Insights into the Acceleration Mechanism of Intracellular N and Fe Co-doped Carbon Dots on Anaerobic Denitrification Using Proteomics and Metabolomics Techniques.

Bulk carbon-based materials can enhance anaerobic biodenitrification when they are present in extracellular matrices. However, little information is available on the effect of nitrogen and iron co-doped carbon dots (N, Fe-CDs) with sizes below 10 nm on this process. This work demonstrated that Fe-NX formed in N, Fe-CDs and their low surface potentials facilitated electron transfer. N, Fe-CDs exhibited good biocompatibility and were effectively absorbed by Pseudomonas stutzeri ATCC 17588. Intracellular N, Fe-CDs played a dominant role in enhancing anaerobic denitrification. During this process, the nitrate removal rate was significantly increased by 40.60% at 11 h with little nitrite and N2O accumulation, which was attributed to the enhanced activities of the electron transport system and various denitrifying reductases. Based on proteomics and metabolomic analysis, N, Fe-CDs effectively regulated carbon/nitrogen/sulfur metabolism to induce more electron generation, less nitrite/N2O accumulation, and higher levels of nitrogen removal. This work reveals the mechanism by which N, Fe-CDs enhance anaerobic denitrification and broaden their potential application in nitrogen removal.

Role of serotonin, estrogen, and TNF-α in the paroxetine-impaired steroidogenesis and testicular macrophages polarization.

BACKGROUND: Paroxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant, has caused male sexual dysfunction; however, the paroxetine mechanisms of action in testes are still unclear. OBJECTIVES: Paroxetine serotonergic effects in testes were evaluated, focusing on steroidogenesis and the correlation between macrophages population and possible TNF-α-derived oxidative stress. We also verified whether the changes are reversible following treatment interruption. MATERIALS AND METHODS: Adult rats received paroxetine (PG35 and PG65) or tap water (CG) for 35 days. PG65 was maintained without treatment for 30 more days. Intratesticular testosterone (IT), nitrite, and malondialdehyde concentrations were measured. To confirm serotonergic and estrogenic effects, Htr1b and Esr1 expressions were analyzed. The daily sperm production (DSP), frequency of abnormal seminiferous tubules (ST), SC number, ST area, and Leydig cells nuclear area (LCnu) were evaluated. TUNEL+ germ cells, M1 (CD68+ ), and M2 (Perls+ ) macrophages were quantified. 17ß-HSD7, CYP19A1, NDRG2, oxytocin, TNF-α, and iNOS were evaluated by immunoreactions. Oxytocin and NDRG2 protein levels as well as Tnfa mRNA expression were also analyzed. RESULTS: The Htr1b downregulation in testes confirmed the paroxetine serotonergic effect. The testicular sections showed abnormal ST frequency, ST atrophy and reduction of DSP, LCnu, SC number and Perls+ macrophages. TUNEL+ germ cells and LC were associated with strong NDRG2 immunoexpression. Paroxetine reduced IT levels and 17ß-HSD7 immunoexpression in parallel to increased CYP19A1, oxytocin, TNF-α and iNOS. Esr1 and Tnfa overexpression and increased number of CD68+ macrophages were also observed together with high nitrite and malondialdehyde levels. Most parameters were not recovered in PG65. CONCLUSIONS: Paroxetine serotonergic effect impairs LC steroidogenesis, via aromatization, increasing estrogen/testosterone ratio, which in turn upregulate NDRG2, promoting apoptosis, and impairing sperm production. Serotonin-estrogen pathways may be responsible for M2/M1 polarization, Tnfa upregulation, and induction of oxidative stress. The unrecovered testicular changes after treatment discontinuation are due to persistent paroxetine serotonin/estrogen effects.

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor†.

Obstructive sleep apnea is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia, a hallmark of obstructive sleep apnea, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague-Dawley rats were subjected to normoxia (control), mild intermittent hypoxia (10.5% O2), or severe intermittent hypoxia (6.5% O2) from gestational days 10-21. Blood pressure was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mild and severe intermittent hypoxia groups demonstrated elevated blood pressure, reduced plasma nitrate/nitrite, and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor and phosphorylated endothelial nitric oxide synthase, while the levels of endothelin type A receptor and total endothelial nitric oxide synthase remained unchanged following intermittent hypoxia exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mild and severe intermittent hypoxia rats. However, mild and severe intermittent hypoxia rats exhibited impaired endothelium-dependent vasorelaxation responses to endothelin type B receptor agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in endothelin type B receptor-mediated relaxation. Treatment with IRL-1620 during intermittent hypoxia exposure significantly attenuated intermittent hypoxia-induced hypertension in pregnant rats. This was associated with elevated circulating nitrate/nitrite levels, enhanced endothelin type B receptor expression, increased endothelial nitric oxide synthase activation, and improved vasodilation responses. Our data suggested that intermittent hypoxia exposure during gestation increases blood pressure in pregnant rats by suppressing endothelin type B receptor-mediated signaling, providing a molecular mechanism linking intermittent hypoxia and gestational hypertension.

Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction: The INABLE-Training Trial.

OBJECTIVE: To determine whether nitrite can enhance exercise training (ET) effects in heart failure with preserved ejection fraction (HFpEF). METHODS: In this multicenter, double-blind, placebo-controlled, randomized trial conducted at 1 urban and 9 rural outreach centers between November 22, 2016, and December 9, 2021, patients with HFpEF underwent ET along with inorganic nitrite 40 mg or placebo 3 times daily. The primary end point was peak oxygen consumption (VO2). Secondary end points included Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS, range 0 to 100; higher scores reflect better health status), 6-minute walk distance, and actigraphy. RESULTS: Of 92 patients randomized, 73 completed the trial because of protocol modifications necessitated by loss of drug availability. Most patients were older than 65 years (80%), were obese (75%), and lived in rural settings (63%). At baseline, median peak VO2 (14.1 mL·kg-1·min-1) and KCCQ-OSS (63.7) were severely reduced. Exercise training improved peak VO2 (+0.8 mL·kg-1·min-1; 95% CI, 0.3 to 1.2; P<.001) and KCCQ-OSS (+5.5; 95% CI, 2.5 to 8.6; P<.001). Nitrite was well tolerated, but treatment with nitrite did not affect the change in peak VO2 with ET (nitrite effect, -0.13; 95% CI, -1.03 to 0.76; P=.77) or KCCQ-OSS (-1.2; 95% CI, -7.2 to 4.9; P=.71). This pattern was consistent across other secondary outcomes. CONCLUSION: For patients with HFpEF, ET administered for 12 weeks in a predominantly rural setting improved exercise capacity and health status, but compared with placebo, treatment with inorganic nitrite did not enhance the benefit from ET. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02713126.

Assessing the activity of different plant-derived molecules and potential biological nitrification inhibitors on a range of soil ammonia- and nitrite-oxidizing strains.

IMPORTANCE: Synthetic nitrification inhibitors are routinely used with nitrogen fertilizers to reduce nitrogen losses from agroecosystems, despite having drawbacks like poor efficiency, cost, and entry into the food chain. Plant-derived BNIs constitute a more environmentally conducive alternative. Knowledge on the activity of BNIs to soil nitrifiers is largely based on bioassays with a single Nitrosomonas europaea strain which does not constitute a dominant member of the community of ammonia-oxidizing microorganisms (AOM) in soil. We determined the activity of several plant-derived molecules reported as having activity, including the recently discovered maize-isolated BNI, zeanone, and its natural analog, 2-methoxy-1,4-naphthoquinone, on a range of ecologically relevant AOM and one nitrite-oxidizing bacterial culture, expanding our knowledge on the intrinsic inhibition potential of BNIs toward AOM and highlighting the necessity for a deeper understanding of the effect of BNIs on the overall soil microbiome integrity before their further use in agricultural settings.

In situ generation of cold atmospheric plasma-activated mist and its biocidal activity against surrogate viruses for COVID-19.

