Redox State Research Articles

Fumonisin B1 protects against long-chained polyunsaturated fatty acid-induced cell death in HepG2 cells – implications for cancer promotion

Fumonisin B1 (FB1), a food-borne mycotoxin, is a cancer promoter in rodent liver and augments proliferation of initiated cells while inhibiting the growth of normal hepatocytes by disrupting lipid biosynthesis at various levels. HepG2 cancer cells exhibited resistance to FB1-induced toxic effects presumably due to their low content of polyunsaturated fatty acids (PUFA) even though FB1-typical lipid changes were observed, e.g. significantly increased phosphatidylethanolamine (PE), decreased sphingomyelin and cholesterol content, increased sphinganine (Sa) and sphinganine/sphingosine ratio, increased C18:1ω9, decreased C20:4ω6 content in PE and decreased C20:4ω6-PC/PE ratio. Increasing PUFA content of HepG2 cells with phosphatidylcholine (PC) vesicles containing C20:4ω6 (SAPC) or C22:6ω6 (SDPC) disrupted cell survival, cellular redox status and induced oxidative stress and apoptosis. A partially protective effect of FB1 was evident in PUFA-enriched HepG2 cells which may be related to the FB1-induced reduction in oxidative stress and the disruption of key cell membrane constituents indicative of a resistant lipid phenotype. Interactions between different ω-6 and ω-3 PUFA, membrane constituents including cholesterol, and the glycerophospho- and sphingolipids and FB1 in this cell model provide further support for the resistant lipid phenotype and its role in the complex cellular effects underlying the cancer promoting potential of the fumonisins.

In vitro toxicity of Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) on Human Renal and Hepatoma Cells

We evaluate the cytotoxicity, intracellular redox conditions, apoptosis, and methylation of DNMTs/TETs upon exposure to LiTFSI, a novel Per and Polyfluoroalkyl Substances (PFAS) commonly found in lithium-ion batteries, on human renal carcinoma cells (A498) and hepatoma cells (HepG2). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed both Perfluorooctane sulfonate (PFOS) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) had a dose-dependent effect on A498 and HepG2, with LiTFSI being less toxic. Intracellular redox conditions were assessed with a microplate reader and confocal, which showed a significant decrease in Reactive Oxygen Species (ROS) levels and an increase in Superoxide dismutase (SOD) content in both cells. Exposure to LiTFSI enhanced cell apoptosis, with HepG2 being more susceptible than A498. Quantitative analysis of mRNA expression levels of 19 genes associated with kidney injury, methylation, lipid metabolism and transportation was performed. LiTFSI exposure impacted kidney function by downregulating smooth muscle alpha-actin (Acta2) and upregulating transforming growth factor beta 1 (Tgfb1), B-cell lymphoma 2-like 1) Bcl2l1, hepatitis A virus cellular receptor 1 (Harvcr1), nuclear factor erythroid 2-like 2 (Nfe2l2), and hairy and enhancer of split 1 (Hes1) expression. LiTFSI exposure also affected the abundance of transcripts associated with DNA methylation by the expression of ten-eleven translocation (TET) and DNA methyltransferase (DNMT) genes. Furthermore, LiTFSI exposure induced an increase in lipid anabolism and alterations in lipid catabolism in HepG2. Our results provide new insight on the potential role of a new contaminant, LiTFSI in the regulation of oxidative stress, apoptosis and methylation in human renal carcinoma and hepatoma cells.

Targeted Restoration of GPX3 Attenuates Renal Ischemia/Reperfusion Injury by Balancing Selenoprotein Expression and Inhibiting ROS-mediated Mitochondrial Apoptosis.

