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Achieving reliably high production of reactive oxygen species (ROS) in photodynamic therapy (PDT) remains challenging. Graphene quantum dots (GQDs) hold great promise for PDT. However, the photochemical processes leading to GQD-derived ROS generation have not yet been fully elucidated. Physicochemical characteristics of GQDs were comprehensively investigated, including electron paramagnetic resonance analysis of singlet oxygen production. Dark toxicity was assessed and . GQDs demonstrated excellent photoluminescent features, corrosion resistance, high water solubility, high photo/pH-stability, and biocompatibility and very efficient singlet oxygen/ROS generation. The enhanced ROS generation, combined with good biocompatibility and minimal toxicity and support the potential of GQDs for future PDT application.

The nitrate (NO 3 - ) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO 3 - -reducing oral bacteria reduce inorganic dietary NO 3 - to nitrite (NO 2 - ) via the NO 3 - -NO 2 - -NO pathway. Studies of oral NO 3 - -reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO 3 - reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO 3 - -reducing bacteria across each oral site. The genera included Actinomyces , Brevibacillus , Campylobacter , Capnocytophaga , Corynebacterium , Eikenella , Fusobacterium , Granulicatella , Haemophilus , Leptotrichia , Microbacterium , Neisseria , Porphyromonas , Prevotella , Propionibacterium , Rothia , Selenomonas , Staphylococcus , Streptococcus and Veillonella . The highest proportion of NO 3 - -reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO 3 - -reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO 3 - reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO 3 - -reducing bacteria research with physiological outcomes affecting human health.

Dietary nitrate supplementation, which enhances nitric oxide (NO) bioavailability, has previously been shown to contribute to improved exercise performance by reducing both oxygen cost and energy expenditure. In contrast, previous studies have indicated that NO can lower force production in vitro. To examine the role of dietary nitrates in regulating force generation under normal physiological conditions, we undertook an extended nitrate supplementation regime and determined force output and energy cost with a repeated isometric maximum voluntary contraction (MVC) protocol. In a double-blind, randomized, crossover design, eight participants received 0.5 l/day of nitrate-rich (BR) or nitrate-depleted (PL) beetroot juice for 15 days and completed an exercise protocol consisting of 50 MVCs at 2.5 h, 5 days and 15 days after the beginning of the supplementation period. No significant reduction in force output was determined for BR relative to PL for the peak contraction, the mean or the end force, and no significant time effect was found over the course of the supplementation period. There was a reduction in the mean PCr cost of exercise averaged over the BR supplementation trials, but this did not reach statistical significance for end exercise (BR 15.10 ± 4.14 mM, PL 17.10 ± 5.34 mM, P = 0.06) or the mean throughout the protocol (BR 15.96 ± 4.14 mM, PL 17.79 ± 4.51 mM, P = 0.06). However, a significant reduction in PCr cost per unit force output was found for BR at end exercise ( P = 0.04). These results indicate that, under normal physiological conditions, increased NO bioavailability is not associated with a reduction of force-generating capability in human skeletal muscle and confirm that nitrate supplementation reduces the PCr cost of force production.

Watercress ( Nasturtium officinale ) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that watercress contains significantly higher levels of gluconasturtiin, phenethyl isothiocyanate, quercetin-3- O -rutinoside and isorhamnetin, among others, with their content decreasing from flowers (82.11 ± 0.63, 273.89 ± 0.88, 1459.30 ± 12.95 and 289.40 ± 1.37 ng/g of dry extract respectively) to leaves (32.25 ± 0.74, 125.02 ± 0.52, 1197.86 ± 4.24 and 196.47 ± 3.65 ng/g of det extract respectively) to stems (9.20 ± 0.11, 64.7 ± 0.9, 41.02 ± 0.18, 65.67 ± 0.84 ng/g of dry extract respectivbely). Pearson’s correlation analysis has shown that the content of isothiocyanates doesn’t depend only on the bioconversion of individual glucosinolates but also on other glucosinolates of the same group. Overall, we have provided comprehensive analytical data of the major watercress metabolites thereby providing an opportunity to exploit different parts of watercress for potential therapeutic applications.

The role of hydrogen sulfide (H2S) in inflammation remains unclear with both pro‐ and anti‐inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow‐releasing H2S donor) on lipopolysaccharide (LPS)‐evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1–0.5 mM) decreased LPS‐induced production of nitrite (NO2−), PGE2, TNF‐α and IL‐6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) and reduced LPS‐induced NF‐κB activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX‐2, iNOS and TNF‐α converting enzyme (TACE). In the CFA‐treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti‐inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N‐acetyl‐β‐D‐glucosaminidase (NAG) activity and decreased TNF‐α, IL‐1β, IL‐6 and IL‐8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti‐inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro‐inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.

