Arginine-specific gingipains (RgpA/RgpB) knockdown modulates neutrophil machinery.

Background: Gingipains are important virulence factors present in Porphyromonas gingivalis. Arginine-specific gingipains (RgpA and RgpB) are critically associated with increased proteolytic activity and immune system dysfunction, including neutrophilic activity. In this study, we assessed the impact of gingipains (RgpA and RgpB) on neutrophil function. Methods: Peripheral blood samples were obtained; neutrophils were isolated and incubated with P. gingivalis A7436, W50, and the double RgpA/RgpB double knockout mutant E8 at MOI 20 for 2 hours. Neutrophil viability was assessed by Sytox staining. Phagocytic capacity and apoptosis were measured by flow cytometry. Superoxide release was measured by superoxide dismutase and cytochrome c reduction assay. Gene expression of TLR2, p47-phox, p67-phox, and P2 × 7was measured by qPCR. Inflammatory cytokine and chemokine production was measured by IL-1ß, IL-8, RANTES, and TNF-α in cell supernatants. Results: Neutrophil TLR2 gene expression was reduced in the absence of RgpA/RgpB (p < 0.05), while superoxide production was not significantly impacted. RgpA/RgpB-/- significantly impaired neutrophil phagocytic function (p < 0.05) and increased TNF-α production when compared with the wild-type control (p < 0.05). Neutrophil apoptosis was not altered when exposed to RgpA/RgpB-/- E8 (p > 0.05). Conclusion: These data suggest that arginine-specific gingipains (RgpA/RgpB) can modulate neutrophil responses against P. gingivalis infection.

P. gingivalis-derived arginine-specific gingipains impaired the phagocytic and apoptotic function in neutrophils.

Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.

BACKGROUND: Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension. METHODS: To test this hypothesis, we studied CypD acetylation in patients with essential hypertension, defined a pathogenic role of CypD acetylation in deacetylation mimetic CypD-K166R mutant mice and endothelial-specific GCN5L1 (general control of amino acid synthesis 5 like 1)-deficient mice using an Ang II (angiotensin II) model of hypertension. RESULTS: Arterioles from hypertensive patients had 280% higher CypD acetylation coupled with reduced Sirt3 (sirtuin 3) and increased GCN5L1 levels. GCN5L1 regulates mitochondrial protein acetylation and promotes CypD acetylation, which is counteracted by mitochondrial deacetylase Sirt3. In human aortic endothelial cells, GCN5L1 depletion prevents superoxide overproduction. Deacetylation mimetic CypD-K166R mice were protected from vascular oxidative stress, endothelial dysfunction, and Ang II-induced hypertension. Ang II-induced hypertension increased mitochondrial GCN5L1 and reduced Sirt3 levels resulting in a 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. Treatment with mitochondria-targeted scavenger of cytotoxic isolevuglandins (mito2HOBA) normalized GCN5L1/Sirt3 ratio, reduced CypD acetylation, and attenuated hypertension. The role of mitochondrial acetyltransferase GCN5L1 in the endothelial function was tested in endothelial-specific GCN5L1 knockout mice. Depletion of endothelial GCN5L1 prevented Ang II-induced mitochondrial oxidative stress, reduced the maladaptive switch of vascular metabolism to glycolysis, prevented inactivation of endothelial nitric oxide, preserved endothelial-dependent relaxation, and attenuated hypertension. CONCLUSIONS: These data support the pathogenic role of CypD acetylation in endothelial dysfunction and hypertension. We suggest that targeting cytotoxic mitochondrial isolevuglandins and GCN5L1 reduces CypD acetylation, which may be beneficial in cardiovascular disease.

Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension.

BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2-) production. These increases are prevented by scavenging O2- or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension. METHODS: We measured systolic blood pressure in male and female Sprague-Dawley (wild type [WT]), SGLT4 knockout (-/-), and SGLT5-/- rats. Then, we measured basal and Ang II-stimulated (37 nmol/L) O2- production by PTs and conducted gene coexpression network analysis. RESULTS: In male WT and female WT rats, FHS increased systolic blood pressure by 15±3 (n=7; P<0.0027) and 17±4 mm Hg (n=9; P<0.0037), respectively. Male and female SGLT4-/- had similar increases. Systolic blood pressure was unchanged by FHS in male and female SGLT5-/-. In male WT and female WT fed FHS, Ang II stimulated O2- production by 14±5 (n=6; P<0.0493) and 8±3 relative light units/µg protein/s (n=7; P<0.0218), respectively. The responses of SGTL4-/- were similar. Ang II did not stimulate O2- production in tubules from SGLT5-/-. Five gene coexpression modules were correlated with FHS. These correlations were completely blunted in SGLT5-/- and partially blunted by chronically scavenging O2- with tempol. CONCLUSIONS: SGLT5-mediated PT fructose reabsorption is required for FHS to augment Ang II-stimulated proximal nephron O2- production, and increases in PT oxidative stress likely contribute to FHS-induced hypertension.

Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels.

Vascular inflammation underlies the development of hypertension, and the mechanisms by which it increases blood pressure remain the topic of intense investigation. Proinflammatory factors including glucose, salt, vasoconstrictors, cytokines, wall stress, and growth factors enhance contractility and impair relaxation of vascular smooth muscle cells. These pathways share a dependence upon redox signaling, and excessive activation promotes oxidative stress that promotes vascular aging. Vascular smooth muscle cell phenotypic switching and migration into the intima contribute to atherosclerosis, while hypercontractility increases systemic vascular resistance and vasospasm that can trigger ischemia. Here, we review factors that drive the initiation and progression of this vasculopathy in vascular smooth muscle cells. Emphasis is placed on the contribution of reactive oxygen species generated by the Nox1 NADPH oxidase which produces extracellular superoxide (O2•-). The mechanisms of O2•- signaling remain poorly defined, but recent evidence demonstrates physical association of Nox1 with leucine-rich repeat containing 8 family volume-sensitive anion channels. These may provide a pathway for influx of O2•- to the cytoplasm, creating an oxidized cytoplasmic nanodomain where redox-based signals can affect both cytoskeletal structure and vasomotor function. Understanding the mechanistic links between inflammation, O2•- and vascular smooth muscle cell contractility may facilitate targeting of anti-inflammatory therapy in hypertension.

Regulatory effect of bacterial melanin on the isoforms of new superoxide-producing associates from rat tissues in rotenone-induced Parkinson's disease.

According to recent research, selective neuronal vulnerability in Parkinson's disease (PD) results from several phenotypic traits, including calcium-dependent, feed-forward control of mitochondrial respiration leading to elevated reactive oxygen species and cytosolic calcium concentration, an extensive axonal arbor, and a reactive neurotransmitter. Therefore, antioxidant therapy is a promising direction in the treatment of PD. In vitro studies have indicated the survival-promoting activity of bacterial melanin (BM) on midbrain dopaminergic neuron cultures. It has been established that BM has a number of protective and anti-inflammatory properties, so there is a high probability of a protective effect of BM in the early stages of PD. In this study, PD was induced through the unilateral intracerebral administration of rotenone followed by bacterial melanin. Tissues (brain, lungs, and small intestine) from the observed groups underwent isolation and purification to extract isoforms of new thermostable superoxide (О2-)-producing associates between NADPH-containing lipoprotein (NLP) and NADPH oxidase-Nox (NLP-Nox). The optical absorption spectral characteristics, specific amounts, stationary concentration of the produced О2-, and the content of NADPH in the observed associates were determined. The optical absorption spectra of the NLP-Nox isoforms in the visible and UV regions in the experimental groups did not differ from those of the control group. However, compared with the control group, the specific content of the total fractions of NLP-Nox isoforms associated with PD groups was higher, especially in the small intestine. These findings suggest that the described changes may represent a novel mechanism for rotenone-induced PD. Furthermore, bacterial melanin demonstrated antioxidant properties and regulated membrane formation in the brain, lung, and small intestine. This regulation occurred by inhibiting the release of new membrane-bound formations (NLP-Nox associates) from these membranes while simultaneously regulating the steady-state concentration of the formed О2-.

[Pro-oxidation status of rotator cuff tissue and expression of Beclin-1 and mTOR in patients with rotator cuff injury].

OBJECTIVE: To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy. METHODS: Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR. RESULTS: There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05). CONCLUSION: Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.

Antisense oligodeoxynucleotides against dynamin-related protein 1 reduce remifentanil-induced hyperalgesia by modulating spinal N-methyl-D-aspartate receptor expression in rats.

Background: Spinal N-methyl-D-aspartate (NMDA) receptor activation is attributed to remifentanil-induced hyperalgesia (RIH). However, the specific mechanism and subsequent treatment is still unknown. Previous studies have shown that the dynamin-related protein 1 (DRP1)-mitochondria-reactive oxygen species (ROS) pathway plays an important role in neuropathic pain. This study examined whether antisense oligodeoxynucleotides against DRP1 (AS-DRP1) could reverse RIH. Methods: The authors first measured changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) at 24 hours before remifentanil infusion and 4, 8, 24, and 48 hours after infusion. The expression levels of DRP1 and NR2B were measured after behavioral testing using Western blotting. In addition, DRP1 expression was knocked down by intrathecal administration of AS-DRP1 to investigate the effects of DRP1 on RIH. The behavioral testing, the expression levels of spinal DRP1 and NR2B, and dorsal mitochondrial superoxide were measured. Changes in mitochondrial morphology were assessed using electron microscopy. Results: After remifentanil exposure, upregulation of spinal DRP1 and NR2B was observed along with a reduction in PWMT and PWTL. In addition, AS-DRP1 improved RIH-induced PWTL and PWMT (P < 0.001 and P < 0.001) and reduced remifentanil-mediated enhancement of spinal DRP1 and NR2B expression (P = 0.020 and P = 0.022). More importantly, AS-DRP1 reversed RIH-induced mitochondrial fission (P = 0.020) and mitochondrial superoxide upregulation (P = 0.031). Conclusions: These results indicate that AS-DRP1 could modulate NMDA receptor expression to prevent RIH through the DRP1-mitochondria-ROS pathway.

Pro-oxidation status of rotator cuff tissue and expression of Beclin-1 and mTOR in patients with rotator cuff injury / 中国骨伤

OBJECTIVE@#To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy.@*METHODS@#Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR.@*RESULTS@#There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05).@*CONCLUSION@#Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.

Chemokine Receptor CXCR-2 Initiates Atrial Fibrillation by Triggering Monocyte Mobilization in Mice.

Atrial fibrillation (AF) is frequently associated with increased inflammatory response characterized by infiltration of monocytes/macrophages. The chemokine receptor CXCR-2 is a critical regulator of monocyte mobilization in hypertension and cardiac remodeling, but it is not known whether CXCR-2 is involved in the development of hypertensive AF. AF was induced by infusion of Ang II (angiotensin II; 2000 ng/kg per minute) for 3 weeks in male C57BL/6 wild-type mice, CXCR-2 knockout mice, bone marrow-reconstituted chimeric mice, and mice treated with the CXCR-2 inhibitor SB225002. Microarray analysis revealed that 4 chemokine ligands of CXCR-2 were significantly upregulated in the atria during 3 weeks of Ang II infusion. CXCR-2 expression and the number of CXCR2+ immune cells markedly increased in Ang II-infused atria in a time-dependent manner. Moreover, Ang II-infused wild-type mice had increased blood pressure, AF inducibility, atrial diameter, fibrosis, infiltration of macrophages, and superoxide production compared with saline-treated wild-type mice, whereas these effects were significantly attenuated in CXCR-2 knockout mice and wild-type mice transplanted with CXCR-2-deficient bone marrow cells or treated with SB225002. Moreover, circulating blood CXCL-1 levels and CXCR2+ monocyte counts were higher and associated with AF in human patients (n=31) compared with sinus rhythm controls (n=31). In summary, this study identified a novel role for CXCR-2 in driving monocyte infiltration of the atria, which accelerates atrial remodeling and AF after hypertension. Blocking CXCR-2 activation may serve as a new therapeutic strategy for AF.

Evidence for a Physiological Mitochondrial Angiotensin II System in the Kidney Proximal Tubules: Novel Roles of Mitochondrial Ang II/AT1a/O2- and Ang II/AT2/NO Signaling.

The present study tested the hypotheses that overexpression of an intracellular Ang II (angiotensin II) fusion protein, mito-ECFP/Ang II, selectively in the mitochondria of mouse proximal tubule cells induces mitochondrial oxidative and glycolytic responses and elevates blood pressure via the Ang II/AT1a receptor/superoxide/NHE3 (the Na+/H+ exchanger 3)-dependent mechanisms. A PT-selective, mitochondria-targeting adenoviral construct encoding Ad-sglt2-mito-ECFP/Ang II was used to test the hypotheses. The expression of mito-ECFP/Ang II was colocalized primarily with Mito-Tracker Red FM in mouse PT cells or with TMRM in kidney PTs. Mito-ECFP/Ang II markedly increased oxygen consumption rate as an index of mitochondrial oxidative response (69.5%; P<0.01) and extracellular acidification rate as an index of mitochondrial glycolytic response (34%; P<0.01). The mito-ECFP/Ang II-induced oxygen consumption rate and extracellular acidification rate responses were blocked by AT1 blocker losartan (P<0.01) and a mitochondria-targeting superoxide scavenger mito-TEMPO (P<0.01). By contrast, the nonselective NO inhibitor L-NAME alone increased, whereas the mitochondria-targeting expression of AT2 receptors (mito-AT2/GFP) attenuated the effects of mito-ECFP/Ang II (P<0.01). In the kidney, overexpression of mito-ECFP/Ang II in the mitochondria of the PTs increased systolic blood pressure 12±3 mm Hg (P<0.01), and the response was attenuated in PT-specific PT-Agtr1a-/- and PT-Nhe3-/- mice (P<0.01). Conversely, overexpression of AT2 receptors selectively in the mitochondria of the PTs induced natriuretic responses in PT-Agtr1a-/- and PT-Nhe3-/- mice (P<0.01). Taken together, these results provide new evidence for a physiological role of PT mitochondrial Ang II/AT1a/superoxide/NHE3 and Ang II/AT2/NO/NHE3 signaling pathways in maintaining blood pressure homeostasis.

IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD.

BACKGROUND AND OBJECTIVES: Systemic inflammation modulates cardiovascular disease risk and functionality of HDL in the setting of CKD. Whether interventions that modify systemic inflammation can improve HDL function in CKD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a post hoc analysis of two randomized, clinical trials, IL-1 trap in participants with GFR 15-59 ml/min per 1.73 m2 (study A) and IL-1 receptor antagonist in participants on maintenance hemodialysis (study B), to evaluate if IL-1 blockade had improved the anti-inflammatory activity (IL-6, TNF-α, and Nod-like receptor protein 3), antioxidant function (superoxide production), and net cholesterol efflux capacity of HDL. HDL function was measured using LPS-stimulated THP-1 macrophages or peritoneal macrophages of apoE-deficient mice exposed to the apoB-depleted, HDL-containing fraction obtained from the plasma of the study participants, collected before and after the interventions to block IL-1 effects. Analysis of covariance was used for between group comparisons. RESULTS: The mean age of the participants was 60±13 years, 72% (n=33) were men, and 39% (n=18) were black. There were 32 CKD (16 IL-1 trap and 16 placebo) and 14 maintenance hemodialysis (7 IL-1 receptor antagonist and 7 placebo) participants. Compared with placebo, IL-1 inhibition, in study A and B reduced cellular expression of TNF-α by 15% (P=0.05) and 64% (P=0.02), IL-6 by 38% (P=0.004) and 56% (P=0.08), and Nod-like receptor protein 3 by 16% (P=0.01) and 25% (P=0.02), respectively. The intervention blunted superoxide production in the treated arm compared with placebo, with the values being higher by 17% in the placebo arm in study A (P<0.001) and 12% in the placebo arm in study B (P=0.004). Net cholesterol efflux capacity was not affected by either intervention. CONCLUSIONS: IL-1 blockade improves the anti-inflammatory and antioxidative properties of the HDL-containing fraction of plasma in patients with stages 3-5 CKD, including those on maintenance hemodialysis.

The Influence of Alkali Metal Ions on the Stability and Reactivity of Chromium(III) Superoxide Moieties Spanned by Siloxide Ligands.

In recent years, it has become clear that the presence of redox-inactive Lewis acidic metal ions can decisively influence the reactivity of metal-dioxygen moieties that are formed in the course of O2 activation, in molecular complexes, and metalloenzymes. Superoxide species are often formed as the primary intermediates but they are mostly too unstable for a thorough investigation. We report here a series of chromium(III) superoxide complexes [L2 Cr]M2 O2 (THF)y (L=- OSiPh2 OSiPh2 O- , M+ =Li+ , Na+ , K+ and y=4, 5), which could be accessed, studied spectroscopically and partly crystallized at low temperatures. They only differ in the two incorporated Lewis acidic alkali metal counterions (M+ ) and it could thus be shown that the nature of M+ determines considerably its interaction with the superoxide ligand. This interaction, in turn, has a significant influence on the stability and reactivity of these complexes towards substrates with OH groups. Furthermore, we show that stability and reactivity are also highly solvent dependent (THF versus nitriles), as donor solvents coordinate to the alkali metal ions and thus also influence their interaction with the superoxide moiety. Altogether, these results provide a comprehensive and detailed picture concerning the correlation between spectroscopic properties, structure, and behavior of such superoxides, that may be exemplary for other systems.

Impact of Sleep Deprivation on the Hypothalamic-Pituitary-Gonadal Axis and Erectile Tissue.

INTRODUCTION: It is unclear how sleep deprivation (SD) exerts a negative effect on men's health in terms of hypogonadism. AIM: To evaluate the hypothalamic-pituitary-gonadal (HPG) axis in subjects with SD and ultimately to evaluate the erectile tissue in response to the hormonal changes. METHODS: 56 male Wistar rats were used. First, 16 rats (16 weeks old) were subjected to 72 hours of SD, and the following were compared with 16 control rats: (i) levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and cortisol; (ii) the expression of the kisspeptin mRNA in the brain; and (iii) assessment of immunohistochemistry (IHC) of brain and testis. To further investigate whether testosterone reduction due to SD could affect erectile tissue, an additional 24 rats were divided into 3 groups (control, SD, and SD with T supplementation [SDT]) and compared: (i) T and cortisol levels were quantified, and (ii) endothelial nitric oxide synthase (eNOS)/ neuronal nitric oxide synthase (nNOS)/NOX-2 expression in cavernosal tissue was assessed by measuring mRNA levels and performing Western blotting and IHC. MAIN OUTCOME MEASURE: Compared with the levels in the control group, the LH level was markedly decreased, and T levels were subsequently decreased in the SD group, whereas the level of the kisspeptin mRNA and IHC for kisspeptin, GnRH, and FSH were not different. RESULTS: In cavernosal tissues, levels of the eNOS/nNOS mRNAs and proteins tended to be lower, and NOX-2 levels (mRNA and protein) tended to be higher in the SD group than those in the control group and SDT group. IHC for eNOS/nNOS revealed lower-intensity staining in the SD group than in the control and SDT groups, whereas the NOX-2 intensity was higher in the SD group than in the other groups. A lower cortisol level was observed in the control group than in the SD and SDT groups, whereas the level was similar between the SD and SDT groups. The intracavernosal pressure/mean arterial blood pressure (%) values were also decreased in the SD group but not on testosterone injection. CLINICAL IMPLICATIONS: Even short-term SD can produce secondary hypogonadism, which impairs men's health. STRENGTH & LIMITATIONS: To the best of our knowledge, this study is the first to show the effects of SD on the whole HPG axis. The weakness is that this study only investigated acute SD. CONCLUSION: Based on the findings from this study, acute SD causes pituitary hypogonadism, and reduced T levels decrease erectile function by inducing superoxide accumulation in the cavernosal tissue and inhibiting nitric oxide synthase activity. Lee DS, Choi JB, Sohn DW. Impact of Sleep Deprivation on the Hypothalamic-Pituitary-Gonadal Axis and Erectile Tissue. J Sex Med 2019;16:5-16.

