Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways.

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.

Sodium arsenite and arsenic trioxide differently affect the oxidative stress of lymphoblastoid cells: An intricate crosstalk between mitochondria, autophagy and cell death.

Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments.

Sodium arsenite induces hepatic stellate cells activation by m6A modification of TGF-ß1 during liver fibrosis.

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-ß/Smad signaling, which could be reversed by TGF-ß1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-ß1 and enhanced the TGF-ß1 mRNA stability. Notably, NaAsO2-induced TGF-ß/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-ß1, which may open up new therapeutic options for LF brought on by environmental hazards.

mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells.

The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.

Purification, kinetic characterization of thermostable multicopper oxidase from the oyster mushroom and its versatility for greener agro-pulp bio bleaching in the paper industry.

Production of a thermostable laccase from Pleurotus florida was reported for the first time, both in submerged and solid-state fermentation using agro-industrial residues. This enzyme was purified using ammonium sulphate precipitation (60-90%), Sephadex G-100 and DEAE column ion exchange chromatography, respectively. The laccase was purified to 21.49 fold with an apparent molecular weight of 66 kDa and had an optimal pH of 5 with temperature stability at 60°C. Metal ions such as Cu2+ (91.26 µmole/mL/min), Mg2+ (68.15 µmole/mL/min), and Fe2+ (1.73 µmole/mL/min) enhanced the laccase activity, but Fe2+ (1.73µmole/mL/min) inhibited the enzyme activity. The purified laccase had Km and Vmax of 16.68 mM and 26.73 µmole/mL/min for guaiacol as a substrate. The isolated enzyme was characterized by FT-IR which revealed bands at 3655.0 cm-1, 2894.7 cm-1, and 1151.7 cm-1 corresponding to primary amines, C-H stretch, and amide -III, respectively. The enzymatic bio bleaching of paddy straw pulp was found to be most effective which resulted in a lowering of kappa number and yellowness by 19.47% & 17.84% whereas an increase in brightness and whiteness by 41.92%. & -19.61%. Thus, this might be stated that the crude laccase from P. florida can be exploited to reduce the toxic waste load for managing environmental pollution and helps in enhancing the yield and quality of the paper.

Lysine specific demethylase 1 inhibits sodium arsenite activation of HSCs by regulating SESN2/AMPK/ULK1 signaling pathway activity.

Lysine specific demethylase 1 (LSD1) is a histone demethylase that specifically catalyzes the demethylation of histone H3K4 (H3K4me1/2) and regulates gene expression. In addition, it can mediate the process of autophagy through its demethylase activity. Sestrin2 (SESN2) is a stress-induced protein and a positive regulator of autophagy. In NaAsO2-induced mouse fibrotic livers and activated hepatic stellate cells (HSCs), LSD1 expression is decreased, SESN2 expression is increased, and autophagy levels are also increased. Overexpression of LSD1 and silencing of SESN2 decreased the level of autophagy and attenuated the activation of HSCs induced by NaAsO2. LSD1 promoted SESN2 gene transcription by increasing H3K4me1/2 in the SESN2 promoter region. 3-methyladenine (3-MA) and chloroquine were used to inhibit autophagy of HSCs, and the degree of activation was also alleviated. Taken together, LSD1 positively regulates SESN2 by increasing H3K4me1/2 enrichment in the SESN2 promoter region, which in turn increases the level of autophagy and promotes the activation of HSCs. Our results may provide new evidence for the importance of LSD1 in the process of autophagy and activation of HSCs induced by arsenic poisoning. Increasing the expression and activity of LSD1 is expected to be an effective way to reverse the autophagy and activation of HSCs induced by arsenic poisoning.

Transcriptomic profile of human iPSC-derived podocyte-like cells exposed to a panel of xenobiotics.

Podocytes play a critical role in the formation and maintenance of the glomerular filtration barrier and injury to these cells can lead to a breakdown of the glomerular barrier causing permanent damage leading to progressive chronic kidney disease. Matured podocytes have little proliferative potential, which makes them critical cells from a health perspective, but also challenging cells to maintain in vitro. Differentiating podocyte-like cells from induced pluripotent stem cells (iPSC) provides a novel and continuous source of cells. Here, we investigated the effect of a 24-h exposure to eight compounds, including the known glomerular toxins doxorubicin and pamidronate, on transcriptomic alterations in iPSC derived podocytes. Doxorubicin (50 nM), pamidronate (50 µM), sodium arsenite (10 µM), and cyclosporine A (15 µM) had a strong impact on the transcriptome, gentamicin (450 µg/ml), lead chloride (15 µM) and valproic acid (500 µM) had a mild impact and busulfan (50 µM) exhibited no impact. Gene alterations and pathways analysis provided mechanistic insight for example, doxorubicin exposure affected the p53 pathway and dedifferentiation, pamidronate activated several pathways including HIF1alpha and sodium arsenite up-regulated oxidative stress and metal responses. The results demonstrate the applicability of iPSC derived podocytes for toxicological and mechanistic investigations.

