Glutathione Peroxidase Gene Research Articles

GPX2 predicts recurrence-free survival and triggers the Wnt/β-catenin/EMT pathway in prostate cancer.

ObjectiveThis study aimed to establish a prognostic model related to prostate cancer (PCa) recurrence-free survival (RFS) and identify biomarkers.MethodsThe RFS prognostic model and key genes associated with PCa were established using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression from the Cancer Genome Atlas (TCGA)-PRAD and the Gene Expression Omnibus (GEO) GSE46602 datasets. The weighted gene co-expression network (WGCNA) was used to analyze the obtained key modules and genes, and gene set enrichment analysis (GSEA) was performed. The phenotype and mechanism were verified in vitro.ResultsA total of 18 genes were obtained by LASSO regression, and an RFS model was established and verified (TCGA, AUC: 0.774; GSE70768, AUC: 0.759). Three key genes were obtained using multivariate Cox regression. WGCNA analysis obtained the blue module closely related to the Gleason score (cor = –0.22, P = 3.3e − 05) and the unique gene glutathione peroxidase 2 (GPX2). Immunohistochemical analysis showed that the expression of GPX2 was significantly higher in patients with PCa than in patients with benign prostatic hyperplasia (P < 0.05), but there was no significant correlation with the Gleason score (GSE46602 and GSE6919 verified), which was also verified in the GSE46602 and GSE6919 datasets. The GSEA results showed that GPX2 expression was mainly related to the epithelial–mesenchymal transition (EMT) and Wnt pathways. Additionally, GPX2 expression significantly correlated with eight kinds of immune cells. In human PCa cell lines LNCaP and 22RV1, si-GPX2 inhibited proliferation and invasion, and induced apoptosis when compared with si-NC. The protein expression of Wnt3a, glycogen synthase kinase 3β (GSK3β), phosphorylated (p)-GSK3β, β-catenin, p-β-catenin, c-myc, cyclin D1, and vimentin decreased; the expression of E-cadherin increased; and the results for over-GPX2 were opposite to those for over-NC. The protein expression of GPX2 decreased, and β-catenin was unchanged in the si-GPX2+ SKL2001 group compared with the si-NC group.ConclusionWe successfully constructed the PCa RFS prognostic model, obtained RFS-related biomarker GPX2, and found that GPX2 regulated PCa progression and triggered Wnt/β-catenin/EMT pathway molecular changes.

Evaluation of metabolic stress status in common carp (Cyprinus carpio) exposed to the fungicide folpet

Among pesticides, fungicides are the most extensively used ones in agriculture and their effects on fish health and indirectly human health are needed to evaluate. Folpet has been used for over 50 years as a fungicide across the world. The mechanism of action of folpet on non-target aquatic organisms is so poorly understood and there is no available information about potential acute toxicity of folpet and its mechanism of action in non-target aquatic organisms. With this motivation, two successive experiments were set up: first, 96 h-LC50 value of folpet for common carp (Cyprinus carpio) was determined; and second, effects of different sublethal concentrations (0, 0.025, 0.50, 0.1 and 0.15 mg/L) of folpet on hematological serum biochemical blood parameters, DNA damages, expression levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and cortisol receptor (HSP70) genes were evaluated in this study. It was calculated that 0.199 mg/L of folpet was the 96 h-LC50 value. After the folpet exposure for 14 days, significant decreases in red blood cells, hemoglobin, hematocrit, serum total protein, and GST gene expression levels were observed while serum glucose, liver enzymes activities, and expression levels of CAT, SOD, GPx, HSP70 genes increased. Also, folpet induced a significant genotoxic effect on the blood cells regarding to DNA damages. Consequently, the results have shown the toxic effects of folpet even at the lowest concentration on common carp.

