Antioxidants, Volume 13, Issue 5 (May 2024) – 88 articles

YCA1, the only metacaspase in Saccharomyces cerevisiae, plays important roles in the regulation of chronological lifespan, apoptosis, and cytokinesis. YCA1 has protein hydrolase activity and functions by cleaving itself and target proteins. However, there are few reports about the regulation of YCA1 activity. In this study, we observed that reactive sulfane sulfur (RSS) can inhibit the activity of YCA1. In vitro experiments demonstrated that RSS reacted with the Cys₂₇₆ of YCA1, the residue central to its protein hydrolase activity, to form a persulfidation modification (protein-SSH). This modification inhibited both its self-cleavage and the cleavage of its substrate protein, BIR1. To investigate further, we constructed a low-endogenous-RSS mutant of S. cerevisiae, BY4742 Δcys3, in which the RSS-producing enzyme cystathionine-γ-lyase (CYS3) was knocked out. The activity of YCA1 was significantly increased by the deletion of CYS3. Moreover, increased YCA1 activity led to reduced chronological lifespan (CLS) and CLS-driven apoptosis. This study unveils the first endogenous factor that regulates YCA1 activity, introduces a novel mechanism of how yeast cells regulate chronological lifespan, and broadens our understanding of the multifaceted roles played by RSS. Full article

Lemon is a fruit rich in antioxidant properties and has several health benefits, namely the reduction of skin edema and anticarcinogenic properties, which are due to its high content of bioactive compounds. Melatonin can improve and preserve the properties of lemon for longer and also has health benefits. The aim of this study was to evaluate the effects of oral administration of lemon juice after melatonin treatment on murinometric parameters of wild-type (WT) mice and transgenic mice carrying human papillomavirus (HPV). Two trials were performed for oral administration of the lemon extract compound: in drinking water and in diet. First of all, lemons were treated by immersion with melatonin at 10 mM. Then, lemons were squeezed, and the juice obtained was freeze-dried and stored to be subsequently added to drinking water or diet, according to the assay. Thus, mice were divided into eight groups in the drink assay (each with n = 5): group 1 (G1, WT, control), group 2 (G2, WT, 1 mL lemon), group 3 (G3, WT, 1.5 mL lemon), group 4 (G4, WT, 2 mL lemon), group 5 (G5, HPV16, control), group 6 (G6, HPV16, 1 mL lemon) group 7 (G6, HPV16, 1.5 mL lemon) and group 8 (G6, HPV16, 2 mL lemon). The diet assay was divided into four groups: group 1 (G1, WT, control), group 2 (G2, WT, 4 mL lemon), group 3 (G3, HPV16, control) and group 4 (G4, HPV16, 4 mL lemon). In the drink assay, the highest concentration of melatonin (308 ng/100 mL) was for groups 4 and 8, while in the food assay, there was only one concentration of melatonin (9.96 ng/g) for groups 2 and 4. Both trials lasted 30 days. During this time, body weight, food and water were recorded. Afterward, they were sacrificed, and samples were collected for different analyses. At the concentrations used, the lemon juice with melatonin had no adverse effects on the animals’ health and showed a positive outcome in modifying weight gain and enhancing antioxidant activity in mice. Moreover, a reduction in the incidence of histological lesions was observed in treated animals. Further research is needed to better understand the effects of lemon extract on health and treatment outcomes in this animal model. Full article

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues. Thus, there is a need to develop therapeutic approaches to reduce nRT toxicities. Avasopasem manganese (AVA) is a selective superoxide dismutase mimetic that protects against IR-induced oral mucositis and lung fibrosis. We tested the efficacy of AVA in enhancing RT in STSs and in promoting wound healing. Using colony formation assays and alkaline comet assays, we report that AVA selectively enhanced the STS (liposarcoma, fibrosarcoma, leiomyosarcoma, and MPNST) cellular response to radiation compared to normal dermal fibroblasts (NDFs). AVA is believed to selectively enhance radiation therapy by targeting differential hydrogen peroxide clearance in tumor cells compared to non-malignant cells. STS cells demonstrated increased catalase protein levels and activity compared to normal fibroblasts. Additionally, NDFs showed significantly higher levels of GPx1 activity compared to STSs. The depletion of glutathione using buthionine sulfoximine (BSO) sensitized the NDF cells to AVA, suggesting that GPx1 may, in part, facilitate the selective toxicity of AVA. Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs. Full article

