, constitutes a new drug target, indicating that iron overload and immune activation should be targeted to treat depression due to TDT.

Introduction: Lowered thiol or sulfhydryl (-SH) groups and glutathione (GSH) metabolism may be associated with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The main objectives of this study were to systematically review and meta-analyze the evidence on the associations among -SH groups, GSH, GSH peroxidase (GPx), GSH reductase (GR) and GSH transferase (GST) and PCa/BPH. Methods: Four electronic databases were searched for studies that reported -SH and GSH variables in PCa/BPH and healthy controls (HC) and the data were meta-analyzed by calculating Hedges’s g with 95% confidence intervals. Results: Twenty studies were included in this meta-analysis including 800 PCa and 791 BPH patients and 592 HC. Total -SH (g=-1.750, -2.341/-1.159), GPx (g=-0.789, -1.234/-0.344), GSH (g=-2.219, -4.132/-0.305), and the combination of -SH, GPx, and GSH (g=-1.271, -1.271/-0.800) were significantly lower in PCa patients than in HC. -SH (g=-1.752, -3.123/-0.381) and the combination of -SH, GPx, and GSH (g=-0.813, -1.298/-0.327) were significantly lower in BPH patients than in HC. GPx was significantly lower in PCa than in BPH patients (g=-0.455, -0.896/-0.014). Heterogeneity levels were very high, but Egger’s test showed that none of the biomarkers showed significant publication bias. Conclusion: Thiol/GPx antioxidant defenses are significantly attenuated in patients with PCa while patients with BPH occupy an intermediate risk group position between PCa patients and HC. Those results suggest that reduced thiol-related antioxidant mechanisms play a crucial role in prostatic disorders, especially in PCa. Future research should examine whether thiols/GPx antioxidants are associated with the onset of PCa/BHP.

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p<0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

Objective: To examine the associations between menstruation features and symptoms and hormone-immune-metabolic biomarkers. Methods: Forty-one women completed questionnaires assessing characteristic menstruation symptoms, duration of menstrual cycle and number of pads used/day and completed the Daily Record of Severity of Problems (DRSP) during the consecutive days of their menstrual cycle. Menses-related symptoms (MsRS) were computed from the sum of 10 pre- and post-menses symptoms and the menstruation blood and duration index (MBDI) was computed based on the daily number of pads and duration of menses. We assayed serum levels of various biomarkers at days 7, 14, 21, and 28 of the subjects’ menstrual cycle. Results: MBDI was significantly associated with a) MsRS including low abdominal cramps, and gastro-intestinal (GI) and pain symptoms (positively); b) plasma levels of haptoglobin (Hp), CCL5, insulin growth factor (IGF)-1, and plasminogen activator inhibitor (PAI)1 (all positively); and c) estradiol and paraoxonase (PON)1 arylesterase activity (both inversely). MsRS were significantly predicted by CCL5 and IGF-1 (both positively) and progesterone (inversely). Low-abdominal cramps, and gastro-intestinal and pain symptoms were associated with lower progesterone levels. The MBDI+MsRS score was significantly predicted by the cumulative effects of (in descending order of importance): Hp, IGF-1, PON1 arylesterase, estradiol and PAI. Conclusion: Menstruation-related features including estimated blood loss, duration of menses, cramps, pain and GI symptoms are associated with hormone-immune-metabolic biomarkers, which mechanistically may explain those features. Women with an increased MBDI+MsRS index ≥ 0.666 percentile may be considered to have menstruation-related distress, including dysmenorrhea symptoms.

