Oxidative Stress Conditions Research Articles

Connecting the Dots: Telomere Shortening and Rheumatic Diseases.

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.

Dietary supplementation with pterostilbene activates the PI3K-AKT-mTOR signalling pathway to alleviate progressive oxidative stress and promote placental nutrient transport

BackgroundProgressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport.ResultsPTE increased the antioxidant capacity and immunoglobulin content in mothers’ blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces.ConclusionsThese findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity.Graphical

In laying hens, chronic heat stress-induced renal fibrosis is potentially promoted by indoxyl sulfate

Indoxyl sulfate (IS), a uremic toxin, is a harmful factor that damages kidneys. Chronic heat stress in laying hens causes renal injury; however, whether IS accumulation is involved in this injury remains unknown. We selected 20 Boris brown laying hens (27 weeks old) and randomly assigned them to two groups (n = 10), one group was exposed to chronic heat stress (32 °C for 4 weeks), whereas the other was maintained at 24 °C. Chronic heat exposure significantly increased plasma and renal IS concentrations (P < 0.05). Exposure to heat also increased renal expression of the aryl hydrocarbon receptor (AhR) and its target genes (CYP1A4 and CYP1B1). Furthermore, chronic heat exposure tended to increase the 2-thiobarbituric acid reactive substances content (P = 0.08) and significantly decreased the antioxidant capacity in the kidney, while increasing the transcription levels of nuclear factor κB and fibrosis-related genes (COLA1A1, αSMA, TGF-β, Smad3, and VCAM-1) and the area of renal fibrosis. Our results indicate that chronic heat exposure induces systemic and renal IS accumulation in laying hens. This accumulated IS may activate the AhR pathway and chronically disrupt the oxidative stress status and antioxidant activity, thus promoting renal fibrosis and dysfunction in laying hens.

12349 Increased Total Oxidative Status/Total AntioxidantCapacityandReduced Microparticle Size In Diabetes Kidney Disease

Abstract Disclosure: S.C. Oliveira: None. A. Bridi: None. B.G. Rossato: None. R.N. Moresco: None. J.C. Silveira: None. M.W. Lauria: None. F.V. Comim: None. Diabetic kidney disease (DKD) is an important cause of morbimortality in the adult population with Type 1 Diabetes Mellitus (T1DM). Our cross-sectional study explored the association of abnormalities in extracellular vehicles (EVs) and oxidative stress markers in three distinct groups of clinical outpatients: normal controls, T1DM (without DKD), and DKD. Clinical and biochemical data were obtained from these groups. The isolation and characterization of EVs from serum were obtained through a series of processes, including the ultracentrifugation and characterization of EVs was identified by specific protein markers by western blot morphology checked by Scanning Electron Microscope (FEI Tecnai 20; LAB6 emission; 200 kV). EVs particle size and concentration were determined by NanoSight NS300 instrument (Malvern Panalytical, UK). Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), Advanced Oxidation of Protein Products (AOPP), (Ferric Reducing Antioxidant Power), C reactive Protein, Uric Acid, Aloxan levels were determined in the serum or the plasma.Overall, 124 patients were evaluated: 61 normal controls, 42 T1DM (without DKD), and 21 DKD defined according the KDIGO guidelines. The three groups were similar regarding age (mean± SD) of 40.3 ± 13.7 years, BMI 25.8 ± 5.1 Kg/m2, and Abdominal Circumference 89.6 ± 12.3 cm. The albumin/creatinine ratio was statistically different among the groups, being its (median [95%CI]) of 4.0 [3.9-5.14] mg/g in Controls, 6.4[5.5-10.0]mg/g in T1DM, and 81.4 [48.5 -1415] mg/g in DKD (p&amp;lt;0.001). The DKD patients exhibited higher SBP and an increased proportion of retinopathy and neuropathy than T1DM, but HBa1c levels were similar between the two diabetes groups. Patients with DKD show an increased TOS/TAC Ratio ( μmol H2O2 Equiv/L /mmol Trolox Equiv/L) (ANOVA p&amp;lt;0.001) superior to T1DM and controls. The mean ± SD was 61.1 ± 31.0 in Controls, 103.0± 68 in T1DM, and 145.0± 62.8 in DKD. Interestingly, T1DM exhibited an increased TOS/TAC Ratio than Controls. No modifications in AOPP or FRAP could be observed among the three groups.There is a gradual decrease in EVs size (but not concentration) in patients with DKD in comparison to T1DM and controls, and T1DM with controls. The mean of the moda size of EVs was (mean + SE) 144.5 ± 3.04 nm in Controls versus 136.14 ± 3.5 nm in T1DM, and 135.4 ± 3.6nm in DKD (ANOVA p=0.04). The concentration was (mean ± SE) 4.57 x109 ± 5.57 x108 particles/mL in Controls, 3.58 x109 ± 2.9 x108 particles/mL in T1DM and 3.94 x109 ± 3.7 x108 particles/mL in DKD (NS).Our results suggest an association of increased oxidative stress status (TOS/TAC ratio) and reduced microvesicles size in the presence of T1DM; both abnormalities progress towards the development of DKD. Presentation: 6/3/2024