Several medicinal herbal plants are extensively used as sources of bioactive compounds with beneficial effects on human health. This study assessed the procyanidin and polyphenol profiles together with the antioxidant potential of seven herbal medical matrices. To achieve this aim, procyanidin extraction from grape pomace was optimized and validated by monitoring monomeric-trimeric procyanidins. The proposed quantification method was applied to the seven medical herbs, and it proved to be a very efficient protocol for procyanidin-rich extracts analysis. In addition, the Paullinia cupana Kunth. seed was identified as a very rich source of procyanidins (about 5 mg/g dry matrix of each dimeric and about 3 mg/g dry matrix trimeric) with high antioxidant properties. The polyphenolic profile was assessed by HPLC-HESI-MS/MS analysis. The in vitro antioxidant activity was evaluated by DPPH assay to explore the antioxidant properties of the extracts, which were substantially higher in Peumus boldus Molina leaves extracts (935.23 ± 169 μmol of Trolox equivalent/g of dry weight) concerning the other matrices. Moreover, a high Pearson coefficient value was observed between the total flavonoid content (TFC) and DPPH in comparison with the total polyphenol content (TPC) and DPPH, indicating flavonoids as the principal bioactive with antioxidant activity in the extracts. Full article

Hypertension reduces the bioavailability of vascular nitric oxide (NO) and contributes to the onset of vascular dementia (VaD). A loss of NO bioavailability increases inflammation and oxidative stress. 2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a novel nitric oxide donor (NOD) which is undergoing phase I clinical trials in China for the treatment of VaD. In this study, we investigated the protective effects of W1302 in VaD rats induced by the permanent occlusion of a bilateral common carotid arteries model related to spontaneous hypertension (SHR-2VO), and we further explored the underlying mechanisms. Nimodipine was used as a positive control. Our results showed that W1302 treatment for 4 weeks (10 mg/Kg/day) exhibited stronger improvement in the spatial learning and memory deficits in SHR-2VO rats compared with nimodipine with slightly lower systolic blood pressure (SBP). Meanwhile, W1302 treatment significantly increased NO and cGMP production, restored mitochondrial membrane potential and attenuated oxidative stress as evidenced by increasing ATP production and reducing malondialdehyde (MDA) levels in the brain. Furthermore, W1302 treatment markedly inhibited the iNOS activity and decreased TNF-α expression via inhibiting the nuclear factor kappa B (NF-κB) signaling pathway. Nimodipine treatment also restored these aberrant changes, but its ATP production was weaker than that of W1302, and there was no significant effect on NO release. Taken together, W1302 exhibited beneficial effects on complications in VaD with hypertension, which is involved in suppressing oxidative damage, and the inflammatory reaction might be mediated by an increase in NO release. Therefore, W1302 has therapeutic potential for the treatment of VaD caused by chronic cerebral hypoperfusion-associated spontaneous hypertension. Full article

Cadmium (Cd) is a heavy metal that is highly toxic to humans and animals. Its adverse effects have been widely associated with mitochondrial alterations. However, there are not many treatments that target mitochondria. This study aimed to evaluate the impact of sulforaphane (SFN) pre-exposure against cadmium chloride (CdCl₂)-induced toxicity and mitochondrial alterations in the nematode Caenorhabditis elegans (C. elegans), by exploring the role of the insulin/insulin-like growth factor signaling pathway (IIS). The results revealed that prior exposure to SFN protected against CdCl₂-induced mortality and increased lifespan, body length, and mobility while reducing lipofuscin levels. Furthermore, SFN prevented mitochondrial alterations by increasing mitochondrial membrane potential (Δψm) and restoring mitochondrial oxygen consumption rate, thereby decreasing mitochondrial reactive oxygen species (ROS) production. The improvement in mitochondrial function was associated with increased mitochondrial mass and the involvement of the daf-16 and skn-1c genes of the IIS signaling pathway. In conclusion, exposure to SFN before exposure to CdCl₂ mitigates toxic effects and mitochondrial alterations, possibly by increasing mitochondrial mass, which may be related to the regulation of the IIS pathway. These discoveries open new possibilities for developing therapies to reduce the damage caused by Cd toxicity and oxidative stress in biological systems, highlighting antioxidants with mitochondrial action as promising tools. Full article

