Antioxidants, Volume 13, Issue 5 (May 2024) – 109 articles

Environmental contamination by heavy metals (HMs) has emerged as a significant global issue in recent decades. Among natural substances, food-deriving polyphenols have found a valuable application in chelating therapy, partially limited by their low water solubility. Thus, three different hydroalcoholic extracts titrated in quercetin (QE), ellagic acid (EA), and curcumin (CUR) were formulated using maltodextrins as carriers, achieving a powder with a valuable water solubility (MQE 91.3 ± 1.2%, MEA 93.4 ± 2.1, and MCUR 89.3 ± 2%). Overcoming the problem of water solubility, such formulations were tested in an in vitro simulated gastrointestinal digestion experiment conducted on a water sample with standardized concentrations of the principal HMs. Our results indicate that regarding the nonessential HMs investigated (Pb, Cd, As, Sb, and Hg), MQE has been shown to be the most effective in increasing the HMs’ non-bioaccessible concentration, resulting in concentration increases in Cd of 68.3%, in As of 51.9%, in Hg of 58.9%, in Pb of 271.4, and in Sb of 111.2% (vs control, p < 0.001) in non-bioaccessible fractions. Regarding the essential HMs, MEA has shown the greatest capability to increase their intestinal bioaccessibility, resulting in +68.5%, +61.1, and +22.3% (vs control, p < 0.001) increases in Cu, Zn, and Fe, respectively. Finally, considering the strong relation between the antiradical and chelating activities, the radical scavenging potentials of the formulations was assayed in DPPH and ABTS assays. Full article

BRCA1 mutations predispose women to breast and ovarian cancer. The anticancer effect of zinc is typically linked to its antioxidant abilities and protecting cells against oxidative stress. Zinc regulates key processes in cancer development, including DNA repair, gene expression, and apoptosis. We took a blood sample from 989 female BRCA1 mutation carriers who were initially unaffected by cancer and followed them for a mean of 7.5 years thereafter. There were 172 incident cases of cancer, including 121 cases of breast cancer, 29 cases of ovarian cancers, and 22 cancers at other sites. A zinc level in the lowest tertile was associated with a modestly higher risk of ovarian cancer compared to women with zinc levels in the upper two tertiles (HR = 1.65; 95% CI 0.80 to 3.44; p = 0.18), but this was not significant. Among those women with zinc levels in the lowest tertile, the 10-year cumulative risk of ovarian cancer was 6.1%. Among those in the top two tertiles of zinc level, the ten-year cumulative risk of ovarian cancer was 4.7%. There was no significant association between zinc level and breast cancer risk. Our preliminary study does not support an association between serum zinc level and cancer risk in BRCA1 mutation carriers. Full article

Cyanobacteria in recent times have been touted to be a suitable source for the discovery of novel compounds, including antioxidants and antibiotics, due to their large arsenal of metabolites. This study presents the in vitro antioxidant and in silico evaluation of Cylindrospermum alatosporum NR125682 and Loriellopsis cavenicola NR117881, isolated from freshwater ponds around the campus of the University of Zululand, South Africa. The isolates were confirmed using 16S rRNA. Various crude extracts of the isolated microbes were prepared through sequential extraction using hexane, dichloromethane, and 70% ethanol. The chemical constituents of the crude extracts were elucidated by FTIR and GC-MS spectroscopy. The antioxidant potential of the extracts was determined by the free radical (DPPH, ABTS, ^•OH, and Fe²⁺) systems. Molecular docking of the major constituents of the extracts against β-lactamase was also evaluated. GC-MS analysis indicated the dominating presence of n-alkanes. The extracts exhibited varying degrees of antioxidant activity (scavenging of free radicals; an IC₅₀ range of 8–10 µg/mL was obtained for ABTS). A good binding affinity (−6.6, −6.3 Kcal/mol) of some the organic chemicals (diglycerol tetranitrate, and 2,2-dimethyl-5-(3-methyl-2-oxiranyl)cyclohexanone) was obtained following molecular docking. The evaluated antioxidant activities, coupled with the obtained docking score, potentiates the antimicrobial activity of the extracts. Full article

Fermented Rosa rugosa ‘Dianhong’ petals with brown sugar, a biologically active food popularized in Dali Prefecture, Northwest Yunnan, China, are rich in bioactive compounds, especially polyphenols, exhibiting strong antioxidant activity. This study evaluated their antioxidant activities, total phenolic contents, and concentrations of polyphenols at different fermentation conditions using different assays: DPPH free-radical scavenging activity, Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), Folin–Ciocalteu assays, and HPLC–MS/MS and HPLC–DAD methods. The results indicated that fermentation significantly increased (p < 0.05) the antioxidant activity and polyphenol concentration of R. rugosa ’Dianhong.’ Furthermore, Saccharomyces rouxii TFR-1 fermentation achieved optimal bioactivity earlier than natural fermentation. Overall, we found that the use of Saccharomyces rouxii (TFR-1) is a more effective strategy for the production of polyphenol-rich fermented R. rugosa ‘Dianhong’ petals with brown sugar compared to natural fermentation. Full article