The Serratia sp. strain C2 confers tomato tolerance to high salt, virus infection and both stresses in combination

Besides increasing plant growth, several Plant Growth Promoting Rhizobacteria (PGPR), can enhance tolerance to biotic and/or abiotic stresses of numerous plant species. While cultivated plants are frequently subject to combined stresses in the field, there is limited knowledge of the effect of PGPR on plants undergoing simultaneous stress conditions. Therefore, we tested the beneficial properties of the halotolerant PGPR Serratia sp. strain C2, previously shown to enhance salt stress tolerance in barley, on tomato plants exposed to salinity, to Potato Virus Y (PVY) infection, and both stresses simultaneously. In our experimental conditions, C2 inoculation improved tomato tolerance to salt stress and positively correlated with a 46–68 % decrease in the level of PVY RNA compared to non-inoculated tomato plants. Morphometric, physiological and biochemical analyses (e.g., chlorophyll, sugar and proline accumulation, oxidative stress status and NDVI) indicated that C2 treatments had beneficial effects on tomato growth under simple and combined stress conditions. This is the first report of a PGPR enhancing tolerance not only to individually induced salinity and PVY infection, but also to both stresses in combination. Moreover, the expression analysis of selected genes involved in stress responses and RNA silencing-mediated antiviral immunity suggests that C2 can interfere with distinct defence response pathways to enhance stress tolerance in tomato. These pioneering results support the perspective of using PGPR as multi-spectrum and multi-host biostimulants for improving plant growth and protection from biotic, abiotic, and combined stresses to promote sustainable crop production in the face of environmental changes.

Cytotoxic Potencies of Zinc Oxide Nanoforms in A549 and J774 Cells.

Zinc oxide nanoparticles (NPs) are used in a wide range of consumer products and in biomedical applications, resulting in an increased production of these materials with potential for exposure, thus causing human health concerns. Although there are many reports on the size-related toxicity of ZnO NPs, the toxicity of different nanoforms of this chemical, toxicity mechanisms, and potency determinants need clarification to support health risk characterization. A set of well-characterized ZnO nanoforms (e.g., uncoated ca. 30, 45, and 53 nm; coated with silicon oil, stearic acid, and (3-aminopropyl) triethoxysilane) were screened for in vitro cytotoxicity in two cell types, human lung epithelial cells (A549), and mouse monocyte/macrophage (J774) cells. ZnO (bulk) and ZnCl2 served as reference particles. Cytotoxicity was examined 24 h post-exposure by measuring CTB (viability), ATP (energy metabolism), and %LDH released (membrane integrity). Cellular oxidative stress (GSH-GSSG) and secreted proteins (targeted multiplex assay) were analyzed. Zinc oxide nanoform type-, dose-, and cell type-specific cytotoxic responses were seen, along with cellular oxidative stress. Cell-secreted protein profiles suggested ZnO NP exposure-related perturbations in signaling pathways relevant to inflammation/cell injury and corresponding biological processes, namely reactive oxygen species generation and apoptosis/necrosis, for some nanoforms, consistent with cellular oxidative stress and ATP status. The size, surface area, agglomeration state and metal contents of these ZnO nanoforms appeared to be physicochemical determinants of particle potencies. These findings warrant further research on high-content "OMICs" to validate and resolve toxicity pathways related to exposure to nanoforms to advance health risk-assessment efforts and to inform on safer materials.