This study tested the hypothesis that the increases in salivary and plasma [NO2−] after dietary NO3− supplementation would be greater when oral temperature and pH were independently elevated, and increased further when oral temperature and pH were elevated concurrently. Seven healthy males (mean ± SD, age 23 ± 4 years) ingested 70 mL of beetroot juice concentrate (BR, which provided ~6.2 mmol NO3−) during six separate laboratory visits. In a randomised crossover experimental design, salivary and plasma [NO3−] and [NO2−] were assessed at a neutral oral pH with a low (TLo-pHNorm), intermediate (TMid-pHNorm), and high (THi-pHNorm) oral temperature, and when the oral pH was increased at a low (TLo-pHHi), intermediate (TMid-pHHi), and high (THi-pHHi) oral temperature. Compared with the TMid-pHNorm condition (976 ± 388 µM), the mean salivary [NO2−] 1–3 h post BR ingestion was higher in the TMid-pHHi (1855 ± 423 µM), THi-pHNorm (1371 ± 653 µM), THi-pHHi (1792 ± 741 µM), TLo-pHNorm (1495 ± 502 µM), and TLo-pHHi (2013 ± 662 µM) conditions, with salivary [NO2−] also higher at a given oral temperature when the oral pH was increased (p < 0.05). Plasma [NO2−] was higher 3 h post BR ingestion in the TMid-pHHi, THi-pHHi, and TLo-pHHi conditions, but not the TLo-pHNorm and THi-pHNorm conditions, compared with TMid-pHNorm (p < 0.05). Therefore, despite ingesting the same NO3− dose, the increases in salivary [NO2−] varied depending on the temperature and pH of the oral cavity, while the plasma [NO2−] increased independently of oral temperature, but to a greater extent at a higher oral pH.

Watercress is an enriched source of phenethyl isothiocyanate (PEITC), among other phytochemicals, with an antioxidant capacity. The aim of this study was to (i) chemically characterize and (ii) biologically evaluate the profile of the main health-promoting compounds contained in edible (i.e., mixture of leaves and lateral buds) and non-edible (i.e., stems) parts of watercress in an in vitro model of malignant melanoma consisting of human malignant melanoma (A375), non-melanoma (A431) and keratinocyte (HaCaT) cells. The extraction of the main constituents of watercress was performed by subjecting the freeze-dried edible and non-edible samples through different extraction protocols, whereas their concentration was obtained utilizing analytical methodologies. In addition, cell viability was evaluated by the Alamar Blue assay, whereas levels of oxidative stress and apoptosis were determined by commercially available kits. The edible watercress sample contained a higher amount of various nutrients and phytochemicals in the hexane fraction compared to the non-edible one, as evidenced by the presence of PEITC, phenolics, flavonoids, pigments, ascorbic acid, etc. The cytotoxicity potential of the edible watercress sample in the hexane fraction was considerably higher than the non-edible one in A375 cells, whereas A431 and HaCaT cells appeared to be either more resistant or minimally affected, respectively. Finally, levels of oxidative stress and apoptotic induction were increased in both watercress samples, but the magnitude of the induction was much higher in the edible than the non-edible watercress samples. Herein, we provide further evidence documenting the potential development of watercress extracts (including watercress waste by-products) as promising anti-cancer agent(s) against malignant melanoma cells.

Hydrogen sulfide (H2S) has recently been proposed as an endogenous mediator of inflammation and is present in human synovial fluid. This study determined whether primary human articular chondrocytes (HACs) and mesenchymal progenitor cells (MPCs) could synthesize H2S in response to pro‐inflammatory cytokines relevant to human arthropathies, and to determine the cellular responses to endogenous and pharmacological H2S. HACs and MPCs were exposed to IL‐1β, IL‐6, TNF‐α and lipopolysaccharide (LPS). The expression and enzymatic activity of the H2S synthesizing enzymes cystathionine‐β‐synthase (CBS) and cystathionine‐γ‐lyase (CSE) were determined by Western blot and zinc‐trap spectrophotometry, respectively. Cellular oxidative stress was induced by H2O2, the peroxynitrite donor SIN‐1 and 4‐hydroxynonenal (4‐HNE). Cell death was assessed by 3‐(4,5‐dimethyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (DCm) was determined in situ by flow cytometry. Endogenous H2S synthesis was inhibited by siRNA‐mediated knockdown of CSE and CBS and pharmacological inhibitors D,L‐propargylglycine and aminoxyacetate, respectively. Exogenous H2S was generated using GYY4137. Under basal conditions HACs and MPCs expressed CBS and CSE and synthesized H2S in a CBS‐dependent manner, whereas CSE expression and activity was induced by treatment of cells with IL‐1β, TNF‐α, IL‐6 or LPS. Oxidative stress‐induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H2S synthesis or by CBS/CSE‐siRNA treatment. These data suggest CSE is an inducible source of H2S in cultured HACs and MPCs. H2S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.

The addition of hydrogen peroxide (H2O2) to cultured cells is widely used as a method to modulate redox-regulated cellular pathways, including the induction of programmed cell death in cell culture experiments and the testing of pro- and antioxidant compounds. Here, we assessed the effect on the cellular response to H2O2 of pre-adapting squamous cell carcinoma cells (A431) to the standard cell culture oxygenation of 18.6% O2, compared to cells pre-adapted to a physiological skin O2 concentration (3.0% O2). We showed that cells pre-adapted to 18.6% O2 resisted H2O2-induced cell death compared to cells pre-adapted to 3.0% O2 for 96 h prior to treatment with H2O2. Moreover, the enzymatic activities of catalase and glutathione reductase, as well as the protein expression levels of catalase, were higher in cells pre-adapted to 18.6% O2 compared to cells pre-adapted to 3.0% O2. H2O2-resistant cells, pre-adapted to 18.6% O2, exhibited increased nuclear Nrf-2 levels. It is concluded that A431 cells pre-adapted to standard cell culture oxygenation conditions resist H2O2-induced cell death. This effect may be related to their heightened activation of Nrf-2.

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential.