Inhibition Of Catalase Activity Research Articles

Indole N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions.

Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.

Metabolic variation and oxidative stress responses of clams (Ruditapes philippinarum) perturbed by ofloxacin exposure

Ofloxacin (OFL), one of the most widely used fluoroquinolone antibiotics, has been frequently detected in marine environments. Nonetheless, researchers are yet to focus on the effects of OFL on the benthos. In the present study, marine clams (Ruditapes philippinarum) were exposed to OFL (0.5, 50, and 500 μg/L) for 14 d, followed by a 7 d depuration period. The accumulation of OFL, antioxidative defense responses, neurotoxicity, burrowing behavior, and metabolomic changes in clams were evaluated. The results indicated that OFL could accumulate in clams, albeit with a low bioaccumulation capacity. The intermediate (50 μg/L) and high (500 μg/L) levels of OFL induced significant antioxidative responses in the gills and digestive glands of clams, mainly manifesting as the inhibition of catalase activities and the induction of superoxide dismutase and glutathione S-transferase activities, which ultimately elevated the content of malondialdehyde, causing oxidative damage. Furthermore, the significant induction of acetylcholinesterase activities was observed, coinciding with a significant increase in burrowing rates of clams. The high level of OFL affected glycerophospholipid, arachidonic acid, steroid hormone biosynthesis, unsaturated fatty acids biosynthesis, and glycolysis/glycogenesis metabolism. In conclusion, this study has contributed to the understanding of the physiological and biochemical effects and molecular toxicity mechanisms of OFL to marine bivalves.

Differential response of catalase to As (III) and As (V): Potential molecular mechanism under valence effect

Arsenic (As) is the most prolific contaminant in food, triggering arseniasis primarily via contaminated rice and drinking contaminated water. However, toxicological data for arsenite (As (III)) and arsenate (As (V)) on antioxidant enzyme catalase (CAT) at molecular level is shortage. The interaction mechanism of As (III) and As (V) with CAT was investigated using enzyme activity detection, multi–spectroscopic techniques, isothermal titration calorimetry and computational simulations. Results indicated As (III) and As (V) induced protein skeleton relaxation, secondary structure transformation, fluorescence sensitization and particle alteration of CAT, particularly As (III). Moreover, As (III)/As (V) bound to CAT through hydrogen bonding and hydrophobic. As (III) and As (V) contacted with core residues His 74, Asn 147 and His A74, Trp A357, respectively, thereby inhibiting CAT activity. Overall, As (III) is more aggressive against the structure and physiological function of CAT than As (V). Our findings enhance the understanding of health risk related to dietary As exposure.

H2S-Powered Nanomotors for Active Therapy of Tumors by Inducing Ferroptosis and Lactate-Pyruvate Axis Disorders.

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.

Comparative analysis of antioxidant enzyme activity and defence responses in root‐knot nematode resistant and susceptible carrot cultivars

AbstractRoot‐knot nematodes (RKNs) are one of the most serious pests of carrot plants. Resistance cultivars are a cost‐effective and ecofriendly management strategy for nematodes. To develop these, it is essential to understand the genetic, molecular and biochemical aspects underpinning RKN infection. Here, Meloidogyne javanica penetration and development, defence reactions and antioxidant enzyme activity were investigated in a resistant carrot cultivar (TN‐99‐129) compared to the susceptible cultivar TN‐99‐62. No significant difference was found in the number of J2s penetrating the roots of both cultivars. At 2 days post‐inoculation (DPI), necrosis symptoms were observed around the head of penetrated nematodes. Cell death also increased in the roots of the nematode‐infected TN‐99‐129 cultivar. Callose deposition happened at 6 DPI, and lignin content increased with delay (21 DPI) in the inoculated resistant cultivar. In addition, the reactive oxygen species metabolism process in resistant and susceptible cultivars was significantly different. In TN‐99‐129, catalase activity inhibition was observed at the early (2 DPI) phases of infection, and increasing superoxide dismutase activity and a relative decrease in catalase activity during nematode development. The activity of guaiacol peroxidase also increased significantly in the resistant cultivar, but no significant difference was observed in the activity of ascorbate peroxidase. This study explains the process of defence reactions in the TN‐99‐129 carrot cultivar during RKN penetration and development. The exhaustive characterization of the defence mechanism of a novel source of resistance to RKN in carrots constitutes a significant step toward their use in crop breeding.

An ultra-sensitive photoelectrochemical biosensing platform based on the AgVO3/BiOI heterojunction for an enzyme activity inhibition reaction.