Lodoxamide-Loaded Nanofibrous Wound Dressings Promote Wound Healing via Downregulation of IL-1β, NFK-β, and GPx Genes

Diabetic wounds are major clinical challenges which need immediate care to prevent complications such as limb amputation. There are a variety of treatment strategies available for the treatment of diabetic wounds among which wound dressings are the most effective and provide better therapeutic outcome. Lodoxamide was loaded into gelatin scaffolds in order to develop a potential wound dressing material for diabetic wound healing. Electrospinning method was used for the fabrication of wound dressings containing three different concentrations of 1 w/w%, 3 w/w%, and 6 w/w% of Lodoxamide. The developed scaffolds were studied regarding their various physicochemical and biological properties. In vitro study showed that the dressings containing 3% drug had significantly higher cell viability and cytoprotection under oxidative stress. Therefore, this formulation was chosen for treating diabetic wounds in a rat model of excisional diabetic wound. In vivo study showed that gelatin/3% Lodoxamide group had higher wound healing compared with other experimental groups. Gene expression studies showed that the wounds treated with drug-delivering wound dressings showed significantly lower tissue expression level of glutathione peroxidase gene, IL-1β gene, and NFK-β gene.

Resveratrol Protects BEAS-2B Cells against Erastin-Induced Ferroptosis through the Nrf2/Keap1 Pathway.

Ferroptosis is a newly discovered type of cell death that is different from other types of cell death morphologically and biologically. It is considered to play an important role in many pulmonary diseases. Currently, the regulatory roles of antioxidation in lung epithelial ferroptosis have not been fully explored. In this study, we show that resveratrol protected erastin-induced ferroptosis in BEAS-2B cells. Erastin led to increased reactive oxygen species production and iron deposition in BEAS-2B cells, which could be rescued by resveratrol. Furthermore, we observed that resveratrol led to modulating ferroptosis-associated gene glutathione peroxidase 4 expression and regulating glutathione in BEAS-2B cells. Resveratrol exerted an antioxidant property in erastin-induced ferroptosis of BEAS-2B cells by activating the nuclear factor-erythroid 2-related factor 2/Kelch-like ECH-associated protein signaling pathway. Finally, these findings demonstrate that resveratrol protects BEAS-2B from erastin-induced ferroptosis.

Effect of long-term manganese exposure on oxidative stress, liver damage and apoptosis in grouper Epinephelus moara ♀ × Epinephelus lanceolatus ♂

Manganese is an indispensable trace element, however, it may be present at high concentrations in water and sediments of aquatic ecosystems due to natural and anthropogenic activities, and can interfere with physiological and biochemical mechanisms in fish. This study was conducted to determine the toxic effects associated with exposure to Mn2+ (0, 0.5, 1, 2, and 4 mg/L) for 30 d, regarding liver damage and apoptosis in Yunlong grouper (Epinephelus moara♀×E. lanceolatus♂). Expression of superoxide dismutase (sod) and catalase (cat) genes in the liver was significantly increased on days 10 and 20 following Mn2+ exposure (4 mg/L), but was reduced on day 30. Similarly, expression of glutathione peroxidase (gpx) and glutathione reductase (gr) genes was elevated after 10 d of exposure to 2 and 4 mg/L Mn2+, but decreased after 20 and 30 d. After 30 d of exposure to high concentrations (2 and 4 mg/L) of Mn2+, liver tissue showed hepatic sinusoidal gap congestion, dilatation, cell vacuolation, and necrosis. In addition, the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) as well as 8-hydroxydeoxyguanosine (8-OHdG) levels were significantly increased after Mn2+ exposure. Moreover, Mn2+ exposure altered the expression pattern of some pivotal genes associated to apoptosis (p53, bax, bcl-2, apaf-1, caspase-9, and caspase-3), which suggested that Mn2+ exposure induces apoptosis through the mitochondrial pathway. The above results showed that excessive Mn2+ induced apoptosis and liver damage in grouper through elicitation of oxidative stress. These insights help elucidate the mechanism by which Mn2+ induces toxicity in marine fish, and provide a new perspective regarding the detrimental effects of heavy metals in fish.

Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms

Background The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin. Results In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity. Conclusion Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.

