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Objective: This study aimed to examine the impact of cupric citrate on broilers and compare it with the copper sulfate groups and a control group. Methods: A total of 360 1-day-old Ross 308 broilers were randomly assigned into 5 groups, each with 6 replicates of 12 broilers per treatment. The control group was fed a basal diet without any copper supplementation. In contrast, the other groups received basal diets supplemented with either 50 mg/kg (CS-50) or 100 mg/kg (CS-100) of copper in the form of copper sulfate, or 50 mg/kg (CC-50) or 100 mg/kg (CC-100) of copper in the form of cupric citrate, for a period of 42 days. Results: The results showed that copper supplementation affected the average daily gain (ADG) from day 1 to 21 (p = 0.026) and day 1 to 42 (p = 0.025) in a source-dependent manner. Copper source also influenced the energy digestibility (p = 0.004), with the CC-100 being the most effective treatment. Notably, birds in the CC-100 groups had significantly reduced concentrations of Escherichia coli (p<0.05) in the cecum, and the Lactobacillus in the ileum, compared to the control group. Dietary copper supplementation also increased the pH in the duodenum (p<0.05) irrespective of the sources and levels. In addition, the source of copper affected the activities of ceruloplasmin (p = 0.014) and Cu-Zn superoxide dismutase (p = 0.025) in the serum, with the CC-100 group showing the highest levels of both enzymes. Conclusion: Copper supplementation generally improves the growth, nutrient utilization, intestinal microflora, gastrointestinal pH, and antioxidant defences of broilers. Moreover, cupric citrate is as effective as copper sulfate even at equal or lower concentrations. [ABSTRACT FROM AUTHOR]

Silicon (Si) is involved in the mitigation effect of plants to various environmental stresses. However, the mechanisms of aluminum (Al) detoxification by Si needs to be further clarified, especially in soybean. Here, the role of Si in the amelioration of programmed cell death (PCD) caused by Al exposure was explored in soybean roots. Results showed that supplying Si reduced the cell death, Hsr203J (a PCD marker gene) expression, mitochondrial cytochrome c release and caspase-3-like protease activity under Al stress, indicating that Si alleviated Al-induced PCD dependent on mitochondrial pathway. Exogenous H2O2 treatment could induce PCD of root tips exposed to Al, and applying Si reduced the production of H2O2 and O2−• in Al-treated roots, indicating that Si alleviated the occurrence of PCD by removing the accumulation of reactive oxygen species (ROS) under Al exposure. Furthermore, the activities of antioxidant enzymes and the contents of small molecule antioxidants were increased by applying Si under Al exposure. Overall, these results indicate that Si can eliminate Al-induced ROS accumulation and thus alleviate PCD by increasing the activity of antioxidant systems, which provides a theoretical basis for the improvement of crop growth in acid soils. [ABSTRACT FROM AUTHOR]

Sulfite oxidase deficiencies, either caused by deficiency of the apoenzyme or the molybdenum cofactor, and ethylmalonic encephalopathy are inherited disorders that impact sulfur metabolism. These patients present with severe neurodeterioration accompanied by cerebral cortex and cerebellum abnormalities, and high thiosulfate levels in plasma and tissues, including the brain. We aimed to clarify the mechanisms of such abnormalities, so we assessed the ex vivo effects of thiosulfate administration on energetic status and oxidative stress markers in cortical and cerebellar tissues of newborn rats. Thiosulfate (0.5 µmol/g) or PBS (vehicle) was injected into the fourth ventricle of rat pups. Thirty minutes after the injection, animals were euthanized and the brain structures were utilized for the experiments. Our data showed that thiosulfate decreased the reduced glutathione (GSH) concentrations, and superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) activities in the cortical structure. Thiosulfate also increased DCFH oxidation, hydrogen peroxide generation and glutathione reductase activity. In the cerebellum, thiosulfate reduced SOD and glutathione peroxidase activities but increased GST and CAT activities as well as DCFH oxidation. Regarding energy metabolism, thiosulfate specifically decreased complex IV activity in the cortex, whereas it increased cerebellar complex I and creatine kinase activities, indicating bioenergetic disturbances. The results suggest that the accumulation of thiosulfate causing redox disruption and bioenergetic alterations has a prominent role in the pathogenesis of sulfur metabolism deficiencies. [ABSTRACT FROM AUTHOR]

Abstract Avian pathogenic Escherichia coli (APEC) is a significant pathogen infecting poultry that is responsible for high mortality, morbidity and severe economic losses to the poultry industry globally, posing a substantial risk to the health of poultry. APEC encounters reactive oxygen species (ROS) during the infection process and thus has evolved antioxidant defense mechanisms to protect against oxidative damage. The imbalance of ROS production and antioxidant defenses is known as oxidative stress, which results in oxidative damage to proteins, lipids and DNA, and even bacterial cell death. APEC uses transcription factors (TFs) to handle oxidative stress. While many TFs in E. coli have been well characterized, the mechanism of the YbdO TF on protecting against oxidative damage and regulating the virulence and pathogenicity of APEC has not been clarified. Here we focus on the regulatory mechanism of YbdO on the pathogenicity of APEC. The results from this study showed that YbdO attenuated the pathogenicity of APEC in chicks infection models by inhibiting the expression of virulence genes fepG and ycgV using quantitative real-time reverse transcription PCR (RT-qPCR) experiments. The electrophoretic mobility shift assays (EMSA) confirmed that YbdO specifically bound to the promoters of fepG and ycgV. Additionally, YbdO increases H2O2-induced oxidative damage to APEC via repressing the expression of oxidative stress response genes sodA, soxR, ahpC, ahpF, katG, and oxyR by binding to their promoter regions. The repression effect facilitates host immune response to eliminate APEC and to generate beneficial immune protection to the body, thereby indirectly attenuating the pathogenicity of APEC. These findings might provide further insights into the mechanism of oxidative damage to APEC and offer new perspectives for further studies on the prevention and control of APEC infections.

Avian pathogenic Escherichia coli (APEC) is a significant pathogen infecting poultry that is responsible for high mortality, morbidity and severe economic losses to the poultry industry globally, posing a substantial risk to the health of poultry. APEC encounters reactive oxygen species (ROS) during the infection process and thus has evolved antioxidant defense mechanisms to protect against oxidative damage. The imbalance of ROS production and antioxidant defenses is known as oxidative stress, which results in oxidative damage to proteins, lipids and DNA, and even bacterial cell death. APEC uses transcription factors (TFs) to handle oxidative stress. While many TFs in E. coli have been well characterized, the mechanism of the YbdO TF on protecting against oxidative damage and regulating the virulence and pathogenicity of APEC has not been clarified. Here we focus on the regulatory mechanism of YbdO on the pathogenicity of APEC. The results from this study showed that YbdO attenuated the pathogenicity of APEC in chicks infection models by inhibiting the expression of virulence genes fepG and ycgV using quantitative real-time reverse transcription PCR (RT-qPCR) experiments. The electrophoretic mobility shift assays (EMSA) confirmed that YbdO specifically bound to the promoters of fepG and ycgV. Additionally, YbdO increases H2O2-induced oxidative damage to APEC via repressing the expression of oxidative stress response genes sodA, soxR, ahpC, ahpF, katG, and oxyR by binding to their promoter regions. The repression effect facilitates host immune response to eliminate APEC and to generate beneficial immune protection to the body, thereby indirectly attenuating the pathogenicity of APEC. These findings might provide further insights into the mechanism of oxidative damage to APEC and offer new perspectives for further studies on the prevention and control of APEC infections. [ABSTRACT FROM AUTHOR]

The effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding. [ABSTRACT FROM AUTHOR]

Tyrosinemia type 1 (TT1) is caused by fumarylacetoacetate hydrolase activity deficiency, resulting in tissue accumulation of upstream metabolites, including succinylacetone (SA), the pathognomonic compound of this disease. Since the pathogenesis of liver and kidney damage observed in the TT1‐affected patients is practically unknown, this study assessed the effects of SA on important biomarkers of redox homeostasis in the liver and kidney of adolescent rats, as well as in hepatic (HepG2) and renal (HEK‐293) cultured cells. SA significantly increased nitrate and nitrite levels and decreased the concentrations of reduced glutathione (GSH) in the liver and kidney, indicating induction of reactive nitrogen species (RNS) generation and disruption of antioxidant defenses. Additionally, SA decreased the GSH levels and the activities of glutathione peroxidase, glutathione S‐transferase, glutathione reductase, and superoxide dismutase in hepatic and renal cells. Noteworthy, melatonin prevented the SA‐induced increase of nitrate and nitrite levels in the liver. Therefore, SA‐induced increase of RNS generation and impairment of enzymatic and nonenzymatic antioxidant defenses may contribute to hepatopathy and renal disease in TT1. Summary: This study presents evidence that succinylacetone, a major compound accumulating in tyrosinemia type 1, significantly induces the production of reactive nitrogen species and disturbs the antioxidant defenses in the liver and kidney, which may play a role in the pathogenesis of the hepatorenal injury observed in patients. [ABSTRACT FROM AUTHOR]

Heat stress is a major environmental stressor that affects fish metabolism, growth, and death rates. This research examined the impact of dietary rutin addition (0, 100, 300, or 500 mg/kg) for 60 days on juvenile hybrid fish (Carassius auratus cuvieri, WCC, ♀ × Carassius auratus red var, RCC, ♂, WR) (27.97 ± 0.56 g) under heat stress conditions (32 ± 1 °C for 48 h). The analysis focused on blood parameters, oxidative stress biomarkers, and hepatic hsp70 and hsp90 gene expression in WR. The results demonstrated that rutin supplementation elevated blood glucose levels and the liver activities of glutathione reductase, glutathione peroxidase, catalase, and total superoxide dismutase in comparison to the control group. Additionally, rutin supplementation also significantly reduced serum cortisol and hepatic malondialdehyde levels while upregulating hepatic hsp70 and hsp90 gene expression. These findings suggest that rutin supplementation enhances antioxidant responses and alleviates the impact of heat stress on fish physiological and biochemical markers and heat shock protein gene expression. [ABSTRACT FROM AUTHOR]

Rice-fish farming is an ancient and enduring aquaculture model in China. This study aimed to assess the variations in digestive enzymes, antioxidant properties, glucose metabolism, and nutritional content between Carassius auratus reared in paddy fields and ponds. Notably, the levels of amylase and trypsin in C. auratus from rice paddies were considerably higher compared to those from ponds. Additionally, the hepatic catalase (CAT) activity in fish from paddy (2.45 ± 0.16 U/mg) exceeded that of their pond counterparts (2.27 ± 0.25 U/mg). Regarding glucose metabolism, the activities of key enzymes such as Na+/K+-ATPase (NKA) (paddy: 82.45 ± 6.11 U/g; pond: 78.53 ± 7.18 U/g), hexokinase (HK) (paddy: 9.55 ± 0.58 U/g; pond: 8.83 ± 0.72 U/g), glucokinase (GK) (paddy: 4.09 ± 0.21 IU/g; pond: 3.44 ± 0.33 IU/g), glucose-6-phosphatase (G6Pase) (paddy: 85.71 ± 4.49 IU/g; pond: 79.12 ± 9.34 IU/g), and glucose-6-phosphate dehydrogenase (G6PDH) (paddy: 47.23 ± 3.22 U/g; pond: 42.31 ± 4.93 U/g) were significantly elevated in rice paddy-cultured fish compared to those in ponds. Conversely, phosphor-pyruvate kinase (PK) (paddy: 418.15 ± 31.89 U/g; pond: 570.16 ± 56.06 U/g) activity was markedly reduced in the paddy group. Hepatic glycogen content (paddy: 15.70 ± 0.98 ng/g; pond: 14.91 ± 1.24 ng/g) was also substantially higher in fish from paddy, although no significant differences in muscle glycogen content (paddy: 7.14 ± 0.59 ng/g; pond: 6.70 ± 0.52 ng/g) were observed between the two environments. In terms of nutritional composition, fish raised in paddy exhibited higher crude protein (paddy: 18.46 ± 0.47 g/100 g muscle; pond: 15.57 ± 0.25 g/100 g muscle) and crude ash (paddy: 1.19 ± 0.02 g/100 g muscle; pond: 0.97 ± 0.02 g/100 g muscle) than those in ponds, whereas the crude fat (paddy: 0.87 ± 0.04 g/100 g muscle; pond: 1.66 ± 0.04 g/100 g muscle) was notably lower in paddy fish. Furthermore, fish from rice paddies had a greater total content of monounsaturated fatty acids (MUFA) (paddy: 4.25 ± 0.24 g/100 g muscle; pond: 6.73 ± 0.27 g/100 g muscle), non-essential amino acids (NEAA) (paddy: 9.04 ± 0.3 g/100 g muscle; pond: 7.19 ± 0.21 g/100 g muscle), and delicious amino acids (DAA) (paddy: 7.11 ± 0.2 g/100 g muscle; pond: 5.45 ± 0.19 g/100 g muscle) compared to those from pond cultures. These findings suggest that rice-fish co-culture systems can yield healthier and more environmentally sustainable aquatic products by improving feed digestion and optimizing nutrient metabolism. [ABSTRACT FROM AUTHOR]

This study investigates the impact of maternal nutrition during lactation on inflammation and oxidative stress in the offspring of diet-induced obese rats, along with the potential benefits of leptin supplementation during suckling. Dams were fed either a standard diet (SD), a western diet (WD) before and during gestation and lactation (WD-dams), or a WD switched to an SD during lactation (Rev-dams). Offspring were supplemented with leptin or vehicle during suckling and then fed an SD or WD until four months. Offspring of the Rev-dams exhibited improved metabolic indicators, including lower body weight, reduced plasma levels of TNF-alpha, a higher adiponectin/leptin (A/L) ratio, enhanced liver antioxidant defenses, and decreased inflammation markers in white adipose tissue (WAT) compared to WD-dams, with sex differences. Leptin supplementation further modulated these markers, reducing oxidative stress in liver and inflammation in WAT and liver (e.g., hepatic Tnfa expression decreased by 45% (males) and 41% (females) in the WD group on an SD), and improving the A/L ratio, with effects varying by maternal conditions and sex. In conclusion, this study underscores the importance of maternal nutrition and leptin intake during suckling in shaping long-term metabolic and inflammatory health in offspring, offering strategies to mitigate the adverse effects of maternal obesity on future generations. [ABSTRACT FROM AUTHOR]

In this presented study, the aim was to investigate the toxic effects of bisphenol S (BPS), one of the bisphenol A analogues, on the thyroid glands of male Wistar albino rats. Toward this aim, the rats (n = 28) were given a vehicle (control) or BPS at 3 different doses, comprising 20, 100, and 500 mg/kg of body weight (bw) via oral gavage for 28 days. According to the results, BPS led to numerous histopathological changes in the thyroid tissue. The average proliferation index values among the thyroid follicular cells (TFCs) displayed increases in all of the BPS groups, and significant differences were observed in the BPS-20 and BPS-100 groups. The average apoptotic index values in the TFCs were increased significantly in the BPS-500 group. The serum thyroid-stimulating hormone and serum free thyroxine levels did not show significant changes after exposure to BPS; however, the serum free triiodothyronine levels displayed significant decreases in all 3 of the BPS groups. BPS was determined to cause significant increases in the antioxidant enzyme activities of catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, as well as a significantly decreased content of reduced glutathione. The malondialdehyde level in the thyroid tissue was elevated significantly in the BPS-500 group. The data obtained herein revealed that BPS has thyroid-disrupting potential based on structural changes, follicle cell responses, and biochemical alterations including a decreased serum free triiodothyronine level and increased oxidative stress. [ABSTRACT FROM AUTHOR]

Survival rates for childhood cancer survivors (CCS) have improved, although they display a risk for early frailty due to the long-term effects of chemo/radiotherapy, including early aging. This study investigates antioxidant defenses and oxidative damage in mononuclear cells (MNCs) from CCS, comparing them with those from age-matched and elderly healthy individuals. Results show impaired antioxidant responses and increased oxidative stress in CCS MNCs, which exhibited uncoupled oxidative phosphorylation, leading to higher production of reactive oxygen species, similar to metabolic issues seen in elderly individuals. Key antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, hexose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase, showed reduced activity, likely due to lower expression of nuclear factor erythroid 2–related factor 2 (Nrf2). This imbalance caused significant damage to lipids, proteins, and DNA, potentially contributing to cellular dysfunction and a higher risk of cancer recurrence. These oxidative and metabolic dysfunctions persist over time, regardless of cancer type or treatment. However, treatment with N-acetylcysteine improved Nrf2 expression, boosted antioxidant defenses, reduced oxidative damage, and restored oxidative phosphorylation efficiency, suggesting that targeting the redox imbalance could enhance long-term CCS health. [ABSTRACT FROM AUTHOR]

The purpose of this study was to ascertain the changes in the main biochemical composition of the aromatic plants, such as Curcuma longa and Allium cepa, which are infected with their corresponding pathogenic fungus and the medicinal plants, which include Tinospora cordifolia, Ocimum tenuiflorum, and Alloe vera. Fungal infections' effects on total protein, MDA, H2O2, total phenols, total flavonoids and total tannins. Additionally, we assessed the activity of antioxidant enzymes in each of the five plants that were tested after they were infected with fungi. When comparing several plants afflicted with fungal infections to controls, a notable difference was seen in all metrics. Despite being medicinal plants, the aforementioned five plants experience a significant reduction in output as a result of numerous fungal diseases. Furthermore, the detrimental impact of pathogens during the course of infection on plant leaves was closely linked to variations in the concentration of its primary biochemical groups. Controlling fungal diseases through the implementation of suitable management measures is therefore crucial to safeguarding the plant with significant commercial value. [ABSTRACT FROM AUTHOR]

Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear. Methods: In this study, MRC-5 cells were treated with these compounds to evaluate reactive oxygen species (ROS) production, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, and the activities of SOD, CAT, and GPx. Additionally, the interactions between HMs and ROS with the IκBα/NF-κB/p65 complex were analyzed using molecular docking. Results: Correlation analysis among biomarkers revealed positive relationships between pro-oxidant damage and antioxidant responses, particularly in cells treated with CH2Cl2 and BrCHCl2. Conversely, negative relationships were observed between ROS levels and NF-κB/p65 levels in cells treated with CH2Cl2 and CHCl3. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was −3.3 kcal/mol for BrCHCl2, −3.5 kcal/mol for both CHCl3 and O2•, and −3.6 kcal/mol for H2O2. Conclusions: Chloride and bromide atoms were found in close contact with IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located within this domain, facilitating the phosphorylation of this protein. Similarly, both ROS interacted with the IPT domain in the RHD region, with H2O2 forming a side-chain oxygen interaction with Leu280 adjacent to the phosphorylation site of p65. However, the negative correlation between ROS and phospho-NF-κB/p65 suggests that steric hindrance by ROS on the C-terminal domain of NF-κB/p65 may play a role in the antioxidant response. [ABSTRACT FROM AUTHOR]

The objective of this work was to investigate the impact of silicon on the regulation of antioxidant defense mechanisms, which in turn provide resistance against different plant infections that attack medicinal plants including Alloe vera, Ocimum tenuiflorum, Tinospora cordifolia, as well as aromatic plants such as Allium cepa and Curcuma. Initially, we analyzed the overall levels of phenols, flavonoids, tannins, protein, MDA, and H2O2 in all 5 plants that were infected with their specific pathogenic fungus. Subsequently, we assessed the effects of treating the plants with an external chemical spray of Silicon. Moreover, we assessed the activity of antioxidant enzymes in both sick and silicon treated circumstances. The findings of our study showed notable differences in all parameters among plants affected by fungal diseases, healthy plants treated with silicon, and infected plants treated with silicon, in comparison to the control group. The results of our study indicate that the addition of silicon (Si) before to treat fungal-infected medicinal and aromatic plants led to higher levels of antioxidant enzyme activity, including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), and peroxidase (POD), compared to control, Si-treated, and pathogenic fungus-inoculated plants. Taken together, this work emphasizes the protective function of silicon in our experimental medicinal and aromatic plants against harmful fungus by enhancing the activity of antioxidant enzymes. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to consolidate the effects of dietary methionine and its analogs on broilers' oxidant/antioxidant status in the blood and liver. A comprehensive search of electronic databases identified 15 studies that met the requirements for a meta-analysis. The meta-analysis was conducted using a random-effects model, and the effect size was calculated as the standardized mean difference with 95 % confidence intervals. Heterogeneity was evaluated using the Cochrane Q test and I2 statistics. The meta-analysis revealed that methionine supplementation significantly reduced oxidative stress markers, such as malondialdehyde (MDA)and protein carbonyl PC, and increased antioxidant parameters, including glutathione (GSH), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The meta-analysis found significant increases in GSH and GPX levels across two methionine source subgroups, while MDA and PC levels decreased only in the methionine analogs group. GSSG levels were elevated specifically in the DL-/L-methionine group, with no change in TAC (total antioxidant capacity) levels. In terms of challenge type, GSH and GPX levels rose significantly in both normal and environmental stress conditions, while MDA decreased; however, SOD, GSSG, and TAC levels remained unchanged. The analysis of methionine dosage showed that GSH increased in both ≤2.5 and 2.6–4 fold subgroups, while SOD only increased in the ≤2.5 fold subgroup. Lastly, the administration period analysis indicated increases in GPX and GSH for both 1–21 and 22–42 days, with PC levels decreasing. The study also found that methionine supplementation can be an effective strategy to reduce oxidative stress and enhance antioxidant defenses in broilers, particularly under environmental stress conditions. The results suggest that methionine supplementation can be a valuable tool for reducing oxidative stress and improving the overall health of broilers.

