Novel coumarin-functionalized inulin derivatives: Chemical modification and antioxidant activity assessment.

In this paper, a series of target derivatives were synthesized by introducing coumarin into inulin structure using three-step chemical modification, and their structures were characterized by FTIR, 1H NMR, and 13C NMR. At the same time, the antioxidant activities of inulin derivatives were determined, including DPPH-radical scavenging activity, superoxide-radical scavenging activity, PTIO-radical scavenging activity and reducing ability. The test results showed that the antioxidant activities of inulin derivatives containing coumarin were significantly increased. Especially, inulin derivatives showed excellent DPPH radical-scavenging ability (IC50 0.09-0.11 mg/mL). Meanwhile, the scavenging ability of PTIO-radical was increased by more than 80%, and the IC50 values were all between 0.23 and 0.26 mg/mL. At the concentration below 1 mg/mL, the scavenging rate of all inulin derivatives could even reach 100%. This study provides a feasible way to synthesize inulin derivatives with significant activity, which may be developed into new antioxidants in medicine and cosmetics.

Improved Synthesis of Asymmetric Curcuminoids and Their Assessment as Antioxidants.

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon's method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n-BuNH2 in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41-76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b, 9d, 9e, 9f, 9g, 9h, 9i, 9j, and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC50 = 37.57 ± 0.89 µM) and 9e (IC50 = 37.17 ± 1.76 µM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC50 = 11.36 ± 0.65 µM) and 9i (IC50 = 10.91 ± 0.77 µM) displayed potent 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC50 = 10.14 ± 1.04 µM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.

Assessment of anti-inflammatory and antioxidant activity of quercetin-rutin blend (SophorOx™) - an invitro cell based assay.

OBJECTIVES: Quercetin & Rutin, are bioactive compounds that are widely used for various therapeutic properties. There's been growing interest in the biological activities of these polyphenols belonging to the class of flavonoids known to have various health benefits. Quercetin is now popularly recognized as a phytochemical remedy for a plethora of disease groups such as metabolic syndrome (more specifically diabetes), obesity/weight management and mood disorders. Due to its unique chemical structure, the most prominent property of Quercetin is probably its antioxidant capability. It acts as a free radical scavenger to form resonance-stabilized phenoxyl radicals. Certain in vitro studies have also shown quercetin to have anti-viral, anti-carcinogenic and platelet aggregation properties. Rutin has also been shown to exert diverse biological effects such as anti-tumor activities, reduction of inflammatory cytokines and antimicrobial activities. The current study was designed to further confirm the antioxidant and anti-inflammatory property of a Quercetin-Rutin blend (SophorOx™). METHODS: The analysis was performed in a cell-based assay using RAW 264.7 macrophage cell line. SophorOx™ was screened for cytotoxicity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to obtain optimum concentrations for experimental assays. SophorOx™ was measured for pro-inflammatory cytokine levels (TNF-α & IL-6) and nitric oxide (NO) levels. Additionally, ROS (reactive oxygen species) levels in RAW cells were estimated using a cell-permeant reagent 2'7'-dichlorofluorescein diacetate (DCFH-DA). RESULTS: SophorOx™ at 10 µM concentration, exhibited an anti-inflammatory property with significant inhibitory levels of TNF-α (∼28.25%) and IL-6 (∼32.25%). SophorOx™ at similar concentrations reduced nitric oxide levels to 70.55% in lipopolysaccharide (LPS) stimulated RAW 264.7 cells. Raw 264.7 cells stimulated with LPS exhibited a significant increase in intracellular ROS and this was significantly reduced (78.2% reduction) at lower concentrations (0.3 µM) of SophorOx™. CONCLUSIONS: The anti-inflammatory effects of SophorOx™ were investigated in LPS stimulated RAW 264.7 macrophages. Data suggests, that SophorOx™ reduced levels of nitric oxide, intracellular ROS and pro-inflammatory cytokines (TNF-α & IL-6) at low concentrations without affecting the viability of RAW cells. Present invitro trial suggests that SophorOx™ is a potent antioxidant and anti-inflammatory agent and displays a prominent ability to block mediators of oxidative stress and inflammation.

Non-clinical assessment of lubrication and free radical scavenging of an innovative non-animal carboxymethyl chitosan biomaterial for viscosupplementation: An in-vitro and ex-vivo study.

OBJECTIVE: Lubrication and free radical scavenging are key features of biomaterials used for viscosupplementation (VS) of joints affected by osteoarthritis (OA). The objective of this study was to describe the non-clinical performance characterization of KiOmedine® CM-Chitosan, a non-animal carboxymethyl chitosan, in order to assess its intended action in VS and to compare it to existing viscosupplements based on crosslinked hyaluronan (HA) formulations. METHOD: The lubrication capacity of the tested viscosupplements (VS) was evaluated in-vitro and ex-vivo. In-vitro, the coefficient of friction (COF) was measured using a novel tribological system. Meanwhile, an ex-vivo biomechanical model in ovine hindlimbs was developed to assess the recovery of join mobility after an intra-articular (IA) injection. Free radical scavenging capacity of HA and KiOmedine® CM-Chitosan formulations was evaluated using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. RESULTS: In the in-vitro tribological model, KiOmedine® CM-Chitosan showed high lubrication capacity with a significant COF reduction than crosslinked HA formulations. In the ex-vivo model, the lubrication effect of KiOmedine® CM-Chitosan following an IA injection in the injured knee was proven again by a COF reduction. The recovery of joint motion was optimal with an IA injection of 3 ml of KiOmedine® CM-Chitosan, which was significantly better than the crosslinked HA formulation at the same volume. In the in-vitro TEAC assay, KiOmedine® CM-Chitosan showed a significantly higher free radical scavenging capacity than HA formulations. CONCLUSION: Overall, the results provide a first insight into the mechanism of action in terms of lubrication and free radical scavenging for the use of KiOmedine® CM-Chitosan as a VS treatment of OA. KiOmedine® CM-Chitosan demonstrated a higher capacity to scavenge free radicals, and it showed a higher recovery of mobility after a knee lesion than crosslinked HA formulations. This difference could be explained by the difference in chemical structure between KiOmedine® CM-Chitosan and HA and their formulations.