Background: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase (PON)1 status may occur in TLE and those psychiatric conditions. Methods: We examined paraoxonase (PON)1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in 40 normal controls and 104 TLE patients, 27 without comorbidities, and 77 with comorbidities including mood disorders (n=25), anxiety disorders (n=27) and psychosis (n=25). Outcomes: CMPAase and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than in normal controls. The areas under the ROC curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (±0.037) for MTS. Partial Least Squares (PLS) path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (p<0.0001) and psychopathology (p<0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination scores. Interpretation: The severity of TLE and comorbidities are to a large extent explained by lowered PON1 enzyme activities and by effects of the Q192R genotype which are mediated by lowered CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Objective: To examine whether 1) immune and nitro-oxidative stress (IO&NS) biomarkers are associated with premenstrual syndrome (PMS); and 2) changes in IO&NS biomarkers during the menstrual cycle (MC) are associated with PMS symptoms and plasma estradiol and progesterone. Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days and MC Associated Syndrome (MCAS) was diagnosed when the summed DRSP score during the MC is > 0.666 percentile. We assayed plasma levels of complement C3 and C4, highly sensitive C-reactive protein (hsCRP), haptoglobin (Hp), advanced oxidation protein products (AOPP), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), sulfhydryl (-SH) groups and the activity of paraoxonase (PON)1 at days 7 (D7), 14 (D14), 21 (D21) and 28 (D28) of the MC. Results: All biomarkers, except hsCRP, showed significant alterations during the MC. Arylesterase (AREase) was lowered at D28, while LOOH increased at D14 and C4 at D21 in women with MCAS. The total DRSP score was predicted by the combined effects of C4 (positively) and AREase and malondialdehyde (MDA) (both inversely associated). Progesterone lowered levels of LOOH, AOPP and C3 and estradiol lowered levels of Hp while both sex hormones increased 4-(chloromethyl)phenyl acetate (CMPA)ase and AREase activities and levels of -SH groups. Conclusion: PMS/MCAS is not accompanied by a peripheral inflammatory response. Lowered MDA and antioxidant defenses and increased C4 may play a role in MC-associated symptoms while sex hormones may have a protective effect against oxidative stress toxicity.

Carvacrol has long been studied for its natural antifungal potential and food preservative. But the exact mode of its action remained highly complex as a general, but especially for Penicillium digitatum (P. digitatum) largely remained unexplored. Herein, a 1H-NMR-based metabolomic technique was used to investigate the antifungal mechanism of carvacrol. The metabolomic profiling data showed that alanine, aspartate, glutamate and glutathione metabolism were imbalanced in the fungal hyphae. A strong positive correlation was seen between aspartate, glutamate, alanine and glutamine, while negative correlation among glutathione and lactate. These metabolic changes revealed that carvacrol-induced oxidative stress had disturbed the energy production and amino acid metabolism of P. digitatum. Current study will improve the understanding of the metabolic changes posed by plant-based fungicides in order to control citrus fruit green mold caused by P. digitatum. Moreover, the study will provided certain experimental and theoretical basis for the development of novel citrus fruit preservatives.

In 2001, the first author of this paper reported that schizophrenia is associated with an increased frequency of the haptoglobin (Hp)-2 gene. The precursor of Hp-2 is zonulin, a molecule that affects intercellular tight junction integrity. Recently, we reported increased plasma IgA/IgM responses to Gram-negative bacteria in deficit schizophrenia indicating leaky gut and gut dysbiosis. The current study was performed to examine the integrity of the paracellular (tight and adherens junctions) and transcellular (cytoskeletal proteins) pathways in deficit versus non-deficit schizophrenia. We measured IgM responses to zonulin, occludin, E-cadherin, talin, actin and vinculin in association with IgA responses to Gram-negative bacteria, CCL-11, IgA responses to tryptophan catabolites (TRYCATs), immune activation and IgM to malondialdehyde (MDA) and NO-cysteinyl in 78 schizophrenia patients and 40 controls. We found that the ratio of IgM to zonulin + occudin / talin + actin + viculin (PARA/TRANS) was significantly greater in deficit than in non-deficit schizophrenia and higher in schizophrenia than controls and was significantly associated with increased IgA responses to Gram-negative bacteria. IgM responses to zonulin were positively associated with schizophrenia (versus controls), while IgM to occludin was significantly associated with deficit schizophrenia (versus non-deficit schizophrenia and controls). A large part of the variance (90.8%) in negative and PHEM (psychosis, hostility, excitation and mannerism) symptoms was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, IgM to E-cadherin and malondialdehyde (MDA) and memory dysfunctions, while 53.3% of the variance in the latter was explained by PARA/TRANS ratio, IgA to Gram-negative bacteria, CCL-11, TRYCATs and immune activation. The results show an upregulated paracellular pathway with breakdown of the tight and ahherens junctions and increased bacterial translocation in deficit schizophrenia. These dysfunctions in the intestinal paracellular route together with lowered natural IgM, immune activation and production of CCL-11 and TRYCATs contribute to the phenomenology of deficit schizophrenia.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in natural regulatory autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative specific epitopes (OSEs), nitroso (NO) and nitro (NO₂) adducts in schizophrenia remain unknown.This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl and NO₂-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls.Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO₂-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2 – 42.2 %) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO₂-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall.These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in lowered IgM responses to MDA and azelaic acid (part of the CIRS) attenuate the negative immune-regulatory feedback on the primary immune response and that this process may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

CrHZSM-5 was placed in an electric field with appropriate strength in a quartz packed bed reactor with CO2 as oxidant to analyze its catalytic activity. Olefin yield increases with decrease in band gap since lattice oxygen mobility increases by reducing band gap. Fermi level change at the catalyst surface affects the catalytic activity. One way to change Fermi level is use electric field. In high voltage electric field, energy band was curved, bending of the energy band promoted the activity and Fermi level position is increasing. The CCD experiments were carried out with Design-Expert 7.3 software to determine the interaction between four operating variables, namely: temperature, electrical current, gap distance and metal loading. The levels of the independent variables were: temperature (550-700 °C), electrical current (0-12 mA), gap distance (6-14 mm), metal loading (0.5-7.5 %wt.). The conversion of LPG (Liquefied petroleum gas) was greatly increased by weak and effective application of an electric field to the catalyst bed. The obtained results indicated that the maximum yield value (46.94%) can be achieved under 673.66 °C, input electrical current of 11.01 mA, gap distance of 6.55 mm and metal loading of 3.98 wt.%.

Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24-h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.

The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.

Reactive oxygen species (ROS) encompass various molecular oxygen derivatives naturally produced during aerobic metabolism, including superoxide anion, hydrogen peroxide, and hydroxyl radical. Excessive ROS production leads to oxidative distress, causing cellular damage and contributing to various pathologies, often alongside inflammation. Endogenous sources of ROS include mitochondrial activity and NADPH oxidases. The antioxidant system, comprising enzymes such as superoxide dismutase, peroxiredoxin, and catalase, mitigates ROS-induced damage. This review explores the regulation of ROS by membrane receptors, focusing on B1 and B2 kinin receptors and histamine H2 receptors, which are implicated in vasodilation, angiogenesis, inflammation, and gastric acid secretion. Understanding these interactions provides insights into ROS modulation and its role in disease mechanisms.

The present study investigated the photoprotective effect of the ultrasonic-assisted ethanol extract (USHE) from Sargassum horneri, a brown seaweed containing fucosterol (6.22 ± 0.06 mg/g) and sulfoquinovosyl glycerolipids (C23H43O11S, C25H45O11S, C25H47O11S, C27H49O11S), against oxidative damage in ultraviolet B (UVB)-exposed HaCaT keratinocytes. USHE indicated the antioxidant activity with increasing ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. Moreover, USHE increased cell viability by markedly reducing the production of intracellular reactive oxygen species (ROS) in UVB-exposed HaCaT keratinocytes. Additionally, USHE reduced the apoptosis, and sub-G1 cell population, and increased the mitochondrial membrane potential. Moreover, USHE modulated the protein expression levels of anti-apoptotic molecules (Bcl-xL, Bcl-2, and PARP), and pro-apoptotic molecules (Bax, cleaved caspase-3, p53, cleaved PARP, and cytochrome C). This modulation accorded with the upregulation of cytosolic heme oxygenase (HO)-1, NAD(P)H quinone oxidoreductase 1 (NQO 1), and nuclear factor erythroid-2-related factor 2 (Nrf2), collectively known as components of the antioxidant system. These findings suggest that USHE has a photoprotective effect in UVB-exposed HaCaT keratinocytes and can be utilized to develop cosmeceuticals for UVB protection.

Background: This study aimed to investigate the effects of intradialytic concurrent (resistance-endurance) training combined with melatonin (MEL) supplementation on oxidative stress, inflammation, and cellular damage in hemodialysis (HD) patients. Methods: Thirty-two hemodialysis (HD) patients were randomly assigned to three groups: Exercise (EX)-MEL, EX-Placebo (PLA), and Control (C)-PLA. Participants in the EX-MEL and EX-PLA groups underwent 12 weeks of concurrent training. Before nocturnal sleep, they ingested either 3 mg of MEL (EX-MEL) or a placebo (EX-PLA and C-PLA). Blood samples were collected at baseline and after 12 weeks of intervention to assess lipid peroxidation [malondialdehyde (MDA)], antioxidant biomarkers [ferric reducing antioxidant power (FRAP), reduced glutathione (GSH), total thiol (THIOL)], total bilirubin (TBIL), uric acid (UA), biomarkers of muscle and liver damage [aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), creatine kinase (CK), lactate dehydrogenase (LDH), Gamma-glutamyltransferase (Gamma-GT)], and inflammation [C-reactive protein (CRP)]. Results: EX-MEL demonstrated a decrease of MDA (p

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (Non Communicable Diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin and hesperidin or a similar product long-term. Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Grape pomace is a winery byproduct rich in polyphenols with antioxidant capacity, which makes it an attractive product for use in pig diets. The study aimed to investigate the effect of 0, 5, and 10% inclusion of dehydrated grape pomace (DGP) in finishing pig diets. Including 10% of DGP in the diets increased (P&lt;0.05) daily feed intake, backfat thickness at the first rib, P2 backfat thickness, fat area, and fat to meat ratio and decreased (P&lt;0.05) the percentage of lean meat. Grape pomace did not affect TBARS and fresh meat quality characteristics, except for intramuscular fat. When 10% DGP was included in the diet, intramuscular fat, ΣSFA, ΣMUFA, and Σω-3 increased and ω-6:ω-3 ratio was reduced. In conclusion including up to 10% of DGP in the diet of finishing pigs did not affect growth performance, and the oxidative stability of processed meat, but increased the adiposity of the carcasses. Meat quality was improved through an increase in intramuscular fat and ω-3 fatty acids at 10% inclusion. It is feasible to include DGP in pig diets at a level of at least 10%, which would contribute to the rational use and reduction of environmental liability of by-products from the winery industry.

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homologue, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives of the study of NOXs in CVDs.

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning as a sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function and regulate transcription in response to different stressors. In this study, we showed that cell lines vary based on their antioxidation potential at basal conditions. The transcriptome of HEK293 cells was tested following knockdown (KD) of DJ-1 using siRNAs which reduced the DJ-1 transcripts to only 12% of the original level. We compared the expression levels of 14k protein-coding transcripts, and 4.2k non-coding RNAs relative to control cells treated with non-specific siRNAs. Among the coding genes, ~200 upregulated differentially expressed genes (DEGs) signified a coordinated antiviral innate immune response. Most genes were associated with regulation of type 1 interferons (IFN) and induction of inflammatory cytokines. About a quarter of these genes were also induced in cells treated by non-specific siRNAs that were used as a negative control. Beyond the antiviral response, 114 genes were specific to KD of DJ-1 with enrichment in RNA metabolism and mitochondrial functions. A smaller set of downregulated genes (58 genes) were associated with dysregulation in membrane structure, cell viability, and mitophagy. We propose that KD of DJ-1 diminish its protective potency against oxidative stress, rendering the cells labile and responsive to dsRNA signal by activation of a large number of genes, many of which drive apoptosis, cell death, and inflammatory signatures. The KD of DJ-1 highlights its crucial role in regulating genes associated with antiviral responses, RNA metabolism, and mitochondrial functions, apparently through alteration in STAT activity and downstream signaling. Given that DJ-1 is highly expressed in metastatic cancers, targeting DJ-1 could be a promising therapeutic strategy where manipulation of DJ-1 levels may reduce cancer cell viability and enhance the efficacy of cancer treatments.