Renal ischemia/reperfusion (IR) injury is the leading cause of acute kidney injury in both autologous and transplanted kidneys. Low-level glutathione peroxidase 3 (GPX3) is associated with renal IR injury. The exact mechanism of targeted GPX3 restoration in renal IR injury has yet to be determined. The distribution of GPX3 in different tissues and organs of the body was investigated. The level of GPX3 in renal IR injury was assessed. To confirm the action of GPX3 and its mechanisms, IR models were used to introduce adeno-associated virus 9 containing GPX3, as well as hypoxia/reoxygenation-exposed normal rat kidney cells that consistently overexpressed GPX3. Reverse molecular docking was used to confirm whether GPX3 was a target of ebselen. GPX3 is abundant in the kidneys and decreases in expression during renal IR injury. GPX3 overexpression reduced renal IR injury and protected tubular epithelial cells from apoptosis. Proteomics analysis revealed a strong link between GPX3 and mitochondrial signaling, cellular redox state, and different expression patterns of selenoproteins. GPX3 inhibited reactive oxygen species-induced mitochondrial apoptosis and balanced the disordered expression of selenoproteins. GPX3 was identified as a stable selenoprotein that interacts with ebselen. Ebselen enhanced the level of GPX3 and reduced IR-induced mitochondrial damage and renal dysfunction. Targeted restoration of GPX3 attenuates renal IR injury by balancing selenoprotein expression and inhibiting reactive oxygen species-mediated mitochondrial apoptosis, indicating that GPX3 could be a potential therapeutic target for renal IR injury.

Impact of organic carbon on heavy metals of river sediments and aquatic ecosystems: A review

AbstractOrganic carbon with variable chemical composition sourced primarily from terrestrial and aquatic biogenic input has a significant impact on sediment heavy metal mobility. The present scientific view is unclear in deciphering the role of labile organic carbon in changing sediment heavy metal concentration. The present review critically assesses the impact of various forms of carbon on different geochemically bound heavy metal fractions and their monitoring. It is evident from the review that, the biochemical form of organic carbon (based on degradability and biopolymeric forms), carbon‐geochemical association, and density of organic carbon (light or heavy carbon fractions) plays an important role in determining the bioavailability and toxicity of metals for aquatic organisms. Besides the organic carbon, various sediment conditions that define the behavior of heavy metals include pH, redox condition, sulfide concentration, salinity, temperature, etc. Therefore, it is recommended that carbon relation with heavy metal mobility and stability should be included under long‐term sediment management plans to maintain the sediment quality of the river system.

Associations of methylene tetrahydrofolate reductase (MTHFR) polymorphism with hepatocellular carcinoma in Egyptian population

Liver serves as a hub for key metabolic pathways such as folate cycle that provides one-carbon units for a network of metabolic reactions. Methylenetetrahydrofolate reductase (MTHFR) is a rate limiting enzyme in folate metabolism and thus it is vital for DNA methylation, synthesis and repair [1]. The objective of this study was to evaluate an eventual association between MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population.Blood samples from patients and controls from Mansoura university hospital were used after signed consent and approval from Medical ethical committee. The two genetic loci were designed for amplification and genotyped by using PCR–RFLP.Our results clarify that, the most important predictors for HCC are T/T genotype of variant C677T and C/C genotype of variant (A1298C) with odds ratio 3.28 and 2.99 respectively. Also, MTHFR variant C677T genotype C/C or T/T combined with MTHFR variant A1298C genotype C/C were associated with an increased risk of HCC, with the OR, 2.6 and 7 respectively. CT genotype of MTHFR variant C677T showed significant difference between HCC grades and C allele of variant C677T showed significant difference in BCLC stages of HCC.Our data indicates that, the two variants (C677T and A1298C) constitute a risk factor for the development of HCC and this could be attributed to the low activities of the enzyme MTHFR that disturb one carbon metabolism and subsequently, DNA synthesis, repair and methylation, thus cellular redox state, growth, and proliferation.

Geochemistry of Arsenic and Salinity-Contaminated Groundwater and Mineralogy of Sediments in the Coastal Aquifers of Southwest Bangladesh

