Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation.

Hematopoietic disorders, particularly hemolytic anemias, commonly lead to bone loss. We have previously reported that actively proliferating cancer cells stimulate osteoclastogenesis from late precursors in a RANKL-independent manner. We theorized that cancer cells exploit the physiological role of bone resorption to support expanding hematopoietic bone marrow and examined if hematopoietic cells can trigger osteoclastogenesis. Using phlebotomy-induced acute anemia in mice, we found strong correlation between augmented erythropoiesis and increased osteoclastogenesis. Conditioned medium (CM) from K562 erythroleukemia cells and primary mouse erythroblasts stimulated osteoclastogenesis when added to RANKL-primed precursors from mouse bone marrow or RAW264.7 cells. Using immunoblotting and mass spectrometry, PRDX2 was identified as a factor produced by erythroid cells in vitro and in vivo. PRDX2 was detected in K562-derived exosomes, and inhibiting exosomal release significantly decreased the osteoclastogenic capacity of K562 CM. Recombinant PRDX2 induced osteoclast formation from RANKL-primed primary or RAW 264.7 precursors to levels comparable to achieved with continuous RANKL treatment. Thus, increased bone marrow erythropoiesis secondary to anemia leads to upregulation of PRDX2, which is released in the exosomes and acts to induce osteoclast formation. Increased bone resorption by the osteoclasts expands bone marrow cavity, which likely plays a supporting role to increase blood cell production.

Association of glutamate cystein ligase (GCL) activity Peroxiredoxin 4 (prxR4) and apelin levels in women with preeclampsia.

INTRODUCTION: Preeclampsia is a common disease of pregnancy that is characterized by symptoms such as high blood pressure and proteinuria. Peroxiredoxin 4 (Prx4), is a protein with antioxidant properties which is produced in placenta and protects it from antioxidant stress and recurrent miscarriage. For regeneration of Peroxiredoxin 4 need to glutathione (GSH) and Glutamate-cysteine ligase (GCL) enzyme controls the pathway of glutathione regeneration. Apelin is a paired internal ligand with a G protein coupled receptor and is associated with angiotensin receptor (AT1) as a blood pressure regulator. This study was designed to evaluate GCL enzyme activity and Peroxiredoxin 4, glutathione and apelin levels in serum of women with preeclampsia. MATERIAL AND METHODS: Thirty pregnant women with preeclampsia and 30 healthy pregnant women were enrolled in this study. All participants were diagnosed by clinical examination and confirmation by Obstetrician-Gynecologist. The GCL enzyme activity and concentration of Prx4 and apelin in serum samples were measured using ready-to-use non-competitive ELISA methods while glutathione level was determined using Ellman's reagent. RESULTS: The GCL enzyme activity and Prx4 level were significantly lower in preeclampsia compared with control group (p < 0.05). In addition, marked reductions were observed in the concentrations of glutathione and apelin in preeclampsia compared to the healthy pregnant women (p < 0.05). CONCLUSION: This study identified the role of the GCL and Prx4 system in preeclampsia disorder and may be one of the ways to prevent and reduce the risks of preeclampsia in high-risk women using diet control and stress reduction.

Association of Peroxiredoxin 1 and brain-derived neurotrophic factor serum levels with depression and anxiety symptoms in patients with irritable bowel syndrome.

BACKGROUND: Oxidative stress is considered a possible mechanism of irritable bowel syndrome (IBS) and depression. This study determined the possible association of serum peroxiredoxin 1 (PRDX1; a key antioxidant enzyme) and brain-derived neurotrophic factor (BDNF) with anxiety and depression symptoms in IBS patients. METHODS: According to the Rome IV diagnostic criteria, 177 IBS patients from February 2019 to July 2019 were included. Serum levels of PRDX1, BDNF, and TNFα were detected by enzyme-linked immunosorbent assay. Levels of anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RESULTS: Compared with normal IBS patients, patients with anxiety and depression symptoms had significantly higher serum PRDX1 (p<0.001; p=0.002) and TNFα (p<0.001; p = 0.002) and significantly lower BDNF (p < 0.001; p = 0.002). Serum PRDX1 (r = 0.659, p < 0.001; r = 0.466, p < 0.001) and TNFα (r = 0.531, p < 0.001; r = 0.449, p < 0.001) were positively correlated with SAS and SDS, respectively, whereas BDNF was negatively correlated with SAS (r = 0.594, p < 0.001) and SDS (r = 0.534, p < 0.001). Multivariable regression analysis revealed that IBS severity, BDNF, and PRDX1 were significant predictors of anxiety. BDNF was also a significant predictor of depression. CONCLUSION: Elevated PRDX1 and decreased BDNF in serum may be closely related to psychological symptoms in IBS. Results of this study suggested that PRDX1 may be an important target for IBS treatment in fighting against intestinal and psychological symptoms.

C-Reactive Protein Predicts Further Ischemic Events in Patients With Transient Ischemic Attack or Lacunar Stroke.

Patients who have experienced a first cerebral ischemic event are at increased risk of recurrent stroke. There is strong evidence that low-level inflammation as measured by high sensitivity C-reactive protein (hs-CRP) is a predictor of further ischemic events. Other mechanisms implicated in the pathogenesis of stroke may play a role in determining the risk of secondary events, including oxidative stress and the adaptive response to it and activation of neuroprotective pathways by hypoxia, for instance through induction of erythropoietin (EPO). This study investigated the association of the levels of CRP, peroxiredoxin 1 (PRDX1, an indicator of the physiological response to oxidative stress) and EPO (a neuroprotective factor produced in response to hypoxia) with the risk of a second ischemic event. Eighty patients with a diagnosis of lacunar stroke or transient ischemic attack (TIA) were included in the study and a blood sample was collected within 14 days from the initial event. Hs-CRP, PRDX1, and EPO were measured by ELISA. Further ischemic events were recorded with a mean follow-up of 42 months (min 24, max 64). Multivariate analysis showed that only CRP was an independent predictor of further events with an observed risk (OR) of 1.14 (P = 0.034, 95% CI 1.01-1.29). No association was observed with the levels of PRDX1 or EPO. A receiver operating curve (ROC) determined a cut-off CRP level of 3.25 µg/ml, with a 46% sensitivity and 81% specificity. Low-level inflammation as detected by hs-CRP is an independent predictor of recurrent cerebrovascular ischemic events.

Peroxiredoxin-1 aggravates lipopolysaccharide-induced septic shock via promoting inflammation.

Septic shock induced by lipopolysaccharide (LPS) is characterized by serious systemic inflammatory response and robust production of pro-inflammatory cytokines from activated macrophages. Damage-associated molecular patterns (DAMPs) secreted by activated macrophages are key contributors to septic shock. However, the current knowledge on those DAMPs that promote inflammatory response under LPS-induced septic shock remains poorly understood. Here, we report that Peroxiredoxin 1 (Prdx1) plays a detrimental role in LPS-induced septic shock. Intraperitoneal injection of LPS elicited a progressive course of septic shock in mice, which was characterized by significant lethality along with robust production of cytokines (IL-1ß, IL-6 and TNF-α). Removal of Prdx1 strongly protected mice from LPS-induced death, and decreased IL-1ß, IL-6 and TNF-α productions. Additionally, primary macrophages deficient in Prdx1 are less able to produce much more IL-1ß, IL-6 and TNF-α. Collectively, we provide a demonstration for Prdx1 contributing to LPS-induced septic shock likely via promoting inflammation.

Identification of Protein Expression Changes in Hepatocellular Carcinoma through iTRAQ.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor associated with a poor prognosis. Serum biomarkers of HCC have the potential to improve the diagnosis, provide a means to monitor the tumors, and predict their malignancy. Proteins that are expressed differentially between HCC patients and normal controls have the potential to be biomarkers. METHOD: Serum samples from 10 confirmed HCC patients and 10 controls were collected. The differentially expressed proteins in the serum were identified using an isobaric tags for relative and absolute quantitation- (iTRAQ-) based method. Potential serum biomarkers were validated by ELISA in another 20 HCC patients and 20 controls. Their expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. RESULTS: A total of 260 proteins were measured in the serum of HCC patients and compared to those in sex- and age-matched normal controls. Forty-one proteins displayed significant changes, with 26 being downregulated and 15 being upregulated. Upregulated proteins included alpha-1-antitrypsin (A1AT) and peroxiredoxin 2 (PRDX2), and downregulated proteins included paraoxonase 1 (PON1) and C-reactive protein (CRP). We then used ELISA to measure serum levels of A1AT, PRDX2, PON1, and CRP in another 20 patients with HCC and found that only PON1 levels were consistent with the iTRAQ result. In TCGA dataset, PON1 expression was downregulated in HCC tissues (P < 0.001) and low expression of PON1 was associated with poor survival in HCC patients (P < 0.001) and low expression of PON1 was associated with poor survival in HCC patients (. CONCLUSIONS: PON1 could act as a biomarker for HCC to assist in the diagnosis of HCC.

Blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue injury in chronic hepatitis C patients.

Oxidative stress is the process by which reactive molecules and free radicals are formed in cells. In this study, we report the blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue in chronic hepatitis C (CHC) patients by using real-time PCR. A total of 144 untreated patients diagnosed with CHC having genotype 3a and 20 healthy controls were selected for the present study. Liver biopsy staging and grading of CHC patients were performed using the METAVIR score. Total RNA was extracted from liver tissue and blood samples, followed by cDNA synthesis and real-time PCR. The relative expression of genes was calculated using the ΔΔCt method. The expression profile of 84 genes associated with oxidative stress and antioxidants was determined in liver tissue and blood samples. In liver tissue, 46 differentially expressed genes (upregulated, 27; downregulated, 19) were identified in CHC patients compared to normal samples. In blood, 61 genes (upregulated, 51; downregulated; 10) were significantly expressed in CHC patients. A comparison of gene expression in liver and whole blood showed that 20 genes were expressed in a similar manner in the liver and blood. The expression levels of commonly expressed liver and blood-based genes were also correlated with clinical factors in CHC patients. A receiver operating curve (ROC) analysis of oxidative stress genes (ALB, CAT, DHCR24, GPX7, PRDX5, and MBL2) showed that infections in patients with CHC can be distinguished from healthy controls. In conclusion, blood-based gene expression can reflect the behavior of oxidative stress genes in liver tissue, and this blood-based gene expression study in CHC patients explores new blood-based non-invasive biomarkers that represent liver damage.

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder.

BACKGROUND: It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. METHODS: We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another-comparable-group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. RESULTS: The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. CONCLUSIONS: Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

Peroxiredoxin 4 levels in patients with PCOS and/or obesity.

BACKGROUND: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in increased oxidative stress conditions. It is found to be positively associated with cardiovascular risk. The aim of the study was to investigate peroxiredoxin 4 levels in women with polycystic ovarian syndrome (PCOS) and/or obesity. METHODS: In this cros-sesctional study were included 80 patients. Anthropometric measurements and biochemical tests, including peroxiredoxin 4 measurement, were performed. RESULTS: There was a tendency towards lower peroxiredoxin 4 levels in non-obese PCOS subjects (5674.8 ± 3822.4 pg/ml), higher in obese PCOS (6588.9 ± 3731.0 pg/ml) and even higher in obese patients without PCOS (7724.6 ± 4840.4 pg/ml). Patients with abdominal obesity according to waist circumference and waist-to-hip ratio had significantly higher levels of peroxiredoxin compared to those without (7108.2 ± 4568.0 vs. 5079.8 ± 2555.4 pg/ml; p = 0.015 and 7310.6 ± 2646.2 vs. 4785.0 ± 2646.2 pg/ml; p = 0.013). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, hypertension, dislipidemia, hyperandrogenemia, metabolic syndrome. Peroxiredoxin 4 showed weak positive correlation to weight (r = 0.228; p = 0.044) and visceral adiposity index (r = 0.278; p = 0.031) and higher to erythrocyte sedimentation rate (r = 0.4; p < 0.01), but not to hormonal parameters and insulin sensitivity indexes. CONCLUSIONS: Non-obese patients with PCOS have a tendency towards lower peroxiredoxin 4 levels compared to obese patients with and without PCOS. Patients with abdominal obesity have significantly higher peroxiredoxin 4 levels than those without. We were not able to prove correlation between peroxiredoxin 4 levels and hormonal and carbohydrate status of the PCOS patients.

Identification and characterization of peroxiredoxin 1 from Lateolabrax japonicus under biotic and abiotic stresses.

The peroxiredoxins (Prxs) belong to a novel and evolutionarily conserved superfamily, which can protect cells from oxidative damage caused by ROS and play a vital role in immune responses. In the present study, a 995 base pairs (bp) Prx1 cDNA sequence (LjPrx1) with an open reading frame of 594 bp, which encoding 197 amino acid polypeptides was obtained from L. japonicus. Transcriptional expression analysis indicated that the LjPrx1 mRNA was ubiquitously expressed in all tissues tested, while a comparatively high expression level was detected in head-kidney and blood. After the recombinant LjPrx1 protein was acquired using a prokaryotic expression method, the antioxidant activity was assessed by the catalyzing hydrogen peroxide assay method, and the results showed that the recombinant LjPrx1 possessed an antioxidant activity in a temperature-dependent manner. To further study the function roles of LjPrx1 related to biotic and abiotic stresses, the head-kidney and blood were chosen for the following experiments, and a positive correlation between the expression of LjPrx1 and the different stresses was detected using qRT-PCR. In conclusion, this study provides useful information about the role of the LjPrx1 gene in defense against a variety of toxic factors in L. japonicus, which would broaden our current knowledge of Prx1.

Evaluation of Schistosoma japonicum thioredoxin peroxidase-1 as a potential circulating antigen target for the diagnosis of Asian schistosomiasis.

Asian schistosomiasis caused by Schistosoma japonicum is a serious zoonotic disease endemic in China, the Philippines and parts of Indonesia. Mass drug administration in endemic areas resulted to decline in disease severity and intensity. The low intensity of infection limits the use of current parasitological methods for schistosomiasis diagnosis. Detection of parasite circulating antigens might provide more informative result as it may indicate the true status of infection. In this study, S. japonicum thioredoxin peroxidase-1 (SjTPx-1) a 22 kDa secreted antioxidant enzyme expressed throughout the life stages of the parasite was evaluated for its potential use as a biomarker for schistosomiasis japonica infection. Rabbit polyclonal antibody and mouse monoclonal antibodies (mAbs) were raised against the recombinant SjTPx-1 (rSjTPx-1). The antibodies produced against the recombinant antigen was confirmed to detect the native SjTPx-1 in crude adult worm lysate. Likewise, the specific binding of mAbs to parasite TPx-1 and not to mammalian peroxiredoxin-1 orthologues was also confirmed. The double antibody sandwich ELISA developed in this study was able to detect at least 1 ng/ml of rSjTPx-1. In addition, this method was able to detect the antigen from all serum samples of experimentally infected rabbit and mice. The diagnostic potential of SjTPx-1 in human clinical samples was also evaluated, in which 4 out of 10 stool-confirmed serum samples had detectable levels of the antigen. The results suggest that SjTPx-1 can be a potential biomarker for Asian zoonotic schistosomiasis.

Spectrophotometric assays for measuring redox biomarkers in blood and tissues: the NADPH network.

Nicotinamide adenine dinucleotide (NAD+/NADH) along with its phosphorylated form (NADP+/NADPH) are two molecules ubiquitously present in all organisms, and they play key roles as cofactors in fundamental catabolic and anabolic processes, respectively. The oxidation of NADPH to NADP+ initiates a cascade of reactions, where a network of molecules is implicated. The molecules of this cascade form a network with eminent translational potential in redox metabolism. A special point of interest is that spectrophotometric assays have been developed both for NADH/NADPH and the molecules directly regulated by them. Therefore, crucial molecules of the NADPH-dependent redox network can be measured, and the results can be used to assess the bioenergetic and/or oxidative stress status. The main aim of this review is to collectively present the NADPH-related molecules, namely NADPH, NADH, NAD+ kinase, NADPH oxidase, peroxiredoxin, thioredoxin, thioredoxin reductase, and nitric oxide synthase, that can be measured in blood and tissues with the use of a spectrophotometer, which is probably the most simple, inexpensive and widely used tool in biochemistry. We are providing the researchers with reliable and valid spectrophotometric assays for the measurement of the most important biomarkers of the NADPH network in blood and other tissues, thus allowing the opportunity to follow the redox changes in response to a stimulus.

[Concentration of proinflammatory cytokines, peroxiredoxin-1 and glutathione peroxidase activity in the blood plasma of patients with coronary artery disease undergoing coronary artery bypass grafting].

76 patients with coronary heart disease (who had undergone coronary artery bypass grafting) were examined to investigate the role of pro-inflammatory cytokines and enzymes involved in redox regulation, in the mechanisms of development of systemic inflammatory response syndrome. Patients were divided into 2 groups: 1st - patients with coronary heart disease, who as a result of clinical trials has not been set postpericardiotomy syndrome; 2nd - patients with coronary heart disease who have been diagnosed postpericardiotomy syndrome. The blood plasma of both groups indicated intensification of production of interleukin-6, intrleukin-8, as well as - an imbalance in the peroxiredoxin-1 and glutathione peroxidase. These changes by patients with postpericardiotomy syndrome are observed at the earliest time and differed depth of expression. The results of this work confirm the high potential of the investigated indicators for prevention and monitoring postpericardiotomy syndrome development.

Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients.

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a broad spectrum of clinical presentations and incompletely understood pathogenesis. This autoimmune disease is characterized by alterations in both the innate and adaptive immune system that lead to the loss of immunologic tolerance. In autoimmune diseases particularly in SLE, early diagnosis, flare or remission phases can be difficult to identify. Proteomics can help to find new therapeutic targets and it also could help to better understand the cellular mechanisms. The aim of this study was to observe the variations in plasma and Peripheral Blood Mononuclear Cells (PBMCs) proteome in order to increase our knowledge about pathogenesis and to find possible diagnostic markers and/or therapeutic targets for improving diagnosis and treatment. The comparative proteomic analyses showed that several proteins were differentially expressed in the PBMCs from SLE patients. Among these, PRDX2 may be used as candidate biomarker or target protein for further investigations. In plasma, we showed that plasma clusterin levels increased in SLE patients compared to healthy controls, but this increase is not statistically significant. These proteomic results provide suggestions for understanding the molecular mechanisms of SLE, as well as the physiological changes correlated with SLE disease.

Diagnostic performance of peroxiredoxin 1 to determine time-of-onset of acute cerebral infarction.

Accurately determining time-of-onset of cerebral infarction is important to clearly identify patients who could benefit from reperfusion therapies. We assessed the kinetics of peroxiredoxin 1 (PRDX1), a protein involved in oxidative stress during the acute phase of ischemia, and its ability to determine stroke onset in a population of patients with known onset of less than 24 hours and in a control group. Median PRDX1 levels were significantly higher in stroke patients compared to controls. PRDX1 levels were also higher from blood samples withdrawn before vs. after 3 hours following stroke onset, and before vs. after 6 hours. ROC analysis with area under the curve (AUC), sensitivity (Se) and specificity (Sp) determined from the Youden index was performed to assess the ability of PRDX1 levels to determine onset. Diagnostic performances of PRDX1 levels were defined by an AUC of 69%, Se of 53% and Sp of 86% for identifying cerebral infarction occurring <3 hours, and an AUC of 68%, Se of 49% and Sp of 88% for cerebral infarction occurring <6 hours. These first results suggest that PRDX1 levels could be the basis of a new method using biomarkers for determining cerebral infarction onset.

Serum Proteomics Analysis in Rats of Immunosuppression Induced by Chronic Stress.

The immune system can be damaged by chronic stress. However, for this process, the involved molecular alterations and their regulatory roles played in immunosuppression still remain unclear. This study was aimed to identify the differences in serum protein expressions that are closely associated with the effect of chronic stress on immune function. Serum protein levels of rats in control group and chronic stress group were measured by iTRAQ analysis. Subsequently, among the 121 differentially expressed proteins screened between the two groups, 46 proteins were upregulated (>1.5-fold, P < 0.05), while 75 proteins were downregulated (<0.67-fold, P < 0.05). Bioinformatics analysis revealed that most of the differentially expressed proteins were in relation with the metabolic, cellular, response stimulus and immune system processes. The significantly differential expression of ceruloplasmin, haptoglobin, catalase and peroxiredoxin-1 were picked out for reconfirmation by ELISA analysis. The results were consistent with those obtained by iTRAQ. What is more, the roles of above-mentioned four proteins, apolipoprotein B-100 and heat-shock protein 90 in immunosuppression induced by chronic stress were discussed. Taken together, these findings may provide a new insight into better understanding the molecular mechanisms of immunosuppression induced by chronic stress.

Increased peroxiredoxin 4 levels in patients with prediabetes compared to normal glucose tolerance subjects.

BACKGROUND: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in oxidative stress conditions. Its levels are positively associated with cardiovascular risk. The aim of this study was to compare serum peroxiredoxin 4 levels between obese subjects with prediabetes and with normal glucose tolerance. METHODS: In this study, we included 80 patients with mean age 50·4 ± 10·6 years and divided them into two age and BMI-matched groups - group 1 with obesity without glycaemic disturbances (n = 41) and group 2 with obesity and prediabetes (n = 39). Oral glucose tolerance test with measurement of immunoreactive insulin was performed in all participants, and the levels of peroxiredoxin 4 were measured using ELISA method. RESULTS: We found significantly higher levels of peroxiredoxin 4 in patients with prediabetes compared to controls (2851·2 ± 4576·6 pg/ml vs 1088·0 ± 753·3 pg/ml; P = 0·022). There was a mild but statistically significant correlation between peroxiredoxin 4 and weight (r = 0·232; P = 0·038), waist circumference (r = 0·239; P = 0·044), creatinine (r = 0·264; P = 0·019), liver enzymes (ASAT - r = 0·289; P = 0·019 and ALAT - r = 0·305; P = 0·07) and white blood cells count (r = 0·317; P = 0·005). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, as well as with and without metabolic syndrome (MetS), although the levels of peroxiredoxin 4 increased with the number of components of MetS. CONCLUSIONS: The levels of peroxiredoxin 4 are higher in patients with prediabetes, but are similar in subjects with and without insulin resistance, which suggests that the main factor for its increased levels is hyperglycaemia and not insulin sensitivity state.

Peroxiredoxin 1 induces inflammatory cytokine response and predicts outcome of cardiogenic shock patients necessitating extracorporeal membrane oxygenation: an observational cohort study and translational approach.

BACKGROUND: Extracellular peroxiredoxin 1 (Prdx1) has been implicated to play a pivotal role in regulating inflammation; however, its function in tissue hypoxia-induced inflammation, such as severe cardiogenic shock patients, has not yet been defined. Thus, the objective of this study was to test the hypothesis that Prdx1 possesses prognostic value and instigates systemic inflammatory response syndrome in cardiogenic shock patients undergoing extracorporeal membrane oxygenation (ECMO) support. METHODS: We documented the early time course evolution of circulatory Prdx1, hypoxic marker carbonic anhydrase IX, inflammatory cytokines including IL-6, IL-8, IL-10, MCP-1, TNF-α, IL-1ß, and danger signaling receptors (TLR4 and CD14) in a cohort of cardiogenic shock patients within 1 day after ECMO support. In vitro investigations employing cultured murine macrophage cell lines and human monocytes were applied to clarify the relationship between Prdx1 and inflammatory response. RESULTS: Prdx1 not only peaked earlier than all the other cytokines we studied during the initial course, but also predicted a worse outcome in patients who had higher initial Prdx1 plasma levels. The Prdx1 levels in patients positively correlated with hypoxic markers carbonic anhydrase IX and lactate, and inflammatory cytokines. In vitro study demonstrated that hypoxia/reoxygenation induced Prdx1 release from human monocytes and enhanced the responsiveness of the monocytes in Prdx1-induced cytokine secretions. Furthermore, functional inhibition by Prdx1 antibody implicated a crucial role of Prdx1 in hypoxia/reoxygenation-induced IL-6 secretion. CONCLUSIONS: Prdx1 release during the early phase of ECMO support in cardiogenic shock patients is associated with the development of systemic inflammatory response syndrome and poor clinical outcomes. Thus, circulating Prdx1 provides not only prognostic information but may be a promising target against ischemia/reperfusion injury.

The Combination of Biomarkers for Prognostication of Long-Term Outcome in Patients Treated with Mild Hypothermia After Out-of-Hospital Cardiac Arrest-A Pilot Study.

To explore if the brain biomarker neuron-specific enolase (NSE) in combination with a biomarker for stress; CT-proAVP (copeptin), oxidation; peroxiredoxin 4 (Prx4), inflammation; procalcitonin (PCT), or with biomarkers from the heart; midregional proatrial natriuretic peptide (MR-proANP), or troponin T (TnT) can improve the prognostic accuracy of long-term outcome after out-of-hospital cardiac arrest (OHCA). Serum samples from cardiac arrest patients, treated at 33°C for 24 hours, were collected serially at 12, 24, and 48 hours after cardiac arrest. The concentration of the investigated biomarkers was measured using stored samples, and long-term outcome was evaluated by the cerebral performance category (CPC) at 6 months. Poor outcome was defined as CPC 3-5. Sixty-two patients with OHCA of presumed cardiac cause were included. NSE had best prognostic accuracy for poor outcome at 48 hours with a receiver operating characteristic area under curve (AUC) of 0.94 (95% confidence interval [CI] 0.87-1). The combination of NSE with TnT, both at 48 hours, increased the AUC to 0.98 (95% CI 0.95-1, likelihood ratio [LR] test p-value 0.07, net reclassification index [NRI] <0.001); NSE and MR-proANP, both at 12 hours, yielded an AUC of 0.91 (95% CI 0.80-1, LR test p-value 0.0014, NRI p-value 0.003); NSE at 48 hours with MR-proANP at 12 hours yielded an AUC of 0.97 (95% CI 0.92-1, LR test p-value 0.055, NRI p-value 0.04). This pilot study suggests that a combination of biomarkers with NSE could be beneficial for improving early prognostication of long-term outcome following OHCA.

Increased serum peroxiredoxin 5 levels in myasthenia gravis.

Extracellular peroxiredoxin 5 (PRX5) is known to be an inflammatory mediator. The serum PRX5 levels of 40 patients with anti-acetylcholine receptor antibody-positive MG and those of 40 controls were measured. PRX5 levels in patients with MG were higher than those in the controls (P=0.045). Thymoma-associated MG patients showed higher PRX5 levels than late-onset MG patients and controls (P<0.05). There were significant associations between the serum PRX5 levels and high mobility group box 1 levels. PRX5 elevation in MG could be related to the neuromuscular junction breakdown and plays a pivotal role in the pathogenic inflammation of MG.