Protein Oxidation Research Articles

Influence of edible flowers on the physicochemical and oxidative stability of raw ground beef patties

This study investigates the antioxidant and physicochemical characteristics of raw ground beef patties and raw ground beef patties treated with varying percentages of roselle (Hibiscus sabdariffa L.) and rose (Rosa canina L.) powders during 7 days of storage at 4°C. The analysis included key parameters such as antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, lipid oxidation through 2-thiobarbituric acid reactive substances (TBARS), protein oxidation markers (carbonyls, Schiff bases, and free thiols), water-holding capacity, pH, color, and texture. Both roselle and rose powders enhanced the antioxidant capacity of the patties, reducing oxidative markers (TBARS, carbonyls, Schiff bases, and free thiols) during storage. Additionally, improved water-holding capacity and reduced pH were observed across all treated patties, with minimal impact on texture. However, while roselle powder showed beneficial effects, patties treated with rose powder exhibited superior overall results. The more favorable outcomes in rose-treated patties, particularly in oxidative stability and physicochemical properties, can be attributed to the higher concentrations of bioactive compounds, such as phenolic acids and flavonoids, present in rose powder. These compounds likely contributed to enhanced free radical scavenging activity, providing stronger protection against lipid and protein oxidation. Furthermore, rose powder maintained more stable color and physicochemical properties, with patties showing acceptable color and minimal texture degradation by the 7th day of storage. These findings highlight the potential of rose powder as a highly effective natural additive for extending the shelf life and preserving the quality of ground beef patties, positioning it as a promising ingredient for future applications in the food industry.

The Role of the cGAS/STING Pathway in Arsenic-Induced Neurotoxicity: Insights from the Crosstalk Between Astrocytes and Neurons.

Arsenic is a detrimental environmental toxicant linked to neurological damage; however, the mechanisms involved remain incompletely understood. Chronic proinflammatory responses are thought to play a central role in arsenic-induced neurotoxicity. Astrocytes, which are the predominant glial cells in the central nervous system (CNS), release significant amounts of proinflammatory cytokines upon overactivation. However, the molecular mechanisms driving this response remain to be elucidated. This study aimed to elucidate the mechanisms underlying arsenic-induced astrocyte activation and the subsequent neuronal damage, both in vivo and in vitro. In a rat model of arsenic exposure, significant neuropathological damage was detected in the CA3 region of the hippocampus. Specifically, markers of astrocyte activation, such as glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS), as well as the inflammatory cytokine interleukin (IL)-1β, were significantly upregulated, and apoptosis was markedly increased, indicating neurotoxic damage. Furthermore, in vitro experiments revealed that arsenic exposure induced substantial upregulation of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), GFAP, iNOS, and IL-1β in astrocytes, accompanied by an increase in IL-1β secretion into the culture supernatant. In addition, co-culturing neurons with conditioned medium from arsenic-exposed astrocytes resulted in significant neuronal apoptosis. Importantly, the cGAS-STING pathway inhibitor H-151 effectively suppressed the arsenic-induced astrocyte activation and IL-1β secretion, while also reducing neuronal apoptosis in the conditioned medium. Collectively, these results indicate that arsenic exposure activates the cGAS-STING signaling pathway in astrocytes, enhancing proinflammatory activation and IL-1β expression, which in turn mediates neuronal apoptosis, representing a critical mechanism underlying arsenic-induced neurotoxicity.

Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model

Background/Objectives: Fragile X Syndrome (FXS) is associated with intellectual disability, hyperactivity, social anxiety and signs of autism. Hyperactivation of NADPH oxidase has been previously described in the brain of the male Fmr1-KO mouse. This work aims to demonstrate the efficacy of Apocynin, a specific NADPH oxidase inhibitor, in treating Fragile X mouse hallmarks. Methods: Free radicals, lipid and protein oxidation markers and behavioural and learning paradigms were measured after chronic treatment with orally administered vehicle, 10 mg/kg/day or 30 mg/kg/day of Apocynin. Results: The results revealed a reduction in testis weight, an increase in peritoneal fat, and no variation in body weight after chronic treatment. Furthermore, a reduction in hyperactivity was detected in Apocynin-treated male Fmr1-KO mice. Additionally, the higher dose of 30 mg/kg/day also improves behaviour and learning in the male Fmr1-KO mice, normalising free radical production and oxidative parameters. Moreover, a reduction in phospho-EKR1 and P47-Phox protein signals was observed in specific brain areas. Conclusions: Thus, chronic treatment with Apocynin could lead to a new therapeutic option for the Fragile X Syndrome.

Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models

BackgroundSkeletal muscle atrophy significantly affects quality of life and has socio-economic and health implications. This study evaluates the effects of entacapone (ENT) on skeletal muscle atrophy linked with oxidative stress and proteolysis.MethodsC2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Four murine models were employed: diaphragm atrophy from mechanical ventilation, Dex-induced atrophy, lipopolysaccharide (LPS)-induced atrophy, and hyperlipidemia-induced atrophy. Each model utilized entacapone (10 mg/kg), with sample sizes: Control (9), MV (11), MV + ENT (5) for diaphragm atrophy; Control (4), Dex (4), Dex + ENT (5) for Dex model; Control (4), LPS (4), LPS + ENT (5) for LPS model; and similar for hyperlipidemia. Measurements included muscle strength, myofiber cross-sectional area (CSA), proteolysis, oxidative stress markers [uperoxide dismutase 1 (SOD1), uperoxide dismutase 2 (SOD2), 4-hydroxynonenal (4-HNE)], and lipid levels.ResultsOur findings confirm Dex-induced muscle atrophy, evidenced by increased expression of muscle atrophy-associated proteins, including Atrogin-1 and Murf-1, along with decreased diameter of C2C12 myotubes. Atrogin-1 levels rose by 660.6% (p < 0.05) in the Dex group compared to control, while entacapone reduced Atrogin-1 by 84.4% (p < 0.05). Similarly, Murf-1 levels increased by 365% (p < 0.05) in the Dex group and were decreased by 89.5% (p < 0.05) with entacapone. Dexamethasone exposure induces oxidative stress, evidenced by the upregulation of oxidative stress-related proteins Sod1, Sod2, and 4-HNE. Entacapone significantly reduced the levels of these oxidative stress markers, enhancing GSH-PX content by 385.6% (p < 0.05) compared to the Dex-treated group. Additionally, ENT effectively reduced the Dex-induced increase in MDA content by 63.98% (p < 0.05). Furthermore, entacapone effectively prevents the decline in diaphragm muscle strength and myofiber CSA in mice. It also mitigates diaphragm oxidative stress and protein hydrolysis. Additionally, entacapone exhibits the ability to attenuate lipid accumulation in the gastrocnemius muscle of hyperlipidemic mice and alleviate the reduction in muscle fiber CSA.ConclusionOur findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions.

Hepatic GPx1 and GIT1 expression altered by ethanol exposure during third trimester-equivalent development

Background Ethanol (EtOH) exposure throughout gestation and breastfeeding leads to multiple adverse outcomes in the hepatic system. Under oxidative stress, alterations in the liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of low expression of G-protein-coupled receptor (GPCR)-kinase interacting (GIT1). Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester of human equivalent development. Methods We exposed rats during the third trimester equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expression was detected by western blotting, and the antioxidant activity of glutathione peroxidase GPx and the concentration of hepatic carbonyl groups (CG were determined by spectrophotometry. Serum biochemistry parameters such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. Results We found that ethanol decreased both GIT1 and GPx1 selenoprotein expression, affecting GPx antioxidant activity and increasing protein oxidation. Conclusions These results demonstrate for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decrease in GIT1 expression [1].

