Maintenance Of Redox Balance Research Articles

Export of heme by the feline leukemia virus C receptor regulates mitochondrial biogenesis and redox balance in the hematophagous insect Rhodnius prolixus.

Heme is a prosthetic group of proteins involved in vital physiological processes. It participates, for example, in redox reactions crucial for cell metabolism due to the variable oxidation state of its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The export of heme initially attributed to the feline leukemia virus C receptor (FLVCR) has recently been called into question, following the discovery of choline uptake by the same receptor in mammals. Here, we found that RpFLVCR is a heme exporter in the midgut of the hematophagous insect Rhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl-biliverdin, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity, and activated mitochondrial biogenesis, effects not observed in RpHO-silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.

The Role of Glutathione Transferase Omega-Class Variant Alleles in Individual Susceptibility to Ovarian Cancer.

The tumor microenvironment is affected by reactive oxygen species and has been suggested to have an important role in ovarian cancer (OC) tumorigenesis. The role of glutathione transferases (GSTs) in the maintenance of redox balance is considered as an important contributing factor in cancer, including OC. Furthermore, GSTs are mostly encoded by highly polymorphic genes, which further highlights their potential role in OC, known to originate from accumulated genetic changes. Since the potential relevance of genetic variations in omega-class GSTs (GSTO1 and GSTO2), with somewhat different activities such as thioltransferase and dehydroascorbate reductase activity, has not been clarified as yet in terms of susceptibility to OC, we aimed to investigate whether the presence of different GSTO1 and GSTO2 genetic variants, individually or combined, might represent determinants of risk for OC development. Genotyping was performed in 110 OC patients and 129 matched controls using a PCR-based assay for genotyping single nucleotide polymorphisms. The results of our study show that homozygous carriers of the GSTO2 variant G allele are at an increased risk of OC development in comparison to the carriers of the referent genotype (OR1 = 2.16, 95% CI: 0.88-5.26, p = 0.08; OR2 = 2.49, 95% CI: 0.93-6.61, p = 0.06). Furthermore, individuals with GST omega haplotype H2, meaning the concomitant presence of the GSTO1*A and GSTO2*G alleles, are more susceptible to OC development, while carriers of the H4 (*A*A) haplotype exhibited lower risk of OC when crude and adjusted haplotype analysis was performed (OR1 = 0.29; 95% CI: 0.12-0.70; p = 0.007 and OR2 = 0.27; 95% CI: 0.11-0.67; p = 0.0054). Overall, our results suggest that GSTO locus variants may confer OC risk.

Mitochondrial Peroxiredoxin 6 Declines with Aging in Parallel with Increases in Hydrogen Peroxide Generation

Oxidative stress in cells and tissues arise from an imbalance between the generation of free radicals and the ability to detoxify these reactive oxygen species (ROS). Peroxiredoxins (PRDXs) are a family of widely distributed enzymes that act as master antioxidant regulators by scavenging peroxides and peroxynitrites. The accumulation of oxidative damage from chronic exposure to oxidative stress such as on DNA, mitochondrial proteins, and lipid macromolecules, is postulated to result in age-associated pathologies and physiological dysfunctions. Peroxiredoxin-6 (PRDX6) contributes to the maintenance of redox balance in a variety of tissues from lung to skeletal muscle. Here, we hypothesized that PRDX6 localizes to the mitochondria and plays a significant role in maintaining mitochondrial function through targeting mitochondrially generated ROS, and that gradual loss of mitochondrial PRDX6 contributes to increased oxidative stress and accumulation of oxidative damage during aging. In this study, respiratory rates and complex activities in isolated skeletal muscle mitochondria obtained from young (3-6 months) and old (20-24 months) C57/BL6J mice were compared. Amplex UltraRed fluorescence was used to determine production rates of mitochondrial hydrogen peroxide (H2O2). Western blot analysis was used to compare protein abundance and ELISA was used to measure lipid peroxidation in skeletal muscle mitochondrial fractions. Our findings revealed that isolated mitochondria from skeletal muscle in old mice generated higher rates of H2O2 from complex I (CI) during state 3 and state 4 (State 3; State 4) derived respiration (3.93 ± 0.41; 3.56 ± 0.38 pmol H2O2..s−1.mg−1) compared to young mouse mitochondria (1.57 ± 0.48; 1.89 ± 0.59 pmol H2O2.s−1.mg−1, p ≤ 0.05). This was also found when saturating amounts of ADP were used to stimulate maximal rates of oxygen consumption (old: 3.65 ± 0.77; young 1.40 ± 0.21 pmol H2O2−1.mg−1, p ≤ 0.05). Furthermore, CI activity was found to be lower in isolated mitochondria from old mice (0.65 ± 0.006 U.ug−1) compared to young mice (2.11 ± 0.64 U.ug−1, p ≤ 0.05). Similarly, mitochondrial PRDX6 abundance was lower while levels of lipid peroxidation product malondialdehyde were higher in skeletal muscle from old animals (old: 2712 ± 1320 pg.mL−1; young: 489 ± 225 pg.mL−1). These results show higher mitochondrial ROS generation rates and oxidative damage in old animals. These data also suggest that loss of PRDX6 in aging leads to mitochondrial dysfunction mediated by diminished CI activity and loss of membrane integrity. We are currently conducting mechanistic studies in cellular models with disrupted PRDX6 expression to confirm the effect of this protein in maintaining mitochondrial function. This study offers novel observations on the significance of mitochondrially localized PRDX6 in antioxidant defense as well as the sources and roles of ROS generation in contributing to an aging phenotype. National Institute of General Medical Sciences (NIGMS, Award Number R35GM146951). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.

Cancer cells demand amino acids beyond their usage as "building blocks" for protein synthesis. As a result, targeting amino acid acquisition and utilization has emerged as a pivotal strategy in cancer treatment. In the setting of leukemia therapy, compelling examples of targeting amino acid metabolism exist at both pre-clinical and clinical stages. This review focuses on summarizing novel insights into the metabolism of glutamine, asparagine, arginine, and tryptophan in leukemias, and providing a comprehensive discussion of perturbing their metabolism to improve the therapeutic outcomes. Certain amino acids, such as glutamine, play a vital role in the energy metabolism of cancer cells and the maintenance of redox balance, while others, such as arginine and tryptophan, contribute significantly to the immune microenvironment. Therefore, assessing the efficacy of targeting amino acid metabolism requires comprehensive strategies. Combining traditional chemotherapeutics with novel strategies to perturb amino acid metabolism is another way to improve the outcome in leukemia patients via overcoming chemo-resistance or promoting immunotherapy. In this review, we also discuss several ongoing or complete clinical trials, in which targeting amino acid metabolism is combined with other chemotherapeutics in treating leukemia.

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis.

Anoikis presents a significant barrier in the metastasis of cancer. As the most aggressive type of thyroid cancer, anaplastic thyroid cancer (ATC) exhibits a high risk of metastasis and is characterized by high mortality. Therefore, investigating the molecular mechanisms of anoikis resistance in ATC is important for devising therapeutic targets in clinical research. Differentially Expressed Genes were screened in ATC cells under attached and detached culture conditions with RNA-seq. Investigate the impact of enolase 2 (ENO2) on apoptosis and spheroid formation by gain and loss of function. Changes of reactive oxygen species (ROS), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were detected to assess redox balance. The transcriptional regulatory role of signal transducer and activator of transcription 1 (STAT1) on ENO2 was validated through Dual-Luciferase Reporter Gene Assay. Explore the impact of ENO2 expression on the formation of lung metastases in nude mice. We found that the glycolysis process was activated in detached ATC cells. Several genes in the glycolysis process, particularly ENO2, a member of the enolase superfamily was upregulated in ATC cells cultured in suspension. The upregulation of ENO2 enabled the maintenance of redox balance by supplying GSH and NADPH, thereby preventing cells from undergoing anoikis. In terms of mechanism, the expression of STAT1 was enhanced in anoikis resistance cells, which in turn positively regulated the expression of ENO2. In vivo, ENO2-suppressed ATC cells resulted in a significantly lower rate of lung colonization compared to control ATC cells. Stable expression of ENO2 and the maintenance of redox balance played a pivotal role in facilitating anoikis resistance of ATC.

