Oxidative Damage Research Articles

Lubricin-Inspired Nanozymes Reconstruct Cartilage Lubrication System with an "In-Out" Strategy.

Lubricin, secreted primarily by chondrocytes, plays a critical role in maintaining the function of the cartilage lubrication system. However, both external factors such as friction and internal factors like oxidative stress can disrupt this system, leading to osteoarthritis. Inspired by lubricin, a lubricating nanozyme, that is, Poly-2-acrylamide-2-methylpropanesulfonic acid sodium salt-grafted aminofullerene, is developed to restore the cartilage lubrication system using an "In-Out" strategy. The "Out" aspect involves reducing friction through a combination of hydration lubrication and ball-bearing lubrication. Simultaneously, the "In" aspect aims to mitigate oxidative stress by reducing free radical, increasing autophagy, and improving the mitochondrial respiratory chain. This results in reduced chondrocyte senescence and increased lubricin production, enhancing the natural lubrication ability of cartilage. Transcriptome sequencing and Western blot results demonstrate that it enhances the functionality of mitochondrial respiratory chain complexes I, III, and V, thereby improving mitochondrial function in chondrocytes. In vitro and in vivo experiments show that the lubricating nanozymes reduce cartilage wear, improve chondrocyte senescence, and mitigate oxidative stress damage, thereby mitigating the progression of osteoarthritis. These findings provide novel insights into treating diseases associated with oxidative stress and frictional damage, such as osteoarthritis, and set the stage for future research and development of therapeutic interventions.

Antibacterial and antibiofilm properties of cinnamon essential oil on Pseudomonas tolaasii and application of potato starch/CEO active pads in preservation of mushroom (Agaricus bisporus)

Pseudomonas tolaasii (P. tolaasii) is considered to be the main pathogen of brown spot disease in mushrooms. Cinnamon essential oil (CEO), a natural bacteriostatic agent, has potential application prospects in the field of food preservation. The purpose of this study was to explore the antibacterial mechanism of CEO on P. tolaasii, and to prepare an active pad to study the preservation effect of mushroom, so as to provide a basis for the development of natural antibacterial agents. P. tolaasii was isolated from browning mushroom and identified by 16S rRNA gene sequencing. The antibacterial and antibiofilm activities of cinnamon essential oil (CEO) on P. tolaasii and its application in mushrooms were investigated. The results indicated that CEO had a significant inhibitory effect on P. tolaasii. After the CEO treatment, the surface of P. tolaasii cells was damaged, and significant leakage of entocyte was observed. In addition, CEO could effectively induce oxidative stress and lipid peroxidation in P. tolaasii cells, and cause irreversible damage to cell membranes, leading to energy and respiratory metabolism disorders. The activity of ROS defense enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were significantly inhibited (P < 0.05), aggravating the oxidative damage to P. tolaasii. The crystal violet staining assay and scanning electron microscopy revealed that CEO treatment not only inhibited biofilm formation, but also effectively eradicated mature biofilm. The application effects displayed that the active pads packing containing CEO had excellent antibacterial effect and maintain the quality of mushroom (Agaricus bisporus). The results of this study will provide references for further research and application of natural food antibacterial agents.

Using CaCO3 armor to alleviate PFOA-induced stress on microorganisms in porous aquatic environments