The immune mechanism of the mTOR/ACC1/CPT1A fatty acid oxidation signaling pathway in Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease (AITD), which is distinguished by high thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb). The differentiation of CD4+T cell subsets in patients with HT is imbalanced, with Treg cells decreased and Th17 cells abnormally activated. Fatty acid oxidation supports the differentiation of Th17 cells and induces inflammation, but the specific mechanism is still unknown. This study aimed to explore the role of fatty acid oxidation and its pathway in the pathogenesis of autoimmune thyroiditis and the immune mechanism. In in vitro experiments, a total of 60 HT patients and 20 healthy controls were selected and their CD4+T cells were sorted by magnetic beads. All 80 samples were divided into 4 groups on average: HC group (Healthy control group), HT group (Hashimoto thyroiditis CD4+T cell inactive group), TCC group(Hashimoto thyroiditis CD4+T cell activation), TCC + ETO group(Hashimoto thyroiditis CD4+T cell activation + Etomoxir group). In in vivo experiments, the mice were randomly divided into 3 groups: Con group(Control group), mTg group (CBA/J mice were injected with mTg for modeling, that is EAT mice group), and mTg + ETO group (Etomoxir intervention in EAT mice group). Fatty acid oxidation substrates of CD4+T cells in human peripheral blood were detected by targeted metabolomics. The expressions of key fatty acid oxidation proteins mTOR, ACC1 and CPT1A were detected by Western blotting. The proportion of CD4+T cell subtype differentiation in human and mouse models was detected by flow cytometry. The severity of EAT was detected by HE staining. Compared with healthy controls, the level of CPT1A in CD4+T cells of HT patients was increased, and the intracellular fatty acid content was significantly decreased, indicating that the level of fatty acid oxidation was enhanced in HT patients. After adding Etomoxir, the level of fatty acid oxidation was significantly inhibited, and the imbalance of CD4+T cell subpopulation differentiation in HT patients was reversed. In EAT mice, the mTOR/ACC1/CPT1A pathway was significantly activated, and its expression level was decreased after adding Etomoxir. At the same time, Etomoxir could reverse the reprogramming of abnormal metabolism in EAT mice cells, reduce the spleen index, and improve lymphocyte infiltration in the thyroid. The mTOR/ACC1/CPT1A fatty acid oxidation pathway of CD4+T cells in Hashimoto's thyroiditis was increased, and treatment with Etomoxir could inhibit the activation of this pathway, and reverse the reprogramming of abnormal metabolism in CD4+T cells, thereby reducing Hashimoto's thyroiditis.

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that ferroptosis, a non-apoptotic, iron-dependent cell death pathway, is also involved in the pathophysiology of CT organ toxicity. CT provokes organ ferroptosis via system Xc-/GPX-4/GSH/SLC7A11 axis depletion, ferritinophagy, iron overload, lipid peroxidation and upregulation of ferritin-related proteins. Cisplatin (CP) and doxorubicin (DOX) are common CT drugs indicated to induce ferroptosis in vitro and in vivo. Studies have explored natural preventive and therapeutic strategies using ginger rhizome and its major bioactive compounds, 6-gingerol (6G) and zingerone (ZG), to combat mechanisms of CT side effect toxicity. Ginger extract, 6G and ZG mitigate non-ferroptotic oxidative inflammation, apoptosis and mitochondrial dysfunction mechanisms of CT side effect toxicity, but their effects on CT-induced ferroptosis remain unclear. Systematic investigations are, therefore, needed to unfold the roles of ginger, 6G and ZG on ferroptosis involved in CT side effect toxicity, as they are potential natural agents for the prevention of CT toxicity. This review reveals the ferroptotic and non-ferroptotic toxicity mechanisms of CT and the protective mechanisms of ginger, 6G and ZG against CT-induced, ferroptotic and non-ferroptotic organ toxicities.

Fruit Extracts Incorporated into Meat Products as Natural Antioxidants, Preservatives, and Colorants