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of "NanoExplore Project" [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations—Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers—TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance. [ABSTRACT FROM AUTHOR]

In fish, interspecific interactions between nonnative and other sympatric species are considered determinants in shaping species assemblages. Such interactions can also arise between nonnative fish species only, including salmonids such as the brown trout (Salmo trutta, Linnaeus, 1758) and the rainbow trout (Oncorhynchus mykiss, Walbaum, 1792), returning contrasting outcomes. The present manipulative experiment was aimed at exploring the effect of interspecific competition on the body growth and the oxidative status of parr (2 + -year-old individuals) of the brown trout and the rainbow trout. Allopatric (intraspecific competition) and sympatric (interspecific competition) populations of these species were experimentally recreated in two wild streams. At the end of a 2-month-long experiment, changes in specific growth rate (SGR), oxidative status (i.e., levels of reactive oxygen species and activity of antioxidant enzymes such as superoxide dismutase — SOD, catalase — CAT and glutathione peroxidase — GPx) and oxidative damage (i.e., lipid peroxidation) were investigated in brown and rainbow trout individuals maintained in allopatric or sympatric populations. Sympatric interactions between rainbow and brown trout parr resulted in a significant decrease in SGR of brown trout individuals only. Moreover, an overall modulation of the oxidative status, in terms of an increase in ROS levels coupled with the activation of SOD and CAT activity, occurred in brown trout individuals under sympatric conditions. These findings might suggest that, under sympatric conditions, parr of the rainbow trout are more competitive than brown trout for food acquisition. However, this competition affected the antioxidant defenses of the brown trout only, probably because of reduced ingestion of dietary antioxidants or increased physical activity and aggressive behavior. Thus, interspecific interactions can induce physiological and phenotypic effects on parr of nonnative salmonids, with potential consequences on the establishment of populations of these species in freshwater ecosystems. [ABSTRACT FROM AUTHOR]

Community‐based aquaculture can reduce dependence on natural resources, promote biodiversity conservation, and improve local economies and food security. However, this activity is highly dependent on local conditions regarding natural resources, such as the availability of produced organisms, adequate feeds, and environmental factors. As ectothermic organisms, fish are more susceptible to temperature fluctuations in culture conditions. A set of raw ingredients (e.g., cassava and local beans) produced or available in villages from Cabo Delgado (Mozambique) with nutritional potential for fish feed were selected to produce an experimental diet. The following objectives were defined: (1) evaluate growth performance of tilapia fingerlings fed a diet produced with local ingredients, compared with a commercial‐like diet; and (2) evaluate the response to thermal stress (18, 26, and 32°C) by tilapia fingerlings fed with tested diets. Tilapia fed with an experimental diet presented lower growth rates, lower DNA damage, higher neurophysiological, and antioxidant activity, leading to increased oxidative stress. Regarding energy budget, tilapia fed with the experimental diet presented higher protein content at 26°C and lipids at 18°C, leading to greater energy available at these temperatures. Overall, local ingredients can be successfully used as an additional feed source for tilapia production in community‐based aquaculture in earthen ponds. [ABSTRACT FROM AUTHOR]

Rice-fish farming is an ancient and enduring aquaculture model in China. This study aimed to assess the variations in digestive enzymes, antioxidant properties, glucose metabolism, and nutritional content between Carassius auratus reared in paddy fields and ponds. Notably, the levels of amylase and trypsin in C. auratus from rice paddies were considerably higher compared to those from ponds. Additionally, the hepatic catalase (CAT) activity in fish from paddy (2.45 ± 0.16 U/mg) exceeded that of their pond counterparts (2.27 ± 0.25 U/mg). Regarding glucose metabolism, the activities of key enzymes such as Na+/K+-ATPase (NKA) (paddy: 82.45 ± 6.11 U/g; pond: 78.53 ± 7.18 U/g), hexokinase (HK) (paddy: 9.55 ± 0.58 U/g; pond: 8.83 ± 0.72 U/g), glucokinase (GK) (paddy: 4.09 ± 0.21 IU/g; pond: 3.44 ± 0.33 IU/g), glucose-6-phosphatase (G6Pase) (paddy: 85.71 ± 4.49 IU/g; pond: 79.12 ± 9.34 IU/g), and glucose-6-phosphate dehydrogenase (G6PDH) (paddy: 47.23 ± 3.22 U/g; pond: 42.31 ± 4.93 U/g) were significantly elevated in rice paddy-cultured fish compared to those in ponds. Conversely, phosphor-pyruvate kinase (PK) (paddy: 418.15 ± 31.89 U/g; pond: 570.16 ± 56.06 U/g) activity was markedly reduced in the paddy group. Hepatic glycogen content (paddy: 15.70 ± 0.98 ng/g; pond: 14.91 ± 1.24 ng/g) was also substantially higher in fish from paddy, although no significant differences in muscle glycogen content (paddy: 7.14 ± 0.59 ng/g; pond: 6.70 ± 0.52 ng/g) were observed between the two environments. In terms of nutritional composition, fish raised in paddy exhibited higher crude protein (paddy: 18.46 ± 0.47 g/100 g muscle; pond: 15.57 ± 0.25 g/100 g muscle) and crude ash (paddy: 1.19 ± 0.02 g/100 g muscle; pond: 0.97 ± 0.02 g/100 g muscle) than those in ponds, whereas the crude fat (paddy: 0.87 ± 0.04 g/100 g muscle; pond: 1.66 ± 0.04 g/100 g muscle) was notably lower in paddy fish. Furthermore, fish from rice paddies had a greater total content of monounsaturated fatty acids (MUFA) (paddy: 4.25 ± 0.24 g/100 g muscle; pond: 6.73 ± 0.27 g/100 g muscle), non-essential amino acids (NEAA) (paddy: 9.04 ± 0.3 g/100 g muscle; pond: 7.19 ± 0.21 g/100 g muscle), and delicious amino acids (DAA) (paddy: 7.11 ± 0.2 g/100 g muscle; pond: 5.45 ± 0.19 g/100 g muscle) compared to those from pond cultures. These findings suggest that rice-fish co-culture systems can yield healthier and more environmentally sustainable aquatic products by improving feed digestion and optimizing nutrient metabolism.

Survival rates for childhood cancer survivors (CCS) have improved, although they display a risk for early frailty due to the long-term effects of chemo/radiotherapy, including early aging. This study investigates antioxidant defenses and oxidative damage in mononuclear cells (MNCs) from CCS, comparing them with those from age-matched and elderly healthy individuals. Results show impaired antioxidant responses and increased oxidative stress in CCS MNCs, which exhibited uncoupled oxidative phosphorylation, leading to higher production of reactive oxygen species, similar to metabolic issues seen in elderly individuals. Key antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, hexose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase, showed reduced activity, likely due to lower expression of nuclear factor erythroid 2–related factor 2 (Nrf2). This imbalance caused significant damage to lipids, proteins, and DNA, potentially contributing to cellular dysfunction and a higher risk of cancer recurrence. These oxidative and metabolic dysfunctions persist over time, regardless of cancer type or treatment. However, treatment with N-acetylcysteine improved Nrf2 expression, boosted antioxidant defenses, reduced oxidative damage, and restored oxidative phosphorylation efficiency, suggesting that targeting the redox imbalance could enhance long-term CCS health.

Background: Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CH2Cl2, CHCl3, and BrCHCl2, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear. Methods: In this study, MRC-5 cells were treated with these compounds to evaluate reactive oxygen species (ROS) production, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, and the activities of SOD, CAT, and GPx. Additionally, the interactions between HMs and ROS with the IκBα/NF-κB/p65 complex were analyzed using molecular docking. Results: Correlation analysis among biomarkers revealed positive relationships between pro-oxidant damage and antioxidant responses, particularly in cells treated with CH2Cl2 and BrCHCl2. Conversely, negative relationships were observed between ROS levels and NF-κB/p65 levels in cells treated with CH2Cl2 and CHCl3. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was −3.3 kcal/mol for BrCHCl2, −3.5 kcal/mol for both CHCl3 and O2•, and −3.6 kcal/mol for H2O2. Conclusions: Chloride and bromide atoms were found in close contact with IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located within this domain, facilitating the phosphorylation of this protein. Similarly, both ROS interacted with the IPT domain in the RHD region, with H2O2 forming a side-chain oxygen interaction with Leu280 adjacent to the phosphorylation site of p65. However, the negative correlation between ROS and phospho-NF-κB/p65 suggests that steric hindrance by ROS on the C-terminal domain of NF-κB/p65 may play a role in the antioxidant response.

Abstract Community‐based aquaculture can reduce dependence on natural resources, promote biodiversity conservation, and improve local economies and food security. However, this activity is highly dependent on local conditions regarding natural resources, such as the availability of produced organisms, adequate feeds, and environmental factors. As ectothermic organisms, fish are more susceptible to temperature fluctuations in culture conditions. A set of raw ingredients (e.g., cassava and local beans) produced or available in villages from Cabo Delgado (Mozambique) with nutritional potential for fish feed were selected to produce an experimental diet. The following objectives were defined: (1) evaluate growth performance of tilapia fingerlings fed a diet produced with local ingredients, compared with a commercial‐like diet; and (2) evaluate the response to thermal stress (18, 26, and 32°C) by tilapia fingerlings fed with tested diets. Tilapia fed with an experimental diet presented lower growth rates, lower DNA damage, higher neurophysiological, and antioxidant activity, leading to increased oxidative stress. Regarding energy budget, tilapia fed with the experimental diet presented higher protein content at 26°C and lipids at 18°C, leading to greater energy available at these temperatures. Overall, local ingredients can be successfully used as an additional feed source for tilapia production in community‐based aquaculture in earthen ponds.

Abstract The growing increase in the fish farming sector has favored the establishment of bacterial outbreaks caused by Aeromonas hydrophila in several species. The hexane extract of Hesperozygis ringens (HEHR) (Lamiaceae) leaves increased the survival rate of silver catfish (Rhamdia quelen) experimentally infected by A. hydrophila. However, it is noteworthy that no reports have been found on the possible mechanisms of action of this extract in infected fish. This study aimed to evaluate the effect of the HEHR, administered through single immersion bath, on lipid peroxidation and antioxidant defenses in muscle and liver tissue of silver catfish challenged with A. hydrophila. The results showed that the oxidative status of silver catfish was altered, although oxidative stress was not triggered during the experiment. HEHR at 30 mg/L (HEHR30) was not characterized as a pro-oxidant agent in the presence of infection, unlike florfenicol and HEHR at 15 mg/L treatments in some cases. In short, HEHR30 provided an important increase in hepatic catalase activity, characterizing one of the possible mechanisms involved in the greater survival of fish experimentally infected by A. hydrophila. Additionally, HEHR30 did not induce lipid peroxidation, nor reduced antioxidant defenses of silver catfish infected or not by A. hydrophila.

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2′-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF. [Display omitted] • Yellow fever virus induces increase in reactive oxygen species (ROS). • Yellow fever virus triggers oxidative stress cellular response. • Yellow fever virus reduces the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). • Oxidative stress may be an important factor in the hepatic pathogenesis of Yellow fever. [ABSTRACT FROM AUTHOR]

The saltmarsh plant Halimione portulacoides was shortly exposed to realistic levels of inorganic mercury (iHg) with the aim of investigating the adaptative processes of the roots and leaves regarding redox homeostasis, physiology, and Hg accumulation. Plants were collected at a contaminated (CONT) and a reference (REF) site to address the interference of contamination backgrounds. The influence of major abiotic variables (i.e., temperature and light) was also examined. Total Hg levels, antioxidant enzymes, lipid peroxidation (LPO), and photosynthetic activity were analyzed after 2 and 4 h of exposure. A poor accumulation of Hg in the roots was noticed, and no translocation to the stems and leaves was found, but plants from the CONT site seemed more prone to iHg uptake (in winter). Despite this, antioxidant modulation in the roots and leaves was found, disclosing, in winter, higher thresholds for the induction of enzymatic antioxidants in CONT leaves compared to REF plants, denoting that the former are better prepared to cope with iHg redox pressure. Consistently, CONT leaves exposed to iHg had remarkably lower LPO levels. Exposure did not impair photosynthetic activity, pinpointing H. portulacoides' ability to cope with iHg toxicity under very-short-term exposure. Biochemical changes were noticed before enhancements in accumulation, reinforcing the relevance of these responses in precociously signaling iHg toxicity. [ABSTRACT FROM AUTHOR]

Dicamba (DIC) is one of the most applied auxin herbicides worldwide. Sublethal effects in the South American native fish Jenynsia lineata exposed to DIC concentrations close to environmental concentrations (0.03–30 µg/L) during 48 h were analysed thorough the evaluation of catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD) activities and malondialdehyde (MDA) and H2O2 levels for detecting potential oxidative stress. In gills MDA increased showing oxidative damage probably because of an inefficient antioxidant defense. This response evidenced the important role of gills as an organ of direct contact with waterborne contaminants. In addition, other changes in the biomarkers of oxidative stress were observed such as the inhibition of SOD activities in brain and the inhibition of GST in liver. These results show that short- term exposures to environmentally relevant concentrations of DIC could induce sublethal effects in native fish. [ABSTRACT FROM AUTHOR]

The psychostimulant methylphenidate (MPH) is the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), but has numerous adverse side effects. The PPARγ receptor agonist pioglitazone (PIO) is known to improve mitochondrial bioenergetics and antioxidant capacity, both of which may be deficient in ADHD, suggesting utility as an adjunct therapy. Here, we assessed the effects of PIO on ADHD-like symptoms, mitochondrial biogenesis and antioxidant pathways in multiple brain regions of neonate rats with unilateral striatal lesions induced by 6-hydroxydopamine (6-OHDA) as an experimental ADHD model. Unilateral striatal injection of 6-OHDA reduced ipsilateral dopaminergic innervation by 33% and increased locomotor activity. This locomotor hyperactivity was not altered by PIO treatment for 14 days. However, PIO increased the expression of proteins contributing to mitochondrial biogenesis in the striatum, hippocampus, cerebellum and prefrontal cortex of 6-OHDA-lesioned rats. In addition, PIO treatment enhanced the expression of the phase II transcription factor Nrf2 in the striatum, prefrontal cortex and cerebellum. In contrast, no change in the antioxidant enzyme catalase was observed in any of the brain regions analyzed. Thus, PIO may improve mitochondrial biogenesis and phase 2 detoxification in the ADHD brain. Further studies are required to determine if different dose regimens can exert more comprehensive therapeutic effects against ADHD neuropathology and behavior. [ABSTRACT FROM AUTHOR]

The psychostimulant methylphenidate (MPH) is the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), but has numerous adverse side effects. The PPARγ receptor agonist pioglitazone (PIO) is known to improve mitochondrial bioenergetics and antioxidant capacity, both of which may be deficient in ADHD, suggesting utility as an adjunct therapy. Here, we assessed the effects of PIO on ADHD-like symptoms, mitochondrial biogenesis and antioxidant pathways in multiple brain regions of neonate rats with unilateral striatal lesions induced by 6-hydroxydopamine (6-OHDA) as an experimental ADHD model. Unilateral striatal injection of 6-OHDA reduced ipsilateral dopaminergic innervation by 33% and increased locomotor activity. This locomotor hyperactivity was not altered by PIO treatment for 14 days. However, PIO increased the expression of proteins contributing to mitochondrial biogenesis in the striatum, hippocampus, cerebellum and prefrontal cortex of 6-OHDA-lesioned rats. In addition, PIO treatment enhanced the expression of the phase II transcription factor Nrf2 in the striatum, prefrontal cortex and cerebellum. In contrast, no change in the antioxidant enzyme catalase was observed in any of the brain regions analyzed. Thus, PIO may improve mitochondrial biogenesis and phase 2 detoxification in the ADHD brain. Further studies are required to determine if different dose regimens can exert more comprehensive therapeutic effects against ADHD neuropathology and behavior.

The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione S-transferase (GST), as well as the concentrations of sulfhydryl (SH) groups and glutathione (GSH) were analyzed in five age classes of the Mediterranean centipede Scolopendra cingulata as follows: embryo, adolescens, maturus junior, maturus, and maturus senior. The data obtained showed the presence of SOD, CAT, GSH-Px, GR, GST, and SH groups in embryos. The transition from embryo to adolescens was accompanied by an increase in the activities of all studied enzymes, in response to the increased production of ROS due to the increased metabolic activity of the centipede associated with growth and development. Our results show that trends in antioxidant enzyme (AOE) activities were not uniform among adult age classes, suggesting that maturus junior, maturus, and maturus senior differentially respond and/or have different susceptibility to ROS. On the other hand, GSH concentration in embryos was undetectable, highest in adolescens and decreased in the latter part of life. Pearson correlation analysis in embryos showed that the activities of the AOEs were strongly and positively correlated with each other but negatively correlated with GSH and SH groups. At later age classes, SOD, CAT, GSH-Px, GR, GSH, and SH groups were no longer significantly correlated with GST. In the discriminant analysis, the variables that separated the age classes were GR, GST, SH groups, and body length. Body length was directly related to the age of individuals, clearly indicating that development/aging affects the regulation of antioxidant defense in this species. [ABSTRACT FROM AUTHOR]

Ni and Cd are widely used together in the manufacture of cells and batteries. The incorrect disposal of these products can result in environmental contamination, posing risks to the organisms exposed to these contaminants. However, the effects of the mixture of Ni and Cd in freshwater fishes are still unclear in the current literature, especially in relation to biomarkers of oxidative stress. Thus, the objective of the current work was to compare the sublethal effects caused by the mixture of cadmium (Cd) and nickel (Ni) with the effects of these metals individually, in the fish Astyanax altiparanae. The animals were exposed for 72 h to 20 μg L-1 of Cd, 1.5 mg L-1 of Ni, or a mixture of these two metals at the concentrations mentioned. After exposure, tissue samples were collected to evaluate hematological and plasma parameters, biomarkers of oxidative stress in the gills, and acetylcholinesterase (AChE) activity in brain and muscle. Exposure to the mixture caused alterations that were not observed in the groups exposed to the metals individually, such as increased activity of catalase and glutathione-S-transferase, and a reduction in AChE activity in the brain. Thus, we concluded that exposure to the mixture of Cd and Ni is more harmful to A. altiparanae than exposure to these metals separately. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a rare genetic disease characterized by a dysfunctional DNA repair and an oxidative stress accumulation due to defective mitochondrial energy metabolism, not counteracted by endogenous antioxidant defenses, which appear down-expressed compared to the control. Since the antioxidant response lack could depend on the hypoacetylation of genes coding for detoxifying enzymes, we treated lymphoblasts and fibroblasts mutated for the FANC-A gene with some histone deacetylase inhibitors (HDACi), namely, valproic acid (VPA), beta-hydroxybutyrate (OHB), and EX527 (a Sirt1 inhibitor), under basal conditions and after hydrogen peroxide addition. The results show that VPA increased catalase and glutathione reductase expression and activity, corrected the metabolic defect, lowered lipid peroxidation, restored the mitochondrial fusion and fission balance, and improved mitomycin survival. In contrast, OHB, despite a slight increase in antioxidant enzyme expressions, exacerbated the metabolic defect, increasing oxidative stress production, probably because it also acts as an oxidative phosphorylation metabolite, while EX527 showed no effect. In conclusion, the data suggest that VPA could be a promising drug to modulate the gene expression in FA cells, confirming that the antioxidant response modulation plays a pivotal in FA pathogenesis as it acts on both oxidative stress levels and the mitochondrial metabolism and dynamics quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide receptor radionuclide therapy with 177Lu-DOTATATE is an efficient treatment for patients suffering from metastasized neuroendocrine tumours. Nevertheless, suboptimal effects have been observed in the majority of patients. Hence, strategies to improve 177Lu-DOTATATE efficacy are desirable. Lu-177 induces oxidative stress, eventually leading to tumour cell death. Inhibition of the antioxidant defence mechanisms, using buthionine sulfoximine (BSO), represents an attractive strategy to increase 177Lu-DOTATATE efficacy. In cells and an animal model, the combination of 177Lu-DOTATATE and BSO was more effective than 177Lu-DOTATATE alone. In addition, it did not result in additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE. [ABSTRACT FROM AUTHOR]