Effect of topical application of ibuprofen/arginine on the in-office bleaching-induced tooth sensitivity: A randomized, triple-blind controlled trial.

OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.

Short-term effects of sodium arsenite (AsIII) and sodium arsenate (AsV) on carbohydrate metabolism in the perfused rat liver.

The actions of arsenite and arsenate on carbohydrate metabolism in the once-through perfused rat liver were investigated. The compound inhibited lactate gluconeogenesis with an IC50 of 25 µM. It also increased glycolysis and fructolysis at concentrations between 10 and 100 µM. This effect was paralleled by strong inhibition of pyruvate carboxylation (IC50 = 4.25 µM) and by a relatively moderate diminution in the ATP levels. The inhibitory action of arsenate on pyruvate carboxylation and lactate gluconeogenesis was 103 times less effective than that of arsenite. For realistic doses and concentrations («1 mM), impairment of metabolism by arsenate can be expected to occur solely after its reduction to arsenite. Arsenite, on the other hand, can be regarded as a strong short-term modifier of lactate gluconeogenesis and other pathways. The main cause of the former is inhibition of pyruvate carboxylation, a hitherto unknown effect of arsenic compounds.

Unraveling the mechanisms behind sodium persulphate-induced changes in petroleum-contaminated aquifers' biogeochemical parameters and microbial communities.

Sodium persulphate (PS) is a highly effective oxidising agent widely used in groundwater remediation and wastewater treatment. Although numerous studies have examined the impact of PS with respect to the removal efficiency of organic pollutants, the residual effects of PS exposure on the biogeochemical parameters and microbial ecosystems of contaminated aquifers are not well understood. This study investigates the effects of exposure to different concentrations of PS on the biogeochemical parameters of petroleum-contaminated aquifers using microcosm batch experiments. The results demonstrate that PS exposure increases the oxidation-reduction potential (ORP) and electrical conductivity (EC), while decreasing total organic carbon (TOC), dehydrogenase (DE), and polyphenol oxidase (PO) in the aquifer. Three-dimensional excitation-emission matrix (3D-EEM) analysis indicates PS is effective at reducing fulvic acid-like and humic acid-like substances and promoting microbial metabolic activity. In addition, PS exposure reduces the abundance of bacterial community species and the diversity index of evolutionary distance, with a more pronounced effect at high PS concentrations (31.25 mmol/L). Long-term (90 d) PS exposure results in an increase in the abundance of microorganisms with environmental resistance, organic matter degradation, and the ability to promote functional genes related to biological processes such as basal metabolism, transmission of genetic information, and cell motility of microorganisms. Structural equation modeling (SEM) further confirms that ORP and TOC are important drivers of change in the abundance of dominant phyla and functional genes. These results suggest exposure to different concentrations of PS has both direct and indirect effects on the dominant phyla and functional genes by influencing the geochemical parameters and enzymatic activity of the aquifer. This study provides a valuable reference for the application of PS in ecological engineering.

Acesulfame degradation by thermally activated persulfate: Kinetics, transformation products and estimated toxicity.

The existence of the artificial sweetener acesulfame (ACE) in quantities of significance can negatively impact water quality, and its consumption has been associated with deleterious health effects. The present investigation explores the efficacy of heat-activated sodium persulfate (SPS) for eliminating ACE. The complete degradation of 0.50 mg L-1 of ACE was achieved within 45 min under a reaction temperature of 50 °C and 100 mg L-1 of SPS. The impact of thermal decomposition on ACE at a temperature of 60 °C was negligible. This study considers several factors, such as the SPS and ACE loading, the reaction temperature, the initial pH, and the water matrix of the reactor. The results indicate that the method's efficiency is positively correlated with higher initial concentrations of SPS, whereas it is inversely associated with the initial concentration of ACE. Furthermore, higher reaction temperatures and acidic initial pH levels promote the degradation of acesulfame. At the same time, certain constituents of the water matrix, such as humic acid, chlorides, and bicarbonates, can hinder the degradation process. Additionally, the data from LC-QToF-MS analysis of the samples were used to investigate transformation through suspect and non-target screening approaches. Overall, ACE's eight transformation products (TPs) were detected, and a potential ACE decomposition pathway was proposed. The concentration of TPs followed a volcano curve, decreasing in long treatment times. The ecotoxicity of ACE and its identified TPs was predicted using the ECOSAR software. The majority of TPs exhibited not harmful values.