AIMS: To provide an alternative to ultra violet light and vapourized hydrogen peroxide to enhance decontamination of surfaces as part of the response to the COVID-19 pandemic. METHODS AND RESULTS: We developed an indirect method for in situ delivery of cold plasma and evaluated the anti-viral activity of plasma-activated mist (PAM) using bacteriophages phi6, MS2, and phiX174, surrogates for SARS-CoV-2. Exposure to ambient air atmospheric pressure derived PAM caused a 1.71 log10 PFU ml-1 reduction in phi6 titer within 5 min and a 7.4 log10 PFU ml-1 reduction after 10 min when the the PAM source was at 5 and 10 cm. With MS2 and phiX174, a 3.1 and 1.26 log10 PFU ml-1 reduction was achieved, respectively, after 30 min. The rate of killing was increased with longer exposure times but decreased when the PAM source was further away. Trace amounts of reactive species, hydrogen peroxide and nitrite were produced in the PAM, and the anti-viral activity was probably attributable to these and their secondary reactive species. CONCLUSIONS: PAM exhibits virucidal activity against surrogate viruses for COVID-19, which is time and distance from the plasma source dependent.

Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. METHODS: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute-sponsored trials were analyzed according to the tertiles of IL-6. RESULTS: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro-B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P < 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P < 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. CONCLUSIONS: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status. (Clinical Trial Registrations: Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure [RELAX], NCT00763867; Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction, NCT02053493; Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF, NCT02742129; Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction [HFpEF], NCT02713126).

Effect of hypoandrogenism on expression of transient receptor potential vanilloid channels in rat penile corpus cavernosum and erectile function.

BACKGROUND: Hypoandrogenism is a cause of erectile dysfunction (ED). Vascular smooth muscle cell contraction and relaxation are regulated by TRPV1-4 channels. However, the influence of hypoandrogenism on TRPV1-4 and its relationship with erectile function remain unclear. AIM: To reveal whether hypoandrogenism affects erectile function by influencing TRPV1-4 expression in the corpus cavernosum of rats. METHODS: Male Sprague-Dawley rats (N = 36) aged 8 weeks were assigned to 6 groups at random (n = 6): sham operation, castrated, castrated + testosterone replacement, sham operation + transfection, castrated + transfection, and castrated + empty transfection. Four weeks after castration, 20 µL of lentiviral vector (1 × 108 TU/mL) carrying the TRPV4 gene was injected into the penile cavernous tissue of the transfection groups. One week after transfection, the maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP) and the content of TRPV1-4, phosphorylated eNOS (p-eNOS)/eNOS, and nitric oxide (NO) in penile cavernous tissue of each group were measured. OUTCOMES: Under low androgen conditions, TRPV4 expression in endothelial cells in the rat penile cavernosum was sharply reduced, resulting in a decrease in p-eNOS/eNOS and NO content, which could inhibit erectile function. RESULTS: In rat penile cavernous tissue, TRPV1-4 was expressed in the cell membranes of endothelial cells and smooth muscle cells. The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue was markedly reduced in the castrated group as compared with the sham group (P < .05). The ICPmax/MAP and the content of TRPV4, p-eNOS/eNOS, and NO end product nitrite level in rat penile cavernous tissue were markedly improved in the castrated + transfection group vs the castrated group (P < .01). CLINICAL IMPLICATIONS: Upregulation of TRPV4 expression in penile cavernosum tissue might be a viable therapeutic for ED caused by hypoandrogenism. STRENGTHS AND LIMITATIONS: The specific mechanism of TRPV4 in ED needs to be further verified by androgen receptor or TRPV4 gene knockout experiments. CONCLUSION: Hypoandrogenism may cause ED by reducing the expression of TRPV4 in rat penile cavernous tissue. Upregulation of TRPV4 expression in penile cavernous tissue can increase the ratio of p-eNOS/eNOS and NO levels and ameliorate the erectile function of castrated rats.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

Does apocynin increase liver regeneration in the partial hepatectomy model?