Nowadays, natural antioxidants, especially those found in fruits, are preferred over synthetic ones when used in a variety of meat products. Natural alternatives are preferred by consumers because synthetic additives in meat products have been connected to allergic reactions and other health-related problems. Fruits are abundant in phenolic compounds, providing them with particularly powerful antioxidants. Lipid oxidation is inhibited, allowing meat products to have an extended shelf life when enriched with fruit-derived components. The present study explores the potential of bioactive compounds derived from fruits, specifically phenolics, to improve the quality of meat products by virtue of their antimicrobial, antioxidant, and color-stabilizing qualities. In this review, the effects of 18 fruits on oxidative stability, antimicrobial activity, and color enhancement in meat products were investigated. The first section of this paper focuses on a presentation of the phytochemical composition and overall biological characteristics of the fruits. The thiobarbituric acid test, the peroxide value, and oxidative protein changes were used to assess oxidative stability. By scavenging free radicals or chelating metals, the phenolic compounds not only prevent lipid peroxidation but also protect myoglobin from oxidation, thereby improving the color of meat substitutes. Phenolic compounds provide antimicrobial actions by compromising bacterial cell walls, disrupting membrane integrity, or inhibiting essential enzymes necessary for microbial growth. Fruit extracts have shown effectiveness against foodborne pathogens and spoiling bacteria. Adding fruits to meat products is a promising way to improve their nutritional profile, sustainability, and quality. In order to guarantee consumer safety, future studies must concentrate on thorough toxicological analyses of fruit extracts meant to be used in food.

Biomarkers and Seaweed-Based Nutritional Interventions in Metabolic Syndrome: A Comprehensive Review

Metabolic Syndrome (MetS) is a complex, multifactorial condition characterized by risk factors such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, which significantly contribute to the development of cardiovascular disease (CVD), the leading cause of death worldwide. Early identification and effective monitoring of MetS is crucial for preventing serious cardiovascular complications. This article provides a comprehensive overview of various biomarkers associated with MetS, including lipid profile markers (triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio), inflammatory markers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), leptin/adiponectin ratio, omentin and fetuin-A/adiponectin ratio), oxidative stress markers (lipid peroxides, protein and nucleic acid oxidation, gamma-glutamyl transferase (GGT), uric acid) and microRNAs (miRNAs) such as miR-15a-5p, miR5-17-5p and miR-24-3p. Additionally, this review highlights the importance of biomarkers in MetS and the need for advancements in their identification and use for improving prevention and treatment. Seaweed therapy is also discussed as a significant intervention for MetS due to its rich content of fiber, antioxidants, minerals and bioactive compounds, which help improve cardiovascular health, reduce inflammation, increase insulin sensitivity and promote weight loss, making it a promising nutritional strategy for managing metabolic and cardiovascular health.

Gene ontology defines pre-post- hatch energy dynamics in the complexus muscle of broiler chickens

BackgroundChicken embryos emerge from their shell by the piercing movement of the hatching muscle. Although considered a key player during hatching, with activity that imposes a substantial metabolic demand, data are still limited. The study provides a bioenergetic and transcriptomic analyses during the pre-post-hatching period.MethodsWeight and morphology alongside content determination of creatine and glycogen were analysed. Transcriptome identified differentially expressed genes and enriched biological processes associated with hatching muscle development, catabolism, and energy provision. Using gene set enrichment, we followed the dynamics of gene-sets involved in energy pathways of oxidative phosphorylation, protein catabolism, glycolysis/gluconeogenesis, and glycogen metabolism.ResultsResults show several significant findings: (A) Creatine plays a crucial role in the energy metabolism of the hatching muscle, with its concentration remaining stable while glycogen concentration is depleted at hatch and placement. (B) The hatching muscle has the capacity for de-novo creatine synthesis, as indicated by the expression of related genes (AGAT, GAMT). (C) Transcriptome provided insights into genes related to energy pathways under conditions of pre-hatch oxygen and post-hatch glucose limitations (oxidative phosphorylation: NDUF, MT-ND, SDH, UQCR, COX, MT-CO, ATP5, MT-ATP; glycolysis/gluconeogenesis: FBP,G6PC, PFKM; glycogen metabolism: PPP1, PYGL, GYG1). (D) The post-hatch upregulation of protein catabolic processes genes (PSMA, RNF, UBE, FBX), which align with the muscle's weight dynamics, indicates a functional shift from movement during hatching to lifting the head during feeding.ConclusionsThere is a dynamic metabolic switch in the hatching muscle during embryo-to-hatchling transition. When glycogen concentration depletes, energy supply is maintained by creatine and its de-novo synthesis. Understanding the hatching muscle's energy dynamics is crucial, for reducing hatching failures in endangered avian species, and in domesticated chickens.

Therapeutic targeting of the oxidative stress generated by pathological molecular pathways in the neurodegenerative diseases, ALS and Huntington's.

Neurodegenerative disorders are characterized by a progressive decline of specific neuronal populations in the brain and spinal cord, typically containing aggregates of one or more proteins. They can result in behavioral alterations, memory loss and a decline in cognitive and motor abilities. Various pathways and mechanisms have been outlined for the potential treatment of these diseases, where redox regulation is considered as one of the most common druggable targets. For example, in amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) pathology, there is a downregulation of the antioxidant response nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. TDP-43 proteinopathy in ALS is associated with elevated levels of reactive oxygen species and mitochondrial dyshomeostasis. In ALS with mutant FUS, poly ADP ribose polymerase-dependent X ray repair cross complementing 1/DNA-ligase recruitment to the sites of oxidative DNA damage is affected, thereby causing defects in DNA damage repair. Oxidative stress in Huntington's disease (HD) with mutant huntingtin accumulation manifests as protein oxidation, metabolic energetics dysfunction, metal ion dyshomeostasis, DNA damage and mitochondrial dysfunction. The impact of oxidative stress in the progression of these diseases further warrants studies into the role of antioxidants in their treatment. While an antioxidant, edaravone, has been approved for therapeutics of ALS, numerous antioxidant molecules failed to pass the clinical trials despite promising initial studies. In this review, we summarize the oxidative stress pathways and redox modulators that are investigated in ALS and HD using various models.

Storage causes protein oxidation of soybean meal and affects antioxidant status, digestive performance and meat quality of broilers.

This study investigated the protein oxidation of soybean meal (SBM) stored in a warehouse and the effects of SBM on growth performance, antioxidant status, digestive performance, intestinal morphology, and breast muscle quality of broilers. In total, 160 one-day-old Arbor Acres Plus broilers (half male and half female) were randomly divided into two groups with ten replicates of eight birds each: The control group was served with a basal diet including SBM stored at -20°C (FSBM), and the experimental group was served with a basal diet including SBM stored in a warehouse at room temperature for 45 days (RSBM). Compared with FSBM, the protein carbonyl level in RSBM was increased, the free and total thiol levels and in vitro digestibility of protein were decreased. The RSBM decreased the serum glutathione (GSH) level and the hepatic total superoxide dismutase (T-SOD) activity at days 21 and 42 when compared with FSBM. Further, RSBM reduced the duodenal T-SOD activity, jejunal catalase (CAT), and T-SOD activities at day 21, and decreased the duodenal CAT and T-SOD activities, jejunal T-SOD activity, and ileal GSH level and T-SOD activity at days 21 and 42 when compared with FSBM. Besides, the trypsin activity and the ratio of villus height to crypt depth in small intestines of broilers at days 21 and 42 were reduced when fed with a RSBM-contained diet. Compared with FSBM, the 24-h drip loss, shear force, and 24- and 48-h cooking loss of breast muscle were increased of RSBM group, the opposite result was observed for muscle lightness at 48 h. Room temperature storage for 45 days led a protein oxidation and decreased in vitro digestibility in SBM, and fed RSBM impaired growth performance, antioxidant status, and meat quality, reduced trypsin activity, and affected the small intestine morphology in broilers.

The mechanism of peanut shell flavonoids inhibiting the oxidation of myofibrillar protein: An elucidation of the antioxidative preservation action of peanut shell flavonoids on chilled pork.

Flavonoids, a significant subclass of polyphenols, possess antioxidant properties and contribute to the preservation of chilled meat. In this paper, a phosphate buffer solution (pH = 6.25, simulated chilled pork) and a Fenton oxidation system (simulated myofibrillar protein oxidation process during storage) were established to explain the antioxidative preservation of chilled pork using peanut shell flavonoids (PSFs). The results indicated that PSFs changed the secondary structure of myofibrillar protein (MP), significantly inhibiting the oxidation of amino acids and the formation of carbonyl groups in MP (P < 0.05). Because PSFs and amino acids in chilled pork were combined to form complex through non-covalent bond in a pH 6.25 environment and covalent bond in a Fenton oxidation system. The antioxidant capacity of the complex was significantly enhanced (P < 0.05). The molecular docking technique predicted the antioxidant binding sites were Cys176, Ala182 and Val 124. This study provides a theoretical foundation for the preservation of chilled pork using PSFs.