Sera from Rheumatoid Arthritis Patients Induce Oxidative Stress and Pro-Angiogenic and Profibrotic Phenotypes in Human Endothelial Cells.

Background: Rheumatoid arthritis (RA) is a long-term autoimmune condition marked by persistent inflammation of the joints and various systemic complications, including endothelial dysfunction, atherosclerosis, and pulmonary fibrosis. Oxidative stress is a key contributor to the pathogenesis of RA, potentially exacerbating vascular damage and promoting pro-angiogenic and profibrotic processes. Objective: This study aims to investigate the effects of sera from RA patients on human umbilical vein endothelial cells (HUVECs), focusing on the induction of oxidative stress, endothelial cell proliferation, migration, and collagen type I synthesis. Methods: Twenty-eight serum samples were collected from RA patients and healthy donors (HDs). HUVECs were exposed to these sera, and intracellular reactive oxygen species (ROS) levels were fluorescently detected using H2DCF-DA. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was evaluated through a scratch wound assay, and collagen type I synthesis was measured using a lentiviral vector expressing the green fluorescent protein (GFP) under the control of the human COL1A1 gene promoter. Results: Exposure to RA sera resulted in a significant increase in intracellular ROS levels in HUVECs compared to HD sera, indicating an elevated state of oxidative stress. RA sera also promoted endothelial cell proliferation and migration, suggesting a pro-angiogenic stimulus. Additionally, RA sera significantly increased collagen type I synthesis in HUVECs, implicating a potential role in profibrotic processes associated with RA. Conclusion: The results of this study emphasize the importance of circulating factors in RA sera in promoting oxidative stress, endothelial dysfunction, and pro-angiogenic and profibrotic phenotypes in endothelial cells. These processes may contribute to the vascular and fibrotic complications observed in RA, highlighting the necessity for additional research into focused therapeutic approaches to alleviate these effects.

Sea cucumber-derived extract can protect skin cells from oxidative DNA damage and mitochondrial degradation, and promote wound healing

Our skin serves as the primary barrier against external environmental insults, the latter of which can cause oxidative stress within cells, while various bioactive peptides sourced from natural resources hold promise in protecting cells against such oxidative stress. In this study, we investigate the efficacy of a low molecular weight extract from the sea cucumber Apostichopus japonicus, denoted as Sample-P, in facilitating cell migration and wound healing under oxidative stress conditions in skin cells. The naturally derived compound is a highly complex mix of peptides exhibiting antioxidative properties, as highlighted through liquid chromatography-mass spectrometry peptide screening and an in vitro antioxidant assay. Our results demonstrate that Sample-P is capable of promoting cell migration while preventing severe stress responses such as visible through mTOR expression. To further identify the molecular pathways underpinning the overall protective mechanism of Sample-P, we have utilised a proteomics approach. Our data reveal that Sample-P regulates protein expression associated with ribosomal pathways, glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum (ER), which help in preserving DNA integrity and safeguarding cellular organelles, such as mitochondria and the ER, under oxidative stress conditions in skin cells. In summary, in the presence of H2O2, Sample-P exhibits antioxidative properties at both molecular and cellular levels, rendering it a promising candidate for topical skin treatment to wound healing and to address age-related skin conditions.

Tanshinone IIA delays liver aging by modulating oxidative stress.

Organ-specific aging is increasingly recognized for its research significance, with liver aging demonstrating particular relevance due to its central role in metabolism. We have pioneered the discovery that the expression of ESRRG in the liver positively correlates with age and have established its association with clinical characteristics, including hepatic edema. Our findings link liver aging to a shift in oxidative stress states, where ESRRG, a crucial nuclear receptor responsive to oxidative stress, may be modulated by various small molecules. Through virtual screening of a natural medicinal molecule database followed by further validation, we confirmed that the natural compound Tanshinone IIA mitigates oxidative stress-induced damage in the liver via the ESRRG/Cyp2e1 pathway, thus decelerating liver aging. Importantly, our study also explores the dynamic impact of Tanshinone IIA on ESRRG conformation, providing a profound understanding of its molecular interactions with ESRRG and laying a foundation for the rational design of small molecules based on natural compounds.

