Protein Oxidation Research Articles

Jerked beef as an ultraprocessed convenience food: Desalting strategies to minimize the impact on lipid and protein oxidation

AbstractJerked beef (JB) is a high‐protein convenience food but shows high degree of oxidation owing to its severe ultraprocessing. This study aimed to investigate the effect of desalting processes on oxidative stability of JB. JB were submitted to five desalting procedures: immersion in water at room temperature for 12 h without changing the water (AT12); immersion in water at room temperature for 12 h followed by boiling for 30 min and changing the water between the two procedures (AT12 + C30); immersion in boiled water for 10, 20, and 30 min (C10, C20, and C30, respectively). The desalted JB samples were refrigerated (vacuum packed and stored at 1 ± 1°C) and analyzed at 0 and 60 days. The samples without desalting were used as a control group. AT12 samples had the lowest lipid oxidation (0.05 and 0.07 mg of MDA kg−1, at T60 and T0, respectively). AT12 + C30 had the lowest NaCl content (2.8 and 3.3 g 100 g−1, at T0 and T60, respectively). C10, C20, and C30 showed a lower level of total carbonyls (p < 0.05) (0.04–0.13 nmol mg−1 protein), compared to control (0.53–0.93 nmol mg−1 protein in T0 and T60, respectively). Only boiled, desalted meats showed the volatile compound benzaldehyde. Higher concentration of monounsaturated, polyunsaturated, and total unsaturated fatty acids in JB desalted only in boiling water (C10, C20, and C30), compared to control (p < 0.05). AT12 is the best process to use, with regards to lipid oxidative stability, hardness, and NaCl content. Therefore, we conclude that it is possible to offer commercially desalted JB, as a convenience ultraprocessed product.Practical ApplicationLipid oxidation is accelerated when desalting jerked beef (JB) with boiling water. Desalted JB in boiling water had detectable concentrations of benzaldehyde. •Desalting in water at 25°C/12 h resulted in JB with better oxidative stability.

Benefits of Astaxanthin supplementation: selected issues

INTRODUCTION: Astaxanthin, a carotenoid compound belonging to the xanthophyll group, occurs naturally in algae, yeast, and marine organisms such as shrimp, trout, lobster, and krill. Renowned for its antioxidant prowess, astaxanthin shields mitochondria from harm caused by reactive oxygen species (ROS). Its exceptional antioxidant potency is noteworthy, surpassing that of α-tocopherol (Vitamin E) by 100-fold and eclipsing over 600 other recognized natural carotenoids. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar data regarding the benefits of astaxanthin supplementation. THE STATE OF KNOWLEDGE: Astaxanthin, offers a range of health benefits. It modulates immune responses, inhibits cancer cell growth, reduces bacterial presence and gastric inflammation. With potent antioxidant properties, it also serves as a neuroprotective agent by combating neuroinflammation. Additionally, astaxanthin shows promise in preventing and treating liver diseases, thanks to its antioxidant, anti-inflammatory, and signaling pathway regulation properties. Overall, antioxidants like astaxanthin, whether from diet or supplements, help combat lipid and protein oxidation, thereby slowing down the progression of atherosclerosis. CONCLUSION: Astaxanthin emerges as a promising candidate for treating various pathological conditions linked to oxidative damage and impaired mitochondria function. These conditions span across cardiovascular diseases, neurodegenerative disorders and liver diseases. It could also help healthy people like athletes in enhancement of overall quality of life.

A glutamine metabolic switch supports erythropoiesis.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.

EPA or DHA enhanced oxidative stress and aging protein expression in brain of d-galactose treated mice

EPA or DHA enhanced oxidative stress and aging protein expression in brain of d-galactose treated mice

Influence of Chitosan/Lycopene on Myoglobin and Meat Quality of Beef During Storage

Myoglobin (Mb) is easily oxidized, which causes the discoloration of meat. In addition, various microorganisms are responsible for meat spoilage. Chitosan and lycopene can be used to protect the color and extend the shelf life of meat. In this study, a series of coatings with different ratios (1:0, 3:1, 1:1, 1:3, 0:1) of chitosan to lycopene were prepared. Beef was treated with different coatings. The changes in color, relative content of different Mb forms, thiobarbituric acid-reactive substances (TBARS), sulfhydryl content, carbonyl content, microbial count, cooking loss, and sensory evaluation during storage were investigated. The results showed that after 8 days, compared to the control, the relative content of oxymyoglobin (OxyMb), the lightness (L*) value, the redness (a*) value, and the composite index (CI) value of beef treated with chitosan/lycopene of 1:3 (w:w, the concentration of lycopene was 0.75% (w:v)) increased by 6.34%, 34.73%, 67.25%, and 116.27%, respectively. Meanwhile, the relative content of metmyoglobin (MetMb) and the yellowness (b*) value decreased by 11.67% and 23.21%, respectively. Additionally, beef treated with chitosan/lycopene of 1:3 also performed well in protein oxidation, fat oxidation, microbial count, and cooking loss. Generally, the beef treated with chitosan/lycopene of 1:3 showed the best comprehensive quality. The coating was suitable for application in beef. These results are promising for food preservation.

Protective role of short-chain fatty acids on intestinal oxidative stress induced by TNF-α.

Inflammatory bowel diseases (IBD) are driven by an exaggerated inflammatory response, which leads to a marked increase in oxidative stress. This, in turn, exacerbates the inflammatory process and causes significant cellular and tissue damage. Intestinal dysbiosis, a common observation in IBD patients, alters the production of bacterial metabolites, including short-chain fatty acids (SCFAs), which are key by-products of dietary fiber fermentation. While the role of SCFAs in intestinal physiology is still being elucidated, this study aimed to investigate their effects on intestinal oxidative stress, particularly under inflammatory conditions induced by the proinflammatory mediator tumour necrosis factor alpha (TNF-α). The Caco-2/TC7 cell line was employed as an in vitro model of the intestinal epithelium, and the cells were treated with a range of SCFAs, including acetate, propionate, and butyrate. The levels of protein and lipid oxidation were quantified, as well as the activity of antioxidant enzymes. Our findings demonstrate that microbiota-derived SCFAs can effectively mitigate TNF-α-induced oxidative stress by modulating antioxidant enzyme activity. The proinflammatory mediator TNF-α induces lipid peroxidation by inhibiting catalase and glutathione peroxidase activities. SCFAs are able to upregulate antioxidant enzyme activity to restore lipid oxidative levels. These results underscore the critical role of the gut microbiota in maintaining intestinal homeostasis and highlight the therapeutic potential of SCFAs in managing oxidative stress-related pathologies.

Copper homeostasis and neurodegenerative diseases

Copper, one of the most prolific transition metals in the body, required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine (DPA), and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2), along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Phytochemicals in Parkinson's Disease: a Pathway to Neuroprotection and Personalized Medicine.

Parkinson's disease (PD) is a complex neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. While current treatments primarily manage symptoms, there is increasing interest in alternative approaches, particularly the use of phytochemicals from medicinal plants. These natural compounds have demonstrated promising neuroprotective potential in preclinical studies by targeting key pathological mechanisms such as oxidative stress, neuroinflammation, and protein aggregation. However, the clinical translation of these phytochemicals is limited due to a lack of robust clinical trials evaluating their safety, efficacy, and pharmacokinetics. This review provides a comprehensive overview of the neuroprotective potential of phytochemicals in PD management, examining the mechanisms underlying PD pathogenesis and emphasizing neuroprotection. It explores the historical and current research on medicinal plants like Mucuna pruriens, Curcuma longa, and Ginkgo biloba, and discusses the challenges in clinical translation, including ethical and practical considerations and the integration with conventional therapies. It further underscores the need for future research to elucidate mechanisms of action, optimize drug delivery, and conduct rigorous clinical trials to establish the safety and efficacy of phytochemicals, aiming to shape future neuroprotective strategies and develop more effective, personalized treatments for PD.

TMET-31. OXIDATIVE STRESS INDUCED PROTEIN AGGREGATION VIA GGCT PRODUCED PYROGLUTAMIC ACID IN DRUG RESISTANT GLIOBLASTOMA

Abstract Drug resistance is a major barrier to cancer therapies and remains poorly understood. Recently, non-mutational mechanisms of drug resistance have been proposed where a more plastic metabolic response can play a major role. Here, we show that upon drug resistance, glioblastoma (GBM) cells have increased oxidative stress, mitochondria function, and protein aggregation. Gamma (y)-glutamylcyclotranserase (GGCT), an enzyme in the y-glutamyl cycle for glutathione production, located on chromosome 7 which is commonly amplified in GBM is also increased upon resistance. We further observe that the byproduct of GGCT – pyroglutamic acid – can bind aggregating proteins and that genetic and pharmacological inhibition of GGCT prevents protein aggregation. Finally, we found increased protein aggregation, GGCT expression, and pyroglutamic acid staining in recurrent GBM patient samples, as well as adjacent normal brain. These findings suggest a new pathway for protein aggregation within drug resistant brain cancer that should be further studied in other brain disorders.

INDICATORS OF FREE RADICAL OXIDATION AND ANTIOXIDANT PROTECTION IN THE ORAL FLUID OF CHILDREN WITH CHRONIC CATARRHAL GINGIVITIS AND DIABETIS MELLITUS

Failure of antioxidant mechanisms leads to an increase in lipid peroxidation products in the body, resulting in a non-specific cascade of cellular membrane damage. Proteins play a crucial role in metabolic processes, but when lipid peroxidation intensifies, protein modifications occur, leading to fragmentation, denaturation, and loss of biological activity. This disruption impairs tissue regenerative processes. The objective of this study was to analyze indicators of free radical oxidation and antioxidant protection in the oral fluid of children with chronic catarrhal gingivitis and type I diabetes mellitus. Materials and methods. A total of 170 children aged 12 to 16 were observed, including 130 who were examined and treated at the Endocrinology Department of the Regional Municipal Non-Profit Institution “Chernivtsi Regional Pediatric Clinical Hospital” for type 1 diabetes mellitus. Among them, 74 children had a disease duration of less than 5 years, including 65 with chronic catarrhal gingivitis. Sixty five children had diabetes for more than 5 years, with 44 of them diagnosed to have chronic catarrhal gingivitis. The children with chronic catarrhal gingivitis were further divided into groups based on their level of glycemic control: 1 child with optimal glycemic control, 66 with suboptimal glycemic control, and 42 with glycemic control at a high risk to life. The control group included 40 practically healthy children: 22 of them had clinically healthy periodontal tissues, and 18 children were diagnosed to suffer from chronic catarrhal gingivitis. Results. The study performed found out that children with chronic catarrhal gingivitis present increased indicators of lipid peroxide oxidation (protein oxidative modification, diene conjugates, malondialdehyde) and decreased activity of the enzyme in the antioxidant protective system of the oral fluid (whole protein, НS-groups, ceruloplasmin, activity of supermutase and catalase) in comparison with indicators of children without dental pathology. The most considerable changes were found in patients with chronic catarrhal gingivitis and type 1 diabetes mellitus, especially when the disease lasted more than 5 years (р<0,05).

Mass Spectrometry-Based Platforms for Protein Lipoxidation Profiling.

Lipid peroxidation, occurring through enzymatic or non-enzymatic processes, generates lipid-derived electrophiles (LDEs), which can covalently modify nucleophilic amino acid residues in proteins, a process known as protein lipoxidation. This modification can alter protein structure and function, either causing damage or regulating signalling pathways. Identifying the protein targets and specific lipoxidation sites provide important clues for unveiling the oxidative stress-related protein interaction network and molecular mechanisms of related diseases. In this review, we present a detailed overview of recent advances in protein LDE modification profiling, with a focus on mass spectrometry (MS)-based chemoproteomic platforms for global protein lipoxidation profiling.

Discovery of Thiazole Carboxamides as Novel Vanin-1 Inhibitors for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a clinically heterogeneous disease demanding more therapeutic targets and intervention strategies. Vanin-1, an oxidative stress-regulating protein, has emerged as a promising target for alleviating inflammation and oxidative stress. In this study, a series of thiazole carboxamide derivatives as vanin-1 inhibitors were designed and synthesized. The preferred compound, X17, demonstrated potent inhibition against vanin-1 at the protein, HT-29 cell, and tissue levels, whose binding mode with the target was confirmed via the cocrystal structure. X17 achieved a high bioavailability of 81% in rats, accompanied by concentration-dependent inhibition of serum vanin-1. In a DSS-induced mouse colitis model, X17 exhibited potent anti-inflammatory and antioxidant activities, repressing the inflammatory factor expressions and myeloperoxidase activity, elevating the colonic glutathione reserve, and restoring the intestinal barrier. Collectively, these findings depict the discovery of a potent vanin-1 inhibitor, providing an opportunity for further drug candidate development for treating IBD.

High dose of liraglutide impairs renal function in female hypertensive rats.

Glucagon-like peptide-1 (GLP-1) receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. SHR female rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg, LL) and high (0.6 mg/kg, LH) doses. Volume intake and excretion were monitored for a period of 24h. In renal tissue, nitrite-NO2-, nitrate-NO3-, advanced protein oxidation products-AOPP, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. AOPP was reduced only in LL. LH augmented collagen and early markers of kidney injury (blood urea nitrogen-BUN, BUN/Cr). LH increased NO3-, reduced NO2-, and caused an aberrant increase in GFR. Both doses' effects were independent of blood pressure and glycemic control. liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.

EIF5A controls mitoprotein import by relieving ribosome stalling at TIM50 translocase mRNA.

Efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A binds ribosomes, alleviating stalling at polyproline-encoding sequences. eIF5A impacts mitochondrial function across species, though the precise molecular mechanism is unclear. We found that eIF5A depletion in yeast reduces the translation and levels of the TCA cycle and oxidative phosphorylation proteins. Loss of eIF5A causes mitoprotein precursors to accumulate in the cytosol and triggers a mitochondrial import stress response. We identify an essential polyproline protein as a direct target of eIF5A: the mitochondrial inner membrane protein and translocase component Tim50. Thus, eIF5A controls mitochondrial protein import by alleviating ribosome stalling along Tim50 mRNA at the mitochondrial surface. Removal of polyprolines from Tim50 partially rescues the mitochondrial import stress response and translation of oxidative phosphorylation genes. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by promoting efficient translation and reducing ribosome stalling of co-translationally imported proteins, thereby positively impacting the mitochondrial import process.

Associations between milk infrared-predicted plasma biomarkers of stress resilience and fertility in dairy cattle: insights for enhancing breeding programs and herd management

Fertility is a crucial aspect of dairy herd efficiency and sustainability. Among factors influencing fertility in dairy cattle, metabolic stress and systemic inflammation of animals are of main relevance, especially in the postpartum stage when ovarian activity begins and cows are inseminated. Our study aimed to infer the associations between milk infrared-predicted blood biomarkers of stress resilience and fertility traits, namely the interval from calving to first service (iCF), days open (DO), and the pregnancy rate at first service (PRF) in a multi-breed population of 89,097 dairy cows. The blood metabolites (15 blood biomarkers related to hepatic damage and function, oxidative stress, and inflammation/innate immunity) were predicted using milk Fourier-transform mid-infrared (MIR) spectroscopy. A gradient boosting machine (GBM) approach with leave-one-batch-out cross-validation (R2 range from 0.45 to 0.82) was implemented to an independent calibration database of 1,367 lactating cows reared in 5 herds. Calibration equations were then applied to a population database of 1,799,186 MIR milk spectral data, that were then merged with fertility data collected by the Breeders Federation of Alto Adige (Bolzano province, Italy) generating a final database of 285,145 records. The 2 databases were merged according to the milk test day (and thus the MIR spectrum) closest to the date of insemination. The interval fertility traits were fitted as the hazard of either receiving the first service after calving at time t for iCF or becoming pregnant after calving at time t for DO in a Cox proportional-hazards model. Statistical analyses were performed including in the model the number of lactations, year of calving, and herd as fixed effects. The independent effect of the MIR-based predictions of metabolites was also included with each metabolite evaluated separately and discretized into 7 levels based on percentiles. Pregnancy rate at first service, on the other hand, was analyzed using logistic regression and the same explanatory variables. The metabolites linked to liver function and damage, such as aspartate aminotransferase, total bilirubin, and alkaline phosphatase, had a relevant influence on iCF and DO in terms of the hazard ratio (HR). Relevant results were also obtained for the biomarkers related to oxidative stress and inflammation/innate immunity. Specifically, increasing levels of ceruloplasmin, total reactive oxygen metabolites, and advanced oxidation protein products resulted in a relevant decrease in the HR of cows becoming pregnant. The logistic regression analysis did not reveal any significant effect of the aforementioned biomarkers on PRF, indicating that the effects of the stress response mainly concern the resumption of the ovarian cycle after calving. The results for the associations of the predicted biomarkers of the stress response with iCF and DO were consistent with expected physiological patterns. In conclusion, the predicted biomarkers investigated revealed to be promising novel phenotypes for assessing animal health and welfare, in the view of enhancing fertility in dairy cattle also through selective breeding, thus improving the overall efficiency of dairy herds.

Accumulation of advanced oxidation protein products promotes age-related decline of type H vessels in bone.

Type H vessels have been proven to couple angiogenesis and osteogenesis. The decline of type H vessels contributes to bone loss in the aging process. Aging is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, whether AOPP accumulation is involved in age-related decline of type H vessels is unclear. Here, we show that the increase of AOPP levels in plasma and bone were correlated with the decline of type H vessels and loss of bone mass in old mice. Exposure of microvascular endothelial cells to AOPPs significantly inhibited cell proliferation, migration, and tube formation, increased NADPH oxidase activity and excessive reactive oxygen species generation, upregulated the expression of vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1, and eventually impaired angiogenesis, which was alleviated by redox modulator N-acetylcysteine and NADPH oxidase inhibitor apocynin. Furthermore, reduced AOPP accumulation by NAC treatment was able to alleviate significantly the decline of type H vessels, bone mass loss and deterioration of bone microstructure in old mice. Collectively, these findings suggest that AOPPs accumulation contributes to the decline of type H vessels in the aging process, and illuminate a novel potential mechanism underlying age-related bone loss.