Understanding complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all main metabolic pathways. When glucose is replaced by galactose cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as REDOX control is not well documented, particularly in endothelial cells where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show higher mitochondrial oxidative capacity, more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main REDOX regulators and found that Bovine Aortic Endothelial Cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those with glucose in the media. Thus, culture of endothelial cells in galactose containing medium may provide a more suitable condition to study in vitro mitochondrial related processes than glucose media, and deeply influence REDOX signaling in these cells.

Purpose: Glyphosate and glyphosate-based herbicides (GBH), extensively utilized as herbicides worldwide, have been associated with numerous health issues. Previous experimental studies have indicated their potential to disrupt selenium homeostasis by either interfering with uptake or increasing oxidative stress. However, there is a significant research gap concerning the connection between glyphosate exposure and selenium status in epidemiological studies, particularly within nationally representative samples. Methods: In this study, we examined data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), involving 3011 participants aged 3 and above. Our main objective was to examine the connection between urinary glyphosate levels, whole blood selenium, and selenium intake. Results: Our analysis did not uncover an association between urinary glyphosate and selenium intake. Nevertheless, we observed a negative correlation between urinary glyphosate levels and whole blood selenium, with a ß coefficient of -1.984, S.E. = 0.639, and P = 0.003 in the final model. We also reported a notable decrease in the average concentrations of whole blood selenium as glyphosate tertiles increased, with P-values for trend of 0.033. Furthermore, the association was particularly prominent among females, non-Hispanic whites, and individuals with lower selenium intake. Conclusions: In this thorough examination of NHANES data, our study uncovers a possible detrimental connection between glyphosate exposure and whole blood selenium levels. These findings underscore the importance of further investigation into the health consequences of glyphosate exposure and its potential influence on selenium status, thereby raising awareness of potential implications for public health.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Retention of placenta (RP) in crossbred cattle poses health, reproductive, and economic challenges linked to oxidative stress, hormonal imbalances, and complex causative factors. Emphasizing the key role of mitochondria in oxidative phosphorylation (OXPHOS) and hormone synthesis, our study is the first to explore differences in OXPHOS activity, mitochondrial content, and mtDNA-encoded gene expression between normal and RP. In addition, gross morphological examination of placental tissues from both groups revealed noticeable disparities in cotyledons of RP as compared to normal placenta. Moreover, OXPHOS complex I specific activity was decreased in RP, and RT-qPCR analysis unveiled a significant reduction in transcript levels of 10 mtDNA-encoded protein genes. While COX3 and ATP8 genes showed no significant changes, ND6 increased in RP. Whereas, mtDNA copy number varied between animals but showed no statistically significant differences among groups. Retained placenta manifests alterations in the transcript levels of various mitochondrial genes, complex activity, and mtDNA content, potentially linked to heightened energy demands or mitochondrial insufficiency, posing an elevated risk. Overall, our study suggests a link between mitochondrial abnormalities, gene expression, and RP. This connection could influence the removal of fetal membranes by affecting energy supply, hormonal balance, and oxidative stress. This study also offers novel insights and serves as a valuable animal model for studying placental insufficiency in humans. Moving forward, comprehensive investigations are imperative to unravel underlying mechanisms and intricate roles of mitochondria in the context of RP, paving the way for targeted interventions to mitigate health, reproductive, and economic challenges in crossbred cattle.