Exploring the ameliorative potential of rutin against High-Sucrose Diet-induced oxidative stress and reproductive toxicity in Drosophila melanogaster

Sucrose is a vital ingredient in numerous food items consumed regularly. However, exposure to excessive sucrose for a prolonged period can promote health issues. The reproductive system has a delicate physiology that can be targeted by various chemical stressors, including sucrose. Hence, the present in vivo study aims to unveil the impacts of the High-Sucrose Diet (HSD) on the reproductive fitness of Drosophila melanogaster. In addition, the present work has also assessed the protective potential of a bioactive compound, rutin, against it. Here, 1st instar larvae were exposed to HSD (30%) alone and in combination with rutin (100-300µM) till their adult stage. HSD disturbed sex comb morphology in adult males, while fecundity and hatchability of eggs in females. Moreover, HSD triggered gonadal ROS production, oxidative stress, and modulated endogenous antioxidants such as SOD, catalase, and glutathione in both sexes. Nuclear fragmentation and tissue injuries, along with protein and lipid oxidation, were also apparent. Elevated levels of cytosolic Iron suggested an active Fenton reaction in adults. Further, HSD modulated the activities of reproductive and metabolic mediators, including vitellogenin, malate dehydrogenase, glucose-6-phosphate dehydrogenase, and angiotensin-converting enzymes that are critical to overall reproductive fitness. Interestingly, co-treatment with rutin, mainly at 200µM, mitigated these adverse effects and restored reproductive fitness. The protective potential of rutin might be attributed to its ability to normalize redox homeostasis, reduce oxidative stress, and optimize critical enzymes involved in reproductive physiology. These findings suggest that rutin has potential therapeutic implications to counteract the reproductive hazards induced by HSD.

Multifunctional Peptide-drug Conjugate CORM-401@R9: A Novel Approach to Combat Oxidative Stress in Cataracts.

Cataracts, the leading cause of blindness globally, are primarily driven by oxidative stress and protein aggregation in the lens. Effective pharmacological treatments for cataracts are still elusive. This study developed a novel multifunctional peptide-drug conjugate, CORM-401@R9 (CO-R9), which activates in response to reactive oxygen species (ROS) and releases carbon monoxide (CO). The conjugate combines poly-arginine-9 peptide (R9) with CORM-401 to improve cellular uptake and CO delivery, targeting the elevated ROS levels characteristic of cataract pathology. In vitro, CO-R9 effectively reduced ROS levels and prevented senescence and apoptosis induced by oxidative stress. Further investigation into the molecular mechanisms reveals that CO-R9 restored redox homeostasis by modulating the expression of key genes and proteins involved in antioxidant defense, anti-apoptotic responses, and molecular chaperoning. This study highlights CO-R9 as a promising therapeutic agent with potential for cataract prevention and treatment.

Beyond glucose: The crucial role of redox signaling in β-cell metabolic adaptation

ObjectiveRedox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic β-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in β-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for β-cell function and health. MethodsWe employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic β-cells. ResultsGlucose stimulation significantly increases ROS levels in β-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation. ConclusionsProper functioning of pancreatic β-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic β-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in β-cell function.

α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats

α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL+ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD+ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.

Protein phosphorylation and oxidative protein modification promote plant photosystem II disassembly for repair

The light-driven water-splitting reaction of photosystem II exposes its key reaction center core protein subunits to irreversible oxidative photodamage. A rapid repair cycle replaces the photodamaged core subunits in plants, but how the large antenna-core supercomplex structures of plant photosystem II disassemble for repair is not currently understood. We find a specific involvement of phosphorylation in removing the peripheral antenna from the core and monomerization of the dimeric cores. However, monomeric cores disassembled further into smaller subcomplexes even in the absence of phosphorylation as suggestive of other unknown mechanisms of disassembly. Here we show that the oxidative modifications of amino acids in core protein subunits of photosystem II are active mediators of the monomeric core disassembly. Oxidative modifications thus likely disassemble only the damaged monomeric cores, ensuring an economical photosystem disassembly process. Taken together, our results suggest phosphorylation and oxidative modification play distinct roles in photosystem II disassembly and repair.

Association of ambient ozone exposure with early cardiovascular damage among general urban adults: A repeated-measures cohort study in China

Longitudinal evidence of long-term ozone exposure on heart rate variability (HRV, an early indicator of cardiovascular damage) is lacking and the potential mechanism remains largely unclear. Our objectives were to evaluate the cross-sectional and longitudinal associations of ozone exposure with HRV alteration, and the potential roles of protein carbonyl (PC, biomarker of oxidative protein damage) and transforming growth factor (TGF)-β1 in this association. This repeated-measures prospective study included 4138 participants with 6617 observations from the Wuhan-Zhuhai cohort. Ozone concentrations were estimated using a high temporospatial resolution model for each participant. HRV indices, PC, and TGF-β1 were also repeatedly measured. Cross-sectional and longitudinal relationships of ozone exposure with HRV alteration were evaluated by linear mixed model. Cross-sectionally, the strongest lag effect of each 10 ppb increment in short-term ozone exposure showed a 12.40 %, 8.47 %, 4.31 %, 8.03 %, 3.69 %, and 2.41 % decrement on very low frequency (VLF, lag 3 weeks), LF (lag 2 weeks), high frequency (HF, lag 0–7 days), total power (TP, lag 2 weeks), standard deviation of all normal-to-normal intervals (SDNN, lag 3 weeks), and square root of the mean squared difference between adjacent normal-to-normal intervals (lag 2 weeks), respectively. Longitudinally, each 10 ppb increment of annual average ozone was related with an annual change rate of −0.024 ms2/year in VLF, −0.009 ms2/year in LF, −0.013 ms2/year in HF, −0.014 ms2/year in TP, and −0.004 ms/year in SDNN. Mediation analyses indicated that PC mediated 20.77 % and 12.18 % of ozone-associated VLF and TP decline, respectively; TGF-β1 mediated 16.87 % and 27.78 % of ozone-associated VLF and SDNN reduction, respectively. Our study demonstrated that ozone exposure was cross-sectionally and longitudinally related with HRV decline in general Chinese urban adults, and oxidative protein damage and increased TGF-β1 partly mediated ozone exposure-related HRV reduction.

Analysis of mitochondrial DNA replisome in autism spectrum disorder: Exploring the role of replisome genes.

Autism spectrum disorder (ASD) is a neurodevelopmental condition often associated with mitochondrial dysfunction, including increased mitochondrial DNA (mtDNA) copy number and impaired energy production. This study investigates the role of the mitochondrial replisome-specifically, the genes TFAM, TWNK, POLG, and TOP1MT-in mtDNA replication and its potential contribution to ASD pathophysiology. We analyzed samples from the oral mucosa of children with ASD and typically developing (TD) controls, assessing mtDNA copy number, gene expression, and protein levels. Our findings revealed a significant increase in mtDNA copy number in the oral mucosa of ASD children, along with partially deleted mtDNA molecules. However, there were no significant changes in the expression of TFAM, TWNK, POLG, or MT-TL1 genes between ASD and TD samples. Additionally, TFAM protein levels, including monomeric, dimeric, and trimeric forms, did not differ significantly. We also observed increased oxidative stress and inflammatory markers in the oral mucosa of ASD children, suggesting that mitochondrial alterations may be linked to inflammation and oxidative damage in ASD. To further investigate the functional impact of TFAM, we overexpressed it in human HEK293 cells and cortical neurons (CN1.4). TFAM overexpression led to increased mtDNA copy number, cell proliferation, and ATP production in HEK293 cells, but did not significantly alter mitochondrial gene expression, protein oxidation, or mtDNA integrity. In CN1.4 neurons, TFAM overexpression increased mitochondrial membrane potential and length, indicating potential changes in mitochondrial dynamics. Overall, our study suggests that while mtDNA alterations are present in ASD, they are not directly driven by changes in mitochondrial replisome gene expression. These findings highlight the complexity of mitochondrial dysfunction in ASD and suggest the need for further investigation into the underlying molecular mechanisms.