Stress tolerance and transcriptomic response analysis of Yersinia enterocolitica adapted to Origanum vulgare L. essential oil

The adaptability of foodborne pathogens to sublethal concentrations of antimicrobials including essential oils poses a great threat to food safety. The aim of this study was to evaluate the effect of pre-exposure of Origanum vulgare L. essential oil (OVEO) on the tolerance of Yersinia enterocolitica and explore its adaptive response mechanism by the RNA-Seq. Our data showed that the OVEO induced the direct-tolerance to OVEO and the cross-tolerance to NaCl, KCl and ROEO. In total, 300 DEGs after sublethal OVEO adaption were identified, including 145 upregulated and 155 downregulated. Firstly, OVEO stress could cause proton motive force (PMF) dissipation, Y. enterocolitica activated the phage shock protein response (3.3–3.7 log2(FC)) and reduced unnecessary energy consumption such as mobility, flagellum formation and quorum sensing to maintain the PMF balance and ensure the normal physiological function. Secondly, genes associated with synthesis and transport of glycerol-3-phosphate were upregulated 1.7–2.2 log2(FC) to repair the structure and function of cell membrane under OVEO stress. Besides, PstSCAB transporter of phosphotransferase system were activated to ensure the energy supply and cell constituents synthesis under OVEO stress. Finally, Y. enterocolitica prevented the cell from oxidization damage by increasing the expression of glutathione peroxidase and amino acid synthesis-associated genes (2.0–3.9 log2(FC)).

Material properties of degradable alloy Fe-30Mn-0.6N and its effect on ferroptosis in synoviocytes.

Ferroalloy has shown potential as implant materials, but little attention has been paid to their effects on synovial tissue ferroptosis. This study aimed to examine the mechanical properties, degradability and biocompatibility of Fe-30Mn-0.6N alloy and effects of it on synovial tissue ferroptosis. Tensile testing showed that Fe-30Mn-0.6N alloys exhibited tensile strength of 487 ± 18 MPa, yield strength of 221 ± 10 MPa, elongation of 16.9 ± 0.3% and Young's modulus of 37.7 ± 1.3 GPa. In vivo experiments, the cross-sectional area of the Fe-30Mn-0.6N alloys decreased by 73.32 ± 12.73% after 8 weeks of implantation. The results of scanning electron microscopy (SEM) and surface elemental analysis (EDS) showed that the Fe-30Mn-0.6N alloys had more Ca, O, C and P element deposition (p < .05). After 2, 4 and 8 weeks of implantation, no inflammatory response was observed in peri-implant synovial tissue of Fe-30Mn-0.6N and Ti-6Al-4V alloys, and Fe-30Mn-0.6N alloys did not affect the expression of the ferroptosis inhibitory gene Glutathione peroxidase 4 (GPX4). Compared with the control group, 30% Fe-30Mn-0.6N alloy extracts did not affect the cell viability (p > .05) in vitro, and intracellular Fe2+ and the reactive oxygen species (ROS) was significantly reduced (p < .05). WB and PCR results showed that the 30% extracts increased the protein activity and mRNA expression of GPX4, FTH1 and SLC7A11 in synoviocytes, but had no effect on PTGS2 and p53. It is concluded that Fe-30Mn-0.6N had degradability and biocompatibility in peri-implant synovial tissue, and did not induce significantly ferroptosis in synoviocytes.

Fenugreek Extract-Loaded Polycaprolacton/Cellulose Acetate Nanofibrous Wound Dressings for Transplantation of Unrestricted Somatic Stem Cells: An In Vitro and In Vivo Evaluation