Buckwheat containing-bread: a scientific inquiry into insulin, polyphenols, antioxidants status, and oxidative stress markers in type-II diabetic individuals

Buckwheat grains contain bioactive components with known effects on cardio-metabolic biomarkers. Previous research on oxidative stress markers made exclusively from wheat flour or two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were considerably higher than fasting values after consuming buckwheat-incorporated bread (BWB), including clinical, animal, and epidemiological studies, suggesting the potential of buckwheat intake to influence parameters such as polyphenol intake, antioxidant status, insulin levels, and oxidative stress markers. However, the specific impact of buckwheat-containing bread on these biomarkers in individuals with type-II diabetes remains a significant gap in our understanding. Our current work aims to address this gap by exploring the effects of buckwheat-containing bread on insulin levels, polyphenol intake, antioxidant status, and markers of oxidative stress. In a randomized crossover study, 16 individuals with type-II diabetes were assigned to consume control bread made exclusively from wheat flour or bread incorporating 50% buckwheat flour. The research followed a crossover design, with a period of one to two washout interventions. Test breads were given at breakfast following a 12 h fast the previous night. After 2 h of bread intake, blood samples were collected at baseline (fasting). The two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were significantly higher than fasting values after consuming buckwheat-incorporated bread (BWB). This suggests that the buckwheat-containing bread improved plasma total polyphenol levels and total antioxidant status. Our research concludes that the intake of bread containing buckwheat positively influences polyphenols in plasma and the status of antioxidants. This suggests that incorporating buckwheat into bread may have favorable effects on biomarkers associated with cardio-metabolic health in individuals with type-II diabetes. By addressing these knowledge gaps, our research aims to inform and engage the scientific community in further exploration of the potential health benefits of buckwheat-containing bread.

Preconditioning of Mesenchymal Stem Cells Enhances the Neuroprotective Effects of Their Conditioned Medium in an Alzheimer's Disease In Vitro Model.

Alzheimer's disease (AD) develops as a result of oxidative damage to neurons and chronic inflammation of microglia. These processes can be influenced by the use of a conditioned medium (CM) derived from mesenchymal stem cells (MSCs). The CM contains a wide range of factors that have neurotrophic, antioxidant, and anti-inflammatory effects. In addition, the therapeutic potential of the CM can be further enhanced by pretreating the MSCs to increase their paracrine activity. The current study aimed to investigate the neuroprotective effects of CM derived from MSCs, which were either activated by a TLR3 ligand or exposed to CoCl2, a hypoxia mimetic (pCM or hCM, respectively), in an in vitro model of AD. We have developed a novel in vitro model of AD that allows us to investigate the neuroprotective and anti-inflammatory effects of MSCs on induced neurodegeneration in the PC12 cell line and the activation of microglia using THP-1 cells. This study demonstrates for the first time that pCM and hCM exhibit more pronounced immunosuppressive effects on proinflammatory M1 macrophages compared to CM derived from untreated MSCs (cCM). This may help prevent the development of neuroinflammation by balancing the M1 and M2 microglial phenotypes via the decreased secretion of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased secretion of IL-4, as well as the expression of IL-10 and TGF-β by macrophages. Moreover, a previously unknown increase in the neurotrophic properties of hCM was discovered, which led to an increase in the viability of neuron-like PC12 cells under H2O2-induced oxidative-stress conditions. These results are likely associated with an increase in the production of growth factors, including vascular endothelial growth factor (VEGF). In addition, the neuroprotective effects of CM from preconditioned MSCs are also mediated by the activation of the Nrf2/ARE pathway in PC12 cells. TLR3 activation in MSCs leads to more potent immunosuppressive effects of the CM against pro-inflammatory M1 macrophages, while the use of hCM led to increased neurotrophic effects after H2O2-induced damage to neuronal cells. These results are of interest for the potential treatment of AD with CM from preactivated MSCs.

The SRC/NF-κB-AKT/NOS3 axis as a key mediator of Kaempferol's protective effects against oxidative stress-induced osteoclastogenesis.