This study aimed to develop a geochemical database by thoroughly analyzing groundwater and sediments from coastal aquifers of southwest Bangladesh. Moreover, we investigated the source of sediment deposition and the mechanisms behind the presence of arsenic and salinity in groundwater. The seasonal distribution patterns of arsenic among the shallow and deep coastal aquifers were found to be 45.12 µg/l and 20.65 µg/l during dry and wet seasons, respectively. Moreover, the groundwater salinity distribution ranged from 3262.88 mg/l to 1930.88 mg/l during the dry and wet seasons. Cored sediment samples showed fine to medium sands of 92%, with silt and clay particles. The petrographic study of authigenic and heavy minerals revealed that the mineral grains were subangular to angular, indicating their textural immaturity of coastal sediments. The reactivity of goethite (FeOOH) and siderite (FeCO3) minerals suggests that the aquifers were subjected to slightly oxidized to moderately reducing conditions, with ORP values ranging from +50.40 mv to −149.5 mv. Such redox conditions could potentially result in the enrichment and mobility of arsenic in the groundwater. Although arsenic concentrations in deep aquifers are relatively low, higher salinity values are found in both shallow and intermediate coastal aquifers.

Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC

Cysteine metabolism occurs across cellular compartments to support diverse biological functions and prevent the induction of ferroptosis. Though the disruption of cytosolic cysteine metabolism is implicated in this form of cell death, it is unknown whether the substantial cysteine metabolism resident within the mitochondria is similarly pertinent to ferroptosis. Here, we show that despite the rapid depletion of intracellular cysteine upon loss of extracellular cystine, cysteine-dependent synthesis of Fe-S clusters persists in the mitochondria of lung cancer cells. This promotes a retention of respiratory function and a maintenance of the mitochondrial redox state. Under these limiting conditions, we find that glutathione catabolism by CHAC1 supports the mitochondrial cysteine pool to sustain the function of the Fe-S proteins critical to oxidative metabolism. We find that disrupting Fe-S cluster synthesis under cysteine restriction protects against the induction of ferroptosis, suggesting that the preservation of mitochondrial function is antagonistic to survival under starved conditions. Overall, our findings implicate mitochondrial cysteine metabolism in the induction of ferroptosis and reveal a mechanism of mitochondrial resilience in response to nutrient stress.

Enrichment mechanism of organic matter and silicon in lower Cambrian shale of the Yangtze Platform

Early Cambrian time witnessed accumulation of high-quality organic-rich siliceous shale deposits that comprise an especially promising shale gas exploration target, especially in China. The present study of the Cambrian Niutitang Formation of the shelf area of the Upper Yangtze Platform utilizes mineralogical and elemental geochemical data to aide in the paleoenvironment reconstruction of these organic-rich deposits. We are especially interested in elucidating organic carbon and silicon enrichment mechanisms of the Niutitang Formation that will benefit shale gas exploration and development of these deposits. The Niutitang Formation can be subdivided into three intervals based on lithology, gamma ray (GR) signature, and TOC abundance. Enriched TOC (average = 6.7%) and nano-size authigenic microcrystalline quartz (Qn) contents of Interval I deposits likely reflect deposition in an environment that experienced persistent euxinic and elevated organic matter delivery associated with enhanced paleoproductivity driven by hydrothermal activity. Interval II shale is interpreted to have accumulated under euxinic-ferruginous conditions that experienced the effects of robust paleoproductivity and diminished terrigenous input related to persistently warm, humid climatic conditions. Enriched TOC (average = 4.9%) and moderate microcrystalline quartz content of these deposits were likely the result of redox conditions and elevated paleoproductivity. Interval III strata appears to have accumulated under oxygenated bottom conditions that experienced moderate paleoproductivity, brackish water and elevated terrigenous detritus input driven by the establishment of cold, dry climatic conditions. The combined results of these conditions are diminished TOC content (average = 0.7%) and enrichment of the sediment in terrestrial quartz. The elevated content of authigenic quartz appears to have diminished the reservoir capacity of Niutitang Formation shale. Interval II organic-rich siliceous shale deposits of Upper Yangtze Platform shelf areas, which have the comparable authigenic microcrystalline quartz content, reservoir performance, and greater organic matter abundance as the rift trough, appear to comprise the stratigraphic horizon with the greatest exploration and development potential. Results of the present study offer theoretical guidance for future shale gas exploration and development efforts in geologically similar regions.