Releasing juvenile fish into resource-depleted waters is regarded as an effective way to restore fishery resources. However, during this stage, released fish are most vulnerable to long-term food deprivation due to environmental changes and low adaptability. Therefore, research regarding the energy regulation of fish under starvation stress is crucial to the optimization of release strategies. In this study, we performed a transcriptome analysis of the liver of Onychostomasima subjected to starvation for 14 days. The results showed that, under long-term starvation, the liver regulated glucose homeostasis by activating the gluconeogenesis pathway. Meanwhile, the fatty acid metabolism pathway was activated to supply acetyl-coA to the TCA cycle, thus increasing mitochondrial ATP production and maintaining the balance of energy metabolism. Nevertheless, the activation of energy metabolism could not completely compensate for the role of exogenous nutrients, as evidenced by the downregulation of many genes involved in antioxidant defenses (e.g., cat, gpx3, mgst1, and mgst2) and immune response (e.g., c3, cd22, trnfrsf14, and a2ml). In summary, our data reveal the effects of long-term starvation on the energy metabolism and defensive regulation of starved juvenile fish, and these findings will provide important reference for the optimization of artificial release. [ABSTRACT FROM AUTHOR]

The saltmarsh plant Halimione portulacoides was shortly exposed to realistic levels of inorganic mercury (iHg) with the aim of investigating the adaptative processes of the roots and leaves regarding redox homeostasis, physiology, and Hg accumulation. Plants were collected at a contaminated (CONT) and a reference (REF) site to address the interference of contamination backgrounds. The influence of major abiotic variables (i.e., temperature and light) was also examined. Total Hg levels, antioxidant enzymes, lipid peroxidation (LPO), and photosynthetic activity were analyzed after 2 and 4 h of exposure. A poor accumulation of Hg in the roots was noticed, and no translocation to the stems and leaves was found, but plants from the CONT site seemed more prone to iHg uptake (in winter). Despite this, antioxidant modulation in the roots and leaves was found, disclosing, in winter, higher thresholds for the induction of enzymatic antioxidants in CONT leaves compared to REF plants, denoting that the former are better prepared to cope with iHg redox pressure. Consistently, CONT leaves exposed to iHg had remarkably lower LPO levels. Exposure did not impair photosynthetic activity, pinpointing H. portulacoides’ ability to cope with iHg toxicity under very-short-term exposure. Biochemical changes were noticed before enhancements in accumulation, reinforcing the relevance of these responses in precociously signaling iHg toxicity.

Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without glutamine. The growth and proliferation rate, colony-forming capacity, apoptosis, cell cycle, redox homeostasis and metabolomic analysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results show that glutamine represents an important metabolite for cell growth and that its deprivation reduces the proliferation of colorectal cancer cells. Glutamine depletion induces cell death and cell cycle arrest in the GO/G1 phase by modulating energy metabolism, the amino acid content and antioxidant defenses. Moreover, the combined glutamine starvation with the glycolysis inhibitor 2-deoxy-D-glucose exerted a stronger cytotoxic effect. This study offers a strong rationale for targeting glutamine metabolism alone or in combination with glucose metabolism to achieve a therapeutic benefit in the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Curcuma longa L. is a spice crop with enormous medicinal and cosmetic properties cultivated worldwide. It was propagated vegetatively by means of rhizomes, as these were underneath soil prone to soil-borne fungal diseases. Treatment of such diseases using chemical fungicides would hinder their nutritional and medicinal value. To overcome such challenges, there are a few alternatives; the major among them was the deployment of disease-free in vitro raised plantlets, and the other was biopriming of these plantlets with Trichoderma viride. Besides fungicidal action, Trichoderma viride has a prominent role in alleviating several biotic/abiotic stresses and it was more often used during acclimatization. In this study, we studied the role of T. viride on successful acclimatization of in vitro C. longa plantlets by modulating plant antioxidant defense systems. We determined the stress levels (MDA and chlorophyll contents) and monitored the antioxidant enzyme activities (CAT, APX and GR) in both T. viride treated and untreated micropropagated plantlets at four different time points (0, 15, 30, 45, 60 days) of acclimatization period. Our results depicted clear enhancement in the antioxidant enzyme activities in T. viride treated than untreated plantlets which signify the role of Trichoderma viride in activating defense mechanisms to combat oxidative stress. Thus, this study would give a clear understanding of the influence of T. viride on in vitro raised plantlets in sustaining adverse acclimatization conditions. [ABSTRACT FROM AUTHOR]

Methylmalonic acidemia is a neurometabolic disorder biochemically characterized by the accumulation of methylmalonic acid (MMA) in different tissues, including the central nervous system (CNS). In this sense, it has been shown that high levels of this organic acid have a key role in the progressive neurological deterioration in patients. Astroglial cells actively participate in a wide range of CNS functions, such as antioxidant defenses and inflammatory response. Considering the role of these cells to maintain brain homeostasis, in the present study, we investigated the effects of MMA on glial parameters, focusing on redox homeostasis and inflammatory process, as well as putative mediators of these events in C6 astroglial cells. MMA decreased cell viability, glutathione levels, and antioxidant enzyme activities, increased inflammatory response, and changed the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NFκB), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and adenosine receptors, suggesting that these transcriptional factors and proteins may underlie the glial responses induced by MMA. Moreover, we also demonstrated the protective roles of melatonin and resveratrol against MMA-induced inflammation and decrease in glutathione levels. In summary, our findings support the hypothesis that astroglial changes are associated with pathogenesis of methylmalonic acidemia. In addition, we showed that these cells might be potential targets for preventive/therapeutic strategies by using molecules, such as melatonin and resveratrol, which mediated glioprotection in this inborn error of metabolism. [ABSTRACT FROM AUTHOR]