Characterization of the mechanical properties of the cortex region of human hair fibers by multiparametric atomic force microscopy mapping.

We show the benefit of the use of atomic force microscopy (AFM) in spectroscopy force mode (FV: force volume) for evaluation of the cosmetic active effectiveness in improving the mechanical properties of human hair fibers cortex region. For this, we characterized human hair fibers without and with chemical damage caused by bleaching process. Fiber and resin (embedding material) data were obtained simultaneously in the mapping in order to have the resin data as a reference to ensure a coherent comparison between data from the different fiber groups. Our AFM results, which were evaluated using statistical tests, demonstrated the degradation of fibers after bleaching, corroborating the findings of transmission electron microscopy analysis and the effectiveness of a cosmetic active ingredient in improving the Young's modulus (elastic modulus) (E) of the damaged fibers. We also found a radial decrease in the natural logarithm of Young's modulus ln(E) along the cross-section of the active group fiber, which is compatible with confocal Raman spectroscopy analysis by other authors, demonstrating variation of the active permeation with depth. We note that Young's modulus was also determined by a tensile tester (macro-scale technique), in which it was not possible to obtain statistically significant differences between the groups, evidencing the advantage of the FV-AFM analysis. We also found an increase in ln(E) accompanied by a decrease in maximum adhesion force between tip and sample (negative Pearson correlation coefficient). This result can be explained by the fact that structures composed of hydrophobic components have a higher Young's modulus than structures composed of hydrophilic components.

Persulfate activated with calcium peroxide to remediate RAFT soil contaminated with diesel in Arctic northern villages: on-site pilot scale study.

A pilot field study was conducted in a Canadian northern village (NV) to assess the remediation efficiency of sodium persulphate (SPS) alkali activated with calcium peroxide (CP) to degrade diesel from Arctic raft soil. A minimum temperature increase in the subsurface due to overall process reactions was required. The projected context of application was imperative to preserve the integrity of the remaining permafrost. The test was performed with two soil columns of 370 L buried in the ground. The columns were contaminated with 7500 mg diesel/kg representative raft soil that was matured for a period of 11 months. The continuous delivery by gravity and the static presence of the oxidizing solution was made over 33 days. During that period, SPS concentration, pH and temperatures, were monitored. SPS was activated prior to its distribution and activation by-products were confined in a surficial tank and under a sludge form. The maturation period resulted in the important natural attenuation of diesel (47%) that occurred in the shallower horizons of the soil profile. About 35% of the diesel remaining after the maturation period was removed by chemical oxidation during the operation period on site. The temperature increase measured during the SPS activation process was not significant while the temperature increase due to diesel degradation by oxidation in the subsurface was evaluated to be below 3°C. The soil columns were not clogged by the by-products as indicated by hydraulic testing before and after oxidizing treatment.

Hydrogen sulfide regulates arsenic-induced cell death in yeast cells by modulating the antioxidative system.

Arsenic (As) is a metal with potentially toxic effects on different organisms. Hydrogen sulfide (H2S) plays a vital role in mitigating heavy metal toxicity by reducing oxidative stress in plants and animals. However, the role of H2S in alleviating arsenic toxicity in yeast cells remains unclear. In this study, the role of NaHS (exogenous physiological H2S) in alleviating As-induced yeast cell death was investigated. Yeast cells in the logarithmic phase were pretreated with 0.05 mmol/L NaHS for 6 h, and then incubated in the YPD medium with or without 1 mmol/L As. After 12 h of treatment, relative survival rate, H2S content, oxidative stress biomarkers, and antioxidant machinery were measured. Our results showed that sodium arsenite-induced yeast cell death and pretreatment with 0.05 mmol/L NaHS significantly alleviated sodium arsenite-induced cell death. Under sodium arsenite conditions, the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) increased, accompanied by the inhibition of the catalase (CAT) activity and the downregulation of CTT1 expression. However, the activities of the superoxide dismutase (SOD) and glutathion peroxidase (GPX) increased, and the expression of SOD1 and GPX2 was markedly upregulated in the group treated with sodium arsenite. When yeast cells were pretreated with NaHS, the intracellular ROS and MDA levels decreased significantly, and the activities of SOD, CAT, and GPX increased significantly. This was associated with a significant increase in relative survival rate and H2S content compared to the arsenic treatment alone. Our findings indicate that NaHS alleviates sodium arsenite-induced yeast cell death, mainly by enhancing the antioxidant defense system.