BACKGROUND: Hepayocyte loss may develop secondary to liver surgery and at this point liver regeneration plays a significant act in terms of liver reserve. The purpose of this research was to investigate the efficacy of apocynin on liver regeneration and preservation after partial hepatectomy in rats. METHODS: A total of 32 rats, have been divided into 4 groups (n: 8) for hepatectomy model. Inflammatory and antiinflammatory parameters were measured from blood and liver tissue samples. In addition, the effects of apocynin were examined immunohistochemically and histopathologically from liver tissue. RESULTS: In liver tissue samples, a significant difference has been found in glutathione peroxidase, total nitrite, catalase, oxidative stress index, total antioxidant and total oxidant status between sham and hepatectomy groups. A significant difference has been achieved between hepatectomy and posthepatectomy-Apocynin in terms of glutathione peroxidase and oxidative stress index. Total antioxidant status, oxidative stress index, and total oxidant status were significantly different only between the sham and the hepatectomy groups. Statistical differences were found between sham and hepatectomy groups and between hepatectomy and pre+post-hepatectomy-Apocynin groups in terms of serum glutathione, malondialdehyde, total nitrite, and L-Arginine. There were significant differences between the sham and hepatectomy groups, between hepatectomy and posthepatectomy-apocynin groups, between posthepatctomy-apocynin and pre+posthepatectomy-apocynin groups in terms of sinusoidal dilatation, intracytoplasmic vacuolization and glycogen loss (p < 0.001), in all histopathologic parameters except sinusoidal dilatation (p < 0.05). However, significant Ki-67 increases have been elaborated in hepatectomy, posthepatectomy-apocynin, and pre+posthepatectomy-apocynin groups compared to sham group (p < 0.001), in pre+posthepatectomy apocynin group compared to hepatectomy and posthepatectomy-apocynin groups (p < 0.001). DISCUSSION: Histopathology, immunohistochemistry, and biochemistry results of this study revealed that apocynin has a protective effect on enhancing liver regeneration in partial hepatectomy cases in rats.

Computed tomography and predictive microbiology for non-invasive evaluation of the impact of dry-cured ham production process conditions on the behaviour of Listeria monocytogenes and Clostridium botulinum.

Variability of salt content in dry-cured ham production can pose microbiological food safety issues, especially in salt reduced and/or non-nitrified products. In this regard, computed tomography (CT) could help to non-invasively characterised the product to further adjust the production process and ensure its safety. The aim of this work was to study the application of CT to estimate aw in dry-cured ham to be used by predictive microbiology to evaluate the impact of the production process on the behaviour of Listeria monocytogenes and Clostridium botulinum. Effect of nitrite elimination and fat content of hams was also evaluated. Thirty hams with two different fat content levels were characterised analytically and using CT at different key points in the process. The safety of the process was evaluated by applying predictive microbiology using both analytical and CT data as model inputs. Results showed that nitrite and fat content had an impact on the predicted growth potential of the pathogens evaluated. After the resting period, if no nitrite is added, the time needed for 1 log increase (tinc) of L. monocytogenes would shorten by 26% and 22% in lean and fat hams, respectively. After week 12, important differences on tinc values for C. botulinum were found between both groups of hams (ca. 40% shorter in fat hams). CT can provide reliable pixel-to-pixel information for predictive microbiology to evaluate the growth of relevant pathogens, but further studies are needed to validate this combination as a tool to evaluate the safety of the production process.

Challenge tests reveal limited outgrowth of proteolytic Clostridium botulinum during the production of nitrate- and nitrite-free fermented sausages.

Nitrate and nitrite salts perform a versatile role in fermented meats, including the inhibition of food pathogens (in particular proteolytic group I Clostridium botulinum). Despite the increasing interest in clean-label products, little is known about the behaviour of this pathogen in response to the removal of chemical preservatives from fermented meat formulations. Therefore, challenge tests with a cocktail of nontoxigenic group I C. botulinum strains were performed to produce nitrate/nitrite-free fermented sausages under different acidification conditions and starter culture formulations, including the use of an anticlostridial Mammaliicoccus sciuri strain. Results showed limited outgrowth of C. botulinum, even in the absence of acidification. The anticlostridial starter culture did not lead to an additional inhibitory effect. The selective plating procedure adopted within this study proofed robust to follow germination and growth of C. botulinum, inhibiting common fermentative meat microbiota. The challenge tests constitute a suitable tool to assess the behaviour of this food pathogen within fermented meats upon nitrate- and nitrite omission.

The effect of orally administered nitrate on renal function and blood pressure in a randomized, placebo-controlled, crossover study in healthy subjects.

BACKGROUND: Several studies have shown inorganic nitrate/nitrite to reduce blood pressure in both healthy subjects and hypertensive patients. An effect presumably caused through bioconversion to nitric oxide. However, studies on inorganic nitrate/nitrite have shown inconsistent results on renal functions such as GFR and sodium excretion. The current study investigated whether orally administered nitrate would decrease blood pressure and increase GFR and urinary sodium excretion. METHODS: In a randomized, placebo-controlled, double-blinded, crossover study, 18 healthy subjects received a daily dose of 24 mmol potassium nitrate and placebo (potassium chloride) during 4 days in a randomized order. Subjects also ingested a standardized diet and completed a 24-h urine collection. GFR was determined by the constant infusion technique and during GFR measurement, brachial blood pressure (BP) and central blood pressure (cBP), heart rate, and arterial stiffness were measured every half hour using the Mobil-O-Graph®. Blood samples was analyzed for nitrate, nitrite, cGMP, vasoactive hormones and electrolytes. Urine was analyzed for nitrate, nitrite, cGMP, electrolytes, ENaCγ, NCC, CrCl, CH2O and UO. RESULTS: No differences in GFR, blood pressure or sodium excretion were found between the treatments with potassium nitrate and placebo. However, both nitrate and nitrite levels in plasma and urine were significantly increased by potassium nitrate intake and the 24-h urinary excretion of sodium and potassium were stable, showing adherence to the standardized diet and the study medication. CONCLUSION: We found no decrease in blood pressure or increase in GFR and sodium excretion of 24 mmol potassium nitrate capsules as compared to placebo after 4 days of treatment. Healthy subjects may be able to compensate the effects of nitrate supplementation during steady state conditions. Future research should focus on long-term studies on the difference in response between healthy subjects and patients with cardiac or renal disease.

Application of oleaster leaves (Elaeagnus angustifolia L.) essential oil and natural nanoparticle preservatives in frankfurter-type sausages: An assessment of quality attributes and stability during refrigerated storage.

The effects of oleaster leave essential oil (OLEOs: 1000 and 2000 ppm) in combination with nisin nanoparticles (200 ppm) and ε-polylysine nanoparticles (2000 ppm) on the physicochemical, microbiological and sensory properties of the emulsion-type sausages without added chemical nitrite/nitrate salts were evaluated during 45 days of storage. Nanoparticle attributes were assessed, including encapsulation efficiency (EE%), zeta potential, nanoparticles size, FTIR analysis, and thermal stability (DSC). Overall, ε-PL nanoparticles (ε-PL-NPs) were thermally more stable and showed higher EE% (91.52%) and zeta potential (37.80%) as compared to nisin nanoparticles (82.85%) and (33.60%), respectively. The use of combined ε-PL-NPs (2000 ppm) + Ni-NPs (200 ppm) with oleaster leaves essential oil (2000 ppm) resulted in a higher pH value (5.88), total phenolic content (10.45 mg/100 g) and lower TBARS (2.11 mg/kg), and also decreased total viable bacteria (1.28 Log CFU/g), Clostridium perfringens (1.43 Log CFU/g), E. coli (0.24 Log CFU/g), Staphylococcus aureus (0.63 Log CFU/g), and molds and yeasts (0.86 Log CFU/g) count in samples at day 45 in comparison to the control (120 ppm nitrite). The consumers approved sensory traits in nitrite-free formulated sausages containing ε-PL-NPs and Ni-NPs combined with OLEOs.

Investigation of the Effects of Opioids on Microglial Nitrite and Nitric Oxide Synthase (iNOS) Production and Phagocytosis during Inflammation.

AIM: This study aimed to investigate how opioids affect phagocytosis and microglial nitrite and nitric oxide synthase (iNOS) production during inflammation. BACKGROUND: Opioids are a group of chemicals that are naturally found in the opium poppy plant and exert a variety of effects on the brain, including pain alleviation in some cases. They are commonly used in surgery and perioperative analgesia. However, research on the impact of opioids on microglial inflammatory factor production and phagocytosis is limited. OBJECTIVES: This study was designed to investigate the effects of opioids on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) generation. Moreover, the influence of opioids on the engulfment of C8-B4 microglial cells after stimulation with LPS was also examined. METHODS: C8-B4 mouse microglial cells were exposed to various concentrations of opioids after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Nitrite production was assayed. The iNOS and Cox-2 were determined by Western blotting, and fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia cultivating with opioids after being activated by LPS. RESULTS: After LPS and IFN-γ stimulation, microglia produced lower amounts of nitric oxide (NO) production with buprenorphine, salvinorin A, and naloxone (P<0.05). When combined with naloxone, no significant differences were found than buprenorphine. It was observed that buprenorphine and salvinorin A could suppress iNOS expression activated by LPS and IFN-γ. Phagocytosis was greatly increased after LPS stimulation, and a significant increase was observed after adding salvinorin A. CONCLUSION: Buprenorphine and salvinorin A were found to reduce NO production and iNOS induction in microglial cells activated by LPS and IFN-γ. Salvinorin A promoted the phagocytosis of microglia cells treated by LPS.

A Common Target of Nitrite and Nitric Oxide for Respiration Inhibition in Bacteria.

Nitrite and nitric oxide (NO) are well-known bacteriostatic agents with similar biochemical properties. However, many studies have demonstrated that inhibition of bacterial growth by nitrite is independent of NO. Here, with Shewanella oneidensis as the research model because of its unusually high cytochrome (cyt) c content, we identify a common mechanism by which nitrite and NO compromise cyt c biosynthesis in bacteria, and thereby inhibit respiration. This is achieved by eliminating the inference of the cyclic adenosine monophosphate-catabolite repression protein (cAMP-Crp), a primary regulatory system that controls the cyt c content and whose activity is subjected to the repression of nitrite. Both nitrite and NO impair the CcmE of multiple bacteria, an essential heme chaperone of the System I cyt c biosynthesis apparatus. Given that bacterial targets of nitrite and NO differ enormously and vary even in the same genus, these observations underscore the importance of cyt c biosynthesis for the antimicrobial actions of nitrite and NO.

The Efficacy of Nitrite Therapy for the Treatment of Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy of nitrite therapy for the treatment of heart failure remains controversial. We conducted a systematic review and meta-analysis to explore the impact of nitrite therapy on heart failure. METHODS: We searched the PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through November 2019 for randomized controlled trials (RCTs) assessing the effect of nitrite therapy on heart failure. This meta-analysis was performed using the random-effect model. RESULTS: Three RCTs are included in the meta-analysis. Overall, compared with the control group for heart failure, nitrite therapy is associated with significantly reduced PCWP (Std. MD=-1.22; 95% CI=-1.81 to -0.63; P < 0.0001) and improved PAC (Std. MD=0.71; 95% CI=0.16 to 1.27; P = 0.01), but reveals no substantial influence on peak VO2 (Std. MD=-0.19; 95% CI=-0.49 to 0.11; P = 0.21), systolic BP (Std. MD=-3.98; 95% CI=-8.24 to 0.28; P = 0.07), mean BP (Std. MD=-1.53; 95% CI=-3.37 to 0.31; P = 0.10), or heart rate (Std. MD=0.40; 95% CI=-0.14 to 0.94; P = 0.15). CONCLUSIONS: Nitrite therapy may show some benefits to heart failure.

Brassinolide Soaking Reduced Nitrite Content and Extended Color Change and Storage Time of Toona sinensis Bud during Low Temperature and Near Freezing-Point Temperature Storage.

Low temperatures are often used to preserve fruits and vegetables. However, low-temperature storage also causes problems, such as chilling injury, nitrite accumulation, and browning aggravation in plants. This study investigated the effects of brassinolide (BR,1.0 mg L-1) solution soaking, storage temperatures (-2 ± 0.5 °C, 4 ± 0.5 °C, and 20 ± 1 °C), and their combinations on nitrite content, color change, and quality of stored Toona sinensis bud. The results showed that low temperature (LT, 4 ± 0.5 °C) and near freezing-point temperature (NFPT, -2 ± 0.5 °C) storage effectively inhibited the decay of T. sinensis bud compared to room temperature (20 ± 1 °C, the control). The combined treatments of BR with LT or NFPT reduced nitrite content and maintained the color and the contents of vitamin C, carotenoids, saponins, ß-sitosterol, polyphenol, anthocyanin, flavonoids, and alkaloids in T. sinensis bud. BR soaking delayed the occurrence of chilling injury during NFPT storage. Meanwhile, BR soaking enhanced the DPPH radical scavenging activity, ABTS activity, and FRAP content by increasing SOD and POD activity and the contents of proline, soluble, and glutathione, thus decreasing MDA and hydrogen peroxide content and the rate of superoxide radical production in T. sinensis bud during NFPT storage. This study provides a valuable strategy for postharvest T. sinensis bud in LT and NFPT storage. BR soaking extended the shelf life during LT storage and maintained a better appearance and nutritional quality during NFPT storage.