Perfluorooctanoic acid (PFOA), even at trace levels, can cause considerable microbial responses in porous aquatic environments. We propose the use of CaCO3 to reduce PFOA migration through the formation of Ca-PFOA bonding, which impede the intracellular penetration of PFOA and thus alleviate PFOA-induced damage to microbes. In this work, a porous environment was simulated by sand columns (100 mm in height), and a thin layer of CaCO3 was placed on the top of the columns. Upon the dissolution of CaCO3, Ca2+ reduced the zeta potential of the effluent as the influent containing 2.4 μM PFOA passed through the CaCO3-containing system. This promoted the bonding of Ca-PFOA, resulting in more than a twofold increase in the blocking efficiency of PFOA during the initial 13 days. A calcite calcium armor (50–100 nm) formed on the cell surface effectively reduced the oxidative damage caused by PFOA: intracellular reactive oxygen species were reduced by 39.3 %, and bioactivity (in adenosine triphosphate) increased by 454.5 %. The alleviation of PFOA-induced stress reduced the synthesis of extracellular polymerizing substances by 67.1 %, but microbial growth remained healthy. CaCO3 introduction stimulated quorum sensing through the generation of C6-HSL to up-regulate the carbon fixation pathway. Under PFOA-induced stress, CaCO3 introduction resulted in a microbial community that was similar to that in the absence of PFOA; additionally, the dominance of denitrifying bacteria as hosts of antibiotic resistance genes (ARGs) decreased, resulting in minimal or no impact on water purification efficiency. Additionally, microbial-induced carbonate precipitation functional microorganisms were enriched as Ca2+ alleviated PFOA-induced stress. In conclusion, CaCO3 effectively alleviated PFOA-induced stress and reduced the environmental effects of PFOA on the porous aquatic environment. Microbial enhancement strategy provides a new perspective for PFOA pollution remediation.

Gut-derived wild blueberry phenolic acid metabolites modulate extrinsic cutaneous damage.

As the first line of defense, the skin is equipped with various physiological mechanisms positioned to prevent incoming oxidative damage from numerous environmental insults. With persistent exposure to the environment, understanding ways to augment the skin defenses is paramount in protecting from premature aging. In this study, we investigated the ability of five dietary phenolic metabolites, typically found in the bloodstream after wild blueberry consumption, to successfully defend the skin from UV light exposure in a novel ex vivo co-culture model of human skin explants and primary endothelial cells. Skin explants, placed in transwell inserts, were exposed to UV, and subsequently co-cultured with endothelial cells. When the endothelial cells had been pretreated with the bioactive metabolites at physiological concentrations (hippuric acid 3000 nM, isoferulic acid 1000 nM, salicylic acid 130 nM, benzoic acid 900 nM, α-hydroxyhippuric acid 400 nM) cutaneous damage was prevented on the co-cultured with UV-challenged skin explants. Co-culture with non-pretreated endothelial cells did not protect skin explants. Specifically, the pretreatment was able to reduce skin lipid peroxidation (measured as 4-hydroxynonenal protein adducts), and pro-inflammatory enzymes such as cyclooxygenase 2 (COX-2) and NADPH oxidase 4 (NOX-4). Furthermore, pretreatment with the metabolites prevented UV-induced release of inflammatory cytokines such as IL-1β and IL-8 as well as nitric oxides (NO) levels. In addition, the metabolites showed an impressive ability to prevent the loss of cutaneous structural proteins including involucrin and collagen type 1. Of note, endothelial cells cultured with UV exposed skin explants exhibited increased oxidative stress demonstrated by heme oxygenase-1 (HO-1) up-regulation which was significantly prevented in the metabolite treated models. These findings highlight the ability of dietary polyphenolic metabolites to improve cutaneous defenses against extrinsic stressors.

P-368 In vitro culture with rutin and VEGF-A before xenotransplantation protects ovarian tissue from ischemia and oxidative damage but not from growing follicle depletion