A new mouse strain with mutation in the NFE2L2 (NRF2 gene

The transcription factor NRF2 is involved in inflammatory reactions, maintenance of redox balance, metabolism of xenobiotics, and is of particular interest for aging studies. In the present work, CRISPR/Cas9 genome editing technology was used to generate NRF2ΔNeh2 mice containing a substitution of eight amino acid residues at the N-terminus of the NRF2 protein, upstream of the functional Neh2 domain, which ensures binding of NRF2 to its inhibitor KEAP1. Heterozygote NRF2wt/ΔNeh2 mice gave birth to homozygous mice with lower than expected frequency, accompanied by their increased embryonic lethality and visual signs of anemia. Mouse embryonic fibroblasts (MEFs) from NRF2ΔNeh2/ΔNeh2 homozygotes showed impaired resistance to oxidative stress compared to wild-type MEFs. The tissues of homozygous NRF2ΔNeh2/ΔNeh2 animals had a decreased expression of NRF2 target genes: NAD(P)H: Quinone oxidoreductase-1 (Nqo1); aldehyde oxidase-1 (Aox1); glutathione-S-transferase A4 (Gsta4); while the relative mRNA level of monocyte chemoattractant protein 1 (Ccl2), vascular cell adhesion molecule 1 (Vcam1) and chemokine Cxcl8 was increased. Thus, the resulting mutation in the Nfe2l2 gene partially impaired the function of this transcription factor, expanding the insights into the functional role of the unstructured N-terminus of NRF2. The obtained NRF2ΔNeh2 mouse line can be used as a model object for studying various pathologies associated with oxidative stress and inflammation.

A New Mouse Strain with a Mutation in the NFE2L2 (NRF2) Gene.

Transcription factor NRF2 is involved in inflammatory reactions, maintenance of redox balance, metabolism of xenobiotics, and is of particular interest for studying aging. In the present work, the CRISPR/Cas9 genome editing technology was used to generate the NRF2ΔNeh2 mice containing a substitution of eight amino acid residues at the N-terminus of the NRF2 protein, upstream of the functional Neh2 domain, which ensures binding of NRF2 to its inhibitor KEAP1. Heterozygote NRF2wt/ΔNeh2 mice gave birth to homozygous mice with lower than expected frequency, accompanied by their increased embryonic lethality and visual signs of anemia. Mouse embryonic fibroblasts (MEFs) from the NRF2ΔNeh2/ΔNeh2 homozygotes showed impaired resistance to oxidative stress compared to the wild-type MEFs. The tissues of homozygous NRF2ΔNeh2/ΔNeh2 animals had a decreased expression of the NRF2 target genes: NAD(P)H:Quinone oxidoreductase-1 (Nqo1); aldehyde oxidase-1 (Aox1); glutathione-S-transferase A4 (Gsta4); while relative mRNA levels of the monocyte chemoattractant protein 1 (Ccl2), vascular cell adhesion molecule 1 (Vcam1), and chemokine Cxcl8 was increased. Thus, the resulting mutation in the Nfe2l2 gene coding for NRF2, partially impaired function of this transcription factor, expanding our insights into the functional role of the unstructured N-terminus of NRF2. The obtained NRF2ΔNeh2 mouse line can be used as a model object for studying various pathologies associated with oxidative stress and inflammation.

The implications of exercise in Drosophila melanogaster: insights into Akt/p38 MAPK/Nrf2 pathway associated with Hsp70 regulation in redox balance maintenance.

This study investigated the potential effects of exercise on the responses of energy metabolism, redox balance maintenance, and apoptosis regulation in Drosophila melanogaster to shed more light on the mechanisms underlying the increased performance that this emerging exercise model provides. Three groups were evaluated for seven days: the control (no exercise or locomotor limitations), movement-limited flies (MLF) (no exercise, with locomotor limitations), and EXE (with exercise, no locomotor limitations). The EXE flies demonstrated greater endurance-like tolerance in the swimming test, associated with increased citrate synthase activity, lactate dehydrogenase activity and lactate levels, and metabolic markers in exercise. Notably, the EXE protocol regulated the Akt/p38 MAPK/Nrf2 pathway, which was associated with decreased Hsp70 activation, culminating in glutathione turnover regulation. Moreover, reducing the locomotion environment in the MLF group decreased endurance-like tolerance and did not alter citrate synthase activity, lactate dehydrogenase activity, or lactate levels. The MLF treatment promoted a pro-oxidant effect, altering the Akt/p38 MAPK/Nrf2 pathway and increasing Hsp70 levels, leading to a poorly-regulated glutathione system. Lastly, we demonstrated that exercise could modulate major metabolic responses in Drosophila melanogaster aerobic and anaerobic metabolism, associated with apoptosis and cellular redox balance maintenance in an emergent exercise model.

Super-enhancer-driven MLX mediates redox balance maintenance via SLC7A11 in osteosarcoma

Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence of transcriptional addiction in cancer cells emphasizes the biological significance and clinical relevance of super-enhancers. In this study, we found that Max-like protein X (MLX), a member of the Myc-MLX network, is driven by super-enhancers. Upregulation of MLX predicts a poor prognosis in osteosarcoma. Knockdown of MLX impairs growth and metastasis of osteosarcoma in vivo and in vitro. Transcriptomic sequencing has revealed that MLX is involved in various metabolic pathways (e.g., lipid metabolism) and can induce metabolic reprogramming. Furthermore, knockdown of MLX results in disturbed transport and storage of ferrous iron, leading to an increase in the level of cellular ferrous iron and subsequent induction of ferroptosis. Mechanistically, MLX regulates the glutamate/cystine antiporter SLC7A11 to promote extracellular cysteine uptake required for the biosynthesis of the essential antioxidant GSH, thereby detoxifying reactive oxygen species (ROS) and maintaining the redox balance of osteosarcoma cells. Importantly, sulfasalazine, an FDA-approved anti-inflammatory drug, can inhibit SLC7A11, disrupt redox balance, and induce massive ferroptosis, leading to impaired tumor growth in vivo. Taken together, this study reveals a novel mechanism in which super-enhancer-driven MLX positively regulates SLC7A11 to meet the alleviated demand for cystine and maintain the redox balance, highlighting the feasibility and clinical promise of targeting SLC7A11 in osteosarcoma.

Inositol polyphosphate multikinase modulates redox signaling through nuclear factor erythroid 2-related factor 2 and glutathione metabolism

Maintenance of redox balance plays central roles in a plethora of signaling processes. Although physiological levels of reactive oxygen and nitrogen species are crucial for functioning of certain signaling pathways, excessive production of free radicals and oxidants can damage cell components. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling cascade is the key pathway that mediates cellular response to oxidative stress. It is controlled at multiple levels, which serve to maintain redox homeostasis within cells. We show here that inositol polyphosphate multikinase (IPMK) is a modulator of Nrf2 signaling. IPMK binds Nrf2 and attenuates activation and expression of Nrf2 target genes. Furthermore, depletion of IPMK leads to elevated glutathione and cysteine levels, resulting in increased resistance to oxidants. Accordingly, targeting IPMK may restore redox balance under conditions of cysteine and glutathione insufficiency.

The underestimated role of mitochondria in vitiligo: From oxidative stress to inflammation and cell death.

