Superoxide Dismutase Protein Research Articles

Protective Effects of α-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia.

The aim of the present study was to observe the protective effects of α-lipoic acid (ALA) on vascular injury in rats with hyperuricemia (HUA). The ALA treatment groups (10, 30 and 90 mg/kg, respectively) were administered with ALA via gavage for 2 weeks. Subsequently, the levels of blood urea nitrogen (BUN), creatinine (CREA), uric acid (UA), total cholesterol (TC), high density lipoprotein-C (HDL-C) and low density lipoprotein-C (LDL-C) were measured; the activities of glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and xanthine oxidase (XOD) were also determined. The thoracic aorta of rats in each experimental group was observed under a light microscope; ultrastructural analysis was performed. SOD and CAT protein contents were investigated by Western blotting. The results revealed that: i) Compared with the model group, the levels of UA were decreased in the ALA groups and the levels of BUN, CREA, TC, and LDL-C decreased in the 30 and 90 mg/kg ALA groups (P<0.05); ii) compared with the model group, the activities of GSH-Px, SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P&lt;0.05); and iii) in the model and 10 mg/kg ALA groups, edema and shedding were observed in endothelial cells. Compared with the model and 10 mg/kg ALA groups, the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells. In summary, the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes, which leads to endothelial cell damage and vascular lesions. ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.

Low Dose Monosodium Glutamate Induced Oxidative Damage and Histopathological Changes on the Renal of Male Rats

Monosodium glutamate (MSG) is a flavour enhancer commonly used in processed food to increase palatability. Several studies have reported that chronic exposure of MSG causes renal fibrosis via oxidative stress mechanism. However, till date, the effects of low dose of MSG on the oxidative stress status and its histopathological observation of renal are still unclear. A total of 18 male Sprague Dawley rats (170 – 200 g) were divided randomly into three groups consisted of the control (received distilled water = 1 ml/kg), MSG60 (received 60 mg/kg MSG) and MSG 120 (received 120 mg/kg MSG) groups. All of the substances were given via force-feed oral for 28 consecutive days. At the end of the study, all rats were sacrificed and the renal were isolated for biochemical and histological evaluation. The superoxide dismutase (SOD) activity and protein carbonyl (PC) level showed significantly increased (p < 0.05) in MSG 60 and MSG 120 group compared to the control group. However, no significant difference was found in glutathione (GSH) and malondialdehyde (MDA) level in all treated groups. The histology observation showed glomerulus shrinkage in MSG60 and MSG120 groups. In conclusion, these findings confirmed low dose of MSG-induced oxidative stress and histopathological changes on the renal of male Sprague-dawley rats. Accordingly, care must be taken on the intake of in our daily basis.

Species-specific consequences of an E40K missense mutation in superoxide dismutase 1 (SOD1).

A glutamic acid to lysine (E40K) residue substitution in superoxide dismutase 1 (SOD1) is associated with canine degenerative myelopathy: the only naturally occurring large animal model of amyotrophic lateral sclerosis (ALS). The E40 residue is highly conserved across mammals, except the horse, which naturally carries the (dog mutant) K40 residue. Here we hypothesized that in vitro expression of mutant dog SOD1 would recapitulate features of human ALS (ie, SOD1 protein aggregation, reduced cell viability, perturbations in mitochondrial morphology and membrane potential, reduced ATP production, and increased superoxide ion levels); further, we hypothesized that an equivalent equine SOD1 variant would share similar perturbations in vitro, thereby explain horses' susceptibility to certain neurodegenerative diseases. As in human ALS, expression of mutant dog SOD1 was associated with statistically significant increased aggregate formation, raised superoxide levels (ROS), and altered mitochondrial morphology (increased branching (form factor)), when compared to wild-type dog SOD1-expressing cells. Similar deficits were not detected in cells expressing the equivalent horse SOD1 variant. Our data helps explain the ALS-associated cellular phenotype of dogs expressing the mutant SOD1 protein and reveals that species-specific sequence conservation does not necessarily predict pathogenicity. The work improves understanding of the etiopathogenesis of canine degenerative myelopathy.