Abstract Study question Can pre-treatment with antioxidant and vascular endothelial factor (VEGF-A) help to maintain healthy tissue structure and follicle pool in xenotransplanted human ovarian tissue? Summary answer Rutin and VEGF-A help to prevent fibrosis and oxidative stress damage in grafted ovarian tissue but cannot preserve growing follicles. What is known already Nowadays, ovarian tissue (OT) cryopreservation and autotransplantation become established fertility preservation methods in numerous countries. However, even if hundreds of children has been born thanks to this procedure, most crucial process during which 70-80% of the follicles are lost in the graft is the transplantation itself. As the graft restores vascularisation and regains its function the tissue undergoes ischemia and oxidative stress. There have been attempts made to improve this critical postoperative period by administration of different growth factors, hormones, antoxidants or mechanical tissue damage. Study design, size, duration Pieces of frozen-tharwed OT (2,5 × 2,5 mm) from 10 women were transplanted into immunodeficient mice for 4 weeks. Before xenotransplantation OT fragments were in vitro cultured for 36h in culture media supplemented with 1 μg/ml rutin and 50 ng/ml VEGF-A (n = 10 OT, pretreated grafted) or without (n = 10 OT, non-pretreated grafted). Frozen-thawed OTs were used as non-grafted controls for ischemia-reperfusion injury, apoptosis and follicle loss evaluation. Participants/materials, setting, methods OTs were received from cancer patients (n = 10) undergoing cryopreservation at National Cancer Institute. Xenotransplantation was performed at Life Sciences Centre, Vilnius University. Retrieved grafts were devided into one small piece for immunochistochemical evaluation of α-SMA and apoptosis by TUNEL, and one bigger piece for qPCR analysis of genes related to tissue integrity (PRDX1, SOD1, FN1, COL6A1, CASP3, ANGPT2, mouse CD31) and follicle development (FOXO3, FSHR, GDF9), house keeping gene being GAPDH/Gapdh. Main results and the role of chance After 4 weeks of grafting, multiple genes and protein expressions were evaluated. Vascularisation evaluation: compared to non-grafted group, in grafted OTs we observed significantly more vessels (α-SMA staining, p &amp;lt; 0.0001 and ANGPT2 expression, p &amp;lt; 0.05), as well 1,5-fold higher relative expression of mouse CD31 in pretreated grafted group vs non-pretreated grafted group. Qxidative stress and apoptosis evaluation: expression of SOD2, PRDX1 and CASP3 genes was lower in both grafted groups compared to non-grafted control, significant alterations between xenotransplanted groups were found. Structural gene evaluation: in non-grafted control we could find higher expression of COL6A1 and FN1 genes compared to grafted groups and statistical difference of COL6A1 expression in between grafted groups (p &amp;lt; 0.05). Follicle pool evaluation: primordial follicle activation was measured by FOXO3 gene expression change, though we did not find significant differences between any of three groups, p = 0.06 was observed between grafted OT groups. Maturing follicles were evaluated by expression changes in GDF9 and FSHR genes. We observed significant decrese in expression of these genes in grafted groups (p &amp;lt; 0.05). Results from TUNEL are awaited, thus are the quantification of apoptotic cells, which will provide valuable insights for correlation with vascularisation and oxidative stress. Limitations, reasons for caution This study was performed only in a long-term xenotransplantation setting, we cannot know if rutin and VEGF-A had a significant influence during the first days of OT transplantation. Due to the small size of OT grafted, counting and distribution of follicles was not performed, Wider implications of the findings This study shows that pretreatment of OTs with rutin and VEGF-A could be potentially used in human setting due to protection of ischemia and oxidative stress, especially if the survival of growing follicles is not required, as it is in cases of prepubertal girls. Trial registration number not applicable

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

O-253 Altered telomerase activity in ovarian follicular cells in patients with polycystic ovary syndrome