Essential oils are natural compounds used by humans for scientific purposes due to their wide range of properties. Eugenol is mostly present in clove oil, while pulegone is the main constituent of pennyroyal oil. To guarantee the safe use of eugenol and pulegone for both humans and animals, this study addressed, for the first time, the effects of these compounds, at low doses (chronic toxicity) and high doses (acute toxicity), in laboratory animals. Thirty-five FVB/n female mice were randomly assigned to seven groups (n = 5): group I (control, non-additive diet); group II (2.6 mg of eugenol + 2.6 mg of pulegone); group III (5.2 mg of eugenol + 5.2 mg of pulegone); group IV (7.8 mg of eugenol + 7.8 mg of pulegone); group V (7.8 mg of eugenol); group VI (7.8 mg of pulegone); and group VII (1000 mg of eugenol + 1000 mg of pulegone). The compounds were administered in the food. Groups I to VI were integrated into the chronic toxicity study, lasting 28 days, and group VII was used in the acute toxicity study, lasting 7 days. Animals were monitored to assess their general welfare. Water and food intake, as well as body weight, were recorded. On the 29th day, all animals were euthanized by an overdose of ketamine and xylazine, and a complete necropsy was performed. Blood samples were collected directly from the heart for microhematocrit and serum analysis, as well as for comet assay. Organs were collected, weighed, and fixed in formaldehyde for further histological analysis and enzymatic assay. Eugenol and pulegone induced behavioral changes in the animals, namely in the posture, hair appearance and grooming, and in mental status. These compounds also caused a decrease in the animals' body weight, as well as in the food and water consumption. A mortality rate of 20% was registered in the acute toxicity group. Both compounds modulated the serum levels of triglycerides and alanine aminotransferase. Eugenol and pulegone induced genetic damage in all animals. Eugenol increased the activity of the CAT enzyme. Both compounds increased the GR enzyme at the highest dose. Moreover, pulegone administered as a single compound increased the activity of the GST enzyme. Histopathological analysis revealed inflammatory infiltrates in the lungs of groups II, III, and IV. The results suggest that eugenol and pulegone may exert beneficial or harmful effects, depending on the dose, and if applied alone or in combination. [ABSTRACT FROM AUTHOR]

Abstract Background Photodynamic therapy (PDT) is a minimally invasive, clinically approved therapy with numerous advantages over other mainstream cancer therapies. 5‐aminolevulinic acid (5‐ALA)‐PDT is of particular interest, as it uses the photosensitiser PpIX, naturally produced in the heme pathway, following 5‐ALA administration. Even though 5‐ALA‐PDT shows high specificity to cancers, differences in treatment outcomes call for predictive biomarkers to better stratify patients and to also diversify 5‐ALA‐PDT based on each cancer's phenotypic and genotypic individualities. Aims The present study seeks to highlight key biomarkers that may predict treatment outcome and simultaneously be exploited to overcome cancer‐specific resistances to 5‐ALA‐PDT. Methods and Results We submitted two glioblastoma (T98G and U87) and three breast cancer (MCF7, MDA‐MB‐231, and T47D) cell lines to 5‐ALA‐PDT. Glioblastoma cells were the most resilient to 5‐ALA‐PDT, while intracellular production of 5‐ALA‐derived protoporphyrin IX (PpIX) could not account for the recorded PDT responses. We identified the levels of expression of ABCG2 transporters, ferrochelatase (FECH), and heme oxygenase (HO‐1) as predictive biomarkers for 5‐ALA‐PDT. GPX4 and GSTP1 expression vs intracellular glutathione (GSH) levels also showed potential as PDT biomarkers. For T98G cells, inhibition of ABCG2, FECH, HO‐1, and/or intracellular GSH depletion led to profound PDT enhancement. Inhibition of ABCG2 in U87 cells was the only synergistic adjuvant to 5‐ALA‐PDT, rendering the otherwise resistant cell line fully responsive to 5‐ALA‐PDT. ABCG2 or FECH inhibition significantly enhanced 5‐ALA‐PDT‐induced MCF7 cytotoxicity, while for MDA‐MB‐231, ABCG2 inhibition and intracellular GSH depletion conferred profound synergies. FECH inhibition was the only synergism to ALA‐PDT for the most susceptible among the cell lines, T47D cells. Conclusion This study demonstrates the heterogeneity in the cellular response to 5‐ALA‐PDT and identifies biomarkers that may be used to predict treatment outcome. The study also provides preliminary findings on the potential of inhibiting specific molecular targets to overcome inherent resistances to 5‐ALA‐PDT.

Oxidative stress is one of most common environmental stresses encountered by fish, especially during their fragile larval stage. More and more studies are aimed at understanding the antioxidant defense mechanism of fish larvae. Herein we characterized the early resistance of zebrafish larvae to oxidative stress and investigated the underlying transcriptional regulations using RNA-seq. We found that pre-exposure of zebrafish larvae to 2 mM H2O2 for 1 or 3 h significantly improved their survival under higher doses of H2O2 (3 mM), suggesting the antioxidant defenses of zebrafish larvae were rapidly built under pre-exposure of H2O2. Comparative transcriptome analysis showed that 310 (185 up and 125 down) and 512 (331 up and 181 down) differentially expressed genes were generated after 1 and 3 h of pre-exposure, respectively. KEGG enrichment analysis revealed that protein processing in endoplasmic reticulum is a highly enriched pathway; multiple genes (e.g., hsp70.1, hsp70.2, and hsp90aa1.2) encoding heat shock proteins in this pathway were sharply upregulated presumably to correct protein misfolding and maintaining the cellular normal functions during oxidative stress. More importantly, the Keap1/Nrf2 system-mediated detoxification enzyme system was significantly activated, which regulates the upregulation of target genes (e.g., gstp1, gsr, and prdx1) to scavenger reactive oxygen species, thereby defending against apoptosis. In addition, the MAPK, as a transmitter of stress signals, was activated, which may play an important role in activating antioxidant system in the early stages of oxidative stress. Altogether, these findings demonstrate that zebrafish larvae rapidly establish resistance to oxidative stress, and this involves changes in protein processing, stress signal transmission, and the activation of detoxification pathways. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) and nickel (Ni) are two of the most toxic metals, wreaking havoc on human health and agricultural output. Furthermore, high levels of Cd and Ni in the soil environment, particularly in the root zone, may slow plant development, resulting in lower plant biomass. On the other hand, endophytic bacteria offer great promise for reducing Cd and Ni. Moreover, they boost plants' resistance to heavy metal stress. Different bacterium strains were isolated from tomato roots. These isolates were identified as Micrococcus luteus and Enterobacter cloacae using 16SrDNA and were utilized to investigate their involvement in mitigating the detrimental effects of heavy metal stress. The two bacterial strains can solubilize phosphorus and create phytohormones as well as siderophores. Therefore, the objective of this study was to see how endophytic bacteria (Micrococcus luteus and Enterobactercloacae) affected the mitigation of stress from Cd and Ni in tomato plants grown in 50 μM Cd or Ni-contaminated soil. According to the findings, Cd and Ni considerably lowered growth, biomass, chlorophyll (Chl) content, and photosynthetic properties. Furthermore, the content of proline, phenol, malondialdehyde (MDA), H2O2, OH, O2, the antioxidant defense system, and heavy metal (HM) contents were significantly raised under HM-stress conditions. However, endophytic bacteria greatly improved the resistance of tomato plants to HM stress by boosting enzymatic antioxidant defenses (i.e., catalase, peroxidase, superoxide dismutase, glutathione reductase, ascorbate peroxidase, lipoxygenase activity, and nitrate reductase), antioxidant, non-enzymatic defenses, and osmolyte substances such as proline, mineral content, and specific regulatory defense genes. Moreover, the plants treated had a higher value for bioconcentration factor (BCF) and translocation factor (TF) due to more extensive loss of Cd and Ni content from the soil. To summarize, the promotion of endophytic bacterium-induced HM resistance in tomato plants is essentially dependent on the influence of endophytic bacteria on antioxidant capacity and osmoregulation. [ABSTRACT FROM AUTHOR]