Atherosclerosis is a complex condition that involves the accumulation of lipids and subsequent plaque formation in the arterial intima. There are various stimuli, cellular receptors, and pathways involved in this process, but oxidative modifications of low-density lipoprotein (ox-LDL) are particularly important in the onset and progression of atherosclerosis. Ox-LDLs promote foam-cell formation, activate proinflammatory pathways, and induce smooth-muscle-cell migration, apoptosis, and cell death. One of the major receptors for ox-LDL is LOX-1, which is upregulated in several cardiovascular diseases, including atherosclerosis. LOX-1 activation in endothelial cells promotes endothelial dysfunction and induces pro-atherogenic signaling, leading to plaque formation. The binding of ox-LDLs to LOX-1 increases the generation of reactive oxygen species (ROS), which can induce LOX-1 expression and oxidize LDLs, contributing to ox-LDL generation and further upregulating LOX-1 expression. This creates a vicious circle that is amplified in pathological conditions characterized by high plasma levels of LDLs. Although LOX-1 has harmful effects, the clinical significance of inhibiting this protein remains unclear. Further studies both in vitro and in vivo are needed to determine whether LOX-1 inhibition could be a potential therapeutic target to counteract the atherosclerotic process. Full article

Dimethyl sulfoxide (DMSO), an organosulfur compound, is widely used as the gold standard solvent in biological research. It is used in cell culture experiments and as a component of formulations in in vivo studies. Unfortunately, parameters related to sulfur metabolism are often not taken into account when using DMSO. Therefore, in this work we aim to show that the addition of DMSO to the culture medium (even in amounts commonly considered acceptable) alters some parameters of sulfur metabolism. For this study, we used three cell lines: a commercially available Caco-2 line (HTB-37, ATCC) and two lines created as part of our early studies (likewise previously described in the literature) to investigate the anomalies of sulfur metabolism in mucopolysaccharidosis. As the negative effects of DMSO on the cell membrane are well known, additional experiments with the partial loading of DMSO into polymerosomes (poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide), PEG-PLGA) were performed to eliminate these potentially disruptive effects. The results show that DMSO is a source of interference in studies related to sulfur metabolism and that there are not just simple effects that can be corrected in the final result by subtracting control values, since complex synergisms are also observed. Full article

Papaya contains high amounts of vitamins A, C, riboflavin, thiamine, niacin, ascorbic acid, potassium, and carotenoids. It is confirmed by several studies that all food waste parts such as the fruit peels, seeds, and leaves of papaya are potential sources of phenolic compounds, particularly in the peel. Considering the presence of numerous bioactive compounds in papaya fruit peels, the current study reports a rapid, cheap, and environmentally friendly method for the production of gold nanoparticles (AuNPs) employing food biowaste (vegetable papaya peel extract (VPPE)) and investigated its antioxidant, antidiabetic, tyrosinase inhibition, anti-inflammatory, antibacterial, and photocatalytic degradation potentials. The phytochemical analysis gave positive results for tannins, saponins, steroids, cardiac steroidal glycoside, protein, and carbohydrates. The manufactured VPPE-AuNPs were studied by UV–Vis scan (with surface plasmon resonance of 552 nm), X-ray diffraction analysis (XRD) (with average crystallite size of 44.41 nm as per the Scherrer equation), scanning electron microscopy–energy-dispersive X-ray (SEM-EDS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), particle size, zeta potential, etc. The mean dimension of the manufactured VPPE-AuNPs is 112.2 d.nm (PDI—0.149) with a −26.1 mV zeta potential. The VPPE-AuNPs displayed a significant antioxidant effect (93.24% DPPH scavenging and 74.23% SOD inhibition at 100 µg/mL); moderate tyrosinase effect (with 30.76%); and substantial α-glucosidase (95.63%) and α-amylase effect (50.66%) at 100 µg/mL. Additionally, it was found to be very proficient in the removal of harmful methyl orange and methylene blue dyes with degradation of 34.70% at 3 h and 24.39% at 5 h, respectively. Taken altogether, the VPPE-AuNPs have been proven to possess multiple biopotential activities, which can be explored by the food, cosmetics, and biomedical industries. Full article