Osteoclasts are integral to the advancement of osteoporosis (OP), and their generation under conditions of oxidative stress (OS) involves various pathways. However, the specific mechanism through which the natural antioxidant kaempferol (KAE) mitigates the influence of OS on osteoclasts remains somewhat uncertain. This study aims to evaluate the effect of KAE on osteoclast formation under OS and explore its possible mechanism. Zebrafish were used to observe the effects of KAE on OP and OS. OP and OS "double disease targets" network pharmacology were used to predict the action target and mechanism of KAE on OP under OS. The effects of KAE on osteoclast differentiation induced by OS were evaluated using RWA264.7 cells induced by LPS. To elucidate the potential mechanism, we detected the expression of related factors and target genes during induction. The presence of KAE exhibited potential in improving the conditions of OP and OS in zebrafish. KAE can reduce the OS of RAW 264.7 cells stimulated by LPS, inhibit the formation of osteoclasts, and change the level of related factors of OS, and reduce the increase of TRAP. The utilization of network pharmacology and target gene expression assay revealed that KAE exerted a down-regulatory effect on the expression of proto-oncogene tyrosine protein kinase (SRC), nuclear factor kappa-B (NF-κB), Serine/Threonine Kinase-1 (AKT1), Nitric Oxide Synthase 3 (NOS3) and Matrix Metallopeptidase-2 (MMP2). Based on the results of this study, KAE may effectively mitigate OS and impede the formation of osteoclasts through the SRC/NF-κB-AKT/NOS3 axis.

Oxyrase-Mediated Improvement in the Quality and Fertility of Crossbred Boar Spermatozoa During Liquid Storage.

The present experiment was carried out to investigate the role of Oxyrase in preserving the invitro quality, redox status and invivo fertility of crossbred boar spermatozoa. A total of 24 ejaculates from 6 crossbred (n = 4 from each boar) boars were collected and extended in Beltsville Thawing Solution (BTS) in 1:2 ratio and divided into three aliquots. The first aliquot served as a control (without Oxyrase). Rest of the two aliquots were supplemented with 0.125 (T1) and 0.25 IU/mL Oxyrase (T2). Semen samples were preserved at 15°C for 5 days and kinematics of spermatozoa by CASA, semen quality parameters and oxidative stress status were evaluated at 0, 72 and 120 h of storage. The findings of studies revealed that supplementation of Oxyrase at 0.25 IU/mL resulted in higher (p < 0.05) total motility, progressive motility, plasma membrane integrity, acrosome integrity and functional integrity of plasma membrane at 72 and 120 h in comparison to the control group. Mitochondrial membrane potential (MMP) was higher (p < 0.05) at 72 and 120 h, whereas higher (p < 0.05) DNA integrity was observed at 120 h in T2. The lipid peroxidation (LPO) was lower (p < 0.05) and superoxide dismutase activity (SOD) and total antioxidant capacity (TAC) were higher (p < 0.05) in the T2 group at 120 h as compared to control. Invivo fertility trials indicated a higher (p < 0.05) litter size in T2 in comparison to other groups. The study concluded that the inclusion of Oxyrase at 0.25 IU/mL in the extender protects the crossbred boar spermatozoa against oxidative damage and improves the invivo fertility.

Thioredoxin-1 protein interactions in neuronal survival and neurodegeneration

Neuronal cell death remains the main aspect of neurodegenerative diseases and the main challenge for treatment strategies. Thioredoxin1 (Trx1) is a major cytoplasmic thiol oxidoreductase protein involved in redox signaling, hence a crucial player in maintaining neuronal health. Trx1 levels are notably reduced in neurodegenerative diseases including Alzheimer's and Parkinson's diseases, however, the impact of this decrease on neuronal physiology remains largely unexplored. This is mainly due to the nature of Trx1 redox regulatory role which is afforded by a rapid electron transfer to its oxidized protein substrates. During this reaction, Trx1 forms a transient bond with the oxidized disulfide bond in the substrate. This is a highly fast reaction which makes the identification of Trx1 substrates a technically challenging task. In this project, we utilized a transgenic mouse model expressing a Flag-tagged mutant form of Trx1 that can form stable disulfide bonds with its substrates, hence allowing identification of the Trx1 target proteins. Autophagy is a vital housekeeping process in neurons that is critical for degradation of damaged proteins under oxidative stress conditions and is interrupted in neurodegenerative diseases. Given Trx1's suggested involvement in autophagy, we aimed to identify potential Trx1 substrates following pharmacologic induction of autophagy in primary cortical neurons. Treatment with rapamycin, an autophagy inducer, significantly reduced neurite outgrowth and caused cytoskeletal alterations. Using immunoprecipitation and mass spectrometry, we have identified 77 Trx1 target proteins associated with a wide range of cellular functions including cytoskeletal organization and neurodegenerative diseases. Focusing on neuronal cytoskeleton organization, we identified a novel interaction between Trx1 and RhoB which was confirmed in genetic models of Trx1 downregulation in primary neuronal cultures and HT22 mouse immortalized hippocampal neurons. The applicability of these findings was also tested against the publicly available proteomic data from Alzheimer's patients. Our study uncovers a novel role for Trx1 in regulating neuronal cytoskeleton organization and provides a mechanistic explanation for its multifaceted role in the physiology and pathology of the nervous system, offering new insights into the molecular mechanisms underlying neurodegeneration.

Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging

Oocytes play a crucial role in transmitting maternal mitochondrial DNA (mtDNA), essential for the continuation of species. However, the effects of mitochondrial reactive oxygen species (ROS) on mammalian oocyte maturation and mtDNA maintenance remain unclear. We investigated this by conditionally knocking out the Sod2 gene in primordial follicles, elevating mitochondrial matrix ROS levels from early oocyte stages. Our data indicates that reproductive aging in Sod2 conditional knockout females begins at 6 months, with oxidative stress impairing oocyte quality, particularly affecting OXPHOS complex II and mtDNA-encoded mRNA levels. Despite unchanged mtDNA mutation load, mtDNA copy numbers exhibited significant variations. Strikingly, reducing mtDNA copy numbers by reducing mtSSB protein, crucial for mtDNA replication, accelerated reproductive aging onset to three months, underscoring the critical role of mtDNA copy number maintenance under oxidative stress conditions. This research provides new insights into the relationship among mitochondrial ROS, mtDNA, and reproductive aging, offering potential strategies for delaying aging-related fertility decline.

Estimating Anticancer Effects of Yohimbine in DMBA-Induced Oral Carcinogenesis Hamster Model: Utilizing Biochemical and Immunohistochemical Techniques.

Yohimbine is a potent bioactive indole alkaloid, isolated from a variety of biological sources and has long been used as a natural stimulant and aphrodisiac, particularly to treat erectile dysfunction. However, some literature also points toward its anticancer effect in different experimental models. The current study aimed to address a clinical concern on the therapeutic utilization of yohimbine as a repurposed drug. We employed 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis model juxtaposed with biochemical investigation of several detoxification and antioxidant markers, such as Cyt p450, Cyt b5, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), glutathione reductase (GR), glutathione S transferase (GST), DT-diaphorase, vitamin C, vitamin E, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The immunohistochemical assessment of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), proliferating cell nuclear antigen (PCNA), and cyclin D1 expression were also performed to observe the effect of yohimbine on these markers. The hamsters treated with DMBA presented the growth of tumors in the buccal pouches, accompanied by significant changes in the liver and buccal mucosa levels of Phase I & II detoxification enzymes and lipid peroxidation (LPO). A significant rise in the range of 2- to 3.5-fold was observed in Cyt p450, Cyt b5, and LPO in DMBA-treated animals. However, oral administration of yohimbine significantly restored the LPO, antioxidant, and detoxifying enzyme activities. Additionally, the levels of COX-2, IL-6, PCNA, and cyclin D1 were also found to be downregulated by yohimbine treatment. In conclusion, yohimbine improved the biochemical and immunohistochemical markers of DMBA-induced oral cancer and reverted to near normal values via ameliorating the underlying inflammation and oxidative stress conditions. Our study highlighted the potential of yohimbine as anticancer agent, especially against oral cancer and suggested its possible use as repurposed drug.

The antibacterial and antioxidant activities of combined Equisetum arvense extract with TiO2 nanoparticles in PMAA films

Studies on the antibacterial effects of natural compounds, particularly those derived from medicinal plants, have garnered a lot of attention because of the enhanced resistance of germs to antibiotics. The resistance of bacteria to plant-derived chemicals may develop much slower if not at all, which enhances the potential for future research in this area. This study investigates the antibacterial effect of Equisetum arvense extract combined with TiO2 nanoparticles and embedded in Polymethacrylic acid films on the growth of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The prepared material was characterized via X-ray Diffraction, Scanning Electron Microscopy, and Atomic Force Microscopy to understand the physicochemical merits of it, and the antibacterial properties were then examined. The results indicate that Equisetum arvense exhibits antibacterial properties against Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. At modest dosages, this plant may offer a novel treatment option for disorders associated with oxidative stress, apoptosis, or hypertonic conditions.