Complex pathophysiology of diabetic wounds causes a delayed wound healing response. Advanced wound dressing materials that deliver biochemical cues are of particular interest in wound healing research. Here, we developed a dual-function delivery vehicle for drug and cell delivery applications to treat diabetic wounds. The delivery system was developed via electrospinning of polycaprolacton/cellulose acetate solution containing fenugreek extract. The produced delivery vehicle was characterized using microstructural studies, cell viability assay, cytoprotection assay, cell migration assay, In Vitro anti-inflammatory assay, free radical scavenging assay, tensile strength studies, swelling studies, and protein adsorption test. Scaffolds were then seeded with 30000 unrestricted somatic stem cells and transplanted into the rat model of excisional diabetic wound. Wound healing assay showed that the co-delivery of fenugreek extract and unrestricted somatic stem cells led to a substantial improvement in the healing activity of electrospun dressings, as evidenced by higher wound contraction, epithelial thickness, and collagen deposition in this group compared with other experimental groups. Gene expression analysis showed that dual-function delivery system could increase the expression level of VEGF, b-FGF, and collagen type II genes. Furthermore, the tissue expression level of IL-1β and glutathione peroxidase genes was significantly reduced in this group compared with other groups. This study shows that the developed system may be considered as a potential treatment modality for diabetic wounds in the clinic.

An accidental discovery of mannan-oligosaccharide's protection effect against air exposure and its potential mechanism in hybrid grouper (Epinephelus lanceolatus ♂ × Epinephelus fuscoguttatus ♀).

The original objective was to explore the potential benefiting effects of three prebiotics in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Therefore, three experimental diets (basal diet + 1% fructooligosaccharide, Diet F; basal diet + 1% inulin, Diet I; basal diet + 0.3% mannan-oligosaccharide, Diet M) and one basal diet (Diet C) were prepared and a feeding trial was conducted. However, at the end of the fourth week into the feeding experiment, a water-leaking accident occurred and fishes of all groups went through an unexpected air exposure event. Surprisingly, different prebiotic-supplemented groups showed significantly different air exposure tolerance: the mortality of M group was significantly lower (P ≤ 0.05) than all the other groups. Examination of antioxidant, non-specific immunity, and stress parameters revealed that comparing to control group, M group showed significantly increased catalase (CAT), acid phosphatase (ACP), and alkaline phosphatase (AKP) activities, decreased superoxide dismutase (SOD) activity, and similar cortisol level (P ≤ 0.05). Real-time PCR experiment revealed that M group significantly increased the expression of CAT, glutathione peroxidase (GPx), and manganese superoxide dismutase (MnSOD) genes in head kidney (P ≤ 0.05). Overall, M exhibited the best anti-air exposure/antioxidative stress effects among the three prebiotics and could be considered a promising feed additive to relieve air exposure/oxidative stress in hybrid grouper culture.

The growth performance, antioxidant and immune responses, and disease resistance of Litopenaeus vannamei fed on diets supplemented with Indian ginseng (Withania somnifera)

In the current study, white-leg shrimp (Litopenaeus vannamei) were fed on diets containing varying doses of Withania somnifera aqueous extract (WSAE) at a rate of 0 (control), 0.5, 1.0, and 2.0 g/kg feed for 56 days. After the feeding trial, shrimps in all groups were challenged with the exposure to Vibrio harveyi for ten days during which animals' mortality was observed. It is noted that the dietary WSAE linearly and quadratically stimulated shrimp's growth indices particularly at the treatment of 2.0 g/kg feed. Compared to the control group, the WSAE-fed L. vannamei had significantly higher villi length, villi width, and absorption area particularly in the treatment of 2.0 g/kg feed. Furthermore, L. vannamei fed on WSAE-enriched diets consumed more feed and exhibited higher total proteolytic activity, lipase, and α-amylase activities as compared with the control group. The dietary WSAE at escalating levels linearly and quadratically enhanced the antioxidant activity (serum superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity, and reduced glutathione) and the immune response (total hemocyte counts, total protein, lysozyme, and phagocytic activity). Similarly, the mRNA expression levels of cMn-SOD, CAT, and GPx genes were linearly and quadratically upregulated in the hepatopancreas of L. vannamei fed on WSAE-enriched diets (especially in the 2.0 g/kg feed treatment), while their lowest levels were significantly observed in the control group. On the other hand, malondialdehyde levels were significantly decreased in WSAE-supplemented shrimp groups, and its highest levels were observed in animals fed on the control diet. After the bacterial exposure, the survival rates of L. vannamei fed on 1.0 and 2.0 g WSAE/kg feed (61.3% and 66.7%, respectively) were higher than those in the control animals. Taken together, the results obtained herein indicate that inclusion of WSAE in diets of L. vannamei effectively enhanced the growth, antioxidant biomarkers, immune response, and resistance to the V. harveyi infection, particularly at the treatment of 2.0 g/kg feed.

From Photocatalysis to Photo-Electrocatalysis: An Innovative Water Remediation System for Sustainable Fish Farming

In this study, the effects of photo-electrocatalysis (PEC) were evaluated as an innovative application of conventional photocatalysis (PC) to remediate water in a recirculating system for rainbow trout (Oncorhynchus mykiss) culture, in relation to fish welfare and health, with a multidisciplinary approach. Three tanks were employed, equipped with conventional biological filters as a control system, and three tanks equipped with the PEC purification system. The concentrations of ammonia, nitrite and nitrate ions in water were monitored, and the fish’s oxidative damage and stress response were evaluated in parallel. The water of the PEC-treated experimental group showed lower ammonia (TAN) and nitrite concentrations and higher nitrate concentration, possibly deriving from TAN oxidation through PEC, also leading to gaseous N2. Histological analysis did not reveal any pathological alteration in the gills and liver of both groups. The superoxide dismutase (sod1), glutathione reductase (GR), glutathione peroxidase (GPx1), and Tumor necrosis factor (TNFα) gene expressions were significantly higher in the control group than in the PEC-treated group, while the Heat shock protein 70 (Hsp70) expression did not show any difference in the two groups. These results indicate that the use of PEC filters has a positive effect on water quality, compared to the use of conventional biological filters, inducing a high level of welfare in O. mykiss.

GsMYB7 encoding a R2R3-type MYB transcription factor enhances the tolerance to aluminum stress in soybean (Glycine max L.)

BackgroundMYB transcription factor (TF) is one of the largest families of TFs in plants and play essential roles in plant growth and development, and is involved in responses to biological and abiotic stress. However, there are few reports on GsMYB7 gene in soybean under aluminum acid stress, and its regulatory mechanism remains unclear.ResultsThe GsMYB7 protein is localized in the nucleus and has transcriptional activation ability. Quantitative real-time PCR (qRT-PCR) results showed that GsMYB7 held a constitutive expression pattern rich in roots. When AlCl3 concentration was 25 µM, the total root surface area (SA) of GsMYB7 transgenic lines were 34.97% higher than that of wild-type Huachun 6 (HC6). While the accumulation of Al3+ in root tip of transgenic plants after aluminum treatment was 17.39% lower than that of wild-type. RNA-sequencing analysis indicated that over 1181 genes were regulated by GsMYB7 and aluminum stress. Among all the regulated genes, the expression levels of glutathione peroxidase, protein kinase, cytochrome and other genes in the transgenic lines were significantly higher than those in wild type by acidic aluminum stress. The bioinformatics and qRT-PCR results showed that 9 candidate genes were induced under the treatments of acidic aluminum stress which were indirectly and/or directly regulated by GsMYB7. After AlCl3 treatments, the transcripts of these genes in GsMYB7 transgenic seedlings were significantly higher than those of wide-type HC6.ConclusionsThe results suggested that GsMYB7 may enhance soybean tolerance to acidic aluminum stress by regulating the downstream genes.

Mortality, Enzymatic Antioxidant Activity and Gene Expression of Cabbage Aphid (Brevicoryne brassicae L.) in Response to Trichoderma longibrachiatum T6.