Therapeutic effect of 6-shogaol on acetaminophen-induced hepatotoxicity in mice: an experimental study.

OBJECTIVE: Acetaminophen (APAP) is one of the most commonly used analgesics and antipyretics. It causes serious liver damage when taken in large quantities by adults or children. Also, 6-shogaol is an active compound obtained from ginger with anti-inflammatory and antioxidant properties. This study aimed at examining the therapeutic effect of 6-shogaol in APAP-induced hepatotoxicity. MATERIALS AND METHODS: The mice were separated into five groups. After the mice were sacrificed, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in the blood, glutathione (GSH) level in the liver tissue homogenate, and levels of induced nitrite oxide synthetase (INOS) and total nitrite/nitrate were measured by spectrophotometric methods. RESULTS: APAP administration significantly increased the serum levels of ALT, AST, and ALP, INOS activity in liver tissue, and total nitrite/nitrate levels compared with control and significantly decreased GSH levels. After APAP toxicity, 6-shogaol and N-acetylcysteine (NAC) administration significantly decreased the levels of ALT, AST, INOS, and total nitrite/nitrate levels and significantly increased GSH levels compared with control. Also, 6-shogaol was found to be better than NAC in increasing the GSH level. CONCLUSIONS: The study showed that 6-shogaol might have an early therapeutic effect on APAP-induced liver damage.

Pueraria montana (Kudzu vine) Ameliorate the Inflammation and Oxidative Stress against Fe-NTA Induced Renal Cancer.

Renal tissue plays a crucial function in maintaining homeostasis, making it vulnerable to xenobiotic toxicity. Pueraria montana has more beneficial potential against the various diseases and has long history used as a traditional Chinese medicine. But its effect against the renal cancer not scrutinize. The goal of this study is to see if Pueraria montana can protect rats from developing kidney tumors caused by diethylnitrosamine (DEN) and ferric nitrite (Fe-NTA). Wistar rats was selected for the current study and DEN (use as an inducer) and Fe-NTA (promoter) for induction the renal cancer. For 22 weeks, the rats were given orally Pueraria montana (12.5, 25, and 50 mg/kg) treatment. At regular intervals, the body weight and food intake were calculated. The rats were macroscopically evaluated for identification of cancer in the renal tissue. The renal tumor makers, renal parameters, antioxidant enzymes, phase I and II enzymes, inflammatory cytokines and mediators were estimated at end of the experimental study. Pueraria montana treated rats displayed the suppression of renal tumors, incidence of the tumors along with suppression of tumor percentage. Pueraria montana treated rats significantly (p < 0.001) increased body weight and suppressed the renal weight and food intake. It also reduced the level of renal tumor marker ornithine decarboxylase (ODC) and [3H] thymidine incorporation along with suppression of renal parameter such as uric acid, blood urea nitrogen (BUN), urea and creatinine. Pueraria montana treatment significantly (p < 0.001) altered the level of phase enzymes and antioxidant. Pueraria montana treatment significantly (p < 0.001) repressed the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and improved the level of interleukin-10 (IL-10). Pueraria montana treatment suppressed the level of prostaglandin (PGE2), cyclooxygenase-2 (COX-2), nuclear kappa B factor (NF-κB) and transforming growth factor beta 1 (TGF-ß1). Pueraria montana suppressed the inflammatory necrosis, size the bowman capsules in the renal histopathology. Pueraria montana exhibited the chemoprotective effect via dual mechanism such as suppression of inflammatory reaction and oxidative stress.