Influence of (ultra-)processing methods on aquatic proteins and product quality.

Aquatic products are a high-quality source of protein for humans, and the changes in protein during aquatic product processing are crucial for nutritional value, product performance, and consumer health. With the advancement of science and technology, aquatic product processing methods have become increasingly diverse. In addition to traditional methods such as thermal processing (steaming, roasting, and frying) and pickling, emerging non-thermal processing technologies, such as high pressure, ultrasound, and irradiation, are also being applied. During (ultra-)processing, aquatic products undergo complex biochemical reactions, among which protein oxidation significantly affects the quality of aquatic products. Protein oxidation can alter the molecular structure of proteins, thereby changing their functional properties and ultimately impacting product quality. This paper primarily explored the effects of protein changes under different processing methods on aquatic product quality and human health, as well as techniques for controlling protein oxidation. It aims to provide a theoretical basis for selecting appropriate processing methods, improving aquatic product quality, and controlling protein oxidation in aquatic products, and to offer scientific guidance for practical production.

Antioxidant and Nutritional Potential of Artichoke (Cynara scolymus L.) By-Product Extracts in Fat-Replaced Beef Burgers with Hydrogel Emulsions from Olive Oil

Beef burger consumption has been questioned due to the burgers’ high levels of saturated fatty acids and the use of synthetic additives for preservation. In order to improve the acceptability and health benefits of this product, two functional ingredients, artichoke and extra-virgin olive oil (EVOO), have been used to formulate four different beef burgers: a control burger (CB), a fat-replaced burger with an EVOO emulsion (FRB), and two FRB formulations with the incorporation of enzymatically treated (FRB-TAE) or untreated (FRB-AE) artichoke extract. Fat replacement significantly affected the lipid profile of the burgers, increasing oleic acid levels and n-3 PUFA such as α-linolenic and eicosapentaenoic acids. Artichoke incorporation exerted beneficial effects on the antioxidant activity, as well as on the total phenolic content of the reformulated burgers, leading to a decrease in color changes, lipid and protein oxidation after 3 days of storage at 4 °C, as well as reducing the formation of volatile compounds such as hexanal, 2,3-Octanedione, or 1-Octen-3-ol. No differences were found between formulations for the sensory parameters studied. These results demonstrate a possible revalorization of artichoke by-products by improving the nutritional properties of beef burgers, revealing a potential application as a higher value-added ingredient in the meat industry.

Upregulation of ACSL, ND75, Vha26 and sesB genes by antiepileptic drugs resulted in genotoxicity in drosophila.

Clobazam (CLB) and Vigabatrin (VGB) are commonly used antiepileptic drugs (AEDs) in the treatment of epilepsy. Here, we have examined the genotoxic effect of these AEDs in Drosophila melanogaster. The Drosophila larvae were exposed to different concentrations of CLB and VGB containing food media. The assessment encompassed oxidative stress, DNA damage, protein levels, and gene expression profiles. In the CLB-treated group, a reduction in reactive oxygen species (ROS) and lipid peroxidation (LPO) levels was observed, alongside increased levels of superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO). Conversely, the VGB-treated group displayed contrasting results, with increased ROS and LPO and decreased SOD, CAT, and NO levels. However, both CLB and VGB induced DNA damage in Drosophila. Proteomic analysis (SDS-PAGE and OHRLCMS) in the CLB and VGB groups identified numerous proteins, including Acyl-CoA synthetase long-chain, NADH-ubiquinone oxidoreductase 75kDa subunit, V-type proton ATPase subunit E, ADP/ATP carrier protein, malic enzyme, and DNA-binding protein modulo. These proteins were found to be associated with pathways like growth promotion, notch signaling, Wnt signaling, neuromuscular junction (NMJ) signaling, bone morphogenetic protein (BMP) signaling, and other GABAergic mechanisms. Furthermore, mRNA levels of ACSL, ND75, Vha26, sesB, and Men genes were upregulated in both CLB and VGB-treated groups. These findings suggest that CLB and VGB could have the potential to induce genotoxicity and post-transcriptional modifications in humans, highlighting the importance of monitoring their effects when used as AEDs.

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.