Nitrite Production Research Articles

Dietary Nitrate Supplementation Does Not Alter Exercise Efficiency at High Altitude - Further Results From the Xtreme Alps Study.

IntroductionNitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. We hypothesized that performing exercise at high altitude would lower circulating nitrate and nitrite levels and that BRJ ingestion would reverse this phenomenon while concomitantly improving key determinants of aerobic exercise performance.MethodsTwenty seven healthy volunteers (21 male) underwent a series of exercise tests at sea level (SL, London, 75 m) and again after 5–8 days at high altitude (HA, Capanna Regina Margherita or “Margherita Hut,” 4,559 m). Using a double-blind protocol, participants were randomized to consume a beetroot/fruit juice beverage (three doses per day) with high levels of nitrate (∼0.18 mmol/kg/day) or a nitrate-depleted placebo (∼11.5 μmoles/kg/day) control drink, from 3 days prior to the exercise trials until completion. Submaximal constant work rate cycle tests were performed to determine exercise efficiency and a maximal incremental ramp exercise test was undertaken to measure aerobic capacity, using breath-by-breath pulmonary gas exchange measurements throughout. Concentrations of nitrate, nitrite and nitrosation products were quantified in plasma samples collected at 5 timepoints during the constant work rate tests. Linear mixed modeling was used to analyze data.ResultsAt both SL and HA, plasma nitrate concentrations were elevated in the nitrate supplementation group compared to placebo (P < 0.001) but did not change throughout increasing exercise work rate. Delta exercise efficiency was not altered by altitude exposure (P = 0.072) or nitrate supplementation (P = 0.836). V̇O2peak decreased by 24% at high altitude (P < 0.001) and was lower in the nitrate-supplemented group at both sea level and high altitude compared to placebo (P = 0.041). Dietary nitrate supplementation did not alter other peak exercise variables or oxygen consumption at anaerobic threshold. Circulating nitrite and S-nitrosothiol levels unexpectedly rose in a few individuals right after cessation of exercise at high altitude.ConclusionWhilst regularly consumed during an 8 days expedition to terrestrial high altitude, nitrate supplementation did not alter exercise efficiency and other exercise physiological variables, except decreasing V̇O2peak. These results and those of others question the practical utility of BRJ consumption during prolonged altitude exposure.

Insights into Anti-Inflammatory Activity and Internalization Pathway of Onion Peel-Derived Gold Nano Bioconjugates in RAW 264.7 Macrophages.

Green synthesis of nanoparticles plays an important role in their efficient therapeutic effects in various biomedical applications. Here, we prepared gold nano bioconjugates (GNBCs) from the ethyl acetate fraction of onion peels and investigated their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophages. The GNBCs were characterized by UV–visible spectroscopy, dynamic light scattering, and transmission electron microscopy. Comparative studies have been conducted among GNBCs, fractionate alone [onion peel drug (OPD)], and the standard drug dexamethasone in various anti-inflammatory assays. It was observed that GNBCs showed comparatively good therapeutic efficacy than the fractionate alone. At the lowest 10 μg/mL concentration, the GNBC and OPD exhibited 70.86 and 91.98% of reactive oxygen species production, 10.88 and 20.97 ng/μL of nitrite production, 337 and 378 pg/mL of TNF-α production, 27.1 and 30.64 pg/mL of IL-6 production, respectively, by maintaining a satisfactory cell viability. Moreover, to understand the mechanistic pathway of GNBCs in their entry into the macrophages, their localization, and duration, uptake studies have been performed where a caveolar-mediated endocytosis pathway is found to be prominent. Hence, this study will lead to the development of cheap, green synthesis of nano bioconjugates and their role in inflammation.

A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model

BackgroundImmunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PurposeThe present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. MethodsThe levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. ResultsIST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. ConclusionThese findings suggest that IST supplementation may be used to enhance immune function.

Inhibition of the extracellular signal-regulated kinase pathway reduces the inflammatory component in nucleus pulposus cells.