An ultra-sensitive photoelectrochemical sensing platform for profenofos detection based on the inhibition of catalase activity was prepared in this work. First, the novel functional nanocomposite material AgVO3/BiOI was prepared by a hot solvent method and successive ion layer adsorption reaction. Then, chitosan was employed as a dispersion medium to disperse and immobilize the catalase. Under visible light irradiation, the prepared CAT/CS/AgVO3/BiOI/ITO nanocomposite electrode generates a stable low photocurrent in hydrogen peroxide solution. When this electrode is immersed in a phosphate buffer solution containing profenofos, the activity of the catalase is inhibited, resulting in an increase in the photocurrent. Under the optimized experimental conditions, the profenofos concentration and increase in photocurrent are linearly related in the concentration range of 1 × 10-10 to 5.0 × 10-8 mol L-1, and the limit of detection is 1.0 × 10-11 mol L-1. This biosensor shows good selectivity for detecting profenofos in fruits and vegetables, and the determination results of profenofos are satisfactory.

Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity

Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.

The Effects of 1,4-Naphthoquinone (NQ) and Naphthazarin (5,8-Dihydroxy-1,4-naphthoquinone, DHNQ) Individually and in Combination on Growth and Oxidative Stress in Maize (Zea mays L.) Seedlings.

This study investigated the effects of 1,4-naphthoquinone (NQ) and naphthazarin (5,8-dihydroxy-1,4-naphthoquinone, DHNQ) individually and in combination, applied at low concentrations (0.1, 1, and 10 nM), on growth, hydrogen peroxide (H2O2) production, catalase activity, and lipid peroxidation in maize seedlings. It was found that NQ at 0.1 and 1 nM and DHNQ at 0.1 nM significantly stimulated the fresh weight of the aboveground parts of the seedlings (APS), while the fresh weight of the underground parts of the seedlings (UPS) was enhanced only at 0.1 nM NQ. Interestingly, DHNQ at higher concentrations (1 and 10 nM) significantly diminished the fresh weight of the APS and UPS. When NQ and DHNQ were applied together, an increase in the fresh weight of the APS at all of the concentrations studied was observed. It was also found that NQ and DHNQ individually and in combination, at all concentrations studied, decreased the H2O2 production in the aboveground and underground parts of maize seedlings. The presence of the DHNQ at higher concentrations (1 and 10 nM) triggered an increase in the catalase (CAT) activity of the UPS and APS compared to the control. However, NQ added at 1 nM decreased the CAT activity of both the UPS and APS, while 10 nM increased the CAT activity of UPS. NQ and DHNQ applied together at 0.1 and 10 nM almost completely inhibited catalase activity in the UPS and APS. The data that were obtained for lipid peroxidation, measured as the malondialdehyde (MDA) concentration, indicated that NQ and DHNQ at all concentrations studied decreased the MDA content of the UPS, while both naphthoquinones increased it in APS. The data presented here are discussed taking into account the mechanisms via which naphthoquinones interact with biological systems.

Activated charcoal alleviates fluoride stress by restricting fluoride uptake and counteracting oxidative damages in the rice cultivar MTU1010

This work was aimed to explore the efficacy of activated charcoal (5 mg g-1 soil) in abating fluoride (25 mg L-1 NaF) stress in rice seedlings, since the protective role of charcoal is widely reported against other forms of abiotic stress. Application of NaF solution reduced germination rate, dry and fresh weight, and shoot and root length of seedlings. Extensive fluoride accumulation lowered the chlorophyll level along with higher electrolyte leakage and formation of H2 O2 , malondialdehyde, and methylglyoxal. Administration of activated charcoal lowered the extent of oxidative damages by inhibiting the uptake of fluoride ions. Exogenous application of activated charcoal also restored the activity of Kreb's cycle enzymes, i.e. PDH, IDH, MDH, and SDH, thereby overcoming the burden of carbon utilization and energy depletion occurring during stress. Additionally, the osmolyte (soluble sugar, proline, glycine-betaine, and amino acid) level was further escalated in presence of activated charcoal. The inhibition in catalase activity in fluoride-stressed seedlings was also restored. The activity of a range of enzymatic antioxidants (guaiacol peroxidase, superoxide dismutase, and ascorbate peroxidase) along with the glyoxalase system associated-enzymes (glyoxalase I and II) was further triggered in stressed seedlings treated with activated charcoal. The enhanced level of carotenoids, ascorbic acid, and total phenolics also enabled efficient scavenging of reactive oxygen species, thereby reducing cellular necrosis in the leaves. Based on the current investigation, it can be concluded that activated charcoal application appears a promising strategy to improve growth and mitigate damages in rice plants, growing in fluoride-polluted soil.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