Abstract Study question Is telomerase machinery altered in cumulus and granulosa cells of patients with Polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART)? Summary answer Patients with PCOS presented an altered expression of telomerase inhibitor factors TRF1 and TRF2 and shorter telomeres in cumulus cells (CCs) and granulosa cells (GCs) What is known already PCOS affects 6%-20% of fertile women; one of the most common features is represented by abnormal folliculogenesis, showing a higher number of follicles at all developmental stages. In PCOS, increased levels of reactive oxygen species (ROS) have been related to abnormal follicular development due to oxidative stress-induced DNA damage. Telomeres, present at the ends of the chromosomes, are essential for maintaining their stability during somatic cell proliferation. When guanine-rich telomeric repeats are exposed to oxidative stress including ROS, they undergo oxidative DNA damage that shortens telomeres in non-dividing cells like follicular cells, thereby potentially altering folliculogenesis. Study design, size, duration A prospective experimental study was conducted at IVIRMA Rome and University Unicamillus from September 2022 to January 2024. CCs and GCs were collected from the follicular fluid of patients undergoing in vitro fertilization (IVF). Twenty-eight patients with PCOS and. Thirty-one normal responders were included in the pilot study. Participants/materials, setting, methods Women with PCOS (n = 28), diagnosed according to the Rotterdam criteria, were included in the study. The healthy control group (CONT) included normal responders (n = 31) undergoing IVF. CCs and GCs were collected on the day of oocyte retrieval and subsequently used for immunofluorescence spot counting of TRF1 and TRF2. In addition, telomere length was measured using a specific kit. qRT-PCRs for TRF1, TRF2 and apoptotic marker BAX genes were performed and expressed as 2^-ΔCT values. Main results and the role of chance Immunofluorescence for TRF1 in the PCOS group presented a higher spot number in CCs compared to the CONT (9.90±0.23 vs 7.96±0.33, p = 0.0009) while TRF2 spots significantly decreased (8.85 ±0.24 vs 11.23±0.28; p = 0.0007). An increase of TRF2 gene expression was observed in CCs of the PCOS group when compared to CONT (0.0052±0.0006 vs 0.0030±0.0003; p = 0.062) no differences were found in the expression of TRF1 (0.0343±0.006 vs 0.026±0.047p=0.68; Bax was significantly increased (0.0139±0.001 vs 0.0102±0,0007 p = 0.007) and telomeres have a shortening trend (0.36±0.36 vs 1±0 p = 0.74). In GC a lower number of TRF1 spots in PCOS vs CONT was observed while TRF2 had just an increasing trend (11.16± 0.586 vs 11.70 ± 1.99, p = 0.61; 16.79 ± 3,85 vs 11.34 ± 0.588; p = 0.68). In GCs of PCOS group vs CONT there was an increase in TRF2 gene expression (0,007 ± 0,001 vs 0.003 ± 0.0004; p = 0.03) and no differences were found in TRF1 (0.032± 0.003 vs 0.003± 0.012 p = 0.25). Ultimately Bax was increased in GCs of PCOS samples vs CONT (0.018 ±0.002 vs 0.011 ±0.0005 p = 0.0006) and the telomeres were significantly shorter (0.0246± 0.0349 vs 1± 0 p &amp;lt; 0.0001). Limitations, reasons for caution A limited number of samples were analyzed in the study and different PCOS sub-phenotypes were not considered. The analysis of CCs could be uninformative due to inter-individual variability in the PCOS sub-phenotypes within the same study group. Wider implications of the findings These findings demonstrate that PCOS patients present a higher expression of telomerase-inhibiting factors TRF1 and TRF2, undergo apoptosis and have significantly shorter telomeres supporting the theory that abnormal folliculogenesis in PCOS affects telomere length, therefore shedding new light on this medical condition and possibly explaining its clinical and biochemical features. Trial registration number not applicable

IL-17A Drives Oxidative Stress and Cell Growth in A549 Lung Epithelial Cells: Potential Protective Action of Oleuropein.

IL-17A drives inflammation and oxidative stress, affecting the progression of chronic lung diseases (asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis). Oleuropein (OLP) is a polyphenolic compound present in olive oil and widely included in the Mediterranean diet. It exerts antioxidant and anti-inflammatory activities, oxidative stress resistance, and anticarcinogenic effects with a conceivable positive impact on human health. We hypothesized that OLP positively affects the mechanisms of oxidative stress, apoptosis, DNA damage, cell viability during proliferation, and cell growth in alveolar epithelial cells and tested its effect in a human alveolar epithelial cell line (A549) in the presence of IL-17A. Our results show that OLP decreases the levels of oxidative stress (Reactive Oxygen Species, Mitochondrial membrane potential) and DNA damage (H2AX phosphorylation-ser139, Olive Tail Moment data) and increases cell apoptosis in A549 cells exposed to IL-17A. Furthermore, OLP decreases the number of viable cells during proliferation, the migratory potential (Scratch test), and the single cell capacity to grow within colonies as a cancer phenotype in A549 cells exposed to IL-17A. In conclusion, we suggest that OLP might be useful to protect lung epithelial cells from oxidative stress, DNA damage, cell growth, and cell apoptosis. This effect might be exerted in lung diseases by the downregulation of IL-17A activities. Our results suggest a positive effect of the components of olive oil on human lung health.

Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review.

This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing invitro and invivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in invitro and invivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Assessing the antioxidant properties of Naringin and Rutin and investigating their oxidative DNA damage effects in breast cancer

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness.

Transcriptional coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress

We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction. These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. Here we present studies designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. We performed cytokine profiling and whole transcriptome and proteome analyses of CF-derived signals in response to MCB-613-10-1. We identified the NRF2 pathway as a direct MCB-613-10-1 therapeutic target for promoting resistance to oxidative stress in CFs. We show that MCB-613-10-1 promotes cell survival of anti-fibrotic CFs exposed to oxidative stress by suppressing apoptosis. We demonstrate that an increase in HMOX1 expression contributes to CF resistance to oxidative stress-mediated apoptosis via a mechanism involving SRC co-activation of NRF2, hence reducing inflammation and fibrosis. We provide evidence that MCB-613-10-1 acts as a protectant against oxidative stress-induced mitochondrial damage. Our data reveal that SRC stimulation of the NRF2 transcriptional network promotes resistance to oxidative stress and highlights a mechanistic approach toward addressing pathologic cardiac remodeling.

Bitter Taste Receptor 46 (hTAS2R46) Protects Monocytes/Macrophages from Oxidative Stress.

Bitter taste receptors (TAS2Rs) are not only responsible for taste perception in the oral cavity, but are spread throughout the body, generating a widespread chemosensory system. In humans, 25 subtypes have been identified and are differentially expressed in tissues and organs, including in the immune system. In fact, several TAS2R subtypes have been detected in neutrophils, lymphocytes, B and T cells, NK cells, and monocytes/macrophages, in which they regulate various protective functions of the innate immune system. Given its recognized anti-inflammatory and antioxidant activity, and the generally protective role of bitter taste receptors, in this work, we studied TAS2R46's potential in the protection of human monocyte/macrophage DNA from stress-induced damage. Through both direct and indirect assays and a single-cell gel electrophoresis assay, we demonstrated that absinthin, a specific TAS2R46 agonist, counteracts the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and reduces DNA damage in both cell types. Even though the release of ROS from monocytes/macrophages is fundamental for contrast pathogen agents, supraphysiological ROS production impairs their function, finally leading to cell death. Our results highlight TAS2R46 as a novel player involved in the protection of monocytes and macrophages from oxidative stress damage, while simultaneously supporting their antimicrobial activity.

Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and dysfunction of RyR2 in the heart of streptozotocin-induced diabetic rats

BackgroundOxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms.MethodsMale Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed.ResultsThere was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats.ConclusionsThese data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.

Can photoperiod improve growth performance and antioxidant responses of pacu (Piaractus mesopotamicus) reared in recirculation aquaculture systems?