Effect of acupuncture on oxidative stress and apoptosis in ovarian hypofunction induced by Tripterygium Glycosides

To explore whether manual acupuncture stimulation of "Shenshu " (BL23), "Guanyuan" (CV4), "Zhongwan" (CV12) can improve the ovarian function by resisting oxidant stress and reducing apoptosis of granulosa cells in rats with ovarian hypofunction. Forty female SD rats with normal estrous cycles were randomly divided into blank control, model, hormone therapy and acupuncture groups (n=10 rats in each group). The ovarian hypofunction model was established by gavage of Tripterygium Glycosides suspension (50 mg·kg-1·d-1) for 14 successive days. Rats of the hormone therapy group were treated by gavage of estrogen and progesterone, and those of the acupuncture group treated by manual acupuncture stimulation of bilateral BL23 or CV4 and CV12 alternatively by using uniform reinforcing-reducing method for 10 s every 5 min (3 times in 10 min). The treatment was performed once daily for 14 days. The blank group was given equal volume of normal saline daily. On the 9th day, the estrous cycle of each rat was observed by means of vaginal smear test. The ovarian index, serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were detected by ELISA. Histopathological changes of the ovary tissue were observed by H.E. staining. The expressions of apoptosis-related proteins Bax and Bcl-2 and their mRNAs of the ovaries were determined by immunohistochemical staining and quantitative real time-PCR separately. The menstrual disorder rate was 100% in the model group, and was significantly higher than those in the hormone therapy (30%) and acupuncture (40%) groups (P<0.01). Following modeling, the ovarian wet weight and index, E2 and SOD contents, Bcl-2 protein and mRNA expressions were significantly decreased (P<0.01, P<0.05), and serum FSH, LH and MDA levels, Bax protein and mRNA expressions were significantly increased (P<0.05, P<0.01) in the model group in comparison with the blank control group. H.E. staining showed a large amount of connective tissue in the ovary, with fewer mature follicles, increase of atresia follicles, significant reduction of luteal tissue, and appearance of scarring tissue in the model group. Compared with the model group, there were more mature follicles, fewer atresia follicles, lower abnormal granulosa cell morphology and lower estrous cycle disorder ratio in both hormone therapy and acupuncture groups. After the interventions, the decreased ovarian wet weight and index, serum E2 and SOD contents, expressions of Bcl-2 protein and mRNA were significantly increased (P<0.05, P<0.01), and the increased levels of FSH and LH, MDA, expressions of Bax protein and mRNA were significantly decreased in both hormone therapy and acupuncture groups (P<0.05, P<0.01). The effect of acupuncture was significantly superior to that of hormone in up-regulating SOD, Bax and Bcl-2 protein expressions (P<0.01). Acupuncture can improve the menstrual disorder in rats with ovarian hypofunction, which is closely related to its effects in improving antioxidant stress ability and regulating the expressions of apoptosis-related protein and mRNA of ovarian gra-nulosa cells.

Cytoplasmic Restriction of Mutated SOD1 Impairs the DNA Repair Process in Spinal Cord Neurons.

Amyotrophic lateral sclerosis (ALS) caused by mutation of superoxide dismutase 1 (SOD1), affects various cellular processes and results in the death of motor neurons with fatal defects. Currently, several neurological disorders associated with DNA damage are known to directly induce neurodegenerative diseases. In this research, we found that cytoplasmic restriction of SOD1G93A, which inhibited the nucleic translocation of SOD1WT, was directly related to increasing DNA damage in SOD1- mutated ALS disease. Our study showed that nucleic transport of DNA repair- processing proteins, such as p53, APEX1, HDAC1, and ALS- linked FUS were interfered with under increased endoplasmic reticulum (ER) stress in the presence of SOD1G93A. During aging, the unsuccessful recognition and repair process of damaged DNA, due to the mislocalized DNA repair proteins might be closely associated with the enhanced susceptibility of DNA damage in SOD1- mutated neurons. In addition, the co-expression of protein disulphide isomerase (PDI) directly interacting with SOD1 protein in neurons enhances the nucleic transport of cytoplasmic- restricted SOD1G93A. Therefore, our results showed that enhanced DNA damage by SOD1 mutation-induced ALS disease and further suggested that PDI could be a strong candidate molecule to protect neuronal apoptosis by reducing DNA damage in ALS disease.

Genome-wide identification and transcriptional expression analysis of superoxide dismutase (SOD) family in wheat (Triticum aestivum).

Superoxide dismutases (SODs) are a family of key antioxidant enzymes that play a crucial role in plant growth and development. Previously, this gene family has been investigated in Arabidopsis and rice. In the present study, a genome-wide analysis of the SOD gene family in wheat were performed. Twenty-six SOD genes were identified from the whole genome of wheat, including 17 Cu/Zn-SODs, six Fe-SODs, and three Mn-SODs. The chromosomal location mapping analysis indicated that these three types of SOD genes were only distributed on 2, 4, and 7 chromosomes, respectively. Phylogenetic analyses of wheat SODs and several other species revealed that these SOD proteins can be assigned to two major categories. SOD1 mainly comprises of Cu/Zn-SODs, and SOD2 mainly comprises of Fe-SODs and Mn-SODs. Gene structure and motif analyses indicated that most of the SOD genes showed a relatively conserved exon/intron arrangement and motif composition. Analyses of transcriptional data indicated that most of the wheat SOD genes were expressed in almost all of the examined tissues and had important functions in abiotic stress resistance. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to reveal the regulating roles of wheat SOD gene family in response to NaCl, mannitol, and polyethylene glycol stresses. qRT-PCR showed that eight randomly selected genes with relatively high expression levels responded to all three stresses based on released transcriptome data. However, their degree of response and response patterns were different. Interestingly, among these genes, TaSOD1.7, TaSOD1.9, TaSOD2.1, and TaSOD2.3 feature research value owing to their remarkable expression-fold change in leaves or roots under different stresses. Overall, our results provide a basis of further functional research on the SOD gene family in wheat and facilitate their potential use for applications in the genetic improvement on wheat in drought and salt stress environments.

Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2.

Mercury is a metal widely dispersed in nature that when in contact with human organism, it damages the cardiovascular system. Long-term mercury exposure for 30days induces endothelial dysfunction without blood pressure changes in normotensive adult rats. However, it is not known whether exposure to mercury can exacerbate endothelial dysfunction and hypertension development in predisposed animals. Thus, we aimed to investigate the effects of long-term mercury exposure on the blood pressure (BP) and in the isolated aortas of young normotensive and prehypertensive spontaneously hypertensive rats (SHRs). Four-week-old male Wistar rats and SHRs were treated daily with mercury chloride (HgCl2) (1st dose, 4.6μg/kg; subsequent dose, 0.07μg/kg/day, im, 30days) or vehicle. BP was assessed weekly and the vascular reactivity to phenylephrine was evaluated in isolated aorta from rats exposed or not to mercury. Mercury exposure did not affect BP in young Wistar rats but accelerated the development of hypertension in young SHRs. Vascular reactivity to phenylephrine increased only in the aorta from mercury-exposed SHRs. While HgCl2 exposure in SHRs did not alter nitric oxide production, we observed increased superoxide anion production and decreased superoxide dismutase-1 protein expression, and enhanced cyclooxygenase-2 (COX-2) participation with increased prostaglandin (PGE2) production and decreased prostacyclin. In the Wistar group, mercury exposure did not alter superoxide anion production or the COX-2 pathway. Mercury exposure accelerated the natural course of hypertension in young SHRs and increased oxidative stress associated with reduced participation of antioxidant enzymes, an activated COX-2 pathway, thereby producing endothelial dysfunction, which is a risk factor in prehypertensive individuals.

Enhancement of host infectivity, immunity, and protective efficacy by addition of sodium bicarbonate antacid to oral vaccine formulation of live attenuated Salmonella secreting Brucella antigens

In the present study, the importance of sodium bicarbonate antacid as an agent for an orally delivered attenuated Salmonella strain secreting Brucella antigens Cu–Zn superoxide dismutase (SodC) and outer membrane protein 19 (Omp19) as a live vaccine candidate against Brucella infection was investigated. First, Brucella antigens SodC and Omp19 were cloned into a prokaryotic constitutive expression vector, pJHL65. Then secretion of proteins was verified after transformation into an attenuated Salmonella typhimurium (ST) strain, JOL1800 (Δlon, ΔcpxR, Δasd, ΔrfaL), using western blot analysis. Mice were orally inoculated with phosphate-buffered saline (PBS) or with a co-mixture Salmonella secreting each antigens at a 1:1 ratio, each containing 1 × 108 CFU/mouse with and without sodium bicarbonate treatment. For antacid treatment, 1.3% w/v sodium bicarbonate was orally administered 30 min before and immediately after immunization with the Salmonella formulation. Humoral and cell-mediated immune responses were evaluated to investigate the efficacy of sodium bicarbonate in an oral formulation. The results indicated that addition of sodium bicarbonate to the vaccine significantly increased (P < 0.05) levels of anti-Brucella-specific systemic IgG responses, lymphocyte proliferation, and CD4+ T cell responses, indicating induction of a mixed Th1–Th2 response. Immunohistochemical assays and bacterial enumeration in intestinal samples also indicated that administration of sodium bicarbonate enhanced colonization of Salmonella. These results indicate that ingestion of the Salmonella formulation with sodium bicarbonate can enhance colonization of Salmonella and induce a significant protective immune response against Brucella compared with a formulation without sodium bicarbonate. Thus, incorporation of sodium bicarbonate as an antacid buffer is highly recommended for this oral live vaccine.

Elucidating the molecular mechanism of TEMPOL-mediated improvement on tolerance under oxidative stress in Saccharomyces cerevisiae

Reactive oxygen species (ROS) appear in universal stress pathways and damage cell components. In this study, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL), a redox-cycling nitroxide and membrane-permeable antioxidant, was investigated for its ability to clear out intracellular ROS induced by hydrogen peroxide (H2O2) shock in Saccharomyces cerevisiae. Cell growth was improved by TEMPOL addition. The mechanism of ROS removal was elucidated by investigating activities of related genes, enzyme, and cofactors. TEMPOL increased the expression of genes involved in oxidative stress response, and enhanced the activities of the superoxide dismutase (SOD) and catalase (CAT) antioxidative proteins. TEMPOL also increased intracellular glutathione (GSH) to remove ROS by supplying more NADPH in cells. Finally, TEMPOL might catalyze the reaction of NADH and ROS due to its dual redox states. Interestingly, the early addition of TEMPOL resulted in a better H2O2 tolerance, because TEMPOL required time to expand its benefits in different metabolic levels for constructing an enzymatic antioxidant defense system and accumulating non-enzymatic reducing power in advance, akin to a “preventive stimulator”.

ASCs-Exosomes Recover Coupling Efficiency and Mitochondrial Membrane Potential in an in vitro Model of ALS.

The amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneurons death. Mutations in the superoxide dismutase 1 (SOD1) protein have been identified to be related to the disease. Beyond the different altered pathways, the mitochondrial dysfunction is one of the major features that leads to the selective death of motoneurons in ALS. The NSC-34 cell line, overexpressing human SOD1(G93A) mutant protein [NSC-34(G93A)], is considered an optimal in vitro model to study ALS. Here we investigated the energy metabolism in NSC-34(G93A) cells and in particular the effect of the mutated SOD1(G93A) protein on the mitochondrial respiratory capacity (complexes I-IV) by high resolution respirometry (HRR) and cytofluorimetry. We demonstrated that NSC-34(G93A) cells show a reduced mitochondrial oxidative capacity. In particular, we found significant impairment of the complex I-linked oxidative phosphorylation, reduced efficiency of the electron transfer system (ETS) associated with a higher rate of dissipative respiration, and a lower membrane potential. In order to rescue the effect of the mutated SOD1 gene on mitochondria impairment, we evaluated the efficacy of the exosomes, isolated from adipose-derived stem cells, administrated on the NSC-34(G93A) cells. These data show that ASCs-exosomes are able to restore complex I activity, coupling efficiency and mitochondrial membrane potential. Our results improve the knowledge about mitochondrial bioenergetic defects directly associated with the SOD1(G93A) mutation, and prove the efficacy of adipose-derived stem cells exosomes to rescue the function of mitochondria, indicating that these vesicles could represent a valuable approach to target mitochondrial dysfunction in ALS.

Protective effects of Lactobacillus plantarum against chronic alcohol-induced liver injury in the murine model.

Long-term alcohol consumption causes liver injuries such as alcoholic hepatitis, fatty liver, and endotoxemia. Some probiotics were demonstrated to exert beneficial effects in the gastrointestinal tract. The present study was aimed to evaluate the protective effects of Lactobacillus plantarum CMU995 against alcohol-induced liver injury. The mice were orally administered L. plantarum CMU995 for 1week, followed by the administration of alcohol and different tested substances daily for 6weeks. The liver injury was examined by measuring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), anti-oxidative enzyme, endotoxin, inflammatory cytokines, and lipid accumulation in the liver or serum among different groups. L. plantarum CMU995 exhibited beneficial effects on alcohol-induced liver injury via reduction in the serum concentration of AST, ALT, cholesterol, triglycerides, endotoxin, TNF-α, IL-1β, and oxidative stress. Furthermore, we also found that the levels of glutathione (GSH), superoxide dismutase (SOD), and intestinal tight junction protein zonula occludens-1 (ZO-1) were considerably higher in L. plantarum CMU995-fed groups when compared with placebo group. Meanwhile, the protective effects were demonstrated biological gradients as controversial dose-dependent. We speculate that L. plantarum CMU995 inhibited the migration of alcohol-derived endotoxin into the blood and liver, thereby improving the intestinal barrier. The present evidence may provide a novel microbiota-based strategy to prevent the alcohol-induced liver injury.