Background: Nutritional status and oxidative stress have been implicated in the pathogenesis and persistence of long COVID, but data in patients undergoing hemodialysis (HD) are limited. The present study aimed to investigate the association between pre-infection nutritional status, oxidative stress, and one-year long COVID persistence in HD patients. Methods: This prospective observational cohort study enrolled 115 HD patients with confirmed COVID-19. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score twice: before infection and three months post-infection. Oxidative markers included malondialdehyde (MDAs), ceruloplasmin, transferrin, and sulfhydryl groups. The endpoint was one-year long COVID persistence. Results: Moderate pre-infection CONUT scores were associated with heightened severe undernutrition risk (p &lt; 0.0001), elevated MDAs (p &lt; 0.0001), and reduced ceruloplasmin levels (p = 0.0009) at three months post-COVID-19 compared to light CONUT scores. Pre-infection CONUT score independently predicted post-COVID oxidative damage [OR 2.3 (95%CI 1.2; 4.6), p &lt; 0.0001] and one-year long COVID persistence [HR 4.6 (95%CI 1.4; 9.9), p &lt; 0.0001], even after adjusting for potential confounders. Conclusion: Moderate pre-infection undernutrition in patients undergoing HD associated with increased post-COVID oxidative stress intensity and heightened risk of one-year long COVID persistence.

Contamination of the environment with nano- and microplastic particles exerts a threatened impact on the aquatic ecosystems and sustainable catfish aquaculture. The presence of nanoplastics has been found to have a detrimental impact on both aquatic and terrestrial ecosystems. The present study examines the effect of polystyrene nanoplastics on DNA, erythrocytes, oxidative status and renal of catfish in addition to the potential protective effects of Chlorella vulgaris bioremeditation and selenium to hinder this effect. Six equal groups of fish were used as follows: Group 1: served as a control group and received water free from PS NPs; Group 2: was exposed to PS NPs at a concentration of 5mg/L; Group 3: was exposed to PS NPs (5mg/L) + selenium (1mg/kg diet); Group 4: was exposed to PS NPs (5mg/L) + C. vulgaris (25g/kg diet); Group 5: was supplemented with C. vulgaris (25g/kg diet); and Group 6: was supplemented with selenium (1mg/kg diet). The results indicated that PS NPs induced oxidative stress by significantly elevating MDA activities and slightly reducing antioxidant biomarkers, resulting in DNA damage, increased frequency of micronuclei, erythrocyte alterations, and numerous histopathological alterations in kidney tissue. Selenium and C. vulgaris significantly ameliorated the oxidative/antioxidant status, reduced DNA damage, micronucleus frequency, erythrocyte alterations, and morphology of kidney tissue. Nevertheless, further research is needed to evaluate in detail the mechanism behind the toxicity with nano-microplatics in aquatic system.

The saltmarsh plant Halimione portulacoides was shortly exposed to realistic levels of inorganic mercury (iHg), aiming to investigate adaptative processes of the roots and leaves regarding re-dox homeostasis, physiology, and Hg accumulation. Plants were collected at a contaminated (CONT) and a reference (REF) site, addressing the interference of contamination background. The influence of major abiotic variables (i.e., temperature and light) was also examined. Total Hg lev-els, antioxidant enzymes, lipid peroxidation (LPO), and photosynthetic activity were analyzed after 2 and 4 hours of exposure. Accumulation of iHg in the roots was noticed poorly, and no translocation to stems and leaves was found, but plants from CONT seemed more prone to iHg uptake (in winter). Despite that, antioxidant modulation in roots and leaves was found, disclos-ing, in winter, higher thresholds for the induction of enzymatic antioxidants in CONT leaves compared to REF, denoting that the former are better prepared to cope with iHg redox pressure. Consistently, CONT leaves exposed to iHg had remarkably lower LPO levels. Exposure did not impair the photosynthetic activity, pinpointing H. portulacoides ability to cope with iHg toxicity under a very short-term exposure. Biochemical changes were noticed before enhancements in ac-cumulation, reinforcing the relevance of these responses in precociously signaling iHg toxicity.

Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component begins to play an important part in de-termining the overall picture. Moreover, the lack of therapies to relieve existing symptoms com-plicates the fight against this condition. As a result, the use of animal models has made biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, fol-lowed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function, nerve tissue and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes was recognized for its help against free radicals. To investigate the vit. B12 effect, fish were divided in four different groups and exposed to a pesticide mixture (600 μg L-1 fipronil + 600 μg L-1 pyriproxyfen) and 0.24 μg L-1 vit. B12 for 14 days. The impact of the compound was assessed daily by EthoVision software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of su-peroxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. Results showed significant improvements for locomotor activity parameters and a pos-itive influence of vitamin on sociability. Regarding the state of oxidative stress, a high activity was found for SOD and GPx in the case of vit. B12, while the mixture of pesticides and vitamin had a lower level of MDA. In conclusion, the study brings new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and help the organism function.

2,4-dichlorophenoxyacetic acid (2,4-D) is a globally used herbicide and is frequently found in water samples. This fact has prompted studies on its effects in non-target organisms, revealing significant alterations on liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, biomarkers of toxicity and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among the studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formu-lations in exposure experiments. The most affected biomarkers were related to a decrease in an-tioxidant capacity, including alterations in the activities of catalase and superoxide dismutase, and in the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, we found studies about the effects of 2,4-D in mixtures with other pesticides, as well as hepatoprotection trials. The reviewed data in-dicate that the reduction in antioxidant capacity and oxidative stress play an important role in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not ful-ly understood and further research in this area is needed.

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria (6-hydroxy-L-nicotine) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those no later than July 2023, was conducted. The search focused specifically on articles pertaining to nicotine metabolites, memory, oxidative stress, cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 185 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6-hydroxy-L-nicotine.

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration.

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration.

Coptisine (Cop) exerts a neuroprotective effect in central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, GC-MS based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations which might be mediated through its antioxidant and anti-inflammatory property.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury, caused by several factors, including ischemia, toxins and inflammation, has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. Thus, this review aimed to describe the pharmacological properties of phytocompounds from Amazonian plant species and their effectiveness in the prevention and treatment of Acute Kidney Injury. (AKI). The classes of Amazonian plant compounds with significant biological activities most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although many of them with insufficiently explored potential, mainly in face of AKI, a clinical condition with high morbidity and mortality.

Diabetic nephropathy (DN), one of the primary consequences of diabetes mellitus, affecting many people worldwide. Diabetes affects yearly 463 million adults globally between the ages of 20 and 79, and is the main cause of death under the age of 60. ROS production rises during hyperglycemia and is crucial to the development of diabetic complications. Advanced glycation end products (AGEs) are produced excessively in a diabetic state and accumulate in the kidney, where they change renal architecture and impair renal function. Another important targeted pathway for the formation of DN includes NF-B, Nrf2, NLRP3, Akt/mTOR, and autophagy. About 40% of individuals with diabetes eventually acquire diabetic kidney disease and end stage renal disease that needs hemodialysis, peritoneal dialysis, or kidney transplantation, to survive. The current state of acceptable therapy for this kidney ailment is limited. The studies revealed that some naturally occurring bioactive substances might shield the kidney by controlling oxidative stress, renal fibrosis, inflammation, and autophagy. In order to provide new potential therapeutic lead bioactive compounds for contemporary drug discovery and clinical management of DN, this review was designed to examine the various mechanistic pathways by which current conventional plants derive phytocompounds that are effective for the control and treatment of DN.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.