Superoxide Decay Pathways in Oxygen Reduction Reaction on Carbon-Based Catalysts Evidenced by Theoretical Calculations.

Superoxide decay behavior is evaluated by contrastive potential energy surface analyses from theoretical calculations. The presence of carbon surfaces enhances the superoxide decay through disproportionation instead of electroreduction, which is a non-electrochemical reaction that impedes the increase in energy efficiency for relevant energy conversion applications. Nitrogen doping of carbon effectively retards the disproportionation by influencing the oxygen stretching vibration and changing the proton-coupled electron transfer trend.

Effect of sleeve gastrectomy on renal oxidative stress in type 2 diabetic rats / 国际外科学杂志

Objective@#To investigate the changes of oxidative stress in kidney of type 2 diabetic rats after sleeve gastrectomy and its effect on renal function.@*Methods@#Twenty male SD rats were fed with high-fat diet and injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. Seventeen successful induction models were divided into sham operation group (n=7) and sleeve gastrectomy (SG) group (n=10) by random number table method, and were treated with sham operation and SG respectively. The body weight, 24-hour food intake, fasting blood glucose (FBG)and serum glucagon-like peptide-1 (GLP-1) were measured before and 1, 2, 3 and 4 weeks after operation. The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and malondialdehyde in renal tissue as well as blood urea nitrogen (BUN), creatinine levels and 24-hour urinary microalbumin (UALB) were measured 4 weeks after operation. Masurement data conforming to normal distribution were expressed as Mean±SD, and t-test was used for comparison between two groups.@*Results@#At the 1st, 2nd, 3rd, 4th weeks after operation, the levels of FBG in SG group was lower than those in sham operation group [(11.13±3.27) mmol/L vs (16.74±4.10) mmol/L, (9.53±2.82) mmol/L vs (19.31±3.66) mmol/L, (6.69±2.44) mmol/L vs (20.84±2.71) mmol/L, (6.58±2.96) mmol/L vs (19.99±2.85) mmol/L, all P<0.05]. In the same period, the levels of serum GLP-1 in SG group was higher than those in sham operation group [(22.61±2.92) pg/mL vs (15.42±2.39) pg/mL, (24.72±3.02) pg/mL vs (16.20±2.26) pg/mL, (24.59±2.85) pg/mL vs (15.84±2.75) pg/mL, (26.15±3.23) pg/mL vs (15.77±2.79) pg/mL, all P<0.05]. At the 4th week after operation, BUN[(5.34±0.82) mmol/L], creatinine[(39.78±6.13)]μmol/L, UALB[(31.18±6.88) mg/24 h] and renal creatinine[(5.84±0.85) nmol/mg] in SG group were lower than those in sham operation group [BUN (9.08±1.54) mmol/L, creatinine (64.07±8.63) μmol/L, UALB (67.64±9.07) mg/24 h, creatinine (10.78±1.28) nmol/mg], and the differences were statistically significant (all P<0.05). Renal SOD[(620.05±55.98) U/mg], CAT[(24.72±2.28) U/mg] and GSH-Px[(281.53±27.99) U] in SG Group were lower than those in sham operation group [SOD(392.52±45.97) U/mg, catalase (15.62±2.46) U/mg, GSH-Px (164.71±21.83) U], and the differences were statistically significant (all P<0.05).@*Conclusion@#Sleeve gastrectomy may improve renal function through reducing oxidative stress in the kidney.

Effect of sleeve gastrectomy on renal oxidative stress in type 2 diabetic rats / 国际外科学杂志