Vitiligo is an acquired depigmentary disorder characterized by the depletion of melanocytes in the skin. Mitochondria shoulder multiple functions in cells, such as production of ATP, maintenance of redox balance, initiation of inflammation and regulation of cell death. Increasing evidence has implicated the involvement of mitochondria in the pathogenesis of vitiligo. Mitochondria alteration will cause the abnormalities of mitochondria functions mentioned above, ultimately leading to melanocyte loss through various cell death modes. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in mitochondrial homeostasis, and the downregulation of Nrf2 in vitiligo may correlate with mitochondria damage, making both mitochondria and Nrf2 promising targets in treatment of vitiligo. In this review, we aim to discuss the alterations of mitochondria and its role in the pathogenesis of vitiligo.

BET Protein Inhibitor JQ1 Modulates Mitochondrial Dysfunction and Oxidative Stress Induced by Chronic Kidney Disease.

Among the mechanisms involved in the progression of kidney disease, mitochondrial dysfunction has special relevance. Epigenetic drugs such as inhibitors of extra-terminal domain proteins (iBET) have shown beneficial effects in experimental kidney disease, mainly by inhibiting proliferative and inflammatory responses. The impact of iBET on mitochondrial damage was explored in in vitro studies in renal cells stimulated with TGF-β1 and in vivo in murine unilateral ureteral obstruction (UUO) model of progressive kidney damage. In vitro, JQ1 pretreatment prevented the TGF-β1-induced downregulation of components of the oxidative phosphorylation chain (OXPHOS), such as cytochrome C and CV-ATP5a in human proximal tubular cells. In addition, JQ1 also prevented the altered mitochondrial dynamics by avoiding the increase in the DRP-1 fission factor. In UUO model, renal gene expression levels of cytochrome C and CV-ATP5a as well as protein levels of cytochrome C were reduced These changes were prevented by JQ1 administration. In addition, JQ1 decreased protein levels of the DRP1 fission protein and increased the OPA-1 fusion protein, restoring mitochondrial dynamics. Mitochondria also participate in the maintenance of redox balance. JQ1 restored the gene expression of antioxidant proteins, such as Catalase and Heme oxygenase 1 in TGF-β1-stimulated human proximal tubular cells and in murine obstructed kidneys. Indeed, in tubular cells, JQ1 decreased ROS production induced by stimulation with TGF-β1, as evaluated by MitoSOXTM. iBETs, such as JQ1, improve mitochondrial dynamics, functionality, and oxidative stress in kidney disease.

Zinc improves sexual and erectile function in HAART-treated rats via the upregulation of erectogenic enzymes and maintenance of redox balance

Purpose HAART has been shown to impair sexual function and penile erection via perturbation of penile redox balance, while zinc has been established to exert antioxidant activity. Therefore, this study focused on the role and associated molecular mechanism of zinc in HAART-induced sexual and erectile dysfunction. Materials and methods Twenty male Wistar rats were randomly grouped into four (n = 5 rats per group); the control, zinc-treated, HAART-treated, and HAART + zinc-treated groups. Treatments were per os daily for eight weeks. Results Zinc co-administration significantly improved HAART-induced increase in the latencies of mount, intromission, and ejaculations. Zinc also attenuated HAART-induced reduction in the motivation to mate, penile reflex/erection, and frequencies of mount, intromission, and ejaculations. In addition, zinc co-treatment improved HAART-induced decline in penile NO and cGMP, dopamine, and serum testosterone. More so, zinc prevented HAART-induced rise in penile activities of monoamine oxidase, acetylcholinesterase, phosphodiesterase-5, and arginase. Furthermore, concomitant treatment with zinc ameliorated HAART-induced penile oxidative stress and inflammation. Conclusion In conclusion, our present findings show that zinc improves sexual and erectile function in HAART-treated rats by upregulating erectogenic enzymes via the maintenance of penile redox balance.

RECENT THERAPEUTIC ADVANCES & PRECLINICAL PHASES OF RETINITIS PIGMENTOSA

Retinitis pigmentosa (RP) is a group of hereditary illnesses characterized by a slow loss of retinal photoreceptors, which impairs a long-term vision. It is among the most prevalent forms of hereditary retinal dystrophy and has a sizable cost impact on both the individuals affected and the community as a whole. The typical symptoms of this disorder include nyctalopia, loss of the concentric visual field, and finally loss of the bilateral central vision.The primary effect is a progressive loss of vision. One of the main causes of vision loss and blindness in persons under 60, it affects roughly 1.5 million people globally. There is presently no known cure for RP, and the only approved gene therapy, voretigeneneparvovec, is only given to a tiny subset of patients with known RPE65 mutations. Retinoids, vitamin A supplements, sun protection, visual aids, and medical and surgical treatments to treat ocular comorbidities are now the only available therapies, however these merely serve to halt the diseases progression. Given the limited therapeutic landscape, it is vital to develop fresh, personalized therapy modalities that focus on degeneration of the retina. Although the variety of the gene mutations involved makes it difficult to identify a target treatment for RP, new fundamental research indicates an improvement towards comprehending the causes of retinal degeneration. Discovering novel molecular treatments that can specifically target specific receptors or signaling pathways lays the foundation for more effective medication development. The most recent advancements in potential RP treatments are highlighted in this article, with an emphasis on preclinical stage foundational research on molecular targets, which will form the basis for subsequent drug development. We will discuss the alterations that take place to the molecular pathways connected to the growth of RP, with a focus on the ER stress and apoptotic pathways, redox balance maintenance, and genomic stability. Subsequently proceed over the treatment modalities being looked at, like gene and cell therapy, as well as the most recent studies that are discovering new potential drug targets for RP.

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases.

The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin's immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.

Effect of substitution of taurine for methionine and additional taurine supplementation on the performance and antioxidative capacity of laying hens

Taurine (TAU), a sulfur-containing amino acid that synthesized from methionine and cystine, plays vital roles in maintenance of redox balance. The effect of substitution of TAU for methionine was evaluated in vivo and in vitro. The effects of replacing methionine with TAU and additional TAU supplementation on the performance and antioxidant capacity of laying hens were evaluated. The in vitro cultured chicken primary hepatocytes and intestinal epithelial cells were further employed. Two hubdred eighty-eight 40-wk-old Isa brown laying hens were divided into 4 groups and subjected one to the following treatments: fed with basal diet with 0.17% crystallized DL-Met (CON), the control diet and replace 25% (21% total Met, 21TAU) or 50% (42% total Met, 42TAU) of crystallized DL-Met with taurine, the control diet supplemented with 0.1% taurine (0.1% TAU). The laying rate, feed intake, egg weight, and feed efficiency were not influenced (P > 0.05) by TAU replacement or additional TAU supplementation. In the liver, 0.1% TAU decreased SOD but increased GSH-Px activity (P < 0.01). In duodenum, 42TAU decreased SOD activity (P < 0.05) while 0.1% TAU decreased GSH level and SOD activity (P < 0.05). In the hepatocytes, TAU treatment decreased (P < 0.05) the MDA and GSH contents, whereas increased SOD and GSH-Px activities (P < 0.05). Meanwhile, TAU treatment decreased (P < 0.05) the protein expression of Nrf2 while increase Keap1 expression. The mRNA expression of Nrf2, SOD1, SOD2, CAT, and GCLC were increased (P < 0.05) and GSR were decreased (P < 0.05) by 0.1% TAU. In the intestinal epithelial cells, TAU treatment decreased (P < 0.05) SOD activity, increased (P < 0.05) CAT activity, and decreased (P < 0.05) the mRNA and protein expression of Nrf2. In summary, partial substitution methionine for taurine (21-42%) has no influence on egg performance of hens. Taurine enhances the antioxidative capacity in hepatocyte but not in the enterocytes and if taurine could offer an improved effect on antioxidant capacity needs to be verified under oxidative stress-challenged conditions.