Alcohol is toxic to neurons and can trigger alcohol-related brain damage, neuronal loss, and cognitive decline. Neuronal cells may be vulnerable to alcohol toxicity and damage from oxidative stress after differentiation. To consider this further, the toxicity of alcohol to undifferentiated SH-SY5Y cells was compared with that of cells that had been acutely differentiated. Cells were exposed to alcohol over a concentration range of 0–200 mM for up to 24 h and alcohol effects on cell viability were evaluated via MTT and LDH assays. Effects on mitochondrial morphology were examined via transmission electron microscopy, and mitochondrial functionality was examined using measurements of ATP and the production of reactive oxygen species (ROS). Alcohol reduced cell viability and depleted ATP levels in a concentration- and exposure duration-dependent manner, with undifferentiated cells more vulnerable to toxicity. Alcohol exposure resulted in neurite retraction, altered mitochondrial morphology, and increased the levels of ROS in proportion to alcohol concentration; these peaked after 3 and 6 h exposures and were significantly higher in differentiated cells. Protein carbonyl content (PCC) lagged behind ROS production and peaked after 12 and 24 h, increasing in proportion to alcohol concentration, with higher levels in differentiated cells. Carbonylated proteins were characterised by their denatured molecular weights and overlapped with those from adult post-mortem brain tissue, with levels of PCC higher in alcoholic subjects than matched controls. Hence, alcohol can potentially trigger cell and tissue damage from oxidative stress and the accumulation of oxidatively damaged proteins. Full article

Microplastics (MPs) are plastic particles between 0.1 and 5000 µm in size that have attracted considerable attention from the scientific community and the general public, as they threaten the environment. Microplastics contribute to various harmful effects, including lipid peroxidation, DNA damage, activation of mitogen-activated protein kinase pathways, cell membrane breakages, mitochondrial dysfunction, lysosomal defects, inflammation, and apoptosis. They affect cells, tissues, organs, and overall health, potentially contributing to conditions like cancer and cardiovascular disease. They pose a significant danger due to their widespread occurrence in food. In recent years, information has emerged indicating that MPs can cause oxidative stress (OS), a known factor in accelerating the aging of organisms. This comprehensive evaluation exposed notable variability in the reported connection between MPs and OS. This work aims to provide a critical review of whether the harmfulness of plastic particles that constitute environmental contaminants may result from OS through a comprehensive analysis of recent research and existing scientific literature, as well as an assessment of the characteristics of MPs causing OS. Additionally, the article covers the analytical methodology used in this field. The conclusions of this review point to the necessity for further research into the effects of MPs on OS. Full article

The natural edible characteristics of Chinese herbs have led more and more people to study them as an alternative product to antibiotics. In this study, crude extracts of Glycyrrhiza radix and Atractylodes macrocephala (abbreviated as GRAM) with glycyrrhizic acid content not less than 0.2 mg/g were selected to evaluate the effects of GRAM on the immune and antioxidant capacity of model animals. Thirty 21-day-old male Leghorn chickens were weighed and randomly assigned to one of three groups of ten animals each. The treatments comprised a control group (CON), in which saline was injected at day 31, day 33, and day 35, an LPS-treated group (LPS), in which LPS (0.5 mg/kg of BW) was injected at day 31, day 33, and day 35, and finally a GRAM and LPS-treated group, (G-L) in which a GRAM-treated diet (at GRAM 2 g/kg) was fed from day 21 to day 35 with LPS injection (0.5 mg/kg of BW) at day 31, day 33, and day 35. The results of diarrhea grade and serum antioxidant measurement showed that the LPS group had obvious diarrhea symptoms, serum ROS and MDA were significantly increased, and T-AOC was significantly decreased. The oxidative stress model of LPS was successfully established. The results of immune and antioxidant indexes showed that feeding GRAM significantly decreased levels of the pro-inflammatory factors TNF-α, IL-1β, and IL-6 (p < 0.05) and significantly increased levels of the anti-inflammatory factors IL-4 and IL-10 and levels of the antioxidant enzymes GSH-Px and CAT (p < 0.05). GRAM resisted the influence of LPS on ileum morphology, liver, and immune organs and maintained normal index values for ileum morphology, liver, and immune organs. In summary, this study confirmed the antidiarrheal effect of GRAM, which improved the immune and antioxidant capacity of model animals by regulating inflammatory cytokine levels and antioxidant enzyme activity in poultry. Full article