Intervertebral disc (IVD) degeneration is a spinal disorder that triggers an inflammatory response and subsequent development of spinal pseudoarthrosis. The aim of the present study is to elucidate the role of the extracellular signal-regulated kinase (ERK) pathway in inflammation-induced IVD cells. Inflammatory human nucleus pulposus (NP) cells (NPCs) were induced using tumor necrosis factor-αand the ERK pathway was blocked using a selective molecule-based inhibitor U0126. Gene expression of catabolic and anabolic markers, proinflammatory, and NPCs markers was investigated. The enzymatic activity of matrix metalloproteinases (MMP)2/MMP9 was determined by gelatin zymography and nitrite production was assessed by Griess reaction. The NPC metabolic activity and viability were assessed using resazurin sodium-salt and live/dead assays, and subsequently, the specificity of U0126 on ERK1/2 signaling was determined. The catabolic enzyme MMP3 (p = 0.0001) and proinflammatory cytokine interleukin 6 (p = 0.036)were downregulated by U0126 in NPCs under inflammatory conditions. A significant increase of the cytokeratin 19 (p = 0.0031) was observed, suggesting a partial and possible recovery of the NP phenotype. U0126 does not seem to have an effect on prostaglandin production, aggrecanases, or other anabolic genes. We confirmed that U0126 selectively blocks the ERK phosphorylation and only affects the cell metabolic activity without the reduction of viable cells. Inhibition of ERK signaling downregulates important metalloproteinases and proinflammatory cytokines, and upregulates some NP markers, suggesting its potential to treat IVD degeneration.

CO2 bubble-assisted in-situ construction of mesoporous Co-doped Cu2(OH)2CO3 nanosheets as advanced electrodes towards fast and highly efficient electrochemical reduction of nitrate to N2 in wastewater

The development of high-efficient and cost-effective electrocatalysts is crucial to remove nitrate pollutant in wastewater. Herein, we design and prepare mesoporous Co-doped Cu2(OH)2CO3 malachite nanosheets as an electrocatalyst toward highly efficient nitrate reduction using a facile CO2 bubble-assisted coprecipitation synthesis. The electrocatalytic performance is subject to the Co/Cu ratio of this malachite. Remarkably, compared with the pristine monometal Cu or Co-based electrocatalyst, the optimal electrocatalyst, 0.3Co@Cu2(OH)2CO3, displays fast and highly efficient removal capacity of nitrate with an impressive high total nitrogen (TN) removal of 8628.99 mg N g−1CoCu (398.79 mg N gcat−1 h−1), N2 selectivity of 97.11% as well as negligible nitrite product at 100 mg L−1 NO3--N and 2000 mg L−1 Cl- neutral electrolyte. Above all, high total nitrogen removal efficiency (81.92%) and chemical oxygen demand (73.74%) in actual wastewater. Its excellent electrocatalytic performance is achieved by regulating the electronic structure and the adsorption/desorption of the intermediate. This study discovers a new type of electrode materials for nitrate removal in wastewater.

Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance Against Leishmania mexicana Infection.

IL-4 and IL-13 cytokines have been associated with a non-healing phenotype in murine leishmaniasis in L. mexicana -infected BALB/c mice as demonstrated in IL-4−/−, IL-13−/− and IL-4Rα-/- global knockout mouse studies. However, it is unclear from the studies which cell-type-specific IL-4/IL-13 signaling mediates protection to L. mexicana. Previous studies have ruled out a role for IL-4-mediated protection on CD4+ T cells during L. mexicana infections. A candidate for this role may be non-lymphocyte cells, particularly DCs, as was previously shown in L. major infections, where IL-4 production drives dendritic cell-IL-12 production thereby mediating a type 1 immune response. However, it is unclear if this IL-4-instruction of type 1 immunity also occurs in CL caused by L. mexicana, since the outcome of cutaneous leishmaniasis often depends on the infecting Leishmania species. Thus, BALB/c mice with cell-specific deletion of the IL-4Rα on CD11c+ DCs (CD11ccreIL-4Rα-/lox) were infected with L. mexicana promastigotes in the footpad and the clinical phenotype, humoral and cellular immune responses were investigated, compared to the littermate control. Our results show that CL disease progression in BALB/c mice is independent of IL-4Rα signaling on DCs as CD11ccreIL-4Rα-/lox mice had similar footpad lesion progression, parasite loads, humoral responses (IgE, IgG1, IgG 2a/b), and IFN-γ cytokine secretion in comparison to littermate controls. Despite this comparable phenotype, surprisingly, IL-4 production in CD11ccreIL-4Rα-/lox mice was significantly increased with an increasing trend of IL-13 when compared to littermate controls. Moreover, the absence of IL-4Rα signaling did not significantly alter the frequency of CD4 and CD8 lymphocytes nor their activation, or memory phenotype compared to littermate controls. However, these populations were significantly increased in CD11ccreIL-4Rα-/lox mice due to greater total cell infiltration into the lymph node. A similar trend was observed for B cells whereas the recruitment of myeloid populations (macrophages, DCs, neutrophils, and Mo-DCs) into LN was comparable to littermate IL-4Rα-/lox mice. Interestingly, IL-4Rα-deficient bone marrow-derived dendritic cells (BMDCs), stimulated with LPS or L. mexicana promastigotes in presence of IL-4, showed similar levels of IL-12p70 and IL-10 to littermate controls highlighting that IL-4-mediated DC instruction was not impaired in response to L. mexicana. Similarly, IL-4 stimulation did not affect the maturation or activation of IL-4Rα-deficient BMDCs during L. mexicana infection nor their effector functions in production of nitrite and arginine-derived metabolite (urea). Together, this study suggests that IL-4 Rα signaling on DCs is not key in the regulation of immune-mediated protection in mice against L. mexicana infection.

Curcumin and vinblastine induce apoptosis and impair migration in human cutaneous melanoma cells

Cancer is an important cause of lethality, and melanoma is associated with less than 10% of survival. The traditional treatment includes the use of vinblastine, and it is associated with side effects. Curcumin is extracted from Curcuma longa rhizomes, and studied in many diseases, producing a variety of effects. We investigated the role of various cellular pathways concerning apoptosis, cell cycle enzymes in melanoma cell line SK-MEL-28, after treatment with curcumin, vinblastine, or a combination of both, for 24 hours. After this, we performed cell cycle, apoptosis, wound healing assay, comet assay on cells, and evaluated nitrite accumulation (nitric oxide (NO•) byproduct). Curcumin increased cells in apoptosis and reduced the number of cells in the G1 phase. Vinblastine increased the production of nitrite, and cells in early apoptosis, mainly through the inducement of DNA damage. Cell migration was impaired in all tested groups. In conclusion, curcumin impaired migration, producing NO•, and promoting apoptosis of tumoral cells. Vinblastine also impaired cell migration and increased levels of NO•. Curcumin might be included as an adjuvant in the treatment of melanoma, and help treatment of melanoma, and further studies are needed, especially regarding the synergistic effect of curcumin and vinblastine in the treatment.

Pilot-scale continuous flow granular reactor for the treatment of extremely low-strength recirculating aquaculture system wastewater

To avoid toxic ammonium and nitrite concentrations in aquaculture systems is crucial to maintain the fish production. When recirculating aquaculture systems (RAS) operate in freshwater farms during the dry seasons, the concentrations of these pollutants increase. The objective of the present study is the evaluation of a Continuous Flow Granular Reactor (CFGR) for the treatment of freshwater RAS stream at pilot-scale during two consecutive dry seasons. The CFGR was fed with a extremely low-strength recirculation stream of a trout farm (0.12–1.84 mg NH4+-N/L and 2.2–8.14 mg C/L). Two different configurations were evaluated. The first configuration consisted on a CFGR fed from the bottom, being the up-flow velocity the only shear force to mix the biomass. The second configuration incorporated a mechanical stirrer and a sieve to improve the biomass mixing and retention. The CFGR was operated at short hydraulic retention times (HRT) which ranged from 11 to 68 min. The configuration with a mechanical stirrer and sieve was optimal in terms of biomass retention and nitrogen removal performance. Despite the low nitrogen and organic matter concentrations, granulation was achieved in 55 days, with an average granule diameter up to 0.47 mm. Ammonium and nitrite removal percentages up to 81% and 100% were achieved, respectively. The ammonium and nitrite production rate in the trout farm were lower than the removal achieved by the CFGR, which makes the implementation of this system appropriated to maintain the concentration of these compounds below toxic levels for rainbow trout.

Assessing membrane aerated biofilm reactor configurations in mainstream anammox applications.

Partial nitritation anammox (PNA) membrane aerated biofilm reactors (MABRs) have the potential to be employed in mainstream wastewater treatment and can drastically decrease the energy and carbon requirements for nitrogen removal. Previous PNA MABR studies have looked at 1-stage systems, but no study has holistically compared the performance of different MABR configurations. In this study, a PNA MABR was mechanistically modelled to determine the impact of the reactor configuration (1-stage, hybrid, or 2-stage system) on the location of the preferred niche for anammox bacteria and the overall nitrogen removal performance. Results from this study show that the 2-stage configuration, which used an MABR with a thin biofilm for nitritation and a moving bed biofilm reactor for anammox, had a 20% larger nitrogen removal rate than the 1-stage or hybrid configurations. This suggests that an MABR should focus on maximizing nitrite production with anammox implemented in a second-stage biofilm reactor to achieve the most cost-effective nitrogen removal. However, the optimal configuration will likely be facility specific, as each facility differs in operating costs, construction costs, footprint, and effluent limits. Additional experimentation is required to confirm these results, but this work narrows the number of viable configurations that need to be tested. The results of this study will inform researchers and engineers how to best implement PNA MABRs in mainstream nitrogen removal at larger scales.

Antioxidant-Anti-Inflammatory Evaluation of a Polyherbal Formula.

Most disease—both acute and chronic—results from inflammation, and reactive oxygen species (ROS) are considered some of the strongest stimuli of inflammation. Many studies reported the traditional use of herbal species for treating inflammation, especially when ROS are involved. The present study aims to demonstrate the antioxidant–anti-inflammatory effects of a patented preparation based on Populus nigra and Rosmarinus officinalis extracts and to highlight its applicative potential; the formula was characterized by HPTLC and HPLC and in-vitro studies were conducted on TNF-α-stimulated HUVECs. The antioxidant activity of the formula was determined by DPPH assay and the phosphomolybdenum method; to assess in-vivo anti-inflammatory activity, a rat paw edema model was used; the formula contains high amounts of polyphenols. It exhibited scavenging activity of 50–85% at 1–10 mg/mL, it inhibited nitrite production and ICAM-1 expression in TNF-α-stimulated endothelial cell cultures dose-dependently, at a maximum of 58.7% at the maximum dose administered and exerted an obvious anti-inflammatory effect in vivo, settling early and decreasing at 180 min; a new herbal bioactive product was presented with promising therapeutic potential that can be an adjunct to conventional therapies for diseases based on oxidative stress and inflammation.

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne's Disease.

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

Hydroethanolic Extract of Prunus domestica L.: Metabolite Profiling and In Vitro Modulation of Molecular Mechanisms Associated to Cardiometabolic Diseases.

High consumption of fruit and vegetables has an inverse association with cardiometabolic risk factors. This study aimed to chemically characterize the hydroethanolic extract of P. domestica subsp. syriaca fruit pulp and evaluate its inhibitory activity against metabolic enzymes and production of proinflammatory mediators. Ultra-high-performance liquid chromatography high-resolution mass spectrometry(UHPLC-HRMS) analysis showed the presence of hydroxycinnamic acids, flavanols, and glycoside flavonols, while nuclear magnetic resonance(NMR) analysis showed, among saccharides, an abundant presence of glucose. P. domestica fruit extract inhibited α-amylase, α-glucosidase, pancreatic lipase, and HMG CoA reductase enzyme activities, with IC50 values of 7.01 mg/mL, 6.4 mg/mL, 6.0 mg/mL, and 2.5 mg/mL, respectively. P. domestica fruit extract inhibited lipopolysaccharide-induced production of nitrite, interleukin-1 β and PGE2 in activated J774 macrophages. The findings of the present study indicate that P. domestica fruit extracts positively modulate in vitro a series of molecular mechanisms involved in the pathophysiology of cardiometabolic diseases. Further research is necessary to better characterize these properties and their potential application for human health.

The Compound (E)-2-Cyano-N,3-diphenylacrylamide (JMPR-01): A Potential Drug for Treatment of Inflammatory Diseases.

The compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01) was structurally developed using bioisosteric modifications of a hybrid prototype as formed from fragments of indomethacin and paracetamol. Initially, in vitro assays were performed to determine cell viability (in macrophage cultures), and its ability to modulate the synthesis of nitrite and cytokines (IL-1β and TNFα) in non-cytotoxic concentrations. In vivo, anti-inflammatory activity was explored using the CFA-induced paw edema and zymosan-induced peritonitis models. To investigate possible molecular targets, molecular docking was performed with the following crystallographic structures: LT-A4-H, PDE4B, COX-2, 5-LOX, and iNOS. As results, we observed a significant reduction in the production of nitrite and IL-1β at all concentrations used, and also for TNFα with JMPR-01 at 50 and 25 μM. The anti-edematogenic activity of JMPR-01 (100 mg/kg) was significant, reducing edema at 2–6 h, similar to the dexamethasone control. In induced peritonitis, JMPR-01 reduced leukocyte migration by 61.8, 68.5, and 90.5% at respective doses of 5, 10, and 50 mg/kg. In silico, JMPR-01 presented satisfactory coupling; mainly with LT-A4-H, PDE4B, and iNOS. These preliminary results demonstrate the strong potential of JMPR-01 to become a drug for the treatment of inflammatory diseases.

Bioelectrochemical partial-denitrification coupled with anammox for autotrophic nitrogen removal

The denitrification at low C/N ratio is challenging, usually requiring large amounts of energy and chemical inputs. Here we present a new method of denitrification by coupling autotrophic bioelectrochemical partial-denitrification (PD) with anammox. Nitrite was demonstrated to be stably accumulated by cathodic electrotrophic bacteria, and the small bias voltage of 0.1 V can improve nitrate-to-nitrite transformation ratio (NTR) from 44 ± 12% (no energy input) to 60 ± 9%. Then the nitrite together with ammonium was removed through anammox with a total nitrogen removal of 90 ± 3%, where the contribution of anammox accounted for 78 ± 5%. The self-alkalization of catholyte and the external voltage were found important on achieving PD. Microbial community analysis showed that Thiobacillus, a genus of autotrophic denitrifying bacteria, may play a key role in nitrite production. The log2FC values of napA was 83% higher than nirS, and nirK was significantly (p < 0.01) downregulated, contributing to the occurrence of nitrite accumulation. This proof-of-concept study demonstrated the feasibility of bioelectrochemical PD/A as a novel technology for controllable denitrification in wastewater treatment.

Nile tilapia production in polyculture with freshwater shrimp using an aquaponic system and biofloc technology

This study aimed to evaluate the performance of Nile tilapia, freshwater shrimp, lettuce, and watercress in an aquaponic system used in conjunction with biofloc technology. Experimental units consisted of an aquaponic module comprising two containers, one to accommodate vegetables (500 L media-filled bed with gravel) and the other to stock fish and shrimps (1000 L rearing tank). The experiment was carried out in a randomized complete block design with two treatments [an aquaponic system with clear water (ASCW) and an aquaponic system with biofloc technology (ASBFT)] and two blocks (periods). Each treatment had three replicates within each block, totaling six experimental units per block. The final weights of Nile tilapia (ASCW = 546.0 g; ASBFT: 565.0 g), freshwater shrimp (ASCW = 18.82 g; ASBFT: 18.44 g), and vegetable biomass (ASCW: 1.10 kg/m2 of lettuce and 1.57 kg/m2 of watercress; ASBFT: 0.94 kg/m2 of lettuce and 1.98 kg/m2 of watercress) did not differ significantly between the two treatments. Similarly, there were no significant differences between treatments with respect to other zootechnical performance variables of the evaluated organisms. There was, however, a greater (P < 0.05) accumulation of fat in the fillets of Nile tilapia reared in the ASBFT system (0.97%) than in those of fish reared in the ASCW system (0.76%), as well as a lower oscillation of nitrite levels. Therefore, the use of biofloc technology in conjunction with aquaponics facilitated the maintenance of zootechnical performance and contributed to an increase in the fat content of Nile tilapia fillets and better control of nitrite production.

Nitritation Performance of Zeolite Moving Bed Biofilm Reactor for Ammonium Wastewater Treatment

A new type of zeolite-suspended packing was developed by using zeolite as an important raw material, which was then used to start the zeolite moving bed biofilm reactor (ZMBBR). ZMBBR was compared with the ceramsite moving bed biofilm reactor (CMBBR) packed with ordinary ceramsite-suspended packing to investigate the different nitritation performance. The results showed that stable nitritation was successfully achieved in two reactors by the inhibitory effect of free ammonia (FA), and both of their nitrite accumulation rates (NAR) reached 90%; due to the adsorption of zeolite to ammonium, ZMBBR relieved the inhibition of FA on AOB faster than CMBBR and achieved nitritation earlier; CMBBR and ZMBBR could maintain long-term stable nitrosation when ρ(NH4+-N) was 350 mg·L-1 and 1050 mg·L-1 and NPRAVG was 0.43 kg·(m3·d)-1 and 1.26 kg·(m3·d)-1, respectively, and ARECMBBR=82.21% and AREZMBBR=88.85%. In the process of the influent ρ(NH4+-N) gradually increasing from 250 mg·L-1 to 1250 mg·L-1, the maximum nitrite production rate (NPR) of CMBBR was 0.5634 kg·(m3·d)-1; when ρ(FA) reached 166 mg·L-1 at the influent ρ(NH4+-N) of 750 mg·L-1, CMBBR broke down for the heavy inhibition of FA. The maximum NPR of ZMBBR was 1.800 kg·(m3·d)-1, and the performance of ZMBBR was getting worse after the ρ(FNA) reached the peak value of 1.9611 mg·L-1 at the influent ρ(NH4+-N) of 1250 mg·L-1. Subsequently, the ρ(FA) of ZMBBR reached 158 mg·L-1 rapidly, the NPR dropped significantly to 0.9028 kg·(m3·d)-1, and the performance of ZMBBR became significantly worse. It was demonstrated by high-throughput sequencing analysis that the dominant strain of ZMBBR and CMBBR was Nitrosomonas_europaea, and the relative abundances of N._europaea in ZMBBR and CMBBR were 11.15% and 10.92%, respectively.

Phenolic profile and in vitro anti-inflammatory activity of Mimosa scabrella Bentham honeydew honey in RAW 264.7 murine macrophages.

The anti-inflammatory activity is mainly attributed to the phenolic compounds. Once the geographical location affects the phenolic content of honeys, a relationship between the collection spot and the anti-inflammatory effect of bracatinga (Mimosa scabrella Bentham) honeydew honeys was hypothesized. The inhibitory effect of 14 honey samples on NOx, TNF-α, IL-6, IL-12p70, MCP-1, INF-γ, and IL-10 in RAW 264.7 macrophages inflamed by LPS was evaluated. Fourteen phenolic compounds were identified, mainly syringic acid and rutin. Ten honeys inhibited nitrite production; at least six downregulated TNF-α, IL-12p70, MCP-1, and IFN-γ; only four honey samples inhibited IL-6; and one honey sample inhibited IL-10 levels, showing their variable effects on the inflammatory markers. Principal component analysis grouped samples according to the phenolic content and downregulation of specific inflammatory markers. The bracatinga honeydew honey effectiveness was associated with geographical location, as samples from areas with higher density and diversity of plants had a more significant anti-inflammatory effect. PRACTICAL APPLICATIONS: The present research study investigated the anti-inflammatory potential of bracatinga honeydew honey samples collected from regions with different vegetation coverages. Honey samples collected from locations presenting greater forest diversity and density inhibited inflammatory markers more efficiently. This study reinforces the role of the bracatinga honeydew honey in preventing inflammatory processes and the importance of preserving forests so that products with a greater diversity of compounds and consequently more active can be obtained.

Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats.

Berberine is a natural plant alkaloid and has been reported to possess anti-inflammatory activity. However, berberine's poor bioavailability and low solubility have limited its clinical applicability. Nanoencapsulation of berberine using a suitable carrier can be a promising strategy to improve its efficacy. Therefore, this study aimed to produce berberine-loaded gum nanocomplexes to evaluate their therapeutic effects in a carrageenan-induced rat model. Berberine-loaded gum nanocomplexes were prepared by the ionic complexation between the negative charges of the gums (tragacanth and acacia gum) using a cross-linker for loading cationic berberine and their anti-inflammatory activity was evaluated against carrageenan-induced paw edema in rats. ELISA and qRT-PCR were employed to measure the concentration and mRNA expression level of inflammatory mediators in plasma and paw tissue, respectively. Berberine nanocomplexes were characterized for particle size (219.5nm), zeta potential by the dynamic light scattering (DLS), and for entrapment efficiency (93.2%) Infrared spectroscopy affirmed the loading of berberine in gum nanocomplexes. Transmission electron microscopy of formulation showed the spherical shape of nanocomplexes and small particle size (100-150nm). Pretreatment of rats with berberine nanocomplexes significantly reduced the paw edema in inflamed rat paws, decreased the production of nitrite and TNF-α in plasma and repressed the mRNA expression levels of TNF-α and IL-1β in paw tissue in comparison to berberine per se treated rats. The obtained berberine-loaded gum nanocomplexes produced a better anti-inflammatory effect as compared to berberine alone and hence can be used as an efficient candidate in the treatment of inflammation. The schematic representation of the preparation of the preparation of berberine-loaded tragacanth/acacia gum nanocomplexes and the evaluation in vivo for anti-inflammatory effects.

Enantioselective Synthesis and Pharmacological Evaluation of Aza-CGP37157-Lipoic Acid Hybrids for the Treatment of Alzheimer's Disease.

Hybrids based on an aza-analogue of CGP37157, a mitochondrial Na+/Ca2+ exchanger antagonist, and lipoic acid were obtained in order to combine in a single molecule the antioxidant and NRF2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The four possible enantiomers of the hybrid structure were synthesized by using as the key step a fully diastereoselective reduction induced by Ellman’s chiral auxiliary. After computational druggability studies that predicted good ADME profiles and blood–brain permeation for all compounds, the DPPH assay showed moderate oxidant scavenger capacity. Following a cytotoxicity evaluation that proved the compounds to be non-neurotoxic at the concentrations tested, they were assayed for NRF2 induction capacity and for anti-inflammatory properties and measured by their ability to inhibit nitrite production in the lipopolysaccharide-stimulated BV2 microglial cell model. Moreover, the compounds were studied for their neuroprotective effect in a model of oxidative stress achieved by treatment of SH-SY5Y neuroblastoma cells with the rotenone–oligomycin combination and also in a model of hyperphosphorylation induced by treatment with okadaic acid. The stereocenter configuration showed a critical influence in NRF2 induction properties, and also in the neuroprotection against oxidative stress experiment, leading to the identification of the compound with S and R configuration as an interesting hit with a good neuroprotective profile against oxidative stress and hyperphosphorylation, together with a relevant anti-neuroinflammatory activity. This interesting multitarget profile will be further characterized in future work.

Nitrite Production by Nitrifying Bacteria in Urban Groundwater Used in a Chlorinated Public Bath System in Japan.

In contrast to pathogens, the effects of environmental microbes on the water quality in baths have not yet been examined in detail. We herein focused on a public bath in which groundwater was pumped up as bath water and disinfected by chlorination. Ammonia in groundwater is oxidized to nitrite, thereby reducing residual chlorine. A batch-culture test and bacterial community ana-lysis revealed that ammonia-oxidizing bacteria accumulated nitrite and had higher resistance to chlorination than nitrite-oxidizing bacteria. These results demonstrate that the difference in resistance to chlorination between ammonia-oxidizing and nitrite-oxidizing bacteria may lead to the accumulation of nitrite in baths using groundwater.