In vitro peripheral blood mononuclear cell proliferation, cytokine secretion and oxidative stress modulation by pyrido[2,3-d] pyrimidines

The aim of this work was to study the in vitro effects of new pyrido[2,3-d] pyrimidines, especially 4-(N-phenylethylamino)-5,7-diphenylpyrido[2,3-d] pyrimidine (3a) and 4-(N-benzylamino)-5-(4-chlorophenyl)-7-(3-methoxyphenyl) pyrido[2,3-d]-pyrimidine (3b), on the proliferative responses of human peripheral blood mononuclear cells, cytokine secretion, ATP levels and intracellular redox status. Peripheral blood mononuclear cells were isolated using differential centrifugation on a density gradient of Histopaque. These cells were cultured with the mitogen concanavalin A (Con A) and with different concentrations of the compounds 3a and 3b (1–100 µM). Proliferation (MTT assay), IL-2, INFγ and IL-4 (Elisa kits), ATP levels, cytotoxic effect (micronucleus test) and oxidative markers (intracellular glutathione, superoxide dismutase, catalase, hydroperoxide and carbonyl protein contents) were investigated after 48-h incubation. Our results showed that 3a was immunostimulant at low concentrations but immunosuppressive at high concentrations (50, 100 µM) with a modulation of cytokine secretion. 3b was immunostimulant in a dose-dependent manner. 3a induced an increase in intracellular ATP levels at 1–25 µM but a decrease at 50–100 µM. In the presence of 3b, cell ATP contents increased with 3b concentrations. Peripheral blood mononuclear cell redox markers were consistent with the presence of an oxidative stress induced by high concentrations of 3a and 3b, with a significant increase in the micronucleus frequency in lymphocytes, suggesting cytotoxic effects. However, 3a at low concentrations (1–25 µM) tended to activate antioxidant defense in cells. In conclusion, 3a and 3b modulate cell-mediated immunity, cell energy and redox status at low concentrations.

Effect of Different Temperatures on Germination and Seedling Growth of Primed Seeds of Tomato

In present work the effect of various temperatures on germination and seedling growth were determined, using primed seeds of hybrid variety of tomato (Lycopersicon esculentum Mill. NUN 5024). The hydro (distilled water) and halo (using different concentrations of Mg(NO3)2 ranging from 5 to 10 mM) primed seeds of tomato were placed under different (ranging from 10 to 40°C) temperatures during germination in plant growth chamber and various parameters of seedling growth were studied. Maximum germination percentage, total seedling, and separately root and shoot lengths, fresh and dry weight of seedlings, studied up to 10 days were represented by 7.5 mM Mg(NO3)2-primed seeds at 40°C. While the study continued only with 40°C treated sets up to 25 days in net house under natural conditions, maximum plant height, number of branches and green leaves, leaf area/plant, plant fresh and dry weights, root number/plant, root length, root fresh and dry weight, super oxide dismutase activity (SOD) and protein content were noted in 7.5 mM Mg(NO3)2-primed seeds in respect to all other treatments.

Antioxidant and Hepatoprotective Properties from the Extract and Fractions of Annona senegalensis Pers (Annonaceae) Stem Bark Grown in Nigeria