Экспериментальная биология растений: физиолого-биохимические исследования на Европейском Северо-Востоке (обзор)

The stages of formation and the main results of the phytophysiology development in the Komi Republic were considered. The contribution of the Institute of Biology to the study of the fundamental processes of plant life was noted. Achievements in the study of the physiological and biochemical bases of the production process of agricultural crops, functional plasticity, and stress resistance of wild-growing plants were analyzed. Results that significantly deepen the understanding of the respiration and respiratory pathways involvement in the plant cells metabolism and bioenergetics have been obtained. The participation of alternative mitochondrial oxidase in the complex protective system of the cell, signaling, and the redox balance maintenance under stress has been proven. Current research and priority directions for the long-term period were outlined.

Glutathione: pharmacological aspects and implications for clinical use

Glutathione is a tripeptide found in many tissues which plays a pivotal role in critical physiological processes such as maintenance of redox balance, reduction of oxidative stress by enhancement of metabolic detoxification of both xenobiotic and endogenous compounds, and regulation of immune system function. Glutathione depletion is associated with many chronic degenerative diseases and loss of function with aging and altered glutathione metabolism has been implicated in central nervous system diseases, frailty and sarcopenia, infected state, chronic liver diseases, metabolic diseases, pulmonary and cardiovascular diseases. Therefore, the glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Here we describe the main pharmacological aspects of glutathione, focusing on its synthesis and role in several vital functions including antioxidant defense, detoxification of xenobiotics and modulation of immune function and fibrogenesis and the clinical implications of its depletion and we discuss the different strategies for increasing glutathione cellular levels either by providing specific precursors and cofactors or directly administering the tripeptide.

Antibacterial and antioxidant films based on HA/Gr/TA fabricated using electrospinning for wound healing

Prevention of bacterial contamination, maintenance of redox balance in the environment, and acceleration of wound healing are key requirements for wound dressing. In the present study, hyaluronic acid (HA)/graphene (Gr)-electrospun fibre films loaded with polyphenolic tannic acid (TA) were prepared using electrospinning. The antioxidant activity of the films was then examined to determine whether they contained optimal TA concentrations for subsequent research. Following that, the surface morphology and physicochemical properties of the films were determined and in vitro experiments were conducted to assess their biocompatibility and antibacterial activity. Finally, the in vivo effects of the electrostatically spun fibre films on infected wound healing in mouse models were observed. The HA/Gr/TA-electrospun fibre film with 0.3% w/v TA concentration displayed the best antioxidant activity and better mechanical, water-absorption, water-retention, and degradation properties than the film without TA. In addition, it displayed superior antibacterial activity and biocompatibility, as well acceleration of infected wound healing, than the film without TA. Therefore, the HA/Gr/TA-electrospun fibre film is a promising alternative option for wound dressings.

Metabolic profiling of serum and urine in preeclampsia and gestational diabetes in early pregnancy

PE and GDM are two major metabolic diseases affecting pregnancy. Individuals suffering from GDM are at an increased risk of developing PE in later gestational stages. Current study was done to evaluate first trimester serum and urine metabolome using nuclear magnetic resonance (NMR) spectroscopy to identify metabolites and pathways differentially regulated in both diseases. Serum metabolomics analysis revealed deregulation in larger group of metabolites and pathways as compared to urine between PE/GDM and NT groups. Few metabolites showed altered expression in both aliments. Perturbed metabolites have association with energy metabolism, protein metabolism, insulin sensitivity, gut microbiome and maintenance of redox balance. Deregulation in these metabolic pathways contributes to the pathology of GDM/PE. Our study revealed that serum metabolomic profile of PE and GDM shows overlap in 1st trimester of gestation. It also explored the potential of NMR metabolomics in identification of common biomolecules that could be developed into a clinical tool for early detection of both PE /GDM..