Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer

Ovarian cancer (OC) often presents at an advanced stage and is still one of the most frequent causes of gynecological cancer-related mortality worldwide. The nuclear factor erythroid-2 (NFE2) transcription factors include nuclear factor, erythroid 2 like 1 (NFE2L1), NFE2L2, and NFE2L3. NFE2 members bind to the antioxidant-response element (ARE) region and activate the expression of targeted genes. The distinct functions of NFE2 members in OC remain poorly elucidated. Several online bioinformatics databases were applied to determine gene expression, prognosis, mutations, and immune infiltration correlation in OC patients. NFE2L1 and NFE2L2 were decreased in OC, whereas NFE2L3 was increased. NFE2L2 and NFE2L3 were significantly correlated with the clinical stages of OC. High NFE2L1 level was significantly associated with short progression-free survival (PFS) in patients with OC ( HR = 1.18 , P = 0.021 ), while high NFE2L2 expression strongly correlated with long PFS ( HR = 0.77 , P = 0.00067 ). High NFE2L3 expression was associated with better overall survival and postprogression survival in OC. Functional analysis showed that NFE2 members mainly focused on transcription coactivator activities. Genetic alterations of NFE2 members were found in 13% of OC patients, and amplification ranked the top. The expression of NFE2 members was significantly correlated with immune infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in OC. Our study provides novel insights into the roles and prognostic potential of NFE2 family members in OC.

Is the Clinical Course of Non-Arteritic Ischemic Optic Neuropathy Associated with Oxidative Damage and the Dynamics of the Antioxidant Response?

Purpose: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy’s clinical course with systemic oxidative damage and antioxidant response dynamics in a large series.Methods: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the patient group were analyzed.Results: Vitamin E and MDA levels were significantly higher in the patient group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure, between B12 and cup-to-disc ratio, between antioxidant glutathione and SOD enzyme systems, and between uric acid and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA was found to be very significant. Conclusions: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

Heavy metal–induced stress in eukaryotic algae—mechanisms of heavy metal toxicity and tolerance with particular emphasis on oxidative stress in exposed cells and the role of antioxidant response

Heavy metals is a collective term describing metals and metalloids with a density higher than 5 g/cm3. Some of them are essential micronutrients; others do not play a positive role in living organisms. Increased anthropogenic emissions of heavy metal ions pose a serious threat to water and land ecosystems. The mechanism of heavy metal toxicity predominantly depends on (1) their high affinity to thiol groups, (2) spatial similarity to biochemical functional groups, (3) competition with essential metal cations, (4) and induction of oxidative stress. The antioxidant response is therefore crucial for providing tolerance to heavy metal-induced stress. This review aims to summarize the knowledge of heavy metal toxicity, oxidative stress and antioxidant response in eukaryotic algae. Types of ROS, their formation sites in photosynthetic cells, and the damage they cause to the cellular components are described at the beginning. Furthermore, heavy metals are characterized in more detail, including their chemical properties, roles they play in living cells, sources of contamination, biochemical mechanisms of toxicity, and stress symptoms. The following subchapters contain the description of low-molecular-weight antioxidants and ROS-detoxifying enzymes, their properties, cellular localization, and the occurrence in algae belonging to different clades, as well as the summary of the results of the experiments concerning antioxidant response in heavy metal-treated eukaryotic algae. Other mechanisms providing tolerance to metal ions are briefly outlined at the end.

XRE Family Transcriptional Regulator XtrSs Modulates Streptococcus Suis Fitness of Hydrogen Peroxide Stress

Streptococcus suis is an important emerging zoonosis that causes economic losses in the pig industry and severe threats to public health. Transcriptional regulators play essential roles in bacterial adaptation to host environments. In this study, we identified a novel XRE family transcriptional regulator in S. suis CZ130302, XtrSs, involved in the bacterial fitness to hydrogen peroxide stress. Based on electrophoretic mobility shift and β-galactosidase activity assays, we found that XtrSs autoregulated its own transcription and repressed the expression of its downstream gene psePs, a surface protein with unknown function in S. suis, by binding to a palindromic sequence from the promoter region. Furthermore, we proved that the deletion of the psePs gene attenuated bacterial antioxidant response. Phylogenetic analysis revealed that XtrSs and PsePs naturally co-existed as a combination in most S. suis genomes. Collectively, we demonstrated the binding characteristics of XtrSs in S. suis and provided a new insight that XtrSs played a critical role in modulating psePs to the hydrogen peroxide resistance of S. suis.