ВЛИЯНИЕ НЕФТЯНЫХ УГЛЕВОДОРОДОВ НА БИОХИМИЧЕСКИЕ ПОКАЗАТЕЛИ ЧЕРНОМОРСКОЙ МИДИИ MYTILUS GALLOPROVINCIALIS

Almost all oil components are more or less toxic and have a toxic effect on aquatic organisms, and some groups of petroleum hydrocarbons (PH) can accumulate in organs and tissues and transmitted through food chains. Depending on the duration and scale of PH pollution, a wide range of responses can be observed – from physiological and biochemical, morphological, behavioral anomalies at organism level to structural and functional rearrangements in populations and communities. The study of the biochemical response in tissues of bivalve mollusks living in conditions of elevated PH concentrations in the experiment is necessary to understand the mechanisms of metabolism reorganization and adaptive reactions that occur in the body of hydrobionts when exposed to toxicants. The paper presents the results of a study of the PH effect on the parameters of the prooxidant-antioxidant system parameters (superoxide dismutase and catalase activities, level of lipid peroxidation and oxidized proteins) and amnotransferase activities (alanine aminotransferase and aspartate aminotransferase) in hepatopancreas of the Black Sea mussel Mytilus galloprovincialis in the acute toxicological experiment. The results of the experiment allowed to establish that PH at concentrations of 0.5 mg/l (10 MPC) and 1 mg/l (20 MPC) do not affect the activity of aminotransferases, but stimulate the development of oxidative stress by shifting the prooxidant-antioxidant balance towards the intensification of lipid peroxidation and protein oxidization; at the 1 mg/l concentration PH cause activation of superoxide dismutase and inhibition of catalase activity. Prooxidant-antioxidant system parameters demonstrate high sensitivity to PH and can be used along with other recommended parameters to assess the functional state of mollusks in conditions of oil environmental pollution.

Alpha-momorcharin preserves catalase activity to inhibit viral infection by disrupting the 2b-CAT interaction in Solanum lycopersicum.

Many host factors of plants are used by viruses to facilitate viral infection. However, little is known about how alpha-momorcharin (αMMC) counters virus-mediated attack strategies in tomato. Our present research revealed that the 2b protein of cucumber mosaic virus (CMV) directly interacted with catalases (CATs) and inhibited their activities. Further analysis revealed that transcription levels of catalase were induced by CMV infection and that virus accumulation increased in CAT-silenced or 2b-overexpressing tomato plants compared with that in control plants, suggesting that the interaction between 2b and catalase facilitated the accumulation of CMV in hosts. However, both CMV accumulation and viral symptoms were reduced in αMMC transgenic tomato plants, indicating that αMMC engaged in an antiviral role in the plant response to CMV infection. Molecular experimental analysis demonstrated that αMMC interfered with the interactions between catalases and 2b in a competitive manner, with the expression of αMMC inhibited by CMV infection. We further demonstrated that the inhibition of catalase activity by 2b was weakened by αMMC. Accordingly, αMMC transgenic plants exhibited a greater ability to maintain redox homeostasis than wild-type plants when infected with CMV. Altogether, these results reveal that αMMC retains catalase activity to inhibit CMV infection by subverting the interaction between 2b and catalase in tomato.

Hypochlorous acid produced at the counter electrode inhibits catalase and increases bactericidal activity of a hydrogen peroxide generating electrochemical bandage

Previously, an electrochemical bandage (e-bandage) that uses a three-electrode system to produce hydrogen peroxide (H2O2) electrochemically on its working electrode was developed as a potential strategy for treating biofilms; it showed activity in reducing biofilms in an agar biofilm model. Xanthan gum-based hydrogel, including NaCl, was used as the electrolyte. While H2O2 generated at the working electrode in the vicinity of a biofilm is a main mechanism of activity, the role of the counter electrode was not explored. The goal of this research was to characterize electrochemical reactions occurring on the counter electrode of the e–bandage. Counter electrode potential varied between 1.2 and 1.5 VAg/AgCl; ∼125 µM hypochlorous acid (HOCl) was generated within 24 h in the e-bandage system. When HOCl was not produced on the counter electrode (achieved by removing NaCl from the hydrogel), reduction of Acinetobacter baumannii BAA-1605 biofilm was 1.08 ± 0.38 log10 CFU/cm2 after 24 h treatment, whereas when HOCl was produced, reduction was 3.87 ± 1.44 log10 CFU/cm2. HOCl inhibited catalase activity, abrogating H2O2 decomposition. In addition to H2O2 generation, the previously described H2O2-generating e-bandage generates HOCl on the counter electrode, enhancing its biocidal activity.