Differential Formation of Stress Granules in Radiosensitive and Radioresistant Head and Neck Squamous Cell Carcinoma Cells.

PURPOSE: Stress granules (SGs) are cytoplasmic aggregates in which mRNAs and specific proteins are trapped in response to a variety of damaging agents. They participate in the cellular defense mechanisms. Currently, their mechanism of formation in response to ionizing radiation and their role in tumor-cell radiosensitivity remain elusive. METHODS AND MATERIALS: The kinetics of SG formation was investigated after the delivery of photon irradiation at different doses to head and neck squamous cell carcinoma cell lines with different radiosensitivities and the HeLa cervical cancer cell line (used as reference). In parallel, the response to a canonical inducer of SGs, sodium arsenite, was also studied. Immunolabeling of SG-specific proteins and mRNA fluorescence in situ hybridization enabled SG detection and quantification. Furthermore, a ribopuromycylation assay was used to assess the cell translational status. To determine whether reactive oxygen species were involved in SG formation, their scavenging or production was induced by pharmacologic pretreatment in both SCC61 and SQ20B cells. RESULTS: Photon irradiation at different doses led to the formation of cytoplasmic foci that were positive for different SG markers. The presence of SGs gradually increased from 30 minutes to 2 hours postexposure in HeLa, SCC61, and Cal60 radiosensitive cells. In turn, the SQ20B and FaDu radioresistant cells did not form SGs. These results indicated a correlation between sensitivity to photon irradiation and SG formation. Moreover, SG formation was significantly reduced by reactive oxygen species scavenging using dimethyl sulfoxide in SCC61 cells, which supported their role in SG formation. However, a reciprocal experiment in SQ20B cells that depleted glutathione using buthionine sulfoximide did not restore SG formation in these cells. CONCLUSIONS: SGs are formed in response to irradiation in radiosensitive, but not in radioresistant, head and neck squamous cell carcinoma cells. Interestingly, compared with sodium arsenite-induced SGs, photon-induced SGs exhibited a different morphology and cellular localization. Moreover, photon-induced SGs were not associated with the inhibition of translation; rather, they depended on oxidative stress.

Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation.

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3 mg/kg/day/rat); group III (sodium arsenite + L-AA (200 mg/kg/day/rat) and α-T (400 mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30 days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein-carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kß, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

Arsenic-induced IGF-1 signaling impairment and neurite shortening: The protective roles of IGF-1 through the PI3K/Akt axis.

We recently reported that arsenic caused insulin resistance in differentiated human neuroblastoma SH-SY5Y cells. Herein, we further investigated the effects of sodium arsenite on IGF-1 signaling, which shares downstream signaling with insulin. A time-course experiment revealed that sodium arsenite began to decrease IGF-1-stimulated Akt phosphorylation on Day 3 after treatment, indicating that prolonged sodium arsenite treatment disrupted the neuronal IGF-1 response. Additionally, sodium arsenite decreased IGF-1-stimulated tyrosine phosphorylation of the IGF-1 receptor ß (IGF-1Rß) and its downstream target, insulin receptor substrate 1 (IRS1). These results suggested that sodium arsenite impaired the intrinsic tyrosine kinase activity of IGF-1Rß, ultimately resulting in a reduction in tyrosine-phosphorylated IRS1. Sodium arsenite also reduced IGF-1 stimulated tyrosine phosphorylation of insulin receptor ß (IRß), indicating the potential inhibition of IGF-1R/IR crosstalk by sodium arsenite. Interestingly, sodium arsenite also induced neurite shortening at the same concentrations that caused IGF-1 signaling impairment. A 24-h IGF-1 treatment partially rescued neurite shortening caused by sodium arsenite. Moreover, the reduction in Akt phosphorylation by sodium arsenite was attenuated by IGF-1. Inhibition of PI3K/Akt by LY294002 diminished the protective effects of IGF-1 against sodium arsenite-induced neurite retraction. Together, our findings suggested that sodium arsenite-impaired IGF-1 signaling, leading to neurite shortening through IGF-1/PI3K/Akt.

A regulatory module comprising G3BP1-FBXL5-IRP2 axis determines sodium arsenite-induced ferroptosis.

Arsenic contamination is extremely threatening to the global public health. It was reported that sodium arsenite exposure induces serious kidney injury. However, the underlying mechanism is unclear. Ferroptosis is a newly characterized form of iron-dependent programmed cell death, which is implicated in the pathogenesis of various human diseases, including kidney injury. The lethal accumulation of iron-catalyzed lipid peroxidation is the fundamental biochemical characteristic of ferroptosis. Herein we report that sodium arsenite exposure initiates ferroptosis in mammalian HEK293, MEF and HT1080 cells, and induces ferroptosis-associated acute kidney injury in mice. RNA-binding protein G3BP1, the switch component of stress granules, is indispensable for sodium arsenite-induced ferroptosis in a stress granule-independent manner. Mechanistically, G3BP1 stabilizes IRP2, the master regulator of cellular iron homeostasis, through binding to and suppressing the translation of FBXL5 mRNA, which encodes the E3 ligase component to mediate IRP2 ubiquitination and proteasomal degradation. Sodium arsenite intoxication expedites this G3BP1-FBXL5-IRP2 axis and elevates cellular labile free iron, which is responsible for sodium arsenite exposure-induced lipid peroxidation and ferroptotic cell death. In summary, this study highlights a regulatory module comprising G3BP1-FBXL5-IRP2 axis in determining sodium arsenite-induced ferroptosis and ferroptosis-associated acute kidney injury in mice.

Characterization of Olive Oil Volatile Compounds after Elution through Selected Bleaching Materials-Gas Chromatography-Mass Spectrometry Analysis.

Using different bleaching materials to eliminate or reduce organic volatiles in deteriorated olive oils will positively affect its characteristics. This study aims to identify the volatiles of oxidized olive oil after physical bleaching using selected immobilized adsorbents. Oxidized olive oil was eluted using open-column chromatography packed with silica gel, bentonite, resin, Arabic gum, and charcoal at a 1:5 eluent system (w/v, adsorbent: oxidized olive oil). The smoke point was determined. The collected distilled vapor was injected into GC-MS to identify the volatiles eluted after partial refining with each of these bleaching compounds. The results showed that volatile compounds were quantitatively and qualitatively affected by the type of adsorbents used for the elution of olive oil and the smoking points of eluted oils. The most prominent detected volatile compounds were limonene (14.53%), piperitone (10.35%), isopropyl-5-methyl-(2E)-hexenal (8.6%), methyl octadecenoate (6.57%), and citronellyl acetate (5.87%). Both bentonite and resin were superior in decreasing the ratio of volatile compounds compared with other bleaching materials used. Resin immobilized medium was significantly affected (p < 0.05), raising the smoke point. These results highlighted some information regarding the characteristics of volatile compounds that result after the physical elution of olive oil through selected adsorbents.

Divergent recovery trajectories of intertidal and subtidal coral communities highlight habitat-specific recovery dynamics following bleaching in an extreme macrotidal reef environment.

Coral reefs face an uncertain future punctuated by recurring climate-induced disturbances. Understanding how reefs can recover from and reassemble after mass bleaching events is therefore important to predict their responses and persistence in a rapidly changing ocean. On naturally extreme reefs characterized by strong daily temperature variability, coral heat tolerance can vary significantly over small spatial gradients but it remains poorly understood how this impacts bleaching resilience and recovery dynamics, despite their importance as resilience hotspots and potential refugia. In the macrotidal Kimberley region in NW Australia, the 2016 global mass bleaching event had a strong habitat-specific impact on intertidal and subtidal coral communities at our study site: corals in the thermally variable intertidal bleached less severely and recovered within six months, while 68% of corals in the moderately variable subtidal died. We therefore conducted benthic surveys 3.5 years after the bleaching event to determine potential changes in benthic cover and coral community composition. In the subtidal, we documented substantial increases in algal cover and live coral cover had not fully recovered to pre-bleaching levels. Furthermore, the subtidal coral community shifted from being dominated by branching Acropora corals with a competitive life history strategy to opportunistic, weedy Pocillopora corals which likely has implications for the functioning and stress resilience of this novel coral community. In contrast, no shifts in algal and live coral cover or coral community composition occurred in the intertidal. These findings demonstrate that differences in coral heat tolerance across small spatial scales can have large consequences for bleaching resilience and that spatial patchiness in recovery trajectories and community reassembly after bleaching might be a common feature on thermally variable reefs. Our findings further confirm that reefs adapted to high daily temperature variability play a key role as resilience hotspots under current climate conditions, but their ability to do so may be limited under intensifying ocean warming.