Thymol Deploys Multiple Antioxidative Systems to Suppress ROS Accumulation in Chinese Cabbage Seedlings under Saline Stress

Developing biostimulants is a promising approach for sustainable agriculture under a saline environment. Thymol is a plant-derived compound with a potential antioxidative capacity. However, little is known about whether and how the antioxidative property of thymol plays a role in inducing plant tolerance against abiotic stresses. Here, we find that thymol induces saline tolerance in Chinese cabbage seedlings via enhancing the antioxidative capacity. Treatment with NaCl (100 mM) decreased the seedling fresh weight by 59.9% as compared to a control. Thymol at 20 μM showed the greatest effect on promoting seedling growth under saline stress, with the seedling fresh weight being increased by 71.0% as compared to NaCl treatment. Thymol remarkably decreased the overaccumulation of ROS (hydrogen peroxide and a superoxide radical); cell membrane damage (evaluated by lipid oxidation, membrane integrity, and relative conductivity); and cell death in seedlings under saline stress. Thymol induced three antioxidative systems to lower the ROS level in salt-treated seedlings. First, thymol remarkably activated a set of antioxidative enzymes, such as SOD (superoxide dismutase), APX (ascorbate peroxidase), CAT (catalase), and POD (peroxidase). Second, thymol balanced the cellular redox status by increasing the ratio of AsA/DHA (ascorbic acid/dehydroascorbic acid) and GSH/GSSG (glutathione/oxidized glutathione). Third, thymol significantly enhanced the level-two kinds of antioxidants (total phenol and flavonoid). All of these physiological responses were observed in both the shoots and the roots. In sum, thymol deploys multiple antioxidative systems to help Chinese cabbage seedlings against saline stress. Such findings suggest that thymol has great potential to be developed as a novel biostimulant enhancing crop tolerance against saline stress.

Experimental and Theoretical Predictors for Redox Potentials of Bispyridinylidene Electron Donors.

Bispyridinylidenes are neutral organic molecules capable of two-electron oxidation at a range of redox potentials that are widely tunable by choice of substituent, making them attractive as homogeneous organic reductants and active materials in redox flow batteries. In an effort to readily predict the redox potentials of this important class of compounds, we have developed correlations between the experimental redox potentials and both experimental and theoretical predictors. On the experimental side, we show that multinuclear NMR chemical shifts of related pyridinium ions correlate well with the redox potentials of bispyridinylidenes, with R2 and standard errors (S) reaching 0.9810 and 0.048 V, respectively, when the 13C (N-CH3) and 1H (ortho) chemical shifts are used together. Theoretical studies of the bispyridinylidenes and their doubly oxidized bipyridinium ions gave a range of predictively valuable equations at various levels of computational cost. This ranged from a simple model using only the EHOMO of the bispyridinylidenes (R2 = 0.9689; S = 0.060 V), to a more computationally intensive model which include solvation effects for both redox states which gave the highest predictive value for all methods (R2 = 0.9958; S = 0.022 V). This work will guide further studies of this important class of molecules.

Volatile atmospheres of lava worlds

A magma ocean (MO) is thought to be a ubiquitous stage in the early evolution of rocky planets and exoplanets. During the lifetime of the MO, exchanges between the interior and exterior envelopes of the planet are very efficient. In particular, volatile elements that initially are contained in the solid part of the planet can be released and form a secondary outgassed atmosphere. We determine trends in the H-C-N-O-S composition and thickness of these secondary atmospheres for varying planetary sizes and MO extents, and the oxygen fugacity of MOs, which provides the main control for the atmospheric chemistry. We used a model with coupled chemical gas-gas and silicate melt-gas equilibria and mass conservation to predict the composition of an atmosphere at equilibrium with the MO depending on the planet size and the extent and redox state of the MO. We used a self-consistent mass-radius model for the rocky core to inform the structure of the planet, which we combined with an atmosphere model to predict the transit radius of lava worlds. The resulting MOs have potential temperatures ranging from 1415 to 4229 K, and their outgassed atmospheres have total pressures from 3.3 to 768 bar. We find that MOs (especially the shallow ones) on small planets are generally more reduced, and are thus dominated by H$_2$-rich atmospheres (whose outgassing is strengthened at low planetary mass), while larger planets and deeper MOs vary from CO to CO$_2$-N$_2$-SO$_2$ atmospheres, with increasing $f_ O $. In the former case, the low molecular mass of the atmosphere combined with the low gravity of the planets yields a large vertical extension of the atmosphere, while in the latter cases, secondary outgassed atmospheres on super-Earths are likely significantly shrunk. Both N and C are largely outgassed regardless of the conditions, while the S and H outgassing is strongly dependent on the $f_ O $, as well as on the planetary mass and MO extent for the latter. We further use these results to assess how much a secondary outgassed atmosphere may alter the mass-radius relations of rocky exoplanets.

Childhood obesity accelerates biological ageing: is oxidative stress a link?

Obesity is multifactorial pathophysiological condition with an imbalance in biochemical, immunochemical, redox status and genetic parameters values. We aimed estimate connection between relative leukocyte telomere lengths (rLRL) - biomarker of cellular aging with metabolic and redox status biomarkers values in a group of obese and lean children. The study includes 110 obese and 42 lean children and adolescents, both genders. The results suggested that rLTL are significantly shorter in obese, compared to lean group (p<0,01). Negative correlation of rLTL with total oxidant status, TOS (Spearman's ρ = -0.365, p<0.001) as well as with C reactive protein (Spearman's ρ= -0,363, p<0.001) were observed. Principal component analysis (PCA) extracted three distinct factors (i.e. principal components) entitled as: prooxidant factor with 35% of total variability; antioxidant factor with 30% of total variability and lipid antioxidant - biological ageing factor with 12% of the total variability. The most important predictor of body mass index (BMI) >30kg/m2 according to logistic regression analysis was PCA derived antioxidant factor's score (OR: 1.66, 95th Cl: 1.05-2.6, p=0.029). PCA analysis confirmed oxidative stress importance in biological ageing caused by obesity and its multiple consequences related to prooxidants augmentation and antioxidants exhaustion and gave us clear signs of disturbed cellular homeostasis deepness, even before any overt disease occurrence.

Effect of coastal hypoxia on bacterial diversity as elucidated through 16S rRNA amplicon sequencing

The formation of oxygen-depleted zones in the bottom waters is one of the most widespread phenomena in coastal areas. Upwelling episodes along India’s west coast due to the southwest monsoon increase biological productivity, further lowering the dissolved oxygen in the upwelled waters, which intensifies annually between June and October. Here, we have determined the changes in the microbial community in response to the varying oxygen levels and other physicochemical parameters at the Candolim Time Series Station using high-throughput sequencing. Amplicon Sequence Variants across all the samples collected in different seasons were mostly affiliated to the phyla Proteobacteria, Actinobacteria, Bacteroidetes, Verrucomicrobia, Chloroflexi, Firmicutes and Planctomycetes, with the most dominant being Proteobacteria (21-41%). Statistical analysis revealed that microbial diversity differed significantly with changing DO, ammonia, nitrate and nitrite concentrations during different seasons. The microbial community shift due to seasonal hypoxia results in the differential biogeochemical cycling of essential nutrients, with certain years seeing redox conditions up to sulphate reduction while certain years seeing only nitrogen loss. Future global warming scenarios will serve as a big challenge for understanding the role of microbial diversity and its implications in the cycling of natural elements.

Redox State of Photosynthetic Ferredoxin Under Heat and Light Stress

Redox State of Photosynthetic Ferredoxin Under Heat and Light Stress

Contrasting magma chemistry in the Candelaria IOCG district caused by changing tectonic regimes

