OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis* ; Antibodies, Antineutrophil Cytoplasmic/analysis* ; China/epidemiology* ; Humans ; Kidney Failure, Chronic/complications* ; Lymphocytes ; Peroxidase ; Retrospective Studies

PURPOSE: Various immune cells, including eosinophils and neutrophils, are known to contribute to the development of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the current understanding of the role of neutrophils in the development of CRSwNP still remains unclear. Therefore, we investigated risk factors for refractoriness of CRSwNP in an Asian population. METHODS: Protein levels of 17 neutrophil-related mediators in nasal polyps (NPs) were determined by multiplex immunoassay, and exploratory factor analysis using principal component analysis was performed. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE) or myeloperoxidase (MPO)-positive cells. Tissue eosinophilic nasal polyp (ENP) and tissue neutrophilia (Neu(high)) were defined as greater than 70 eosinophils and 20 HNE-positive cells, otherwise was classified into non-eosinophilic nasal polyp (NENP) and absence of tissue neutrophilia (Neu(low)). RESULTS: In terms of disease control status, NENP-Neu(low) patients showed the higher rate of disease control than NENP-Neu(high) and ENP-Neu(high) patients. Linear by linear association demonstrated the trend in refractoriness from NENP-Neu(low) to NENP-Neu(high) or ENP-Neu(low) to ENP-Neu(high). When multiple logistic regression was performed, tissue neutrophilia (hazard ratio, 4.38; 95% confidence interval, 1.76-10.85) was found as the strongest risk factor for CRSwNP refractoriness. Additionally, exploratory factor analysis revealed that interleukin (IL)-18, interferon-γ, IL-1Ra, tumor necrosis factor-α, oncostatin M, and MPO were associated with good disease control status, whereas IL-36α and IL-1α were associated with refractory disease control status. In subgroup analysis, HNE-positive cells and IL-36α were significantly upregulated in the refractory group (P = 0.0132 and P = 0.0395, respectively), whereas MPO and IL-18 showed higher expression in the controlled group (P = 0.0002 and P = 0.0009, respectively). Moreover, immunofluorescence analysis revealed that IL-36R⁺HNE⁺-double positive cells were significantly increased in the refractory group compared to the control group. We also found that the ratio of HNE-positive cells to α1 anti-trypsin was increased in the refractory group. CONCLUSIONS: Tissue neutrophilia had an influence on treatment outcomes in the Asian CRSwNP patients. HNE-positive cells and IL-36α may be biomarkers for predicting refractoriness in Asians with CRSwNP. Additionally, imbalances in HNE and α1 anti-trypsin may be associated with pathophysiology of neutrophilic chronic rhinosinusitis.
Asian Continental Ancestry Group ; Biomarkers ; Eosinophils ; Fluorescent Antibody Technique ; Humans ; Immunoassay ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-18 ; Interleukins ; Leukocyte Elastase ; Logistic Models ; Nasal Polyps ; Necrosis ; Neutrophils ; Oncostatin M ; Peroxidase ; Principal Component Analysis ; Rhinitis ; Risk Factors ; Sinusitis

The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI.
Acute Lung Injury ; chemically induced ; pathology ; Animals ; Apoptosis ; Bronchoalveolar Lavage Fluid ; chemistry ; Cyclooxygenase 2 ; metabolism ; Ferritins ; metabolism ; Glutathione ; analysis ; Glutathione Peroxidase ; metabolism ; Iron ; analysis ; Iron Overload ; physiopathology ; Lung ; cytology ; pathology ; Malondialdehyde ; analysis ; Mice ; Microscopy, Electron, Transmission ; Mitochondrial Membranes ; ultrastructure ; Oleic Acid

In order to investigate the antioxidant effect of alkylhydroxide peroxidase (ahpC) of Helicobacter pylori (H. pylori) 26695, an ahpC-deficient mutant (H. pylori 26695 ahpC::cat) was generated. ahpC-deficient mutant was grown slowly at lower pressure of oxygen (5% oxygen) compared to the H. pylori 26695. Whole cell proteins isolated form H. pylori 26695 and H. pylori 26695 ahpC::cat were analyzed by MALDI-TOF and tandem-MS. The expression of 15 proteins, including Ppa, HypB, GrpE, Elp, RecA, GroES, Mda66, RibE, NapA, GlnA, BioB, TrxB, Tsf, FumC and Icd, was more than doubled in H. pylori 26695 ahpC::cat. Production of 10 proteins such as UreG, FabE, Adk, Pnp, OorC, AtpA, AtpD, Nqq3, Pfr, and TagD decreased below 50% in H. pylori 26695 ahpC::cat compared to the H. pylori 26695. In microarray analysis, 9 genes including sul1, amiE, frxA, fecA, hyuA, and katA increased in transcription level in H. pylori 26695 ahpC::cat compared to H. pylori 26695. A total of 24 genes, including flaB, protein kinase C inhibitor, cag16, pabC, and sabA, reduced in transcription. 27 genes, including HP0889, showed common expression changes in ahpC, katA, and sodB-deficient mutations. As a result of this study, there were not many genes whose expression was commonly changed by the deletion of each of the three major antioxidant enzymes of H. pylori. These results showed the functions and regulation of the three antioxidant enzymes were different in H. pylori.
Antioxidants ; Helicobacter pylori ; Helicobacter ; Microarray Analysis ; Oxygen ; Peroxidase ; Protein Kinase C ; Proteome ; Ribes

The increasing demand of Chinese materia medica could not be supplied by wild resource, and the cultivated medicinal materials become popular, which led to decreased quality of many medicinal materials due to the difference of the circumstance between the wild and the cultivated. How to improve quality becomes key points of Chinese medicine resource. The leaves of Scutellaria baicalensis were sprayed with H₂O₂, the activities of superoxide dismutase (SOD) and catalase (CAT) changed little, but there had been a marked decrease of peroxidase (POD) and ascorbic oxidase (APX), which showed that the antioxidase system declined. Meanwhile, H₂O₂, as enhanced the expression of phenylalnine ammonialyase (PAL) and β-glucuronidase (GUS) as well as activity of PAL, promoted the biosynthesis and biotransformation of flavonoids. At the day 2 after treated, H₂O₂ of 0.004 μmol·L⁻¹ the contents of the baicalin and the wogonoside decreased slightly, but the contents of the baicalein and the wogonin increased significantly, the baicalein from 0.094% to 0.324%, the wogonin from 0.060% to 0.110%, i. e. increased 246% and 83.3%, respectively.
Ascorbate Oxidase ; metabolism ; Catalase ; metabolism ; Drugs, Chinese Herbal ; chemistry ; Flavanones ; analysis ; Flavonoids ; analysis ; Glucosides ; analysis ; Glucuronidase ; metabolism ; Hydrogen Peroxide ; Peroxidase ; metabolism ; Phenylalanine Ammonia-Lyase ; metabolism ; Scutellaria baicalensis ; metabolism ; Secondary Metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVES: To investigate the interventional effects of 16-week aerobic exercises on the elderly's arteriosclerosis and its mechanism. METHODS: Twenty-seven elderly people with the average age of 62. 70 ±3. 26 joined a 16-week square dance/taijiquan exercise program that conducted 60 minutes each time, six times per week. Arterial stiffness and its related indexes such as systolic pressure(SBP), diastolic pressure(DBP), left brachial-ankle pulse wave velocity (L-baPWV), right brachial-ankle pulse wave velocity(R-baPWV), left ankle brachial index (L-ABI), right ankle brachial index(R-ABI), serum triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione peroxidase (GSH-Px) were detected at 3 time points including before exercise program, by the end of exercise for 8 weeks and 16 weeks. RESULTS: ① Compared with pre-exercise, the R-baPWV and R-ABI of the elderly people were decreased at the end of the 8 week, and the L-baPWV, RbaPWV, R-ABI and L-ABI were decreased significantly at the end of the 16 week. ②Compared with pre-exercise, SBP and DBP were declined markedly (<0.01, <0.05) at the end of the 8 week, SBP, DBP and pulse pressure were decreased significantly (<0.01, <0.05) at the end of the 16 week. ③Compared with pre-exercise, TC and LDL-c were declined markedly (<0.01) at the end of the 8 and the 16 week, and there was no difference of the level of TG and LDL-c between pre-exercise and post-exercise. ④There was no evident difference of serum level of SOD, GSH-Px, MDA between pre-exercise and post-exercise at the end of the 8 week. Compared with pre-exercise, the level of serum SOD, GSH-Px was increased evidently while the content of serum MDA was decreased significantly (<0.01). CONCLUSIONS Sixteen-week aerobic exercises could reduce baPWV and ABI levels, regulate blood pressure, blood lipids and lipid peroxides levels of the elderly evidently, thus improve the controlling quality of atherosclerosis.
Aged ; Ankle ; Ankle Brachial Index ; Arteriosclerosis ; therapy ; Blood Pressure ; Cholesterol ; blood ; Exercise ; Glutathione Peroxidase ; blood ; Humans ; Malondialdehyde ; blood ; Middle Aged ; Pulse Wave Analysis ; Superoxide Dismutase ; blood ; Triglycerides ; blood

BACKGROUND/AIMS: MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. METHODS: We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. RESULTS: The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. CONCLUSIONS: This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.
Animals ; Blotting, Western ; Colon ; Computational Biology ; Defecation ; Diarrhea ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Hyperalgesia ; Hypersensitivity ; Irritable Bowel Syndrome ; Luciferases ; Microarray Analysis ; MicroRNAs ; Models, Animal ; Permeability ; Peroxidase ; Rats ; Real-Time Polymerase Chain Reaction ; Receptors, Cannabinoid ; Serotonin Plasma Membrane Transport Proteins ; Serotonin ; Up-Regulation

This study investigated the correlation between oxidative stress status and key canine sperm parameters and the effect of addition of a superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) combination in egg yolk tris-citrate glucose (EYT-G) extender on semen during 10 days of storage at 4℃. Ten Boxer dogs were divided into two groups, fertile (F) and hypofertile (H), depending on pregnancy and live birth rate status in the previous year. Semen evaluation was performed on the day of collection (D0) and after 5 (D5) and 10 (D10) days of cooled storage. Sperm motility, kinetic parameters, and DNA integrity were assessed. A correlation between oxidative status and key semen parameters in both F and H groups was observed. Total and progressive motilities were significantly higher in the treated (SOD, CAT, and GPx addition) versus control groups at D10 in both F and H groups, and at D5 in the H group. DNA integrity was significantly higher in both treated groups (H and F) at D5 and D10. In conclusion, the addition of SOD, CAT, and GPx in the extender allows preservation of semen quality for up to 10 days of storage at 4℃ in both fertile and hypofertile dogs.
Animals ; Antioxidants ; Catalase ; Cats ; DNA ; Dogs ; Egg Yolk ; Fertility ; Glucose ; Glutathione Peroxidase ; Glutathione ; Live Birth ; Oxidative Stress ; Pregnancy ; Semen Analysis ; Semen Preservation ; Semen ; Sperm Motility ; Spermatozoa ; Superoxide Dismutase ; Superoxides

OBJECTIVETo investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury.

METHODSThe cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 μL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule 1 (ICAM-1).

RESULTSCompared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01).

CONCLUSIONSXBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.

Animals ; CD18 Antigens ; metabolism ; Cell Adhesion ; drug effects ; Docosahexaenoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Leukocytes ; drug effects ; metabolism ; pathology ; Lung ; drug effects ; enzymology ; pathology ; Lung Injury ; blood ; complications ; drug therapy ; Male ; Mice, Inbred C57BL ; Peroxidase ; metabolism ; Sepsis ; blood ; complications ; drug therapy ; Survival Analysis

Objective: To investigate the influence of deep slow-wave sleep deprivation on the oxidative stress of testicular tissue in rats. METHODS: Thirty-six 5-week-old male Wistar rats were equally randomized into deep slow-wave sleep deprivation group (SD1), deep slow-wave sleep and duration sleep deprivation group ( SD2), and a cage control group (CC). The rat model of deep slow-wave sleep deprivation was established using the flowerpot technique. The rats in the SD1 group were interfered every 24 minutes and deprived of 12 hours of sleep at night, those in the SD2 group deprived of 8 minutes of sleep at an interval of 24 minutes and 12 hours of sleep at night, and those in the CC group exposed to 12 hours of daylight and 12 hours of darkness. After 28 days, all the rats were executed for measurement of the testis volume and protein content, determination of the methane dicarboxylic aldehyde (MDA) level and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observation of the pathological changes in the testicular tissue under the microscope. RESULTS: Compared with the CC group, the rats in the SD1 and SD2 groups showed significantly reduced body weight (［268.5 ± 1.6］ vs ［248.1 ± 25.1］and［232.9 ± 10.1］g, P<0.05) and increased relative testis mass (［50.0 ± 1.3］ vs ［57.9 ± 6.1］ and ［54.9 ± 3.5］ ×10⁻², P<0.05). Statistically significant differences were found between the CC and SD2 groups in the contents of protein (［6.3 ± 1.4］ vs ［4.5 ± 0.9］ gpro/L, P<0.05) and MDA (［1.1 ± 0.1］ vs ［1.3 ± 0.3］ nmol/mgpro, P<0.05) and the activities of SOD (［104.3 ± 33.1］ vs ［135.2 ± 26.9］ U/mgpro, P<0.05) and GSH-Px (［15.6 ± 4.0］ vs ［21.7 ± 4.3］ U/mgpro, P<0.05), but not between the CC and SD1 groups (P>0.05). The lumens in the testis were narrowed, with obvious hyperplasia, hyperemia and edema in the peripheral interstitial tissue, but no significant pathologic changes were observed in the testis tissue of the SD1 group. CONCLUSIONS Long-term deprivation of deep slow-wave sleep impairs the structure of the testis tissue and induces oxidative stress response in rats.
Animals ; Body Weight ; Glutathione Peroxidase ; analysis ; Male ; Malondialdehyde ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Wistar ; Sleep Deprivation ; metabolism ; Sleep Stages ; Superoxide Dismutase ; analysis ; Testis ; metabolism ; pathology ; Time Factors ; Weight Loss