The present study investigated the best photoperiod for culturing pacu (Piaractus mesopotamicus) in recirculation aquaculture systems (RAS) based on its growth performance and hematological and oxidative stress responses. Juveniles (∼ 5g) were subjected to five treatments (in triplicate): 24L (light):0D (dark), 15L: 09D, 12L:12D, 9L:15D, and 0L:24D for 45 days. A total of 225 pacu individuals were randomly distributed among 15 tanks of 210L (n = 15 per tank). Zootechnical, hematological (glucose, lactate, hematocrit, and hemoglobin), and antioxidant and oxidative stress parameters (glutathione S-transferase (GST), total antioxidant capacity against peroxyl radicals (ACAP), and lipid peroxidation (LPO) were analyzed. The zootechnical parameters (e.g., weight gain, Fulton's condition factor, and specific growth rate) were better and worse with 9L:15D and 24L:0D photoperiods, respectively. The hepatosomatic index was higher and lower in the 0L:24D and 9L:15D photoperiods. Blood lactate levels and antioxidant and oxidative stress responses were increased in the longest photoperiods (15L:9D and 24L:0D). In contrast, the treatments that showed lower oxidative damage (liver, gills, brain, and muscle) were 9L:15D and 12L:12D. In conclusion, manipulating artificial light is one way to improve fish growth and health, where the best photoperiod for pacu farming in RAS is 9L:15D.

Role of Adenosine Receptor Agonist in a Rat Model of Diabetic-Induced Osteoporosis

Abstract Background Diabetic osteoporosis is caused by chronic hyperglycemia, oxidative stress, advanced glycation end products accumulation and microvascular changes. All these alter signaling pathways involved in bone metabolism. Adenosine receptors (ARs) are expressed in the bone and might play a role in bone homeostasis. Recent data reveal that A2AAR plays a key role in bone homeostasis and regeneration. However, whether it has a role in treatment of osteoporosis induced by diabetes has not been reported. Objective The aim of the present study was to evaluate the effect of CGS-21680, an A2A adenosine receptor agonist, in ameliorating osteoporosis induced by diabetes in a rat model. Materials and Methods Forty adult male Albino-rats were allocated into four groups: Group I: control group; Group II: untreated diabetic induced osteoporosis group; Group III: insulin treated diabetic-induced osteoporosis group; Group IV: adenosine receptor agonist treated diabetic-induced osteoporosis group. Diabetes was induced by a single intraperitoneal injection of STZ at a dose of 40 mg/Kg body weight. At the end of the study the bone marker osteocalcin, serum glucose, insulin, tumor necrosis factor-α, malondialdehyde, glutathione peroxidase, calcium and phosphorus were measured, and bone histopathological analysis was done. Results Compared with the untreated diabetic groups, the A2A adenosine receptor agonist treated group showed less bone loss, which was revealed by the increased cortical bone thickness and trabecular thickness. In addition to decreased oxidative damage and inflammation. Conclusion The decreased oxidative stress and inflammation in the A2A adenosine receptor agonist treated group supports a beneficial effect of A2AAR stimulation in treatment of diabetic induced osteoporosis, which was demonstrated by the improvement in bone microarchitecture.

Deciphering High-Temperature-Induced Lignin Biosynthesis in Wheat through Comprehensive Transcriptome Analysis.

This study systematically investigated the physiological and molecular responses of the wheat mutant 'XC-MU201' under high-temperature stress through comprehensive transcriptome analysis and physiological measurements. RNA sequencing of 21 samples across seven different treatment groups revealed, through Weighted Gene Co-expression Network Analysis (WGCNA), 13 modules among 9071 genes closely related to high-temperature treatments. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed significant enrichment of lignin biosynthesis-related modules under high-temperature conditions, especially at the H-10DAT, H-20DAT, and H-30DAT time points. Experimental results demonstrated a significant increase in lignin content in high-temperature-treated samples, confirmed by tissue staining methods, indicating wheat's adaptation to heat damage through lignin accumulation. The phenylalanine ammonia-lyase gene (TaPAL33) was significantly upregulated under high-temperature stress, peaking at H-30DAT, suggesting its critical role in cellular defense mechanisms. Overexpression of TaPAL33 in the wheat variety 'Xinchun 11' enhanced lignin synthesis but inhibited growth. Subcellular localization of GFP-labeled TaPAL33 in tobacco cells showed its distribution mainly in the cytoplasm and cell membrane. Transgenic wheat exhibited higher PAL enzyme activity, enhanced antioxidant defense, and reduced oxidative damage under high-temperature stress, outperforming wild-type wheat. These results highlight TaPAL33's key role in improving wheat heat tolerance and provide a genetic foundation for future research and applications.