Brucella virulence relies on its successful intracellular life cycle. Modulating host cell death is a strategy for Brucella to survive and replicate intracellularly. Ferroptosis is a novel regulated cell death characterized by iron-triggered excessive lipid peroxidation, which has been proven to be associated with pathogenic bacteria infection. Thus, we attempted to explore if smooth-type Brucella infection triggers host cell ferroptosis and what role it plays in Brucella infection. We assessed the effects of Brucella infection on the lactate dehydrogenase release and lipid peroxidation levels of RAW264.7 macrophages; subsequently, we determined the effect of Brucella infection on the expressions of ferroptosis defense pathways. Furthermore, we determined the role of host cell ferroptosis in the intracellular replication and egress of Brucella. The results demonstrated that Brucella M5 could induce ferroptosis of macrophages by inhibiting the GPX4-GSH axis at the late stage of infection but mitigated ferroptosis by up-regulating the GCH1-BH4 axis at the early infection stage. Moreover, elevating host cell ferroptosis decreased Brucella intracellular survival and suppressing host cell ferroptosis increased Brucella intracellular replication and egress. Collectively, Brucella may manipulate host cell ferroptosis to facilitate its intracellular replication and egress, extending our knowledge about the underlying mechanism of how Brucella completes its intracellular life cycle. Full article

Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993–1998), intake of antioxidants from diet and supplements at a mean age of 52.4 years was estimated using a validated food frequency questionnaire to derive two dietary TAC indices from vitamins C and E, carotenoids and flavonoids: the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). At follow-up 3 (2014–2016), when participants were at a mean age of 72.5 years, depressive symptoms were assessed using the Geriatric Depression Scale, and depression, defined as having ≥5 symptoms, was presented in 3173 (23.1%) participants. Both CDAI and VCEAC indices were inversely associated with odds of depressive symptoms in a stepwise manner: the OR (95% CI) comparing the extreme quartiles was 0.73 (0.64–0.83; P_trend < 0.01) for the CDAI and 0.77 (0.68–0.87; P_trend < 0.01) for the VCEAC. Specifically, higher intakes of vitamin C, carotenoids, and flavonoids were associated with a lower likelihood of depressive symptoms. Our findings support the recommendation of an antioxidant-rich diet for the prevention of depression. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by the disruption of the intestinal barrier. The intestinal barrier is maintained by tight junctions (TJs), which sustain intestinal homeostasis and prevent pathogens from entering the microbiome and mucosal tissues. Ziziphus jujuba Miller (Z. jujuba) is a natural substance that has been used in traditional medicine as a therapy for a variety of diseases. However, in IBD, the efficacy of Z. jujuba is unknown. Therefore, we evaluated ZJB in Caco2 cells and a dextran sodium sulfate (DSS)-induced mouse model to demonstrate its efficacy in IBD. Z. jujuba extracts were prepared using 70% ethanol and were named ZJB. ZJB was found to be non-cytotoxic and to have excellent antioxidant effects. We confirmed its anti-inflammatory properties via the down-regulation of inflammatory factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). To evaluate the effects of ZJB on intestinal barrier function and TJ improvement, the trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran 4 kDa (FITC-Dextran 4) permeability were assessed. The TEER value increased by 61.389% and permeability decreased by 27.348% in the 200 μg/mL ZJB group compared with the 50 ng/mL IL-6 group after 24 h. Additionally, ZJB alleviated body weight loss, reduced the disease activity index (DAI) score, and induced colon shortening in 5% DSS-induced mice; inflammatory cytokines, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were down-regulated in the serum. TJ proteins, such as Zonula occludens (ZO)-1 and occludin, were up-regulated by ZJB in an impaired Caco2 mouse model. Additionally, according to the liquid chromatography results, in tandem with mass spectrometry (LC-MS/MS) analysis, seven active ingredients were detected in ZJB. In conclusion, ZJB down-regulated inflammatory factors, protected intestinal barrier function, and increased TJ proteins. It is thus a safe, natural substance with the potential to be used as a therapeutic agent in IBD treatment. Full article

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate metabolism, synaptic transmission, cellular energetics, etc., of both MCI and AD brains compared to the controls. Some proteins were found to be common targets of oxidation and were observed during the early stages of AD, suggesting that those changes might be critical in the onset of symptoms and/or formation of the pathological hallmarks of AD. Further studies are required to fully elucidate the role of protein oxidation and nitration in the progression and pathogenesis of AD. Full article

This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from databases like PubMed, EBSCO (EDS), and Google Scholar, culminating in the inclusion of 41 studies. The quality of these studies was rigorously assessed to ensure the clarity of objectives, coherence in arguments, comprehensive literature coverage, and depth of critical analysis. Findings revealed that moderate exercise enhances antioxidant defenses through hormesis, while excessive exercise may exacerbate oxidative stress. The review also highlights that while natural dietary antioxidants are beneficial, high-dose supplements could impede the positive adaptations to exercise. In conclusion, the review calls for more focused research on tailored exercise and nutrition plans to further understand these complex interactions and optimize the health outcomes for athletes and the general population. Full article

C. nudiflora is notably rich in flavonoids and phenylethanoid glycosides, making it a significant natural source of antioxidants. We examined the effects of C. nudiflora aqueous extract (CNE) on growth performance, antioxidant function, immunity, intestinal barrier function, nutrient transporters, and microbiota of broilers. A total of 360 one-day-old broilers were randomly assigned to four treatment groups: a basal diet with 0 (control, CON), 300 mg/kg (CNEL), 500 mg/kg (CNEM), and 700 mg/kg (CNEH) CNE for 42 days. CNEL and CNEM groups quadratically increased body weight and average daily gain but decreased feed-to-gain ratios during the starter and whole phases. Regarding the immune response of broilers, CNE treatment linearly down-regulated jejunal myeloid differentiation factor 88 (MyD88) expression and interleukin-1β (IL-1β) and interferon-γ expression in the liver (d 21), while decreasing jejunal IL-1β expression and the concentration of serum tumor necrosis factor-α and interleukin-6 (d 42). The CNEM and CNEH groups had lower MyD88 and nuclear factor kappa B expression in the liver (d 21) compared to the CON group. Broilers in the CNEL and CNEM groups had higher spleen index and thymus index (d 21) and interleukin-10 expression from the liver and jejunal mucosa (d 42) than that in the CON group. For the antioxidant capacity of broilers, CNE treatment linearly decreased the content of malonaldehyde and increased the activity of total antioxidant capacity in serum (d 42). CNEM and CNEH groups linearly increased the activity of superoxide dismutase in serum and heme oxygenase-1 expression in the liver, while increasing the activity of glutathione peroxidase in serum, jejunal nuclear factor E2-related factor 2 expression, and NAD(P)H quinone oxidoreductase 1 expression in the liver (d 42). As for the growth hormone of broilers, CNEM group increased the level of serum insulin-like growth factor 1 and up-regulated jejunal glucagon-like peptide 2 (GLP-2) expression (d 21). Broilers in the CNEM and CNEH groups had higher jejunal GLP-2 expression and growth hormone (GH) expression in the liver and the level of serum GH (d 42) than that in the CON group. Additionally, the villus height and jejunal Occludin and Claudin-1 expression in the CNEM group increased. CNE-containing diets resulted in a linear increase in the expression of jejunal zonula occluden-1 (d 21), villus height to crypt depth ratio, jejunal Occludin, excitatory amino acid transporters-3, and peptide-transporter 1 (d 42). The regulation of Oscillospira, Ruminococcaceae_Ruminococcus, and Butyricicoccus genera indicated that CNEH altered the composition of the cecal microbiota. In general, supplementing broilers with C. nudiflora aqueous extract could boost hormones, immune and antioxidant function, and gut health, improving their growth performance. Hence, CNE was a promising poultry feed additive, with 500 mg/kg appearing to be the optimal dose. Full article

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs. Full article

Valorisation of food by-products, like spent brewer’s yeast and fruit pomaces, represents an important strategy for contributing to sustainable food production. The aims of this study were to obtain Maillard conjugates based on spent yeast protein hydrolysate (SYH) with dextran (D) or maltodextrin (MD) by means of ultrasound treatment and to use them for developing encapsulation systems for the anthocyanins from aronia pomace. The ultrasound-assisted Maillard conjugation promoted the increase of antioxidant activity by about 50% compared to conventional heating and SYH, and was not dependent on the polysaccharide type. The ability of the conjugates to act as wall material for encapsulating various biologically active compounds was tested via a freeze-drying method. The retention efficiency ranged between 58.25 ± 0.38%–65.25 ± 2.21%, while encapsulation efficiency varied from 67.09 ± 2.26% to 88.72 ± 0.33%, indicating the strong effect of the carrier material used for encapsulation. The addition of the hydrolysed yeast cell wall played a positive effect on the encapsulation efficiency of anthocyanins when used in combination with the SYH:MD conjugates. On the other hand, the stability of anthocyanins during storage, as well as their bioavailability during gastrointestinal digestion, were higher when using the SYH:D conjugate. The study showed that hydrolysis combined with the ultrasound-assisted Maillard reaction has a great potential for the valorisation of spent brewer’s yeast as delivery material for the encapsulation of bioactive compounds. Full article

Soybean meal (SBM) is a prevailing plant protein supplement in animal diets because of its nutritional value and availability. This review paper explores the significance of SBM and processed soy products, emphasizing their nutritional and bioactive components, such as isoflavones and soyasaponins. These compounds are known for their antioxidant and anti-inflammatory properties and are associated with a reduced prevalence of chronic diseases. However, the presence of antinutritional compounds in SBM presents a significant challenge. The paper evaluates various processing methods, including ethanol/acid wash, enzyme treatment, and fermentation, which are aimed at enhancing the nutritional value of soy products. It highlights the significance to maintain a balance between nutritional enhancement and the preservation of beneficial bioactive compounds, emphasizing the importance of different processing techniques to fully exploit the health benefits of soy-based products. Therefore, this review illuminates the complex balance between nutritional improvement, bioactive compound preservation, and the overall health implications of soy products. Full article

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights. Full article

Soy isoflavones (SIF) are bioactive compounds with low bioavailability due to their poor water solubility. In this study, we utilized polymerized goat milk whey protein (PGWP) as a carrier to encapsulate SIF with encapsulation efficiency of 89%, particle size of 135.53 nm, and zeta potential of −35.16 mV. The PGWP-SIF nanoparticles were evaluated for their stability and in vitro digestion properties, and their ability to transport SIF was assessed using a Caco-2 cell monolayer model. The nanoparticles were resistant to aggregation when subjected to pH changes (pH 2.0 to 8.0), sodium chloride addition (0–200 mM), temperature fluctuations (4 °C, 25 °C, and 37 °C), and long-term storage (4 °C, 25 °C, and 37 °C for 30 days), which was mainly attributed to the repulsion generated by steric hindrance effects. During gastric digestion, only 5.93% of encapsulated SIF was released, highlighting the nanoparticles’ resistance to enzymatic digestion in the stomach. However, a significant increase in SIF release to 56.61% was observed during intestinal digestion, indicating the efficient transport of SIF into the small intestine for absorption. Cytotoxicity assessments via the MTT assay showed no adverse effects on Caco-2 cell lines after encapsulation. The PGWP-stabilized SIF nanoparticles improved the apparent permeability coefficient (Papp) of Caco-2 cells for SIF by 11.8-fold. The results indicated that using PGWP to encapsulate SIF was an effective approach for delivering SIF, while enhancing its bioavailability and transcellular transport. Full article

Periodontal disease is an inflammatory condition characterized by an aberrant immune response against a dysbiotic dental biofilm, with oxidative stress performing an essential role in its pathogenesis. This paper presents a patent mining, performed in the Orbit Intelligence patent database, related to antioxidant phytochemicals in the technological developments that are working to prevent and treat periodontal disease. To access the documents, the descriptors “PERIODONTAL” and “ANTIOXIDANT” were typed in the title, abstract, and claim search fields. A total of 322 patents demonstrate the growing interest in researching natural antioxidants for scientific and technological purposes. The top ten countries regarding the number of family patents produced were the United States, the European Office, Japan, South Korea, China, India, Mexico, Denmark, Canada, and Great Britain. The most cited compounds were vitamin C, green tea, quercetin, melatonin, lycopene, resveratrol, and curcumin. These compounds have been used for the technological development of gels, membranes, dentifrices, chewing gum, orally disintegrating film, mouthwash, mouth spray, and mouth massage cream and exhibit the ability to neutralize free radicals and reduce oxidative stress, a critical factor in the development and progression of periodontal diseases. The patent documents have shown that using antioxidant compounds in conjunction with traditional periodontal treatments is a promising area of interest in periodontal therapy. Full article

Soil is an environment with numerous niches, where bacteria are exposed to diverse conditions. Some bacteria are exposed earlier than others to pressure, and the emission of signals that other bacteria can receive and perceive may allow a better response to an eminent stimulus. To shed light on how bacteria trigger their response and adapt to changes in the environment, the intra- and interspecific influences of volatiles on bacterial strains growing under non-stressed and cadmium-stressed conditions were assessed. Each strain was exposed to its volatiles emitted by cells growing under different conditions to test whether the environment in which a cell grows influences neighboring cells. The five genera tested showed different responses, with Rhizobium displaying the greatest influence. In a second experiment, 13 strains from different genera were grown under control conditions but exposed to volatiles released by Cd-stressed Rhizobium cells to ascertain whether Rhizobium’s observed influence was strain-specific or broader. Our results showed that the volatiles emitted by some bacteria under stress are differentially perceived and translated into biochemical changes (growth, alteration of the antioxidant response, and oxidative damage) by other bacteria, which may increase the adaptability and resilience of bacterial communities to environmental changes, especially those with a prooxidant nature. Cadmium (Cd) contamination of soils constitutes a risk to the environment and human health. Here, we showed the effects of Cd exposure on bacteria and how volatile communication influences the biochemistry related to coping with oxidative stress. This knowledge can be important for remediation and risk assessment and highlights that new biological features, such as volatile communication, should be considered when studying and assessing the impact of contaminants on soil ecosystems. Full article

Cancer is a major global health concern. To address this, the combination of traditional medicine and newly appreciated therapeutic modalities has been gaining considerable attention. This study explores the combined effects of Aucklandiae Radix (AR) and 43 °C hyperthermia (HT) on human gastric adenocarcinoma (AGS) cell proliferation and apoptosis. We investigated the synergistic effects of AR and HT on cell viability, apoptosis, cell cycle progression, and reactive oxygen species (ROS)-dependent mechanisms. Our findings suggest that the combined treatment led to a notable decrease in AGS cell viability and increased apoptosis. Furthermore, cell cycle arrest at the G2/M phase contributed to the inhibition of cancer cell proliferation. Notably, the roles of heat shock proteins (HSPs) were highlighted, particularly in the context of ROS regulation and the induction of apoptosis. Overexpression of HSPs was observed in cells subjected to HT, whereas their levels were markedly reduced following AR treatment. The suppression of HSPs and the subsequent increase in ROS levels appeared to contribute to the activation of apoptosis, suggesting a potential role for HSPs in the combined therapy’s anti-cancer mechanisms. These findings provide valuable insights into the potential of integrating AR and HT in cancer and HSPs. Full article

Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments. Full article

Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of Lactiplantibacillus plantarum of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE₂) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders. Full article

Ataxia is a common neurological feature of Niemann–Pick disease type C (NPC). In this disease, unesterified cholesterol accumulates in lysosomes of the central nervous system and hepatic cells. Oxidation by reactive oxygen species produces oxysterols that can be metabolised to specific bile acids. These bile acids have been suggested as useful biomarkers to detect NPC. Concentrations of 3β,5α,6β-trihydroxycholanyl glycine (3β,5α,6β-triOH-Gly) and 3β,7β-dihydroxy-5-cholenyl glycine (3β,7β-diOH-Δ5-Gly) were measured in plasma of 184 adults with idiopathic ataxia. All patients were tested with whole genome sequencing containing hereditary ataxia panels, which include NPC1 and NPC2 mutations and other genetic causes of ataxia. Plasma 3β,5α,6β-triOH-Gly above normal (>90 nM) was found in 8 out of 184 patients. One patient was homozygous for the p.(Val1165Met) mutation in the NPC1 gene. The remaining seven included one patient with Friedreich’s ataxia and three patients with autoimmune diseases. Oxidative stress is known to be increased in Friedreich’s ataxia and in autoimmune diseases. Therefore, this subset of patients possibly shares a common mechanism that determines the increase of this bile acid. In a large cohort of adults with ataxia, plasma 3β,5α,6β-triOH-Gly was able to detect the one patient in the cohort with NPC1 disease, but also detected oxidation of cholesterol by ROS in other disorders. Plasma 3β,7β-diOH-Δ5-Gly is not a potential biomarker for NPC1. Full article

Valproic acid (VPA) is a common anti-epileptic drug and known neurodevelopmental toxicant. Although the exact mechanism of VPA toxicity remains unknown, recent findings show that VPA disrupts redox signaling in undifferentiated cells but has little effect on fully differentiated neurons. Redox imbalances often alter oxidative post-translational protein modifications and could affect embryogenesis if developmentally critical proteins are targeted. We hypothesize that VPA causes redox-sensitive post-translational protein modifications that are dependent upon cellular differentiation states. Undifferentiated P19 cells and P19-derived neurons were treated with VPA alone or pretreated with D3T, an inducer of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, prior to VPA exposure. Undifferentiated cells treated with VPA alone exhibited an oxidized glutathione redox couple and increased overall protein oxidation, whereas differentiated neurons were protected from protein oxidation via increased S-glutathionylation. Pretreatment with D3T prevented the effects of VPA exposure in undifferentiated cells. Taken together, our findings support redox-sensitive post-translational protein alterations in undifferentiated cells as a mechanism of VPA-induced developmental toxicity and propose NRF2 activation as a means to preserve proper neurogenesis. Full article