Aphids are one of the most common insect pests in greenhouse and field crops worldwide, causing significant crop yields and economic losses. The objective of this study was to determine the mortality, enzymatic antioxidant activity and gene expression of cabbage aphids (Brevicoryne brassicae L.) in response to Trichoderma longibrachiatum T6 (T6) at different time points from Day 1 to 7 after inoculation. Our results showed that the highest mortality of B. brassicae was observed on Day 7 at a concentration of 1 × 108 spores ml−1 (73.31%) after inoculation with T6 compared with the control on Day 7 (11.51%). The activities of the enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX) and glutathione S-transferase (GST) were increased by 52.98%, 44.77%, 48.26%, 49.39%, 45.13% and 39.67%, respectively on Day 3 after inoculation with T6 compared to the control. Howerver increased days post treatment (dpt) decreased the activities of SOD, POD, CAT, APX, GPX and GST enzymes by 20.79%, 21.05%, 13.75%, 20.45%, 25.38%, and 19.76% repectively on Day 7 compared to control. The transcript levels of SOD, POD, CAT, GPX, and GST genes were increased by 10.87, 9.87, 12.77, 6.22 and 4.07 respectively at Day 3 after inoculation with T6 in comparison to the control. However, the SOD, POD, CAT, GPX, and GST transcription levels decreased by 0.43, 0.44, 0.35, 0.52 and 0.47 respectively, compared to control at Day 7. Our results suggest that the T6 strain has a potential effect on the antioxidant activity and mortality of B. brassicae and therefore could be used as a natural biocontrol agent against B. brassicae in the future.

Individual and combined effects of the dietary Spirulina platensis and Bacillus licheniformis supplementation on growth performance, antioxidant capacity, innate immunity, relative gene expression and resistance of goldfish, Carassius auratus to Aeromonas hydrophila

This study evaluated the individual and combined effects of the dietary Spirulina platensis (SP) and probiotic bacterium Bacillus licheniformis (BL) on the growth performance, immune responses, and disease resistance in goldfish (Carassius auratus). A total of 216 fish (3.39 ± 0.24 g) were randomly distributed in 12 tanks with 18 fish per tank (4 treatments with 3 replications) and fed with diets containing 0% S. platensis and B. licheniformis (T0), 108 CFU/g B. licheniformis (T1), 2.5% S. platensis (T2), and 108 CFU/g B. licheniformis + 2.5% S. platensis (T3(. There were no significant differences in growth parameters. The alternative complement pathway (ACH50) and lysozyme activity were significantly increased in T2 and T3 treatments. No marked differences were observed in total immunoglobulin and protease activity among treatments (P > 0.05). The relative expression of IGF-1 was not affected by experimental diets (P > 0.05). Ghrelin gene showed significantly higher mRNA levels in fish fed with SP and BL (P < 0.05). The relative expression of catalase (CAT), and glutathione reductase (GSR) significantly increased in fish fed with the SP and BL (P < 0.05). No marked difference in glutathione peroxidase (GPX) gene expression was seen between the treatments (P > 0.05). The mRNA levels of lysozyme, IL6, IL-1β, TGF, and TNF2 transcription were higher in fish fed with SP and BL (P < 0.05). No notable difference was observed in TNF1 and IL10 gene expression between treatments (P > 0.05). Moreover, the result of the challenge test with A. hydrophila showed that goldfish fed with SP and BL had a lower mortality rate than the control. In conclusion, the supplementation of SP and BL can be used as feed additives to enhance disease resistance against A. hydrophila infection by stimulating the immune system in goldfish.

Effect of Oligogalacturonides on Seed Germination and Disease Resistance of Sugar Beet Seedling and Root.