Aim: This study was carried out to assess the antioxidant and hepatoprotective properties of the extract and fractions of Annona senegalensis stem bark through in vitro and in vivo experimental models.&#x0D; Study Design: The study followed a completely randomized design (CRD) of groups of treatments and control samples for all the tests.&#x0D; Place and Duration of Study: Department of Pharmacognosy and Environmental Medicines, University of Nigeria, Nsukka, between January and September 2016.&#x0D; Methodology: Phytochemical constituents and in vitro antioxidant activities using different models (reducing power, DPPH free radical scavenging, ABTS radical scavenging, Hydroxyl radical scavenging, Hydrogen peroxide scavenging, β-carotene bleaching, FRAP scavenging and superoxide radical scavenging assays) were carried out. In vivo antioxidant activity was determined from the assays of lipid peroxidation, superoxide dismutase and total protein while hepatoprotective activity was evaluated against CCI4 induced liver damage and elevated serum marker enzymes.&#x0D; Results: The results showed that the extract and fractions of stem bark of A. senegalensis had appreciable amounts of total flavonoids (845.67±93.62 mg/g) and total phenols (866.67±8.41), and exhibited good antioxidant activities at higher concentrations. Doses of the extract and fractions administered at 400 mg/kg protected the CCI4–induced lipid peroxidation and significantly (P = .05) reduced the elevated serum marker enzymes - aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphate (ALP), and bilirubin level on a dose and solvent dependent fashion. At 200 and 400 mg/kg extract, the serum AST was reduced (by 40.34% and 45.66% respectively) as much as the MeOH fraction (43.88%) and control (43.44%), whereas EtOAc fractions gave significantly the best reduction (52.49%). The ethyl acetate fraction gave the best activity among all the fractions.&#x0D; Conclusion: The results showed that the stem bark is a potential source of natural antioxidants and hepatoprotective agents, and justifies its use in traditional herbal practice.

Rational design of linear tripeptides against the aggregation of human mutant SOD1 protein causing amyotrophic lateral sclerosis

Formation of protein aggregation is considered a hallmark feature of various neurological diseases. Amyotrophic lateral sclerosis is one such devastating neurodegenerative disorder characterized by mutation in Cu/Zn superoxide dismutase protein (SOD1). In our study, we contemplated the most aggregated and pathogenic mutant A4V in a viewpoint of finding a therapeutic regime by inhibiting the formation of the aggregates with the aid of tripeptides since new perspectives in the field of drug design in the current era are being focused on peptide-based drugs. Reports from the experimental study have stipulated that the SOD1 derived peptide, “LSGDHCIIGRTLVVHEKADD” was found to have the inhibitory activity against aggregated SOD1 protein. Moreover, it was determined that the hexapeptide, “LSGDHC” was the key factor in inhibiting the aggregates of SOD1. Accordingly, we utilized the computerized algorithms and programs on determining the binding efficiency and inhibitory activity of hexapeptide on mutant SOD1. Following that, we incorporated a cutting-edge methodology with the use of molecular docking, affinity predictions, alanine scanning, steered molecular dynamics (SMD) and discrete molecular dynamics (DMD) in designing the de novo tripeptides, which could act against the aggregated mutant SOD1 protein. Upon examining the results from the various conformational studies, we identified that CGH had an enhanced binding affinity and inhibitory activity against the aggregated mutant SOD1 protein than other tripeptides and hexapeptide. Thus, our study could be a lead for state-of-the-art design in peptide-based drugs for doctoring the cureless ALS disorder.

Cyanobacteria and Glutathione Applications Improve Productivity, Nutrient Contents, and Antioxidant Systems of Salt-Stressed Soybean Plant

Salt stress restricts plant performance by disrupting various physio-biochemical processes like photosynthesis. Plants growing in saline substrates show deficiencies in absorption of some essential elements due to the presence of excessive sodium (Na+) in the rhizosphere, which antagonizes beneficial cations and causing toxicity in metabolism. Cyanobacteria (CB; a natural biofertilizer) play a fundamental role in building-up soil fertility, thus increasing plant performance. Glutathione (GSH) is a well-known antioxidant, which contributes to increase salt tolerance in the plant. This work was conducted as a pot experiment (sand culture) in 2017 to study the combined effect of CB, applied as seed inoculation, and GSH, applied as foliar spray, on growth, pods and seed yields, the contents of antioxidants, osmoprotectants, and nutrients, and the antioxidative enzymes activities of soybean (Glycine max L., cv. Giza 111) plants grown under saline conditions. At fourth leaf stage (21 days after sowing; DAS), CB-pretreated seedlings were supplemented with NaCl (150 mM) along with Hoagland′s nutrient solution, and at the same time seedlings were sprayed with 1 mM GSH. Samples were taken at 60 DAS to assess morphological, physio-biochemical and antioxidant defense systems attributes. Results showed that the integrative application of CB and GSH under saline conditions was effective in improving significantly the growth characteristics, yield components, photosynthetic efficiency (pigments contents and chlorophyll fluorescence), membrane stability index, relative water content, contents of soluble sugars, free proline, ascorbic acid, glutathione, α-tocopherol, and protein, and activities of superoxide dismutase, catalase, and guaiacol peroxidase. The contents of macronutrients (N, P, K+, and Ca2+) were also increased significantly in Glycine max plants compared to the stressed control. In contrast, Na+ content and electrolyte leakage were significantly reduced. Our results recommend using the combined CB (as seed inoculation) and GSH (as foliar spray) application for soybean plantss to grow well under saline conditions.

Influences of urinary kallidinogenase on neuronal apoptosis in cerebral infarction rats through Nrf2/ARE oxidative stress pathway.

To investigate the influences of urinary kallidinogenase on neuronal apoptosis in rats with cerebral infarction through the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) oxidative stress pathway. A total of 30 male rats were divided into group A (model control group), group B (rat model of cerebral infarction) and group C (rat model of cerebral infarction + medical treatment with urinary kallidinogenase). The percentage of cerebral infarct volume and the apoptosis of brain cells in the three groups of rats were detected via 2,3,5-Triphenyltetrazolium chloride (TTC) staining, the pathological morphology of brain tissues in the three groups of rats was observed via hematoxylin and eosin (HE) staining, and the protein levels of Nrf2 and superoxide dismutase 1 (SOD1) in the brain tissues in the three groups of rats were measured using the Western blotting assay. The degree of neurological deficit in group B was remarkably higher than that in group A (p<0.05), and it was markedly decreased in group C compared to that in group B, displaying statistically significant differences (p<0.05). Compared to that in group A, the cell apoptosis was significantly aggravated in group B, while a remarkably alleviated cell apoptosis was observed in group C compared to that of group B, and the differences were statistically significant (p<0.05). The cerebral infarct volume accounted for 34.87% of the whole brain volume in group B, and a mild cerebral infarction was detected in group C, with a percentage of cerebral infarct volume of 21.14%. Group B showed a more evident increase in the cerebral infarct volume than in group C (p<0.05). Compared to those of group A, pyknotic nuclei and neuron staining of brain tissue cells were evidently increased, and the neuronal cell injury was aggravated in group B. Moreover, prominently decreased pyknotic nuclei and neuron staining (p<0.05) as well as mild neuronal cell injury (p<0.05) were detected in group C compared to those in group B. The levels of Nrf2 and SOD1 protein in the brain tissues in group B were remarkably lower than those of group C (p<0.05). Urinary kallidinogenase can inhibit the neuronal apoptosis in rats and protect the rats from cerebral infarction, whose mechanism is associated with the activation of the Nrf2/ARE oxidative stress pathway.

Cyanobacteria and Glutathione Applications Improve Productivity, Nutrient Contents, and Antioxidant Systems of Salt-Stressed Soybean Plant

Salt stress restricts plant performance by disrupting various physio-biochemical processes like photosynthesis. Plants growing in saline substrates show deficiencies in absorption of some essential elements due to the presence of excessive sodium (Na+) in the rhizosphere, which antagonizes beneficial cations and causing toxicity in metabolism. Cyanobacteria (CB; a natural biofertilizer) play a fundamental role in building-up soil fertility, thus increasing plant performance. Glutathione (GSH) is a well-known antioxidant, which contributes to increase salt tolerance in the plant. This work was conducted as a pot experiment (sand culture) in 2017 to study the combined effect of CB, applied as seed inoculation, and GSH, applied as foliar spray, on growth, pods and seed yields, the contents of antioxidants, osmoprotectants, and nutrients, and the antioxidative enzymes activities of soybean (Glycine max L., cv. Giza 111) plants grown under saline conditions. At fourth leaf stage (21 days after sowing; DAS), CB-pretreated seedlings were supplemented with NaCl (150 mM) along with Hoagland′s nutrient solution, and at the same time seedlings were sprayed with 1 mM GSH. Samples were taken at 60 DAS to assess morphological, physio-biochemical and antioxidant defense systems attributes. Results showed that the integrative application of CB and GSH under saline conditions was effective in improving significantly the growth characteristics, yield components, photosynthetic efficiency (pigments contents and chlorophyll fluorescence), membrane stability index, relative water content, contents of soluble sugars, free proline, ascorbic acid, glutathione, α-tocopherol, and protein, and activities of superoxide dismutase, catalase, and guaiacol peroxidase. The contents of macronutrients (N, P, K+, and Ca2+) were also increased significantly in Glycine max plants compared to the stressed control. In contrast, Na+ content and electrolyte leakage were significantly reduced. Our results recommend using the combined CB (as seed inoculation) and GSH (as foliar spray) application for soybean plantss to grow well under saline conditions.

Improvement of neurological function and stress in patients with acute massive cerebral infarction by mild hypothermia: a prospective randomized controlled study

To study the effect of mild hypothermiaon neurological function and oxidative stress in patients with acute massive cerebral infarction. Sixty patients with acute massive cerebral infarction (within 12 hours of onset, the age < 70 years old) admitted to the First Hospital of Qinhuangdao from August 2017 to August 2018 were enrolled. Patients were divided into control group and observation group according to random number table method, with 30 patients in each group. The control group was given conventional treatment such as lowering intracranial pressure, anticoagulation, improving microcirculation, neurotrophy and anti-stress ulcer, while the observation group was received mild hypothermia (after 72 hours of treatment at 32-35 centigrade, it increased about 1 centigrade every 6 hours until the normal temperature). The neurological impairment (the National Institutes of Health Stroke Scale, NIHSS), motor function (Fugl-Meyer score), daily living ability (Bathel index) and coma degree (Glasgow coma scale, GCS) were observed before treatment and 72 hours after treatment. The levels of plasma malondialdehyde (MDA), superoxide dismutase (SOD) and advanced oxidative protein products (AOPP) were measured at same time. After 72 hours of treatment, the therapeutic effect was judged according to the NIHSS score. There was no significant difference in NIHSS score, Fugl-Meyer score, Bathel index and GCS scores, and the levels of plasma MDA, SOD and AOPP between two groups before treatment. Compared with before treatment, NIHSS score and plasma MDA and AOPP levels in the two groups were significantly decreased after treatment, while Fugl-Meyer score, Bathel index, GCS score and plasma SOD activity were significantly increased; and the change of observation group was more significant than those of control group [NIHSS score: 9.78±3.24 vs. 13.44±2.63, MDA (mmol/L): 8.70±2.79 vs. 10.50±3.81, AOPP (μmol/L): 51.10±17.81 vs. 72.60±18.71, Fugl-Meyer score: 55.68±8.38 vs. 46.25±3.92, Bathel index: 66.63±11.25 vs. 56.71±10.81, GCS score: 13.78±1.31 vs. 10.49±1.03, SOD (kU/L): 134.70±29.87 vs. 104.60±25.75, all P < 0.05]. The total effective rate of the observation group was significantly higher than that of the control group [93.3% (28/30) vs. 86.7% (26/30), χ2 = 6.119, P = 0.020]. Mild hypothermia was effective in treating acute massive cerebral infarction. It could significantly improve the neurological function and oxidative stress of patients, improve the quality of life, and was safe and reliable.

The Effects of Resistance Training and Berberine Chloride Supplementation on Oxidative Stress Markers in the Cerebellum Tissue of Diazinon-Poisoned Rats

Background: Diazinon is an insecticide from the organophosphorus group, which can increase the oxidative stress in the body. It has been established that training and antioxidant supplementation can improve oxidative stress system by decreasing malondialdehyde (MDA); meanwhile, increasing the activities of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). Objectives: The aim of this study was to investigate the effect of resistance training (RT) and berberine chloride (BC) supplementation on oxidative stress indices in the cerebellum tissue of diazinon-poisoned rats. Methods: Fifty-six Wistar rats were divided into seven groups (n = 8), including resistance training (RT) (each session 2 sets of 6 repetitions, each one required 8 to 12 active movements with intensity of 10% - 50% of body weight, 3 sessions per week), BC2 (BC: 2 mg/kg), BC15 (BC: 15 mg/kg), RT + BC2, RT + BC15, diazinon, and control. MDA, SOD, and CAT were measured in the cerebellum tissue. Results: RT and BC significantly reduced MDA protein levels (P < 0.01), while increased SOD protein levels (P < 0.01) and CAT protein levels (P < 0.01) in the cerebellum tissue of diazinon-poisoned rats; RT with BC had interactive effects on decreasing MDA (P < 0.01), while increasing SOD (P < 0.01) and CAT protein levels (P < 0.01). Also, the consumption of 15 mg/kg BC rather than 2 mg/kg BC significantly increased SOD protein levels (P = 0.02). Conclusions: It seems that RT combination with BC has Interactive effects on the improvement of oxidative stress markers in the cerebellum tissue of diazinon-poisoned rats.