Iron oxide-copper-gold (IOCG) deposits are a vital source of copper and critical elements for emerging clean technologies. Andean-type IOCG deposits form in continental arcs undergoing extension, and they have a temporal relationship with magmatism although they do not exhibit a close spatial relation with the causative intrusions. The processes required to form IOCG deposits and their potential connections to iron oxide–apatite (IOA)-type mineralization remain poorly constrained, as well as the characteristics of magmatism linked to both deposit types. Here we combine zircon U–Pb geochronology with zircon trace element geochemistry of intrusive rocks associated with the Candelaria deposit, one of the world’s largest IOCG deposits, to unravel distinctive signatures diagnostic of magmatic fertility. Our results reveal a marked transition in the geochemistry of intrusions in the Candelaria district, characterized by changes in the redox state, water content and temperature of magmas over time. The oldest magmatic stage (~ 128–125 Ma), prior to the formation of the Candelaria deposit, was characterized by zircon Eu/Eu* ratios of 0.20–0.42, and redox conditions of ΔFMQ − 0.4 to + 1.0. The earliest magmatic stage related to the formation of Fe-rich mineralization at Candelaria (118–115 Ma) exhibits low zircon Eu/Eu* ratios (0.09–0.18), low oxygen fugacity values (ΔFMQ ~− 1.8 to + 0.2) and relatively high crystallization temperatures. In contrast, the youngest stage at ~ 111–108 Ma shows higher zircon Eu/Eu* (~ 0.37–0.69), higher oxygen fugacity values (ΔFMQ ~ + 0.4 to + 1.3) and a decrease in crystallization temperatures, conditions that are favorable for the transport and precipitation of sulfur and chalcophile elements. We conclude that Candelaria was formed through two distinct ore-forming stages: the first associated with a reduced, high temperature, water-poor magma developed under a low tectonic stress, followed by a more oxidized, water-rich, and low temperature magmatic event related to a compressional regime. The first event led to Fe-rich and S-poor IOA-type mineralization, while the second event with geochemical signatures similar to those of porphyry copper systems, generated the Cu- and S-rich mineralization. This late stage overprinted preexisting IOA mineralization resulting in the formation of the giant Candelaria IOCG deposit.

Variations in flavin redox states during extracellular electron transfer and electron conduction in Shewanella oneidensis

Flavin is one of the most prevalent redox molecules utilized by electroactive bacteria. Electroactive bacteria form a three-dimensional architecture with multiple cell assemblages on electrodes in bioelectrochemical systems. This provokes the importance of unveiling the redox chemistry of flavins during electron transfer not only at the bacteria/electrode interface but also inside cell assemblages. However, it has been difficult to directly compare the redox species contributing to each electron transfer reaction. In this study, to simultaneously detect the flavin redox species at the electrode surface and those in cell assemblages, we conducted bipotentiometric cyclic voltammetry on a colony of Shewanella oneidensis MR-1. The bipotentiometric data showed that flavin mononucleotide proceeds the redox cycle at − 0.43 V (vs. standard hydrogen electrode) in the MR-1 colony assignable to the semiquinone/hydroquinone redox cycle, which was supported by experiments with semiquinone scavenger and gene deletion mutants. Notably, the peak at − 0.43 V was not detected at the electrode surface, indicating that the flavin redox cycles and redox potentials involved in the electron transfer inside MR-1 assemblages differ from those at the MR-1/electrode interface. The measurement system presented herein offers a platform to clarify the redox reactions in cell assemblages as well as at the bacteria/electrode interface.

Cornus mas L. Extract-Mediated Modulations of the Redox State Induce Cytotoxicity in Schizosaccharomyces pombe

The Cornus mas L. fruit is well known for having a high presence of bioactive substances that include phenolic compounds, anthocyanins, vitamins, flavonoids, carotenoids, and ursolic acid. The health-promoting effects of those substances are mainly associated with their antimicrobial, anti-inflammatory, and antioxidant properties. In this study, we investigated the role of Cornus mas L. fruit ethanolic extract on the cell vitality of a model eukaryotic organism, the yeast Schizosaccharomyces pombe. The effect of Cornus mas L. fruit ethanolic extract on cell viability was determined by analyses of cell growth and cell doubling time during exposure to the extract. To determine the ability of Cornus mas L. to reduce or induce oxidative stress, quantification of intracellular reactive oxygen species and malondialdehyde levels was performed. Additionally, the enzyme activity of superoxide dismutase and catalase was evaluated together with the determination of changes in the expression of genes related to oxidative stress response. The data suggest a dose-dependent cytotoxic effect of the Cornus mas L. fruit ethanol extract, as a higher concentration (2%) led to increased oxidative stress and reduced cell viability of S. pombe cells, while a lower concentration (0.5%) showed only a subtle effect on the analyzed parameters. This study provides a new perspective on the possible antimicrobial or medicinal properties of Cornus mas L. fruit ethanol extract due to its ability to induce oxidative stress in the cell.