Oligogalacturonides (OGs) are a bioactive carbohydrate derived from homogalacturonan. The OGs synthesized in this study significantly inhibited the mycelial growth of Rhizoctonia solani AG-4HGI in vitro, even at a low concentration (10 mg/L). The seed vigor test demonstrated that the application of 50 mg/L OGs to sugar beet seeds significantly increased average germination percentage, germination energy, germination index, and seedling vigor index. The same concentration of OGs also improved the seedling emergence percentage of sugar beet when seeds were sown in soil inoculated with D2 and D31 isolates, respectively. The lesion diameter on mature sugar beet roots caused by R. solani AG-4HGI isolates D2 and D31 also decreased by 40.60% and 39.86%, respectively, in sugar beets roots first treated with 50 mg/mL OGs in the wound site, relative to lesion size in untreated/pathogen inoculated wounds. Sugar beet roots treated with 50 mg/mL OGs prior to inoculation with the D2 isolate exhibited up-regulation of the defense-related genes glutathione peroxidase (GPX) and superoxide dismutase (SOD) by 2.4- and 1.6-fold, respectively, relative to control roots. Sugar beet roots treated with 50 mg/mL OGs prior to inoculation with D31 exhibited a 2.0- and 1.6-fold up-regulation of GPX and SOD, respectively, relative to the control. Our results indicate that OGs have the potential to be used for the protection of sugar beet against R. solani AG-4HGI.

Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer.

Simple SummaryGlutathione peroxidase 1 (GPX1), as one of the most important antioxidant enzymes, maintains cellular redox balance by regulating reactive oxygen species levels. In this review, we summarize and discuss the relationship between GPX1 genetic polymorphisms and cancer susceptibility, as well as the dichotomous roles of GPX1 aberrant expressions in the occurrence and development of human malignancies via various biological mechanisms. Our work may deepen the understanding of the critical clinical values and future directions of GPX1 as a potential prognostic biomarker and novel cancer therapeutic target.As the first identified selenoprotein, glutathione peroxidase 1 (GPX1) is a widely and abundantly expressed antioxidant enzyme. GPX1 utilizes glutathione as a substrate to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, thereby reducing intracellular oxidative stress. The GPX1 gene is regulated at transcriptional, post-transcriptional, and translational levels. Numerous case-control studies and meta-analyses have assessed the association between a functional genetic polymorphism of the GPX1 gene, named Pro198Leu (rs1050450 C>T), and cancer susceptibility in different populations. GPX1 polymorphism has type-specific effects as a candidate marker for cancer risk, but the association between GPX1 variants and cancer susceptibility remains controversial in different studies. GPX1 is abnormally elevated in most types of cancer but has complex dichotomous roles as tumor suppressor and promoter in different cancers. GPX1 can participate in various signaling pathways to regulate tumor biological behaviors, including cell proliferation, apoptosis, invasion, immune response, and chemoresistance. In this review, we comprehensively summarize the controversial associations between GPX1 polymorphism and cancer risks and further discuss the relationships between the aberrant expressions of GPX1 and tumorigenesis. Further studies are needed to elucidate the clinical significance of GPX1 as a potential prognostic biomarker and novel therapeutic target in various malignancies.

The effect of density on sex differentiation, sexual dimorphism, stress, and related gene expression in yellow perch.

A 180-day experiment was conducted to evaluate the effects of density on sex differentiation, sexual dimorphism, cortisol level, and stress related gene expression. Yellow perch, Perca flavescens, with initial mean body weight of 0.03 ± 0.001 g were reared in three different stocking densities: 1, 2, and 4 fish/L, termed as low (LD), moderate (MD), and high (HD) density, respectively, in a flow-through tank system. Results showed no significant differences in sex ratio in all density groups compared to normal population 1:1, and sexual size dimorphism (SSD) appeared when male and female were as small as the mean size reaching 11.5 cm and 12.3 cm in total length (TL) or 13.2g and 16.9g in body weight (BW), respectively. This female-biased sexual growth dimorphism was more pronounced in LD, although it was observed across all density groups. A significantly higher condition factor (K) of females than males in the LD group, and significantly higher R values of LD and MD than HD with the length/weight (L/W) linear relationships in females, were observed. Parallelly, fish reared in LD showed significantly higher mean body weight than those in the MD and HD groups, but there were no significant differences between the MD and HD. Similar results were also observed in all the other parameters of weight gain, specific growth rate (SGR), condition factor (K), and survival. These findings suggested that high density not only affected growth itself, but also affected SSD, growth trajectory or body shape, and general wellbeing in fish, especially in females. There were no significant differences in gonadosomatic index (GSI) and viscerosomatic index (VSI) among all the density groups; however, the hepatosomatic index (HSI) of LD was significantly higher than MD and HD, suggesting high density affected liver reserves or functions. Physiologically, plasma cortisol level was significantly highest in the LD among all groups, followed by MD, and lowest in HD. At the molecular level, the expression of the 70-kDa heat shock protein (Hsp70), glutathione peroxidase (GPx), and superoxide dismutase (SOD) genes involved in cellular stress were significantly upregulated in the HD group. The most significantly downregulated expression of these genes was consistently observed in the MD when compared to the LD and HD groups. In conclusion, increasing density induced chronic stress in yellow perch without affecting sex differentiation, but negatively affected expression of stress-related genes and mobilization of liver reserve, resulting in poorer wellbeing and reduced SSD, growth, and survival.

Characteristics of glutathione peroxidase gene and its responses to ammonia-N stress in razor clam Sinonovacula constricta

Glutathione peroxidase (GPX) is a crucial enzyme in the antioxidant defense system. However, the previous studies on the structure and functions of mollusk GPX genes are still very limited. Here, we investigated the GPX gene from Sinonovacula constricta (Sc-GPX), and its expression profiles, protein localization, gene function and association with ammonia tolerance. The full length of sequence of Sc-GPX was 1781 bp, containing an open reading frame (ORF) of 588 bp encoding 195 amino acids. Quantitative expression of seven adult tissues showed that Sc-GPX was most abundant in hepatopancreas, followed by gills. Furthermore, the enzyme activity of Sc-GPX in hepatopancreas increased significantly under different ammonia concentrations (100, 140, and 180 mg/L) (P < 0.01). Further, we explored the mRNA expression level, histological structure and histo-cellular localization in gills and hepatopancreas of Sc-GPX under 140 mg/L ammonia stress. The mRNA expression level in gills and hepatopancreas of Sc-GPX increased significantly (P < 0.05) and immunohistochemistry results suggested that the columnar cells of gills filaments and the endothelial cells of hepatopancreas were the major sites for the action of Sc-GPX protein. In addition, we performed western blotting (WB), RNA interference (RNAi) and single nucleotide polymorphisms (SNPs) in the hepatopancreas of Sc-GPX under ammonia stress (140 mg/L). WB results indicated that the protein expression of Sc-GPX increased significantly (P < 0.01) after ammonia challenge. In addition, expression of Sc-GPX mRNA were significantly downregulated at 24 and 48 h after RNAi (P < 0.01). The association analysis between ammonia-tolerance group and control group identified six SNPs in coding sequence (CDS) of Sc-GPX from 449 individuals. Among them, c.162A > C was missense mutation, which lead to the amino acid change from Lys to Asn. These findings revealed that Sc-GPX may play a critical role in clam ammonia detoxification.

Propionyl-L-Carnitine-Delivering Wound Dressings for the Treatment of Diabetic Wounds: An In Vitro and In Vivo Study

In the current study, a Propionyl-L-carnitine (PLC)-delivering porous wound dressing was developed using lyophilization method. PLC was added into the polymeric solutions at four different concentrations of 1 w/w%, 3 w/w%, 5 w/w%, and 10 w/w% and then lyophilized. Various experiments were performed in order to characterize the developed wound dressings. Cell viability experiments showed that dressings containing 5 w/w% PLC had significantly higher cell viability under normal and oxidative stress conditions. For this reason, the healing activity of this formulation was investigated In Vivo. Rat model of diabetic wound healing was used for the assessment of wound dressings healing activity. Wound healing assay showed that calcium alginate/CMC/5% PLC wound dressings had significantly higher rate of wound closure, epithelial thickness, and collagen deposition compared with other groups. Gene expression studies showed that the developed wound dressings reduced the tissue expression level of Glutathione peroxidase and NFk-β genes. This preliminary study implies the potential application of calcium alginate/CMC/5% PLC to treat diabetic wounds in clinic. However, study in larger animal models is required for its clinical translation.