Epigenetics defines changes in cell function without involving alterations in DNA sequence. Neuroepigenetics bridges neuroscience and epigenetics by regulating gene expression in the nervous system and its impact on brain function. With the increase in research in recent years, it was observed that alterations in the gene expression did not always originate from changes in the genetic sequence, which has led to understanding the role of epigenetics in neurodegenerative diseases (NDDs) including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Epigenetic alterations contribute to the aberrant expression of genes involved in neuroinflammation, protein aggregation, and neuronal death. Natural phytochemicals have shown promise as potential therapeutic agents against NDDs because of their antioxidant, anti-inflammatory, and neuroprotective effects in cellular and animal models. For instance, resveratrol (grapes), curcumin (turmeric), and epigallocatechin gallate (EGCG; green tea) exhibit neuroprotective effects through their influence on DNA methylation patterns, histone acetylation, and non-coding RNA expression profiles. Phytochemicals also aid in slowing disease progression, preserving neuronal function, and enhancing cognitive and motor abilities. The present review focuses on various epigenetic modifications involved in the pathology of NDDs, including AD and PD, gene expression regulation related to epigenetic alterations, and the role of specific polyphenols in influencing epigenetic modifications in AD and PD. Full article

The effects of high-intensity blue light (HIBL, 500/1000 µmol m⁻²s⁻¹, 450 nm) on Solanum lycopersicum mutants with high pigment (hp) and low pigment (lp) levels and cryptochrome 1 (cry1) deficiency on photosynthesis, chlorophylls, phenols, anthocyanins, nonenzymatic antioxidant activity, carotenoid composition, and the expression of light-dependent genes were investigated. The plants, grown under white light for 42 days, were exposed to HIBL for 72 h. The hp mutant quickly adapted to 500 µmol m⁻²s⁻¹ HIBL, exhibiting enhanced photosynthesis, increased anthocyanin and carotenoids (beta-carotene, zeaxanthin), and increased expression of key genes involved in pigment biosynthesis (PSY1, PAL1, CHS, ANS) and PSII proteins along with an increase in nonenzymatic antioxidant activity. At 1000 µmol m⁻²s⁻¹ HIBL, the lp mutant showed the highest photosynthetic activity, enhanced expression of genes associated with PSII external proteins (psbO, psbP, psbQ), and increased in neoxanthin content. This mutant demonstrated greater resistance at the higher HIBL, demonstrating increased stomatal conductance and photosynthesis rate. The cry1 mutant exhibited the highest non-photochemical quenching (NPQ) but had the lowest pigment contents and decreased photosynthetic rate and PSII activity, highlighting the critical role of CRY1 in adaptation to HIBL. The hp and lp mutants use distinct adaptation strategies, which are significantly hindered by the cry1 mutation. The pigment content appears to be crucial for adaptation at moderate HIBL doses, while CRY1 content and stomatal activity become more critical at higher doses. Full article

Agri-food by-products, obtained as waste from the food industry, negatively impact the global economy and the environment. In order to valorize waste materials from fruit juices and tomato sauces as upcycled materials rich in health-promoting compounds, they were characterized in terms of polyphenolic and protein content. The results obtained were compared with those collected for their final products. The recovery of polyphenols was performed via ultrasound-assisted extraction (UAE). A high-performance liquid chromatography–diode array detector (HPLC-DAD) method was developed and validated to depict the quali-quantitative polyphenolic profile of both the by-products and the final products. The antioxidant capacity of the resulting extracts was characterized by UV-Vis spectrophotometric assays in terms of total phenolic content (TPC) and total antioxidant status (TAS). Moreover, the protein content was assessed with the Kjeldahl method too. The results highlighted a significant quantity of polyphenols remaining in peach, apricot, and apple by-products, which were able to exert an antioxidant activity (in the range of 4.95 ± 5.69 × 10⁻¹ to 7.06 ± 7.96 × 10⁻¹ mmol Trolox 100 g⁻¹ of dry weight (DW) sample). Conversely, the tomato by-products were highly rich in proteins (11.0 ± 2.00 to 14.4 ± 2.60 g of proteins 100 g⁻¹ DW). The results proved that all by-products may potentially be sustainable ingredients with nutritional and functional value in a circular bio-economy prospect. Full article

