Decrease In Reactive Oxygen Species Research Articles

Nanoparticle-based amelioration of drought stress and cadmium toxicity in rice via triggering the stress responsive genetic mechanisms and nutrient acquisition

Cadmium and drought are the most destructive of the abiotic stresses with negative consequences in terms of impaired metabolism, restricted nutrient use efficiency and disruptive photosynthesis of plants. The present study investigated the mitigation strategy of both aforementioned stresses by the application of iron oxide (IONPs) and hydrogel nanoparticles (HGNPs) simultaneously probably for the first time. IONPs were biofabricated by using a locally identified Bacillus strain RNT1, while HGNPs were produced chemically followed by the confirmation and characterization of both NPs through nanomaterials characterization techniques. Results of FTIR and XRD showed the capping of NPs by different functional groups together with their crystalline structure, respectively. SEM and TEM analysis showed the spherical shape along with the particle size ranging from 18 to 94 nm of both NPs, while EDS analysis confirmed the elemental purity of NPs. The results revealed that IONPs-treated rice plants increased biomass, antioxidant enzyme contents, photosynthesis efficiency, nutrient acquisition together with the decrease in reactive oxygen species and acropetal Cd translocation under normal and drought stress conditions as compared with control plants. Furthermore, the expression of the Cd transporter genes, OsHMA2, OsHMA3 and OsLCT1 were curtailed in NPs-treated rice plants under normal and drought stress conditions. The overall significance of the study lies in devising the NPs-based solutions of increasing heavy metal pollution and water availability challenges being faced the farmers around the world.

Vina-Ginsenoside R4 from Panax ginseng Leaves Alleviates 6-OHDA-Induced Neurotoxicity in PC12 Cells Via the PI3K/Akt/GSK-3β Signaling Pathway.

Vina-ginsenoside R4 (VGN4) is the first example of protopanaxatriol saponin possessing sugar chains located at C-3 and C-20 of aglycone. However, to the best of our knowledge, no report has been published on the neuroprotective effect of VGN4. In the present work, we investigated the neuroprotective effect of VGN4 against 6-hydroxydopamine (6-OHDA)-induced toxicity and its potential mechanism. Pretreatment of PC12 cells with VGN4 attenuated 6-OHDA-induced cell damage and cell apoptosis, which was correlated with the decrease of reactive oxygen species and the increase of antioxidant enzyme activities including superoxide dismutase and catalase. In addition, VGN4 markedly decreased nuclear translation of the nuclear factor-κB and PI3K/Akt/GSK/3β signaling pathway including p85, PDK1, Akt, and GSK-3β. Further studies revealed that PI3K siRNA attenuated the neuroprotective effect of VGN4 on caspase-3 activity. These data indicate that VGN4 might have the potential to be developed as a new neuroprotective functional food.

Peroxiredoxin2 (Prdx2) Reduces Oxidative Stress and Apoptosis of Myocardial Cells Induced by Acute Myocardial Infarction by Inhibiting the TLR4/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

BackgroundPeroxiredoxin2 (Prdx2) is an endogenous peroxidase and has been found to reduce the oxidative burden in cells and thereby reduce cell damage and apoptosis. Therefore, the purpose of this study was to investigate the effect of Prdx2 on the oxidative level and apoptosis of myocardial cells after acute myocardial infarction (AMI).Material/MethodsWe constructed an AMI model for Sprague-Dawley rats by ligating the left anterior descending coronary artery. We determined the effect of Prdx2 on AMI by detecting changes in Prdx2 in myocardial tissue via western blot and qRT-PCR. In addition, we used recombinant Prdx2 protein to treat rats and detect changes in oxidative stress and apoptosis in rat myocardial tissue to verify the protective effect of Prdx2 on the rat heart.ResultsThe protein and mRNA expression of Prdx2 in myocardial tissue of rats in the AMI group was significantly lower than that in the control group. The oxidative and apoptotic levels of myocardial tissue in Prdx2-administered rats were significantly improved compared to the non-administered group, which was manifested by a decrease in reactive oxygen species (ROS) levels and a decrease in the expression of the caspase family. In addition, Prdx2 also inhibited p65 phosphorylation in myocardial tissues and inhibited TLR4/NF-κB signaling pathway activity.ConclusionsThe expression of Prdx2 was decreased in myocardial tissue after AMI. Prdx2 can reduce apoptosis and ROS caused by AMI by inhibiting the TLR4/NF-κB signaling pathway, thereby reducing myocardial injury caused by AMI.