Bioprospecting of Less-Polar Fractions of Ericaria crinita and Ericaria amentacea: Developmental Toxicity and Antioxidant Activity

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea (FdEa) were analyzed by high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The major identified compounds were: amides of higher aliphatic acids (palmitoleamide, linoleamide, palmitamide, oleamide and erucamide) and related compounds, carotenoid (fucoxanthin), chlorophyll derivatives (pheophytin a and b and their derivatives) and higher terpenes (loliolide, isoamijiol with its oxidation product), β-stigmasterol and (3β,6α)-14-methylergosta-8,24(28)-diene-3,6-diol). The toxic effects observed on the less-polar fractions obtained from Ericaria species on zebrafish Danio rerio embryos could be associated with the high abundance of all five detected amides. The antioxidant activity of the fractions was evaluated by means of five independent assays, including the reduction of the radical cation (ABTS), the oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and the Folin–Ciocalteu method. A higher antioxidant activity of E. amentacea in comparison to that of the E. crinita fractions was found with IC50 concentrations of 0.072 and 1.177 mg/mL, respectively. The correlation between the activity and the chemical composition revealed that the synergistic effect of different compounds impacted their antioxidant response.

mRNA Transcript Analysis of Hypothesis-driven Pathways as Known Responders to Organophosphate Exposure: Rhinella Arenarum Larvae Transcriptome Study

Transcriptional analysis of the network of transcription regulators and target pathways in exposed organisms may be a hard task when their genome remains unknown. We used a whole transcriptome study on Rhinella arenarum larvae exposed to the organophosphorus pesticides azinphos-methyl and chlorpyrifos to evaluate transcriptional effects on a priori selected groups of genes. This approach allowed us to evaluate the effects on hypothesis-selected pathways such as target esterases, detoxifying enzymes, polyamine metabolism and signaling and regulatory pathways modulating them. We could then compare the responses at the transcriptional level with previously described effects at the enzymatic or metabolic levels to obtain global insight into toxicity-response mechanisms. The effects of both pesticides on the transcript levels of these pathways could be considered moderate, while the responses elicited by chlorpyrifos were more potent and earlier than those elicited by azinphos-methyl. Finally, we infer a prevailing downregulation effect of pesticides on signaling pathways and transcription factor transcripts encoding products that modulate/control the polyamine and antioxidant response pathways. We additionally tested and selected potential housekeeping genes based on those reported for other species. These results allow us to go through future confirmatory studies on pesticide gene expression modulation in toad larvae.

Antioxidant Response and Calcium-Dependent Protein Kinases Involvement in Canola (Brassica napus L.) Tolerance to Drought

Canola is an important temperate oil crop that can be severely affected by drought. Understanding the physiological and molecular mechanisms involved in canola tolerance to water deficit is essential to obtain drought-tolerant productive cultivars. To investigate the role of antioxidant response and the possible involvement of calcium-dependent protein kinases (CDPKs) in canola tolerance to drought, we analyzed four genotypes with different sensitivity to water stress. Leaf relative water content, canopy temperature, PSII efficiency, electrolyte leakage index and lipid peroxidation were used as indicators to classify the cultivars as drought-tolerant or drought-sensitive. Antioxidant enzymes superoxide dismutase, guaiacol peroxidase and catalase displayed significantly higher activities in drought-tolerant than in drought-sensitive cultivars subjected to water deficit, suggesting that the efficiency of the antioxidant response is essential in canola drought tolerance. The increased expression of genes BnaCDPK6 and BnaCDPK14 under drought conditions, their differential expression in drought-tolerant and drought-sensitive genotypes, and the presence of multiple cis-acting stress-related elements in their promoter regions suggest that CDPKs are part of the signaling pathways that regulate drought response in canola. We propose the BnaCDPK genes and their regulator elements as potential molecular targets to obtain drought-tolerant productive canola cultivars through breeding or genetic transformation.

Palm oil extracts protected against cadmium chloride poisoning via inhibition of oxidative stress in rats

Background The probable mechanism of an earlier reported capacity of palm oil extracts to confer protection against high dose cadmium poisoning in rats was reported in this study. Similar experimental design earlier reported by us was retained. Rats therefore were sacrificed at intervals of twelve; twenty four and forty eight hours post CdCl2 insult. Results Oxidative stress and antioxidant status (malondialdehyde, superoxide dismutase, catalase and glutathione) were assessed in tissues (liver, kidney, heart, brain, muscle) and serum. Oxidative stress indicators showed a significantly (p < 0.05) increased lipid peroxidation and alterations in antioxidant defence systems occasioned by drop in catalase and superoxide dismutase enzymes (serum, liver, heart, brain and kidneys) of the rats. Also observed were significant (p < 0.05) reduction in the non-enzymatic antioxidant reduced glutathione over time. Pre-administration of rats with the crude palm oil and its extracts modulated cadmium mediated depletion of the antioxidant capacities of rats acutely exposed to cadmium and rising lipid peroxidation profile. Conclusions Regulation of stress and antioxidant response was the underlying mechanism by which the extracts conferred protection against high dose cadmium insult thus suggesting its potential as a viable therapeutic target against its deleterious effects. Graphical Abstract