Marine redox dynamics and biotic response to the mid-Silurian Ireviken Extinction Event in a mid-shelf setting

The early Silurian Llandovery–Wenlock boundary interval is marked by significant marine perturbations and biotic turnover, culminating in the Ireviken Extinction Event and the Early Sheinwoodian Carbon Isotope Excursion. Here, we apply multiple independent redox proxies to the early Wenlock Buttington section, which was deposited in a mid-shelf location in the Welsh Basin, UK. To account for the regional geochemical variability in marine sediments due to factors such as sediment provenance, we first define oxic baseline values for the Welsh Basin, utilizing deeper water, well-oxygenated intervals of late Llandovery age. Our approach documents unstable, oscillating redox conditions on the mid-shelf at Buttington. We suggest that these dynamic redox fluctuations are likely to relate to changes in the position of the chemocline or a migrating oxygen minimum zone. Benthic biota, such as trilobites, brachiopods, bivalves and gastropods, appear to have been relatively unaffected by fluctuating oxic-ferruginous conditions, but were more severely impacted by the development of euxinia, highlighting the inhibiting role of toxic sulfides. By contrast, the redox perturbations appear to have placed extreme stress on graptolites, causing many extinction losses regardless of the specific development of euxinia. Supplementary material: The geochemical data for the Buttington section is available at https://doi.org/10.6084/m9.figshare.c.7165009 Thematic collection: This article is part of the Chemical Evolution of the Mid-Paleozoic Earth System and Biotic Response collection available at: https://www.lyellcollection.org/topic/collections/chemical-evolution-of-the-mid-paleozoic-earth-system

Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Cre-ER(T)/fl mice by altering the coenzyme Q pool.

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43Cre-ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43fl/fl mice and Cx43Cre-ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia-reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165±0.338 vs. 4.18±0.55 nmol/mg protein, p<0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43Cre-ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate.

Curcumin’s effects on growth indices, histological scores, blood metabolites, redox state, immunity, and antioxidant-related genes of red tilapia (Oreochromis sp.)

AbstractCurcumin, a polyphenol, targets multiple signaling molecules and shows activity at the cellular level, supporting its various health benefits. Thereafter, the present study examines the effects of different doses of dietary curcumin on growth indices, feed efficiency, serum metabolites, redox (oxidation) status, immunity, histological assessment, and antioxidant-related genes in red tilapia (Oreochromis sp, Oreochromis aureus x O. mossambicus). A total of 1200 red tilapia with an average weight of 19.1±0.03 g were distributed in 12 cement ponds (3×3.5×1m). Each treatment was assigned three pounds (n=100 replicates). For 60 days, fish were fed baseline diets containing 0, 0.4, 0.6, and 0.8 g of curcumin/kg of diet. The treated fish showed increased body weight and SGR (specific growth rate) compared to the T0 group (P&lt;0.05). Curcumin in the diet significantly improved weight gain, percentages, and FCR (feed conversion ratio), with a dose-dependent effect (P &lt; 0.05). Curcumin supplementation showed no influence on feed intake, fish mortality, or survival rate (P &gt;0.05). The curcumin-treated fish groups improved tissue structure in hepatocytes, pancreatic lumens, hepatic blood sinusoids, and intestine tissue layers, particularly the mucosal layer. The T0.8 group had reduced liver enzymes (AST and ALT) and greater total protein and albumin levels (P&lt;0.05). The T0.6 and T0.8 groups showed significantly lower MDA levels than the other groups (P &lt; 0.05). Curcumin groups demonstrated significantly higher antioxidant indices (CAT, GPx, and SOD) compared to the basal diet (P&lt;0.05). Curcumin administration resulted in significant improvements in IgM and lysosome levels (P&lt;0.05). All supplemented groups had considerably (P&lt;0.05) higher levels of SOD, CAT, and GPx mRNA than the control group. Consequently, administering 0.6–0.8 g/kg of curcumin to red tilapia (Oreochromis sp.) diets may improve the fish’s growth, health, tissue composition, and antioxidant response.