Evidence of altered Redox Homeostasis in Trichothiodystrophy

Trichothiodystrophy (TTD) is a rare hereditary disease whose prominent feature is brittle hair. Additional clinical signs are physical and neurodevelopmental abnormalities and in about half of the cases hypersensitivity to UV radiation. Although the mutations involved in this condition have been characterized, the correlation between the molecular defects and the plethora of clinical symptoms is not well understood. Recently the presence of a redox unbalance in TTD has been suggested although not clear evidences have been reported on this aspect. Therefore, in the present study, we evaluated the redox status of fibroblasts isolated from a TTD patient. In addition, to understand the ability of TTD cells to respond to oxidative insults, the cells were challenged with H2O2 and mitochondrial O2- and mitochondrial membrane potential were measured in different oxidative conditions. In addition, NRF2/BACH protein levels were also analysed in response to H2O2. The results suggested an aberrant mitochondrial response to oxidative stimuli, an increased baseline oxidative stress status in TTD and an altered NRF2/BACH level. This study emphasises that altered redox homeostasis might play a role in TTD pathogenesis and mitochondria functionality could represent an alternative therapeutic target for this condition to improve patients clinical features.

Microplastics originated from Plasmix-based materials caused biochemical and behavioral adverse effects on Daphnia magna

The implementation of advanced recycling techniques represents a key strategy for mitigating the mismanagement and the environmental impact of plastic waste. A limited array of plastic polymers can be efficiently recycled, while a notable portion of plastic waste remains unrecyclable. In Italy, this residual, heterogeneous fraction is referred to as Plasmix. Because of its complexity and non-homogeneous composition, Plasmix is primarily directed towards low-value applications. However, recent developments in laboratory-scale mechanical recycling have enabled the creation of new plastic materials from Plasmix. Prior to their application, these materials must undergo rigorous eco-safety evaluation. The present study aims to assess the potential toxicity of microplastics (MPs) from Plasmix-based materials on the freshwater crustacean Daphnia magna. Specifically, this study investigated sub-individual and individual effects induced by a 21-day exposure to different concentrations of MPs generated from the grinding of naïve and Additivated Plasmix-based materials (hereafter referred to as Px-MPs and APx-MPs, respectively). Sub-individual endpoints focused on changes in oxidative status, including the modulation of antioxidant and detoxifying enzyme activities, as well as oxidative damage, such as lipid peroxidation. Individual level endpoints included alterations in survival and reproduction. Microscopy analyses confirmed the ingestion of both Px-MPs and APx-MPs by D. magna individuals. An oxidative stress condition raised in organisms exposed to Px-MPs, whereas no effect was observed in individuals exposed to APx-MPs. Although survival was not affected, a significant impairment in reproductive output was detected at the end of exposure to all the concentrations of both MP types. These findings suggest that even low concentrations of Px-MPs and APx-MPs could negatively affect the health status of D. magna, underscoring the need for further research to complete the risk assessment of Plasmix-based materials prior to their use in consumer products.

Apigenin With Protective Effect Against Oxidative Injury to Skeletal Muscle Cells via Activation of the Nrf-2HO-1 Pathway

Human skeletal muscle would suffer from an oxidative injury caused by long-term training or exhaustive exercise. It is important to scavenge oxygen free radicals in due course to reduce oxidative damage to human skeletal muscle cells (HSKMC) by some means. Apigenin, as an effective antioxidant, is likely to protect HSKMC against oxidative injury. In this study, tert-butyl hydroperoxide (t-BHP) was used to induce oxidative injured HSKMC. Then, we studied the protective effect of apigenin on cell viability, oxidative stress status, and the expression of antioxidation-related proteins and tried to understand the mechanisms driving these effects. Results show that the cellular viability of HSKMC could be obviously improved by apigenin treatment at the concentration of 80 μM. Pretreatment with celery resulted in the activity of related enzymes approaching normal levels, and decrease the release of malondialdehyde and the level of intracellular reactive oxygen species in HSKMC. The Nuclear factor E2-related factor (Nrf2) signaling pathway could also be activated by apigenin. Therefore, apigenin could attenuate t-BHP induced oxidative injury in HSKMC through enhancement of the activities of related antioxidant enzymes by activating the Nrf2 pathway.