Artisanal Gem Mining in Brazil: Evaluation of Oxidative Stress and Genotoxicity Biomarkers

This study was carried out in the district of Taquaral de Minas, in the municipality of Itinga, located in Jequitinhonha Valley, state of Minas Gerais, which is considered one of the largest yolk-producing regions in Brazil. Miners in gem extraction areas are prone to severe oxidative damage due to their increased exposure to toxic metals, as well as chemical, physical, and biological agents, resulting in diseases such as silicosis. Thus, this work aimed to evaluate occupational exposure in prospectors through biomonitoring techniques using a variety of biomarkers for oxidative stress, genotoxicity, and mutagenicity. Twenty-two miners and seventeen workers who were not occupationally exposed were recruited, totaling thirty-nine participants. The study was approved by the Research Ethics Committee of the Federal University of the Jequitinhonha and Mucuri Valleys. In this study, the levels of total peroxides, catalase activity, and microelements in plasma were evaluated. Additionally, environmental analysis was carried out through the Ames and Allium cepa tests. The results of the lipoperoxidation assessment were significant, with increased frequencies in exposed individuals compared to controls (p &lt; 0.05), as determined by the Mann–Whitney test. Micronutrients in the blood showed lower concentrations in the group exposed to Fe and Se than in individuals not exposed to these elements. The results of the Ames test and Allium cepa test were statistically significant compared to the controls (p &lt; 0.05), as determined by the Mann–Whitney test for genotoxicity and cytotoxicity. Thus, the results of the present study indicate possible environmental contamination and a potential risk to the health of miners, which suggests that further studies are important in the region.

Differential eco-toxicological responses toward Eisenia fetida exposed to soil contaminated with naphthalene and typical metabolites.

Naphthalene (NAP) was frequently detected in polycyclic aromatic hydrocarbons (PAHs)-contaminated soil, and its residues may pose an eco-toxicological threat to soil organisms. The toxic effects of NAP were closely tied to phenolic and quinone metabolites in biological metabolism. However, the present knowledge concerning the eco-toxicological impacts of NAP metabolites at the animal level is scanty. Here, we assessed the differences in the eco-toxicological responses of Eisenia fetida (E. fetida) in NAP, 1-naphthol (1-NAO) or 1,4-naphthoquinone (1,4-NQ) contaminated soils. NAP, 1-NAO, and 1,4-NQ exposure triggered the onset of oxidative stress as evidenced by the destruction of the antioxidant enzyme system. The lipid peroxidation and DNA oxidative damage levels induced by 1-NAO and 1,4-NQ were higher than those of NAP. The elevation of DNA damage varied considerably depending on differences in oxidative stress and the direct mode of action of NAP or its metabolites with DNA. All three toxicants induced different degrees of physiological damage to the body wall, but only 1, 4-NQ caused the shedding of intestinal epithelial cells. The integrated biomarker response for different exposure times illustrated that the comprehensive toxicity at the animal level was 1,4-NQ > 1-NAO > NAP, and the time-dependent trends of oxidative stress responses induced by the three toxicants were similar. At the initial stage, the antioxidant system of E. fetida responded positively to the provocation, but the ability of E. fetida to resist stimulation decreased with the prolongation of time resulting in provocation oxidative damage. This study would provide new insights into the toxicological effects and biohazard of PAHs on soil animals.

Metformin improves cognitive dysfunction through SIRT1/NLRP3 pathway-mediated neuroinflammation in db/db mice.

Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1β, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment.

Obesity Induces DNA Damage in Mammary Epithelial Cells Exacerbated by Acrylamide Treatment through CYP2E1-Mediated Oxidative Stress

Obesity and environmental toxins are risk factors for breast cancer; however, there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a by-product in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with an increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and control water or water supplemented with acrylamide at levels similar to the average daily exposure in humans. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks, while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. The knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and the CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.