Natural Feed Additives Modulate Immunity and Mitigate Infection with Sphaerospora molnari (Myxozoa:Cnidaria) in Common Carp: A Pilot Study.

Myxozoans are a diverse group of cnidarian parasites, including important pathogens in different aquaculture species, without effective legalized treatments for fish destined for human consumption. We tested the effect of natural feed additives on immune parameters of common carp and in the course of a controlled laboratory infection with the myxozoan Sphaerospora molnari. Carp were fed a base diet enriched with 0.5% curcumin or 0.12% of a multi-strain yeast fraction, before intraperitoneal injection with blood stages of S. molnari. We demonstrate the impact of these treatments on respiratory burst, phagocytosis, nitric oxide production, adaptive IgM+ B cell responses, S. molnari-specific antibody titers, and on parasite numbers. Both experimental diets enriched B cell populations prior to infection and postponed initial parasite proliferation in the blood. Curcumin-fed fish showed a decrease in reactive oxygen species, nitric oxide production and B cell density at late-stage infection, likely due to its anti-inflammatory properties, favoring parasite propagation. In contrast, multi-strain yeast fraction (MsYF)-fed fish harbored the highest S. molnari-specific antibody titer, in combination with the overall lowest parasite numbers. The results demonstrate that yeast products can be highly beneficial for the outcome of myxozoan infections and could be used as effective feed additives in aquaculture.

Increased telomerase improves motor function and alpha-synuclein pathology in a transgenic mouse model of Parkinson's disease associated with enhanced autophagy.

Protective effects of the telomerase protein TERT have been shown in neurons and brain. We previously demonstrated that TERT protein can accumulate in mitochondria of Alzheimer's disease (AD) brains and protect from pathological tau in primary mouse neurons. This prompted us to employ telomerase activators in order to boost telomerase expression in a mouse model of Parkinson's disease (PD) overexpressing human wild type α-synuclein. Our aim was to test whether increased Tert expression levels were able to ameliorate PD symptoms and to activate protein degradation. We found increased Tert expression in brain for both activators which correlated with a substantial improvement of motor functions such as gait and motor coordination while telomere length in the analysed region was not changed. Interestingly, only one activator (TA-65) resulted in a decrease of reactive oxygen species from brain mitochondria. Importantly, we demonstrate that total, phosphorylated and aggregated α-synuclein were significantly decreased in the hippocampus and neocortex of activator-treated mice corresponding to enhanced markers of autophagy suggesting an improved degradation of toxic alpha-synuclein. We conclude that increased Tert expression caused by telomerase activators is associated with decreased α-synuclein protein levels either by activating autophagy or by preventing or delaying impairment of degradation mechanisms during disease progression. This encouraging preclinical data could be translated into novel therapeutic options for neurodegenerative disorders such as PD.

EGFR-rich extracellular vesicles derived from highly metastatic nasopharyngeal carcinoma cells accelerate tumour metastasis through PI3K/AKT pathway-suppressed ROS.

Nasopharyngeal carcinoma (NPC) is the most common cancer with high metastatic potential that occurs in the epithelial cells of the nasopharynx. Distant metastases are the primary cause for treatment failure and mortality of NPC patients. However, the underlying mechanism responsible for the initiation of tumour cell dissemination and tumour metastasis in NPC is not well understood. Here, we demonstrated that epidermal growth factor receptor (EGFR) was highly expressed in tumour tissues of NPC patients with distant metastases and was associated with a decrease in reactive oxygen species (ROS). We also revealed that extracellular vesicles (EVs) transfer occurred from highly to poorly metastatic NPC cells, mediating cell–cell communication and enhancing the metastatic potential of poorly metastatic NPC cells. Further experiments indicated that EVs derived from highly metastatic NPC cells induced the up‐regulation of EGFR and down‐regulation of ROS in low metastatic NPC cells. Mechanistically, EGFR‐rich EVs‐mediated EGFR overexpression down‐regulated intracellular ROS levels through the PI3K/AKT pathway, thus promoting the metastatic potential of poorly metastatic NPC cells. Strikingly, treatment with EVs secreted from highly metastatic NPC cells was significantly associated with rapid NPC progression and shorter survival in xenografted mice. These findings not only improve our understanding of EVs‐mediated NPC metastatic mechanism but also have important implications for the detection and treatment of NPC patients accompanied by aberrant EGFR‐rich EVs transmission.

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases.

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.

CsWRKY10 mediates defence responses to Botrytis cinerea infection in Cucumis sativus

Cucumber (Cucumis sativus) is one of the most widely cultivated vegetable crops in the world, and its yield is often reduced due to the infection of Botrytis cinerea (B. cinerea), which causes a serious disease. However, few genes involved in the response to B. cinerea have been identified in cucumber. In this study, we identified that CsWRKY10 plays a key role in the cucumber resistance to B. cinerea because that the overexpression of CsWRKY10 significantly increased the susceptibility to B. cinerea in cucumber. After the pathogen infection, the enzyme activities of catalase, superoxide dismutase and peroxidase in transgenic plants were affected, resulting in the decrease in reactive oxygen species (ROS) contents. In addition, the light microscopic images showed that overexpression of CsWRKY10 promoted the spore germination and mycelia elongation of B. cinerea in cucumber. Importantly, after B. cinerea infection, the contents of jasmonic acid (JA) are decreased, and the expression levels of JA- and salicylic acid- related defence genes significantly changed in transgenic plants. In contrast, overexpression of CsWRKY10 enhanced resistance to Corynespora cassiicola in cucumber. Collectively, this study indicated that CsWRKY10 negatively regulates the resistance of cucumber to B. cinerea by reducing the ROS contents and inhibiting the JA-mediated resistance signalling pathway, but strengthens resistance to Corynespora cassiicola.

Foliar graphene oxide treatment increases photosynthetic capacity and reduces oxidative stress in cadmium-stressed lettuce

The application of graphene oxide (GO) in the environment can have a positive or negative effect on the toxicity of pollutants, but the effect of GO on cadmium (Cd2+)-stressed lettuce has not yet been thoroughly studied. Therefore, we assessed the potential effects of foliar GO sprays on photosynthesis and antioxidant systems in Cd-stressed lettuce. We found that the foliar application of 30 mg L−1 of GO could significantly reduce signs of Cd2+ toxicity in lettuce. We observed increased net photosynthetic rates, stomatal conductance, transpiration rates, chlorophyll content, primary maximum photochemical efficiency of photosystem II, actual quantum yield, photosynthetic electron transport rates, ribulose-1,5-bisphosphate carboxylase and oxygenase concentrations, and biomass in Cd2+-stressed lettuce treated with GO. In addition, the foliar application of 30 mg L−1 of GO reduced the accumulation of the reactive oxygen species O·̄2 and H2O2, malondialdehyde content, and the activity of antioxidant enzymes. The decreased antioxidant enzyme activity could have been due to the decrease in reactive oxygen species. Cd2+ pollution is highly destructive to agricultural products, and the foliar application of GO provides a new potential tactic to improve the tolerance of plants to heavy metals.

β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration.

The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.

Antioxidant Effects of Walnut (Juglans regia L.) Kernel and Walnut Septum Extract in a D-Galactose-Induced Aging Model and in Naturally Aged Rats.

Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-induced aging model and in a naturally aged rat model. Young Wistar rats, treated with D-gal (1200 mg/week), and old rats received daily WK or WSE added to the feed. After 8 weeks, blood, liver, and brain samples were collected and hematological, biochemical, oxidative stress biomarkers, histological, and immunohistochemical analyses were performed. Moreover, acetylcholinesterase activity was investigated in brain homogenates. The outcomes demonstrated significant improvement in cellular antioxidant activity and/or decrease of reactive oxygen species, advanced glycation end products, nitric oxide, malondialdehyde, or increase of glutathione after WK or WSE intake in both models. Additionally, WSE showed hypoglycemic effect, and both WK and WSE lowered acetylcholinesterase activity. Both diets could protect neurons against the induced senescence and could reverse the pathological conditions in the physiological aged brain. Thus, dietary supplementation with WK or WSE can maintain the liver and brain health and reduce the risk of age-related diseases, as well as delaying the onset of aging processes.

Curcumin-loaded poly-ε-caprolactone nanoparticles show antioxidant and cytoprotective effects in the presence of reactive oxygen species

Interest in novel delivery systems that improve the cytoprotective and antioxidant effects of natural drugs has been explored recently due to the increase in the incidence of chronic diseases in which oxidation mechanisms are involved. Curcumin is a phenolic compound recently shown to be clinically significant due to its anti-inflammatory, anticancer, and antioxidant properties. However, this molecule possesses a low bioavailability and a high degradation rate in the presence of light. Therefore, we prepared nanoparticles of poly-ε-caprolactone and Pluronic® F-68 as a stabilizer and loaded these with curcumin (Cur–PCL nanoparticles) for antioxidant and cytoprotective applications. The nanoparticles did not induce cell death, but they did reduce cell proliferation without affecting cell migration and cell adhesion. Interestingly, Cur–PCL and poly-ε-caprolactone nanoparticles reduced the oxidative stress induced by hydrogen peroxide and presented a cytoprotective effect. Remarkably, poly-ε-caprolactone nanoparticles showed a decrement of 30% in reactive oxygen species presence compared to the positive control. The decrease of reactive oxygen species derived from the administration of poly-ε-caprolactone nanoparticles could be attributed to the presence of Pluronic® F-68. Taken together, these data indicated that these nanoparticles might have a clinical application in disorders related to reactive oxygen species formation.

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice.

Obesity has been associated with neurodegeneration and cognitive dysfunctions. Recent data showed that pistachio consumption is able to prevent and ameliorate dyslipidemia, hepatic steatosis, systemic and adipose tissue inflammation in mice fed a high-fat diet (HFD). The present study investigated the neuroprotective effects of pistachio intake in HFD mice. Three groups of mice were fed a standard diet (STD), HFD, or HFD supplemented with pistachio (HFD-P) for 16 weeks. Metabolic parameters (oxidative stress, apoptosis, and mitochondrial dysfunction) were analyzed by using specific assays and biomarkers. The pistachio diet significantly reduced the serum levels of triglycerides and cholesterol in the HFD model. No difference was observed in the index of insulin resistance between HFD and HFD-P. A higher number of fragmented nuclei were found in HFD cerebral cortex compared to STD and HFD-P. A decrease in reactive oxygen species, singlet oxygen and phosphorylated extracellular signal-regulated kinase, and an increase of superoxide dismutase 2 and heme oxygenase expression were found in the brains of the HFD-P samples compared to HFD. Furthermore, the impaired mitochondrial function found in HFD brain was partially recovered in HFD-P mice. These results suggest that the regular intake of pistachio may be useful in preventing obesity-related neurodegeneration, being able to reduce both metabolic and cellular dysfunctions.

Paeoniflorin attenuates early brain injury through reducing oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties. However, it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage (SAH). This study explores the effect of paeoniflorin on early brain injury (EBI) using rat SAH model. We found that paeoniflorin significantly improves neurological deficits, attenuates brain water content and Evans blue extravasation at 72 h after SAH. Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species (ROS), malondialdehyde (MDA), 3-Nitrotyrosine, and 8-Hydroxy-2-deoxy guanosine (8-OHDG) level, increase of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activity, and up-regulates the nuclear factor erythroid‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO-1) pathway. Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin's protective effects. Moreover, paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2, active caspase-3/ neuronal nuclei (NeuN) and TUNEL/DAPI positive cells at 72 h following SAH. Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH.

Abstract 170: Deferoxamine Treatment Decreases Levels Of Reactive Oxygen Species And Cellular Apoptosis In Irradiated Skin

Purpose: Radiation therapy is a cornerstone of oncologic treatment. Unfortunately, radiation can lead to pain and ulceration in the acute phase, as well as stiffness and fibrosis in the chronic phase. Deferoxamine (DFO) is an FDA approved iron chelator that has been shown to increase skin vascularization by stabilizing hypoxia-inducible factor 1-alpha levels and improve radiation-induced fibrosis. However, it is unclear whether there are other mechanisms underlying the therapeutic effects that DFO exhibits on the skin. Previous work has shown that DFO delivered transdermally improves healing in diabetic ulcer wounds by decreasing oxidative stress and cellular apoptosis. This study evaluates the effects of transdermal DFO on reactive oxygen species and cell death in the context of irradiation (IR) to skin. Methods: CD-1 nude immunodeficient mice (n=8) were randomized to one of two conditions: 1. Control patch (IR only) (n=4) and 2. DFO patch (n=4). The study period consisted of a 14-day pre-IR period, followed by a 12-day course of fractionated IR which delivered a total of 30 Gray to all mice. The control group received patches without DFO and the DFO group received patches containing DFO throughout the experiment with patches changed daily. Mouse scalp skin was harvested one day after the completion of IR. Tissue samples were either fixed in 4% PFA, snap frozen in OCT, or directly stored at -80°C. Fixed samples were embedded in paraffin, sectioned, and stained for iron with Prussian blue. Snap frozen samples were cryosectioned at 10um, mounted, stained with dihydroethidium (DHE), and imaged with confocal microscopy. DHE detects reactive oxygen species. Stored samples were mechanically homogenized and enzyme-linked immunosorbent assays (ELISAs) were performed to measure levels of human Bax and Cleaved Caspase-3, markers of apoptosis. Results: Treatment with DFO was associated with decreased levels of iron in the skin, confirming DFO’s role as an iron chelator. DHE fluorescence was more intense in the control patch group than in the DFO patch group (***p<0.0001), indicating that ROS generation decreased with DFO treatment. Similarly, apoptosis was highest in the control group and lowest in the DFO group as shown by higher human Bax protein (*p=0.028) and Cleaved Caspase-3 (**p=0.0038) levels. Conclusions: DFO delivered transdermally leads to a dose-dependent decrease in reactive oxygen species and apoptotic markers. These results provide further insight into the mechanisms underlying its restorative effects on irradiated skin. Future work will investigate the relationship of reactive oxygen species and fibroblast subpopulations in the skin.

Efficacy of fenugreek plant for ascorbic acid assisted phytoextraction of copper (Cu); A detailed study of Cu induced morpho-physiological and biochemical alterations

Phytoremediation via phyto-extraction is well recognized and sustainable principle for the economical removal of heavy metals from contaminated water and soil. The twofold objective of the present research work was to investigate the remediation potential of fenugreek for Cu under the influence of ascorbic acid (AA). The effect of copper-ascorbic acid chelation on the growth regulation of fenugreek (Trigonella foenum-graceum L.) and its potential to accumulate Cu was investigated in hydroponic medium to optimize concentration with complete randomized design (CRD). Juvenile fenugreek plants were treated with different treatments of AA (5 mM) and Cu (100, 250 and 500 μM). The different morpho-physiological parameters of fenugreek plant such as growth, biomass and chlorophylls were significantly reduced under Cu stress. However, the activities of antioxidant enzymes, electrolyte leakage and reactive oxygen species enhanced with increasing concentration of applied Cu. Results indicated significant increase in plant growth, biomass, physiology and antioxidant enzymes and decrease in reactive oxygen species and electrolyte production in AA mediated fenugreek plants compared to controls and Cu only treated plants. However, it was also found that AA enhanced Cu concentration maximum up to 42% in leaf, 18% in stem and 45% in roots as compared to Cu treated only plants. Moreover, application of AA signified the research results revealing to act as growth regulator and chelator under Cu stress.

Monocyte Chemotactic Protein-1 Regulates Proliferation and Contractility of Human Bladder Smooth Muscle Cells Under Hydrostatic Pressure.

Bladder growth and development require continuous mechanical stimuli; however, abnormal mechanical conditions caused by partial bladder outlet obstruction (PBOO) result in detrusor smooth muscle hypertrophy and extracellular matrix accumulation. Our previous study demonstrated that PBOO induced an increase in monocyte chemotactic protein-1 (MCP-1) expression. To extensively illustrate whether and how MCP-1 participates in the remodeling of PBOO, we assess the pivotal effect of MCP-1 and its specific receptor chemokine (C-C motif) receptor 2 (CCR2) on the proliferation and contraction of human bladder smooth muscle cells (hBSMCs) under pathological hydrostatic pressure (HP). HP markedly promoted hBSMC proliferation and enhanced cell contraction along with the increase in MCP-1 expression. Recombinant human MCP-1 (rhMCP-1) enhanced HP-induced hBSMC proliferation and contraction. CCR2 antagonists and MCP-1 silencing reversed HP-induced proliferation and contraction. In addition, MCP-1-induced protein 1 (MCPIP1) silencing attenuated the contraction, but not the proliferation, induced by HP, whereas serum-glucocorticoid regulated kinase 1 (SGK1) silencing prevented the rhMCP-1-induced proliferation of hBSMCs under HP. Decrease of reactive oxygen species (ROS) level downregulated MCP-1 expression; in turn, rhMCP-1 promoted the generation of ROS. In conclusion, we demonstrated that pathological HP-promoted hBSMC proliferation was mainly regulated by the MCP-1/CCR2- SGK1 pathway and hBSMCs contraction was mainly moderated by the MCP-1/CCR2 -MCPIP1 pathway. [Figure: see text].

Overexpression of ethylene response factor ERF96 gene enhances selenium tolerance in Arabidopsis

Ethylene response factors (ERFs) are involved in the regulation of plant responses to biotic and abiotic stresses. Here we provide evidence for a role of ERF96, a member of the ERF transcription factor group IX, in selenite tolerance in Arabidopsis. ERF96 gene was rapidly up-regulated in response to selenite stress. Overexpression of ERF96 enhanced Arabidopsis resistance to selenite stress, while ERF96-silenced plants demonstrated wild-type (WT) resistance to selenite. In addition, the overexpression plants had significantly lower selenium (Se) content in shoots when subjected to selenite stress. Further investigation indicated that overexpression of ERF96 reduced transcript levels of selenite/phosphate transporters PHT1;1 and PHT2;1, which influenced Arabidopsis Se uptake and allocation in the presence of selenite. Moreover, our experiments showed that overexpression of ERF96 enhanced Arabidopsis antioxidant activity. Under selenite stress, ERF96-overexpressing lines exhibited the significant increases in catalase (CAT) and glutathione peroxidase (GPX) activities as well as the glutathione (GSH) content, while had a decrease in reactive oxygen species (ROS) accumulation compared to WT. Taken together, our results demonstrate that ERF96 plays a positive role in the regulation of selenite tolerance in Arabidopsis.

Neuroprotective effects of novel nitrones: In vitro and in silico studies

Neurodegenerative diseases affect millions of people around the world. Several studies point out caspase-3 as a key player in the development and progression of neurological disorders including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and Huntington's diseases. Furthermore, oxidative stress and mitochondrial dysfunction plays an important role in neurodegenerative pathologies leading to neuronal damage and cell death. Pharmacological properties of nitrones such as free radical trapping and neuroprotection has been previously described. In the present work, we have assessed ten non-cytotoxic nitrones for their ability to inhibit apoptosis plus their potential to reduce active caspase-3 and oxidative stress in the hippocampal neuronal cell line HT22. Our results highlight the faculty of nitrones to inhibit apoptosis by a mechanism that involves active caspase-3 reduction and decrease of reactive oxygen species. Moreover, docking and molecular dynamics approaches lead to a detailed analysis at the atomic level of the nitrones binding mode to caspase-3 suggesting that compounds bind in a region close to the catalytic site. All these data place these molecules as excellent hits for further efforts to redesign novel compounds in the search of a new therapy against neurodegenerative disorders.

Lactic acid bacteria exhibit similar antioxidant capacities in Caenorhabditis elegans- and Campylobacter jejuni-infected mice.

Caenorhabditis elegans (C. elegans) is increasingly used as a model organism to screen probiotics for ageing research. In this study, a C. elegans lifespan analysis model exposed to H2O2 and juglone (for chronic and acute assays) was used to preselect lactic acid bacteria (LAB) with resistance to oxidative stress. The mechanism of oxidative stress protection was analyzed. Seven out of ten LAB strains screened for namely 427, X13, 9-5, 422, Z5, G14 and H29M-8M demonstrated higher levels of protection to C. elegans, ranging from 70% to 85% survival rate, in comparison to the inactive strains 408, 13-7 and 430 (35% to 45% survival rate). The survival rates of the seven oxidative stress tolerant strains were correlated to increase in catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) levels and decrease in reactive oxygen species (ROS) expression in C. elegans during H2O2 and juglone exposure. In addition, the transcription of mitogen-activated protein kinase (MAPK) and Nrf2-Keap1-ARE pathway related genes was elevated in the oxidative stress protection of LAB isolates. Finally, a significant correlation was found between the ability of these LAB strains to protect C. elegans from H2O2 or juglone exposure and their antioxidative ability in Campylobacter jejuni-infected mice. Thus the results indicated that the oxidative stress-based lifespan model of C. elegans is useful for screening of LAB with antioxidant efficacy in pathogen-infected mammals.