Blue light is the higher-energy region of the visible spectrum. Excessive exposure to blue light is known to induce oxidative stress and is harmful to the eyes. The stems of Dendrobium nobile Lindl. (Orchidaceae), named Jinchaishihu, have long been used in traditional Chinese medicine (TCM) for nourishing yin, clearing heat, and brightening the eyes. The polysaccharide is one of the major components in D. nobile. However, the effect on ocular cells remains unclear. This study aimed to investigate whether the polysaccharide from D. nobile can protect the eyes from blue light-induced injury. A crude (DN-P) and a partially purified polysaccharide (DN-PP) from D. nobile were evaluated for their protective effects on blue light-induced damage in ARPE-19 and 661W cells. The in vivo study investigated the electroretinographic response and the expression of phototransduction-related genes in the retinas of a Drosophila model. The results showed that DN-P and DN-PP could improve blue light-induced damage in ARPE-19 and 661W cells, including cell viability, antioxidant activity, reactive oxygen species (ROS)/superoxide production, and reverse opsin 3 protein expression in a concentration-dependent manner. The in vivo study indicated that DN-P could alleviate eye damage and reverse the expression of phototransduction-related genes, including ninaE, norpA, Gαq, Gβ76C, Gγ30A, TRP, and TRPL, in a dose-dependent manner in blue light-exposed Drosophila. In conclusion, this is the first report demonstrating that D. nobile polysaccharide pretreatment can protect retinal cells and retinal photoreceptors from blue light-induced damage. These results provide supporting evidence for the beneficial potential of D. nobile in preventing blue light-induced eye damage and improving eyesight. Full article

Our previous study investigated the major flavonoids and antioxidant potential of Asian water lily (Nymphaea lotus L., family Nymphaeaceae) stamens and perianth extracts. Quercetin-3-O-rhamnoside (Que-3-Rha) and kaempferol-3-O-galactoside (Kae-3-Gal) were reported as the two most prominent flavonoids found in these extracts. Many flavonoids have been reported on the skin anti-aging effect that are useful for cosmeceutical/phytopharmaceutical application. However, Que-3-Rha and Kae-3-Gal occurring in this medicinal plant have not yet been evaluated for their ability to inhibit skin-aging enzymes. Therefore, this study aimed (1) to assess the enzyme inhibitory activity of Que-3-Rha and Kae-3-Gal, and (2) to conduct molecular modeling of these compounds against critical enzymes involved in skin aging such as collagenase, elastase, and tyrosinase. In vitro enzymatic assays demonstrated that both of the two most prominent flavonoids exhibited moderate to good inhibitory activity toward these enzymes. These experimental findings were supported by molecular docking analysis, which indicated that Que-3-Rha and Kae-3-Gal showed superior binding affinity to the target enzymes compared to the positive controls. Additionally, computational predictions suggested favorable skin permeability and no severe toxicity for both compounds. The results from molecular dynamic (MD) simulation revealed that all the complexes remained stable during the 200 ns MD simulation. Structural analyses and binding free energy calculations also supported the inhibitory potential of these two flavonoids against skin-aging enzymes. In conclusion, this study provides valuable insights into the anti-aging potential of the two major flavonoids occurring in this medicinal plant, paving the way for further development of cosmeceutical/phytopharmaceutical products targeting skin aging. Full article

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA’s effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice. Full article

Background: The discovery of traditional plants’ medicinal and nutritional properties has opened up new avenues for developing pharmaceutical and dietary strategies to prevent atherosclerosis. However, the effect of the antioxidant Dendrobium officinale polysaccharide (DOP) on atherosclerosis is still not elucidated. Purpose: This study aims to investigate the inhibitory effect and the potential mechanism of DOP on high-fat diet-induced atherosclerosis in Apolipoprotein E knockout (ApoE^−/−) mice. Study design and methods: The identification of DOP was measured by high-performance gel permeation chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). We used high-fat diet (HFD)-induced atherosclerosis in ApoE^−/− mice as an animal model. In the DOP intervention stage, the DOP group was treated by gavage with 200 μL of 200 mg/kg DOP at regular times each day and continued for eight weeks. We detected changes in serum lipid profiles, inflammatory factors, anti-inflammatory factors, and antioxidant capacity to investigate the effect of the DOP on host metabolism. We also determined microbial composition using 16S rRNA gene sequencing to investigate whether the DOP could improve the structure of the gut microbiota in atherosclerotic mice. Results: DOP effectively inhibited histopathological deterioration in atherosclerotic mice and significantly reduced serum lipid levels, inflammatory factors, and malondialdehyde (F/B) production. Additionally, the levels of anti-inflammatory factors and the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased after DOP intervention. Furthermore, we found that DOP restructures the gut microbiota composition by decreasing the Firmicutes/Bacteroidota (F/B) ratio. The Spearman’s correlation analysis indicated that serum lipid profiles, antioxidant activity, and pro-/anti-inflammatory factors were associated with Firmicutes, Bacteroidota, Allobaculum, and Coriobacteriaceae_UCG-002. Conclusions: This study suggests that DOP has the potential to be developed as a food prebiotic for the treatment of atherosclerosis in the future. Full article

The etiology of hearing impairment is multifactorial, with contributions from both genetic and environmental factors. Although genetic studies have yielded valuable insights into the development and function of the auditory system, the contribution of gene products and their interaction with alternate environmental factors for the maintenance and development of auditory function requires further elaboration. In this review, we provide an overview of the current knowledge on the role of redox dysregulation as the converging factor between genetic and environmental factor-dependent development of hearing loss, with a focus on understanding the interaction of oxidative stress with the physical components of the peripheral auditory system in auditory disfunction. The potential involvement of molecular factors linked to auditory function in driving redox imbalance is an important promoter of the development of hearing loss over time. Full article

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency. Full article

Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, Salicornia europaea stands out as a promising edible plant. In this study, young and old S. europaea leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl₄-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl₄-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver’s drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia’s potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD. Full article

Facial nerve injury can cause significant functional impairment, impacting both the peripheral and central nervous systems. The present study evaluated changes in facial motor function, numbers of cholinergic neurons and microglia, and nNOS levels in the facial nucleus of the central nervous system (CNS) following peripheral facial nerve injury. Facial nerve function, as determined by eyeblink and whisker-movement reflexes, was evaluated at baseline and 1, 2, 3, 4, 8, and 12 weeks after inducing facial nerve injury through compression or axotomy. The expression of choline acetyltransferase (ChAT), ionized calcium-binding adaptor molecule 1 (Iba-1), and neuronal nitric oxide synthase (nNOS) in the facial nucleus of the CNS was analyzed 2, 4, and 12 weeks after peripheral facial nerve injury. Compression-induced facial nerve injury was found to lead to temporary facial motor impairment, whereas axotomy resulted in persistent impairment. Moreover, both compression and axotomy reduced ChAT expression and increased Iba-1 and nNOS expression in the facial nucleus, indicating upregulation of an inflammatory response and neurodegeneration. These results indicate that, compared with compression-induced injury, axotomy-induced facial nerve injury results in greater facial motor dysfunction and more persistent microglial and nitric oxide activation in the facial nucleus of the CNS. Full article

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways. Full article

In this work, we aim to find physical evidence demonstrating the crucial role that the effective concentration of antioxidants (AOs) present at the interfacial region of emulsions has in controlling the inhibition of the lipid oxidation reaction. We prepared a series of antioxidants of different hydrophobicities derived from chlorogenic and protocatechuic acids. We first monitored, in intact emulsions, the (sigmoidal) production of conjugated dienes and determined the corresponding induction times, t_ind. Independently, we determined the effective concentrations of the antioxidants in the same intact emulsions. Results show that both the length of the induction periods and the antioxidant interfacial concentrations parallel each other, with a maximum at the octyl-dodecyl derivatives. The ratio between the interfacial antioxidant concentrations and the induction periods remains constant for all AOs in the same series, so that the rates of initiation of lipid oxidation are the same regardless of the hydrophobicity of the antioxidant employed. The constancy in the rate of initiation provides strong experimental evidence for a direct relationship between interfacial concentrations and antioxidant efficiencies. Results suggest new possibilities to investigate lipid peroxidation under non-forced conditions and are of interest to formulators interested in preparing emulsions with antimicrobial properties. Full article

High temperature is a significant environmental stress that limits plant growth and agricultural productivity. GDSL lipase is a hydrolytic enzyme with a conserved GDSL sequence at the N-terminus, which has various biological functions, such as participating in plant growth, development, lipid metabolism, and stress resistance. However, little is known about the function of the GDSL lipase gene in the heat tolerance of rice. Here, we characterized a lipase family protein coding gene HTA1, which was significantly induced by high temperature in rice. Rice seedlings in which the mutant hta1 was knocked out showed enhanced heat tolerance, whereas the overexpressing HTA1 showed more sensitivity to heat stress. Under heat stress, hta1 could reduce plant membrane damage and reactive oxygen species (ROS) levels and elevate the activity of antioxidant enzymes. Moreover, real-time quantitative PCR (RT-qPCR) analysis showed that mutant hta1 significantly activated gene expression in antioxidant enzymes, heat response, and defense. In conclusion, our results suggest that HTA1 negatively regulates heat stress tolerance by modulating the ROS accumulation and the expression of heat-responsive and defense-related genes in rice seedlings. This research will provide a valuable resource for utilizing HTA1 to improve crop heat tolerance. Full article

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe³⁺) was observed in placenta samples stained with Perls’ Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder. Full article

Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies. Full article

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