Salicylic acid enhances the resistance of Neoporphyra haitanensis to pathogen Vibrio mediterranei 117-T6

The economically important seaweed Porphyra are often infected by various diseases during sea farming. As one of the most important phytohormones in disease resistance, the protective effect of salicylic acid (SA) on Neoporphyra haitanensis during Vibrio mediterranei 117-T6 infection was investigated by biochemical methods and transcriptomic profile analysis. The addition of exogenous SA at a moderate concentration alleviated disease caused by the pathogenic bacteria. SA enhanced the photosynthetic activity of thalli by upregulating genes of the photosynthetic system along with genes associated with carbon fixation. A moderate release of H2O2 stimulated by SA was observed, which may be due to the upregulation of the photorespiratory C2 cycle and the inhibition of catalase activity. SA treatment enhanced the activity and transcription of antioxidant enzymes in the glutathione-ascorbate (GSH-AsA) cycle involved in balancing the redox system. In addition, the levels of multiple carotenoids were increased in N. haitanensis thalli, and genes involved in their synthesis were upregulated. The results suggest that exogenous SA may enhance the defense of N. haitanensis against pathogen attack by the release of H2O2. However, to avoid oxidative stress, alga can establish redox balance by activating the GSH-AsA cycle and by regulating the generation of carotenoids. In summary, this study indicates that N. haitanensis may have evolved mechanisms to respond to SA stimulation and protect against invading pathogens. Our research can provide valuable information for the farming of healthy N. haitanensis.

Catalase Inhibition by Aminoalkanol Derivatives with Potential Anti-Cancer Activity-In Vitro and In Silico Studies Using Capillary Electrophoresis Method.

In this work, the investigation of type and inhibitory strength of catalase by two pairs of aminoalkanol derivatives (1,7 diEthyl- and 1,7-diMethyl-8,9-diphenyl-4-azatricyclo (5.2.1.02.6) dec-8-ene- 3,5,10-trione) has been presented. The obtained results allowed for the determination of all kinetic parameters (Km, Vmax, slope angles of Lineweaver–Burk plots, Ki and IC50) on the basis of which it was shown that all four aminoalkanol derivatives are competitive inhibitors of catalase. However, the strength of action of each of them depends on the type of substituents present in the main structure of the molecule. Subtle differences in the potency of individual derivatives were possible to detect thanks to the developed, sensitive method of capillary electrophoresis, which allowed simultaneous monitoring of the mutual changes in the concentrations of substrates and products of the reaction catalyzed by the enzyme. Detailed values of kinetic parameters showed that all derivatives are weak inhibitors of catalase, which in this case is a big advantage because each inhibition of catalase activity is associated with a greater amount of accumulated, harmful reactive oxygen species. The results of docking studies also show the convergence of the binding energies values of individual inhibitors with all kinetic parameters of the investigated catalase inhibition and thus additionally confirm the weak inhibitory strength of all four aminoalkanol derivatives.

Synergizing effects of chemodynamic therapy and chemotherapy against breast cancer by oxaliplatin-loaded polydopamine/BSA@copper ferrite

Chemodynamic therapy (CDT) is defined as the generation of abundant ROS inside tumor tissue by a Fenton reaction-based nanocatalyst, which is characterized by high selectivity and few side effects. However, the rate of ROS generation by Fenton reaction is limited due to a scarcity of Fenton-based catalysts within cells and a high level of intracellular antioxidant agents. In this study, a heterogeneous Fenton nanocatalyst, copper ferrite nanoparticles (CuFe2O4), was synthesized and it was accompanied by oxaliplatin (Oxa), a ROS-producing chemotherapeutic drug. CuFe2O4 was synthesized through the hydrothermal method and bovine serum albumin was used as a biological capping agent. The nanoparticles possessed a high surface area and mesoporous structure with an extremely small particle size of about 6.1 nm. Nanoparticles had a high capacity for oxaliplatin (3.4 mg g−1) and were then modified in situ by polydopamine (PDA) via alkaline-triggered polymerization, resulting in a pH-sensitive drug delivery system. The final construct (CuFe2O4.Oxa@PDA) showed pH-responsive drug release in a time-staggered manner. In vitro studies disclosed that CuFe2O4.Oxa@PDA nanoparticles were internalized by breast cancer cells (4T1), inhibiting tumor cell growth more effectively than free oxaliplatin. Furthermore, less cytotoxicity was observed against normal cells (NIH3T3), indicating that the construct's cytotoxic effects are directed solely at tumor cells. Furthermore, CuFe2O4.Oxa@PDA effectively catalyzed the Fenton reaction inside tumor cells, allowing it to amplify intracellular oxidative stress by lowering intracellular GSH levels and inhibiting catalase activity. Based on these findings, CuFe2O4.Oxa@PDA could be used as an adjuvant nanoparticle along with oxaliplatin-based cancer chemotherapy, significantly reinforcing intratumoral oxidative stress and promoting the clinical efficacy of oxaliplatin.

FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell

BackgroundAlthough FOXO3a can inhibit the cell proliferation of prostate cancer, its relationship with reactive oxygen species (ROS) in prostate cancer (PCa) has not been reported.MethodsWe analyzed the correlation between the expression of FOXO3a and the antioxidant enzyme catalase in prostate cancer with the TCGA and GEPIA databases. We also constructed a PPI network of FOXO3a via the STRING database. The mRNA and protein expression of FOXO3a and catalase were detected by qRT-PCR or western blotting in LNCaP and 22RV1 cells treated with DHT, R1881, or Enzalutamide. The effects of FOXO3a on catalase expression were tested by over-expressing or knocking down FOXO3a in LNCaP cells. Furthermore, the catalase activity and ROS level were detected in LNCaP cells treated with DHT. Cell proliferation and ROS were also analyzed in LNCaP which was treated with antioxidant.ResultsResults showed that the catalase expression was down-regulated in prostate cancer. A positive correlation between FOXO3a and catalase existed. DHT treatment could significantly reduce FOXO3a and catalase expression at mRNA and protein level in LNCaP cells. Catalase expression partly depended on FOXO3a as over-expression and knockdown of FOXO3a could result in the expresssion change of catalase. DHT treatment was found to inhibit catalase activity and increase ROS level in prostate cancer cell. Our study also demonstrated that antioxidant treatment reduced DHT-induced proliferation and ROS production in prostate cancer cell.ConclusionsWe discovered a novel mechanism by which DHT promotes prostate cancer cell proliferation via suppressing catalase activity and activating ROS signaling via a FOXO3a dependent manner.

Effects of chronic dietary hexavalent chromium on bioaccumulation and immune responses in the sea cucumber Apostichopus japonicus

Sea cucumbers Apostichopus japonicus (3.54 ± 0.01 g of wet weight) were exposed to five concentrations of dietary hexavalent chromium (Cr6+) [0 (control), 100, 200, 400, and 800 mg Cr6+/kg dry weight] amended with K2Cr2O7 for 30 days. The bioaccumulation and immune responses [antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT); hydrolytic enzymes: acid phosphatase (ACP) and alkaline phosphatase (AKP)] of sea cucumbers were subsequently evaluated. This study found that the order of Cr accumulation in the experimental tissues was respiratory tree > intestine > body wall. Significantly lower SOD activities occurred in the 400 mg/kg group compared to that in the control group. Higher dietary Cr6+ exposure (400 and 800 mg Cr6+/kg dry weight) did not negatively alter the CAT activities, but significantly inhibited CAT activities in 100 mg/kg group, compared to control group. ACP activities in groups 200, 400 and 800 mg/kg were significantly lower than those in control group, while no significant differences occurred in AKP activities among groups. The present study provides important information into the bioaccumulation and immune responses of the sea cucumber A. japonicus in response to chronic dietary Cr6+ exposure.

Влияние пирогенного воздействия на биологическую активность чернозема обыкновенного в модельных экспериментах

The influence of the pyrogenic effect on the biological properties of Haplic chernozem was investigated. For this, a series of model experiments was set up to simulate fires of various duration and intensity. A significant change in the biological properties of soils was found, as well as differences in the reactions of biological indicators to the pyrogenic effect. In different experiments, a different nature of changes in the reaction of the soil environment and the content of organic carbon, an increase in the content of readily soluble salts, was established. In all experiments, inhibition of catalase activity was noted, changes in peroxidase activity were more contradictory. In one of the experiments, stimulation of peroxidase activity was found. In order to study the methods of restoring the biological activity of post-pyrogenic soils, a model experiment was carried out using potassium humate, complex mineral fertilizer and phytoremediation. At the same time, no unambiguous results were obtained that would make it possible to recommend methods for the accelerated recovery of post-pyrogenic soils. Keywords: BIODIAGNOSTICS, FIRES, POSTPYROGENIC SOILS, ENZYME ACTIVITY, SOIL RESTORATION

Arjunetin as a promising drug candidate against SARS-CoV-2: molecular dynamics simulation studies

Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma