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Background: Noncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet's disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis. Methods: Bioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values. Results: The expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD. Conclusion: Mechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures. Trial registration The protocol for the clinical studies was approved by Cairo University's Faculty of Pharmacy's Research Ethics Committee (approval number: BC 3590) [ABSTRACT FROM AUTHOR]

Abstract Background Noncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet’s disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis. Methods Bioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values. Results The expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD. Conclusion Mechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures. Trial registration The protocol for the clinical studies was approved by Cairo University’s Faculty of Pharmacy’s Research Ethics Committee (approval number: BC 3590)

The aim of this study was to evaluate the changes induced in testicular tissue by administration of dandelion (Taraxacum officinale) extract and its effects on the release of enzymatic antioxidants SOD-2 by immunohistochemical methods in rats with experimental diabetes. Degenerative changes in the seminiferous tubule structure were observed in the testicular sections of the diabetes group. Separations between the basement membrane and the seminiferous epithelium, disruptions in the structure and localization of spermatogenic cells toward the lumen of the seminiferous tubules, thickening of the basement membrane and tunica albuginea, changes in the shape of Sertoli cells, and shrinkage of the nucleus of Leydig cells were observed. While no immunopositivity was observed in spermatogonium and primary spermatocytes in the diabetes group, weak SOD-2 immunoreactivity was observed in other cells of the spermatogenic series and moderate SOD-2 immunoreactivity was observed in the diabetes+dandelion group. In conclusion, it was found that histopathological changes occurred in the testicular tissue and SOD-2 immunoreactivity decreased in diabetes, a chronic metabolic disease. It was concluded that dandelion administration may have beneficial effects on decreased SOD-2 immunoreactivity [ABSTRACT FROM AUTHOR]

Actin in neuronal processes is both stable and dynamic. The origin & functional roles of the different pools of actin is not well understood. We find that mutants that lack mitochondria, ric-7 and mtx-2; miro-1 , in neuronal processes also lack dynamic actin. Mitochondria can regulate actin dynamics upto a distance ~80 μm along the neuronal process. Absence of axonal mitochondria and dynamic actin does not markedly alter the Spectrin Membrane Periodic Skeleton (MPS) in touch receptor neurons (TRNs). Restoring mitochondria inTRNs cell autonomously restores dynamic actin in a sod-2 dependent manner. We find that dynamic actin is necessary and sufficient for the localization of gap junction proteins in the TRNs and for the C. elegans gentle touch response. We identify an in vivo mechanism by which axonal mitochondria locally facilitate actin dynamics through reactive oxygen species that we show is necessary for electrical synapses & behaviour.

Over the last decade, a rapid rise in deaths due to liver disease has been observed especially amongst young people. Nowadays liver disease accounts for approximately 2 million deaths per year worldwide: 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. Besides primary liver malignancies, almost all solid tumours are capable to spread metastases to the liver, in particular, gastrointestinal cancers, breast and genitourinary cancers, lung cancer, melanomas and sarcomas. A big portion of liver malignancies undergo palliative care. To this end, the paradigm of the palliative care in the liver cancer management is evolving from "just end of the life" care to careful evaluation of all aspects relevant for the survivorship. In the presented study, an evidence-based approach has been taken to target molecular pathways and subcellular components for modelling most optimal conditions with the longest survival rates for patients diagnosed with advanced liver malignancies who underwent palliative treatments. We developed an unsupervised machine learning (UML) approach to robustly identify patient subgroups based on estimated survival curves for each individual patient and each individual potential biomarker. UML using consensus hierarchical clustering of biomarker derived risk profiles resulted into 3 stable patient subgroups. There were no significant differences in age, gender, therapy, diagnosis or comorbidities across clusters. Survival times across clusters differed significantly. Furthermore, several of the biomarkers demonstrated highly significant pairwise differences between clusters after correction for multiple testing, namely, "comet assay" patterns of classes I, III, IV and expression rates of calgranulin A (S100), SOD2 and profilin—all measured ex vivo in circulating leucocytes. Considering worst, intermediate and best survival curves with regard to identified clusters and corresponding patterns of parameters measured, clear differences were found for "comet assay" and S100 expression patterns. In conclusion, multi-faceted cancer control within the palliative care of liver malignancies is crucial for improved disease outcomes including individualised patient profiling, predictive models and implementation of corresponding cost-effective risks mitigating measures detailed in the paper. The "proof-of-principle" model is presented. [ABSTRACT FROM AUTHOR]

Introducción: El estrés oxidativo ha sido implicado en el desarrollo y la progresión de la calcificación vascular (CV); sin embargo, aún existen interrogantes sobre esta asociación causal. Objetivo: Analizar en un modelo experimental de insuficiencia renal crónica (IRC) el efecto del estrés oxidativo sobre el desarrollo y la progresión de la CV, evaluando la implicación del microARN-377 (miR-377). Material y métodos: Se estudiaron 2 grupos de ratas Wistar con IRC. El grupo 1 recibió dieta normal en fósforo (IRC+PN). El grupo 2 recibió dieta con alto fósforo (IRC+PA). Se incluyó un grupo de ratas Sham. Trascurridas 20 semanas, las ratas fueron sacrificadas. Resultados: El fósforo y la parathormona séricos no aumentaron en el grupo IRC+PA respecto al IRC+PN, pero sí los niveles de factor de crecimiento fibrobástico 23 (FGF23). En el grupo IRC+PN aumentó tres veces el contenido aórtico de calcio respecto al grupo Sham, un aumento 17 veces superior en el grupo IRC+PA, donde la densidad mineral ósea en tibia proximal descendió significativamente. En el grupo IRC+PN la expresión del miR-377 disminuyó un 65%, sin efecto adicional de la dieta con alto contenido en fósforo. En el grupo IRC+PN aumentó 3 veces la expresión proteica de superóxido dismutasa 2 mitocondrial (SOD-2), y en el grupo IRC+PA lo hizo hasta 6 veces. Conclusiones: La IRC con o sin alto contenido en fósforo en la dieta desencadenó el descenso del miR-377. El exceso de fósforo incrementó la SOD-2 como mecanismo compensador para frenar el estrés oxidativo y el daño vascular. Controlar el contenido en fósforo en la dieta cuando la función renal se ve comprometida permitirá aminorar el daño vascular producido como consecuencia, entre otros factores, del estrés oxidativo.

Background: Oxidative stress is concomitant with acetaminophen (APAP)-induced hepatotoxicity, which has been highlighted as therapeutic targets for such diseases. The berries of Seabuckthorn (Hippophae rhamnoides L.) have been traditionally used in Tibetan medicine for thousands of years. The effect of Seabuckthorn berry polysaccharide on drug- induced liver injury (DILI) has not yet been elucidated.Purpose: This study aims to investigate the protective effects and mechanisms of Seabuckthorn polysaccharide (SP) against APAP-induced hepatotoxicity.Study Design: Sixty C57BL/6 mice were randomly divided into six groups (n = 10 per group), namely the control group (Ctrl), APAP-induced-liver injury group (APAP), NAC pretreated group (NAC), 100 mg/kg SP pretreated group (APAP/SP100), 200 mg/kg SP pretreated group (APAP/SP200) and 200 mg/kg SP pretreated group without APAP challenge (SP200). SP was given orally to mice for 30 consecutive days prior to APAP exposure (300 mg/kg). NAC (150 mg/kg) was administrated 1 h before APAP challenge.Methods: ALT and AST were detected 16 h after APAP treatment; Hepatic expression of GSH, SOD, NO, iNOS and GSH-Px were examined. The expression of p-JNK, Bcl-2/Bax, p62, Keap-1 and SOD-2 was detected by Western blotting. The expression of Nrf-2 and its target genes HO-1, GCLC and NQO-1 were analyzed by RT-PCR and Western blotting.Results: Pretreatment with SP led to decreased levels of ALT and AST in APAP mice, without affecting APAP metabolism. This was accompanied by diminished liver injuries, increased levels of GSH and GSH-Px, reduced NO and iNOS expression. SP increased the activity of SOD as well as SOD-2 expression in APAP mice. SP suppressed APAP-induced JNK phosphorylation and increased the ratio of Bcl-2/Bax. Furthermore, SP decreased the expression of Keap-1 and increased the nuclear expression of Nrf-2. The expression of Nrf-2 target gene HO-1 was increased by SP pretreatment in APAP mice.Conclusion: SP alleviates APAP-induced hepatotoxicity. The protective effects of SP are associated with the activation of the Nrf-2/HO-1-SOD-2 signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress has been implicated in the development and progression of vascular calcification (VC). However, this causal association remains a matter of controversy. Objective: To analyze in an experimental model of chronic renal failure (CRF), the effect of oxidative stress on the development and progression of the VC, assessing the implication of microRNA-377 (miR-377). Material and methods: Two groups of Wistar rats with CRF were studied. Group 1 received normal diet in phosphorus (CRF+NP). Group 2 received a high phosphorus (CRF+HP) diet. A group of sham rats was included. After 20 weeks, the rats were sacrificed. Results: Serum phosphorus and parathormone did not increase in the CRF+HP group compared to CRF+NP, but fibroblast growth factor 23 (FGF23) levels significantly increased. In the CRF+NP group, aortic calcium content increased three-fold over the sham group, a 17-fold increase in the CRF+HP group, where the bone mineral density in the proximal tibia decreased significantly. In the IRC+NP group, the expression of miR-377 decreased by 65%, with no additional effect detected of the diet with high phosphorus content. In the IRC+NP group, the protein expression of mitochondrial superoxide dismutase 2 (SOD-2) increased 3-fold, and in the IRC+HP group it increased up to 6-fold. Conclusions: CRF, with or without high phosphorus dietary content, triggered the descent of miR-377. Excess phosphorus increased SOD-2 as a compensatory mechanism to curb oxidative stress and vascular damage. Controlling phosphorus content in the diet when the renal impairment function is compromised will reduce the vascular damage produced due oxidative stress, among other factors. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress has been implicated in the development and progression of vascular calcification (VC). However, this causal association remains a matter of controversy. Objective: To analyze in an experimental model of chronic renal failure (CRF), the effect of oxidative stress on the development and progression of the VC, assessing the implication of microRNA-377 (miR-377). Material and methods: Two groups of Wistar rats with CRF were studied. Group 1 received normal diet in phosphorus (CRF+NP). Group 2 received a high phosphorus (CRF+HP) diet. A group of Sham rats was included. After 20 weeks, the rats were sacrificed. Results: Serum phosphorus and parathormone did not increase in the CRF+HP group compared to CRF+NP, but fibroblast growth factor 23 (FGF23) levels significantly increased. In the CRF+NP group, aortic calcium content increased three-fold over the Sham group, a 17-fold increase in the CRF+HP group, where the bone mineral density in the proximal tibia decreased significantly. In the CRF+NP group, the expression of miR-377 decreased by 65%, with no additional effect detected of the diet with high phosphorus content. In the CRF+NP group, the protein expression of mitochondrial superoxide dismutase 2 (SOD-2) increased 3-fold, and in the CRF+HP group it increased up to 6-fold. Conclusions: CRF, with or without high phosphorus dietary content, triggered the descent of miR-377. Excess phosphorus increased SOD-2 as a compensatory mechanism to curb oxidative stress and vascular damage. Controlling phosphorus content in the diet when the renal impairment function is compromised will reduce the vascular damage produced due oxidative stress, among other factors. [ABSTRACT FROM AUTHOR]

Photoactivated hypericin increased production of reactive oxygen species in human breast adenocarcinoma MCF-7 as well as in MDA-MB-231 cells 1 h after photodynamic therapy. On the other hand, reactive oxygen species dropped 3 h after photodynamic therapy with hypericin, but only in MCF-7 cells, whereas in MDA-MB-231 cells remained elevated. The difference in the dynamics of reactive oxygen species after hypericin activation was related to increased activity of SOD-2 in MCF-7 cells compared to MDA-MB-231 cells. Indeed, photodynamic therapy with hypericin significantly increased SOD-2 activity in MCF-7 cells, but only slightly in MDA-MB-231 cells. In this regard, SOD-2 activity correlated well with enhanced both mRNA expression as well as SOD-2 protein level in MCF-7 cells. The role of SOD-2 in the resistance of MCF-7 cells to photodynamic therapy with hypericin was monitored using SOD-2 inhibitor - 2-methoxyestradiol. Interestingly, the combination of photodynamic therapy with hypericin and methoxyestradiol sensitized MCF-7 cells to photodynamic therapy and significantly reduced its clonogenic ability. Furthermore, methoxyestradiol potentiated the activation of caspase 3/7 and apoptosis induced by photodynamic therapy with hypericin. [ABSTRACT FROM AUTHOR]

The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls. Method 278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. Results A significant difference in the C-9-T genotype was observed between patients and normal controls but not between diabetic controls and patients with complications. There were significantly more of the diabetic control (DC, n = 62) group (11.3%) than the patients with diabetic nephropathy (DN, n = 73) (1.4%) with the CC genotype (p = 0.03 and χ 2 = 4.27, OR = 9.16 (1.08 < OR < 204.03)). Further significance was found between normal healthy controls (11.4%) and patients with nephropathy (1.4%) with the genotype CC (p = 0.03, χ 2 = 4.68, OR = 0.11 (0.00 < OR < 0.87)). No significant differences were found between these groups for the allelic frequency or between the different complication groups after correction for the number of groups. All groups were in Hardy Weinberg equilibrium. Conclusion The SNP in SOD-2 results in a substitution of C to T, which causes an amino acid change from alanine to valine. The variation in the SOD-2 leader signal affects the processing efficiency of the enzyme. A significantly greater proportion of the diabetic control group had the CC genotype suggesting antioxidant protection against diabetic nephropathy. The healthy control group also had a higher incidence of the protective genotype, which may suggest protective influences from the antioxidant gene in the CC form. [ABSTRACT FROM AUTHOR]

Aims We aimed to explore the impact of surgical 17β-estradiol (E 2 ) deprivation/administration on the expression of antioxidant enzymes with an emphasis on the alteration of the NF-E 2 -related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway under physiological conditions in the livers of CBA/H mice of both sexes. Main methods Hepatic oxidative stress markers were determined by measuring lipid peroxidation and DNA damage using the comet assay. The expression and activities of two isoforms of superoxide dismutase (Sod-1, Sod-2) and catalase (Cat) were studied using real-time PCR, Western blot and spectrophotometrical analyses. The effect of E 2 on Nrf2/Keap1 protein levels and localization was assessed using cytosolic and nuclear fractions. Key findings We demonstrate the E 2 -mediated repression of the antioxidant enzymes Sod-1, Sod-2 and Cat in the livers of ovariectomized mice treated with E 2 and its association with a decreased level of Nrf2/Keap1 proteins in the nucleus. We observed beneficial effects of long-term E 2 administration on lipid peroxidation but not on DNA damage in the livers of ovariectomized mice. Significance The results of this study may additionally confirm the protective ability of E 2 in prolonging the onset of age-related disease in females that ultimately contributes to their longer lifespan. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a pathogen causing chronic hepatitis, cirrhosis, and liver cancer occurring in about 3% of the world's population. Most individuals infected with HCV develop persistent viremia. Oxidative stress may play an important role in the pathogenesis of a number of diseases including HCV infection and diabetes mellitus. Polymorphisms in the antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in HCV and/or in its complications. Patients with HCV and normal, healthy controls were investigated for a superoxide dismutase (SOD-2) polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. Polymorphisms in antioxidant gene SOD-2 were carried out by PCR, restriction fragment length polymorphism assays and by polyacrylamide gel electrophoresis. For the SOD-2 polymorphism, the RNA positive group showed a higher percentage of 'CT' genotype than the RNA negative group (89.3% vs. 66.1%, P = 0.001, χ2 = 11.9). The RNA negative group had more TT genotypes than the RNA positive group (27.4% vs. 6.80%, P = 0.01, χ2 = 11.6). The exposed uninfected group had an increased frequency of the 'CT' genotype (86.2% vs. 66.1%, P = 0.02, χ2 = 5.5). The RNA positives had a higher frequency of the 'CT' from the normal controls (72.1% vs. 89.2%, P = 0.005, χ2 = 7.8). J. Med. Virol. 86:941-947, 2014. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are toxic oxygen-containing molecules that can damage multiple components of the cell and have been proposed to be the primary cause of aging. The antioxidant enzyme superoxide dismutase (SOD) is the only eukaryotic enzyme capable of detoxifying superoxide, one type of ROS. The fact that SOD is present in all aerobic organisms raises the question as to whether SOD is absolutely required for animal life and whether the loss of SOD activity will result in decreased lifespan. Here we use the genetic model organism Caenorhabditis elegans to generate an animal that completely lacks SOD activity (sod-12345 worms). We show that sod-12345 worms are viable and exhibit a normal lifespan, despite markedly increased sensitivity to multiple stresses. This is in stark contrast to what is observed in other genetic model organisms where the loss of a single sod gene can result in severely decreased survival. Investigating the mechanism underlying the normal lifespan of sod-12345 worms reveals that their longevity results from a balance between the prosurvival signaling and the toxicity of superoxide. Overall, our results demonstrate that SOD activity is dispensable for normal animal lifespan but is required to survive acute stresses. Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) scavengers have been shown to relieve persistent pain; however, the mechanism is not clearly understood. Superoxide produced from mitochondrial oxidative phosphorylation is considered the major source of ROS in neurons during excitation where mitochondrial superoxide levels are normally controlled by superoxide dismutase (SOD-2). The present study hypothesizes that capsaicin-induced secondary hyperalgesia is a consequence of superoxide build-up in spinal dorsal horn neurons and SOD-2 is a major determinant. To test this hypothesis, the spinal levels of SOD-2 activity, inactivated SOD-2 proteins, and mitochondrial superoxide were measured and correlated to the levels of capsaicin-induced secondary hyperalgesia in mice with and without SOD-2 manipulations. The data suggest that superoxide accumulation is a culprit in the abnormal sensory processing in the spinal cord in capsaicin-induced secondary hyperalgesia. Our studies also support the notion that SOD-2 nitration is a critical mechanism that maintains elevated superoxide levels in the spinal cord after capsaicin treatment. Finally, our findings suggest a therapeutic potential for the manipulation of spinal SOD-2 activity in pain conditions. [ABSTRACT FROM AUTHOR]

Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways. Vasorelaxation to acetylcholine was significantly impaired in aortic rings from SJL compared to C3H or FVB mice (up to 40%). Relaxation to the endothelium-independent vasodilator sodium nitroprusside (SNP) in SJL mice was also significantly impaired at low concentrations, with decreases in sensitivity and maximal relaxation to SNP compared to C3H and FVB mice. Western blot analyses showed significantly decreased expression (∼40%) of eNOS, PKG and SOD-2 proteins in SJL vasculature compared to C3H. Intact aortas from SJL showed significantly increased nitrotyrosine and decreased SOD-2 expression compared to C3H by immunohistochemistry. Basal levels of superoxide in aortas from SJL were not significantly different than C3H as measured by dihydroethidine. In summary, relatively small alterations in redox (SOD-2) and NO pathways (eNOS and PKG) may contribute to significantly impaired vasorelaxation in SJL mice. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We have cloned, sequenced and mapped a gene (sod-2) encoding manganese superoxide dismutase [EC 1.15.1.1] from the nematode Caenorhabditis elegans. The sod-2 was mapped to chromosome I by hybridization with a YAC polytene filter. The protein-coding region spans 1129 base pairs including 4 introns and encodes a protein of 221 amino acids (aa) (Mr = 24536) of which the first 24 aa are the presumed mitochondorial-targeting signal peptide. The gene sequence of sod-2 was slightly different from an isoform, sod-3. [ABSTRACT FROM PUBLISHER]

Mycobacterium is known for subverting the host defense machinery, and one such mechanism is the inhibition of autophagy. Here, we have demonstrated that Mycobacterium tuberculosis (MTB) secretes a virulence factor; an early secretory antigenic target protein (ESAT-6) into the phagosome, which induces the expression and activity of mitochondrial superoxide dismutase (SOD-2) of macrophages. Using a series of experiments, and Mycobacterium bovis BCG as a model strain (where ESAT-6 protein is not expressed), we have delineated that the protein regulates SOD-2 of macrophages. The expression and augmentation of SOD-2 activity were confirmed by either incubating the macrophages with ESAT-6 protein, transfection of macrophage by esat6 gene using a eukaryotic promoter vector, or by infection with different mycobacterial strains. The induction of acidification of phagosomal compartment containing bacteria was observed in cells that express low levels of SOD-2. This was further confirmed by observing a significant decrease in the M. bovis BCG intracellular load in the sod-2 knocked-down macrophages. • ESAT-6 upregulates expression and activity of mitochondrial SOD and induces intracellular survival of mycobacteria. • First report showing ESAT-6 upregulates SOD-2 which leads to inhibition of acidification of MTB containing phagosome. • The inhibition of SOD-2 mediated acidification of phagosome is important for MTB to survive and multiply in the host. [ABSTRACT FROM AUTHOR]

Manganese superoxide dismutase (SOD-2), an important primary antioxidant enzyme located in mitochondria, plays a critical role in tumor progression. Reportedly, the proinflammatory cytokine, tumor necrosis factor (TNF)-α, can increase SOD-2 expression in a human lung adenocarcinoma cell line in vitro, indicating that TNF-α-mediated inflammation may regulate SOD-2 expression, which may be related to cancer promotion. Using a urethane-induced inflammation-driven lung adenocarcinoma (IDLA) mice model, we investigated whether and how TNF-α-mediated inflammation upregulated SOD-2 expression in lung adenocarcinoma. Our results showed that SOD-2 was mostly expressed on surfactant protein-C + AT-II cells (alveolar type II cell) and tumor cells in IDLA mice, which were surrounded by CD68 + macrophages. Blocking TNF-α-dependent inflammation downregulated SOD-2 expression in inflamed lung tissues at the protumor stage and also inhibited SOD-2 expression in tumor cells in the IDLA model. In human lung adenocarcinoma, both the number of infiltrating CD68 + macrophages and TNF-α expression correlated positively with SOD-2 expression, which is related to lymph node metastasis and TNM stage. We collected the conditioned medium from lipopolysaccharide-activated phorbol myristate acetate-induced THP1 (M1) cells to stimulate A549 and H1299 cells and observed that THP1-M1 upregulated SOD-2 by secreting TNF-α. Blocking SOD-2 expression significantly inhibited TNF-α-induced cell proliferation in A549 and H1299 cells in vitro. Thus, TNF-α-mediated lung inflammation can upregulate SOD-2 expression in lung adenocarcinoma, and macrophages contribute to SOD-2 upregulation by secreting TNF-α., (© 2020 Wiley Periodicals LLC.)

Background: Oxidative stress is concomitant with acetaminophen (APAP)-induced hepatotoxicity, which has been highlighted as therapeutic targets for such diseases. The berries of Seabuckthorn (Hippophae rhamnoides L.) have been traditionally used in Tibetan medicine for thousands of years. The effect of Seabuckthorn berry polysaccharide on drug- induced liver injury (DILI) has not yet been elucidated., Purpose: This study aims to investigate the protective effects and mechanisms of Seabuckthorn polysaccharide (SP) against APAP-induced hepatotoxicity., Study Design: Sixty C57BL/6 mice were randomly divided into six groups (n = 10 per group), namely the control group (Ctrl), APAP-induced-liver injury group (APAP), NAC pretreated group (NAC), 100 mg/kg SP pretreated group (APAP/SP100), 200 mg/kg SP pretreated group (APAP/SP200) and 200 mg/kg SP pretreated group without APAP challenge (SP200). SP was given orally to mice for 30 consecutive days prior to APAP exposure (300 mg/kg). NAC (150 mg/kg) was administrated 1 h before APAP challenge., Methods: ALT and AST were detected 16 h after APAP treatment; Hepatic expression of GSH, SOD, NO, iNOS and GSH-Px were examined. The expression of p-JNK, Bcl-2/Bax, p62, Keap-1 and SOD-2 was detected by Western blotting. The expression of Nrf-2 and its target genes HO-1, GCLC and NQO-1 were analyzed by RT-PCR and Western blotting., Results: Pretreatment with SP led to decreased levels of ALT and AST in APAP mice, without affecting APAP metabolism. This was accompanied by diminished liver injuries, increased levels of GSH and GSH-Px, reduced NO and iNOS expression. SP increased the activity of SOD as well as SOD-2 expression in APAP mice. SP suppressed APAP-induced JNK phosphorylation and increased the ratio of Bcl-2/Bax. Furthermore, SP decreased the expression of Keap-1 and increased the nuclear expression of Nrf-2. The expression of Nrf-2 target gene HO-1 was increased by SP pretreatment in APAP mice., Conclusion: SP alleviates APAP-induced hepatotoxicity. The protective effects of SP are associated with the activation of the Nrf-2/HO-1-SOD-2 signaling pathway., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Summary Objectives The purpose of the this study was to investigate the effect of two months of moderate aerobic exercise training on the relationship between serum leptin concentration with vascular lipid peroxidation and SOD-2 enzyme gene expression in middle-aged inactive men. Methods Twenty untrained middle-aged men were randomly assigned to exercise (Ex) and control (Con) groups. The Ex group performed aerobic exercises for 8 weeks. SOD-2 mRNA was determined by PCR, leptin and vascular lipid peroxidation (MDA) levels were determined by Elisa and autoanalyzer. Results SOD-2 gene expression increased after the second month of moderate aerobic exercise ( P = 0.001) and MDA was reduced in the second month in Ex group ( P = 0.001). Leptin levels decreased after the first and the second month of moderate aerobic exercise (respectively: P = 0.042 and P = 0.001). Mixed Model analysis also showed a significant correlation between MDA and leptin in the exercise group. Conclusion The present study shows that two months of moderate exercise led to a reduction in leptin and MDA levels and to an increase in the SOD-2 gene expression. Also, the decrease in serum leptin concentration seemed to be effective in reducing lipid peroxidation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine how 60-min ischemia changes the expression of hypoxia inducible factor 1α (HIF-1α) and superoxide dismutases (SOD)-1 and -2 in selected regions of porcine uterine horns. The results showed that 60-min ischemia of the porcine uterus conducted at the mid-secretory estrous phase caused decreased HIF-1α and increased SOD-2 gene expression. Higher expression of SOD-2 suggests that this enzyme may play an important role in the suppression of HIF-1α accumulation in an ischemic endometrium., (Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

The mitochondrial free radical theory of aging proposes that aging is a consequence of progressive mitochondrial dysfunction caused by lifelong accumulation of oxidative damage. Aging is therefore expected to accelerate if the rate of this oxidative damage accumulation increases. Studies attempting to test this prediction through modulation of oxidative damage by altering antioxidant defenses have reported conflicting results. Here we investigated the effects of repressing prdx-3, responsible for the detoxification of mitochondrial hydrogen peroxide, in developmentally normal wild-type Caenorhabditis elegans. We report that life span and levels of oxidative protein damage were not altered when prdx-3 was repressed in adult nematodes. We further found evidence that mitochondrial uncoupling increased in response to repression of prdx-3. Nevertheless repression of prdx-3 led to reductions in steady-state levels of ATP, motility, and brood size, indicating the importance of this enzyme to normal life in C. elegans., (Copyright © 2013 Elsevier Inc. All rights reserved.)