Objective To investigate the changes of oxidative stress in kidney of type 2 diabetic rats after sleeve gastrectomy and its effect on renal function.Methods Twenty male SD rats were fed with high-fat diet and injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus.Seventeen successful induction models were divided into sham operation group (n =7) and sleeve gastrectomy (SG) group (n =10) by random number table method,and were treated with sham operation and SG respectively.The body weight,24-hour food intake,fasting blood glucose (FBG)and serum glucagon-like peptide-1 (GLP-1) were measured before and 1,2,3 and 4 weeks after operation.The activities of superoxide dismutase (SOD),catalase,glutathione peroxidase (GSH-Px) and malondialdehyde in renal tissue as well as blood urea nitrogen (BUN),creatinine levels and 24-hour urinary microalbumin (UALB) were measured 4 weeks after operation.Masurement data conforming to normal distribution were expressed as Mean ± SD,and t-test was used for comparison between two groups.Results At the 1st,2nd,3rd,4th weeks after operation,the levels of FBG in SG group was lower than those in sham operation group [(11.13 ±3.27) mmol/L vs (16.74 ±4.10) mmol/L,(9.53 ±2.82) mmol/L vs (19.31 ±3.66) mmol/ L,(6.69 ±2.44) mmol/L vs (20.84 ±2.71) mmol/L,(6.58 ±2.96) mmol/L vs (19.99 ±2.85) mmol/L,all P ＜ 0.05].In the same period,the levels of serum GLP-1 in SG group was higher than those in sham operation group [(22.61 ± 2.92) pg/mL vs (15.42 ± 2.39) pg/mL,(24.72 ± 3.02) pg/mL vs (16.20 ± 2.26) pg/mL,(24.59 ±2.85) pg/mL vs (15.84±2.75) pg/mL,(26.15 ±3.23) pg/mL vs (15.77 ±2.79) pg/mL,all P＜ 0.05].At the 4th week after operation,BUN[(5.34 ±0.82) mmol/L],creatinine[(39.78 ±6.13)] μmoL/L,UALB [(31.18 ± 6.88) mg/24 h] and renal creatinine [(5.84 ± 0.85) nmol/mg] in SG group were lower than those in sham operation group [BUN (9.08 ± 1.54) mmol/L,creatinine (64.07 ± 8.63) μmol/L,UALB (67.64 ±9.07) mg/24 h,creatinine (10.78 ± 1.28) nmol/mg],and the differences were statistically significant (all P＜0.05).Renal SOD[(620.05 ±55.98) U/mg],CAT[(24.72 ±2.28) U/mg] and GSH-Px[(281.53 ± 27.99) U] in SG Group were lower than those in sham operation group [SOD(392.52 ± 45.97) U/mg,catalase (15.62 ± 2.46) U/mg,GSH-Px (164.71 ± 21.83) U],and the differences were statistically significant (all P ＜ 0.05).Conclusion Sleeve gastrectomy may improve renal function through reducing oxidative stress in the kidney.

High Salt Enhances Reactive Oxygen Species and Angiotensin II Contractions of Glomerular Afferent Arterioles From Mice With Reduced Renal Mass.

High salt, Ang II (angiotensin II), and reactive oxygen species enhance progression of chronic kidney disease. We tested the hypothesis that a high salt intake generates specific reactive oxygen species to enhance Ang II contractions of afferent arterioles from mice with reduced renal mass (RRM). C57BL/6 mice were subjected to surgical RRM or sham operations and received 6% or 0.4% NaCl salt diet for 3 months. Ang II contractions were measured in perfused afferent arterioles and superoxide (O2-) and hydrogen peroxide (H2O2) by fluorescence microscopy. RRM enhanced the afferent arteriolar gene expression for p47phox and neutrophil oxidase (NOX) 2 and high salt intake in RRM mice enhanced gene expression for angiotensin type 1 receptors, POLDIP2 and NOX4 and reduced catalase. High salt in mice with RRM enhanced arteriolar O2- and H2O2 generation and maximal contractions to Ang II (10-6 mol/L) that were dependent on O2- because they were prevented by gene deletion of p47phox and on H2O2 because they were prevented by transgenic smooth muscle cell expression of catalase (tgCAT-SMC) and POLDIP2 gene deletion. Three months of tempol normalized arteriolar reactive oxygen species and Ang II contractions. However, arteriolar contractions to lower concentrations of Ang II (10-8 to 10-11 mol/L) were paradoxically inhibited by H2O2 and POLDIP2. In conclusion, both O2- from p47phox/NOX2 and H2O2 from NOX4/POLDIP2 enhance maximal arteriolar Ang II contractions from RRM mice during high salt, but H2O2 and NOX4/POLDIP2 reduce the sensitivity to lower concentrations of Ang II by >100-fold. Tempol prevents all of these changes in function.

Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters.

PURPOSE: To investigate the pathophysiological role of superoxide anion and total reactive oxygen species (ROS) production by the spermatozoa of men with varicocele and its relationship with varicocele grade and semen parameters. MATERIALS AND METHODS: This prospective study included 34 men with grade II-III varicocele, regardless of their fertility status. The control group consisted of 13 healthy men. Semen characteristics were examined according to the 2010 World Health Organization criteria. The swim-up method was used for sperm preparation. Total ROS and superoxide anion production was assayed by luminol- and lucigenin-dependent chemiluminescence (CL), respectively. RESULTS: The men with varicocele had significantly higher total ROS and superoxide anion levels than the healthy control subjects (2.9±0.4 relative light unit (RLU) vs. 2.4±0.1 RLU, p=0.001 for luminol-dependent CL and 2.8±0.4 RLU vs. 2.3±0.2 RLU, p=0.002 for lucigenin-dependent CL). Cases of grade III varicocele had significantly higher superoxide anion and total ROS levels than grade II cases and control subjects (p<0.001). Superoxide anion and total ROS levels were negatively correlated with all semen parameters. CONCLUSIONS: The superoxide anion levels produced by spermatozoa were significantly higher in varicocele patients than in control subjects. ROS production was related to increased varicocele grade, impaired semen concentration, and abnormal morphology in men with varicocele. Our findings suggest that superoxide anion overproduction may be an important step in the cascade of ROS-related damage to spermatozoa, resulting in impaired semen parameters in patients with varicocele.

Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters

PURPOSE: To investigate the pathophysiological role of superoxide anion and total reactive oxygen species (ROS) production by the spermatozoa of men with varicocele and its relationship with varicocele grade and semen parameters. MATERIALS AND METHODS: This prospective study included 34 men with grade II–III varicocele, regardless of their fertility status. The control group consisted of 13 healthy men. Semen characteristics were examined according to the 2010 World Health Organization criteria. The swim-up method was used for sperm preparation. Total ROS and superoxide anion production was assayed by luminol- and lucigenin-dependent chemiluminescence (CL), respectively. RESULTS: The men with varicocele had significantly higher total ROS and superoxide anion levels than the healthy control subjects (2.9±0.4 relative light unit (RLU) vs. 2.4±0.1 RLU, p=0.001 for luminol-dependent CL and 2.8±0.4 RLU vs. 2.3±0.2 RLU, p=0.002 for lucigenin-dependent CL). Cases of grade III varicocele had significantly higher superoxide anion and total ROS levels than grade II cases and control subjects (p < 0.001). Superoxide anion and total ROS levels were negatively correlated with all semen parameters. CONCLUSIONS: The superoxide anion levels produced by spermatozoa were significantly higher in varicocele patients than in control subjects. ROS production was related to increased varicocele grade, impaired semen concentration, and abnormal morphology in men with varicocele. Our findings suggest that superoxide anion overproduction may be an important step in the cascade of ROS-related damage to spermatozoa, resulting in impaired semen parameters in patients with varicocele.

Oxygen-Rich Lithium Oxide Phases Formed at High Pressure for Potential Lithium-Air Battery Electrode.

The lithium-air battery has great potential of achieving specific energy density comparable to that of gasoline. Several lithium oxide phases involved in the charge-discharge process greatly affect the overall performance of lithium-air batteries. One of the key issues is linked to the environmental oxygen-rich conditions during battery cycling. Here, the theoretical prediction and experimental confirmation of new stable oxygen-rich lithium oxides under high pressure conditions are reported. Three new high pressure oxide phases that form at high temperature and pressure are identified: Li2O3, LiO2, and LiO4. The LiO2 and LiO4 consist of a lithium layer sandwiched by an oxygen ring structure inherited from high pressure ε-O8 phase, while Li2O3 inherits the local arrangements from ambient LiO2 and Li2O2 phases. These novel lithium oxides beyond the ambient Li2O, Li2O2, and LiO2 phases show great potential in improving battery design and performance in large battery applications under extreme conditions.