Addressing the role of edaravone in the management of amyotrophic lateral sclerosis and gaps in care and access: expert panel recommendations.

A virtual key opinion leader (KOL) and payer discussion was held on December 5, 2020. In attendance were 2 KOLs, both specialists in amyotrophic lateral sclerosis (ALS) at leading clinics in the United States, and 6 managed care executives from US regional health plans. The objective of this panel was to share opinions, ideas, and information around the treatment of ALS with edaravone, gaps in management and guidelines, and potential solutions. The panel concluded that coverage criteria for edaravone may need to be reassessed and treatment guidelines could be revisited to include a determination of place in therapy for edaravone.

In-vitro, in-vivo, and in-silico assessment of radical scavenging and cytotoxic activities of Oliveria decumbens essential oil and its main components.

We aimed to explore and compare new insights on the pharmacological potential of Oliveria decumbence essential oil (OEO) and its main components highlighting their antioxidant activity in-vitro, in-vivo, and in-silico and also cytotoxic effects of OEO against A549 lung cancer cells. At first, based on GC-MS analysis, thymol, carvacrol, p-cymene, and γ-terpinene were introduced as basic ingredients of OEO and their in-vitro antioxidant capacity was considered by standard methods. Collectively, OEO exhibited strong antioxidant properties even more than its components. In LPS-stimulated macrophages treated with OEO, the reduction of ROS (Reactive-oxygen-species) and NO (nitric-oxide) and down-regulation of iNOS (inducible nitric-oxide-synthase) and NOX (NADPH-oxidase) mRNA expression was observed and compared with that of OEO components. According to the results, OEO, thymol, and carvacrol exhibited the highest radical scavenging potency compared to p-cymene, and γ-terpinene. In-silico Molecular-Docking and Molecular-Dynamics simulation indicated that thymol and carvacrol but no p-cymene and γ-terpinene may establish coordinative bonds in iNOS active site and thereby inhibit iNOS. However, they did not show any evidence for NOX inhibition. In the following, MTT assay showed that OEO induces cytotoxicity in A549 cancer cells despite having a limited effect on L929 normal cells. Apoptotic death and its dependence on caspase-3 activity and Bax/Bcl2 ratio in OEO-treated cells were established by fluorescence microscopy, flow cytometry, colorimetric assay, and western blot analysis. Additionally, flow cytometry studies demonstrated increased levels of ROS in OEO-treated cells. Therefore, OEO, despite showing antioxidant properties, induces apoptosis in cancer cells by increasing ROS levels. Collectively, our results provided new insight into the usage of OEO and main components, thymol, and carvacrol, into the development of novel antioxidant and anti-cancer agents.

Evaluation of Microwave-Assisted Extraction Method for Preparation and Assessment of Thai Herbal Medicine Oral Tablets With Enriched Phytochemical Compounds.

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 µg/mL and 4.02 ± 0.24 µg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

Formulation of Novel Liquid Crystal (LC) Formulations with Skin-Permeation-Enhancing Abilities of Plantago lanceolata (PL) Extract and Their Assessment on HaCaT Cells.

Exposure to reactive oxygen species can easily result in serious diseases, such as hyperproliferative skin disorders or skin cancer. Herbal extracts are widely used as antioxidant sources in different compositions. The importance of antioxidant therapy in inflammatory conditions has increased. Innovative formulations can be used to improve the effects of these phytopharmacons. The bioactive compounds of Plantago lanceolata (PL) possess different effects, such as anti-inflammatory, antioxidant, and bactericidal pharmacological effects. The objective of this study was to formulate novel liquid crystal (LC) compositions to protect Plantago lanceolata extract from hydrolysis and to improve its effect. Since safety is an important aspect of pharmaceutical formulations, the biological properties of applied excipients and blends were evaluated using assorted in vitro methods on HaCaT cells. According to the antecedent toxicity screening evaluation, three surfactants were selected (Gelucire 44/14, Labrasol, and Lauroglycol 90) for the formulation. The dissolution rate of PL from the PL-LC systems was evaluated using a Franz diffusion chamber apparatus. The antioxidant properties of the PL-LC systems were evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA) assessments. Our results suggest that these compositions use a nontraditional, rapid-permeation pathway for the delivery of drugs, as the applied penetration enhancers reversibly alter the barrier properties of the outer stratum corneum. These excipients can be safe and highly tolerable thus, they could improve the patient's experience and promote adherence.

Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Assessment of chemically characterized Salvia sclarea L. essential oil and its combination with linalyl acetate as novel plant based antifungal, antiaflatoxigenic and antioxidant agent against herbal drugs contamination and probable mode of action.

The present investigation reports antifungal and antiaflatoxigenic efficacy of Salvia sclarea essential oil (SSEO) and its combination with Linalyl acetate (LA) (1:1) against herbal drug deteriorating molds and aflatoxin B1 contamination. GC-MS analysis of SSEO showed Linalyl Acetate (LA) (61.33%) and Linalool (LL) (17.59%) as major components. The SSEO and LA combination displayed better antifungal and antiaflatoxigenic activity as compared to SSEO and LA used individually. SSEO and LA combination was effective in reduction of ergosterol and enhanced leakage of vital ions and UV-absorbing materials in a dose dependent manner. The combination caused significant reduction in cellular methylglyoxal content, an aflatoxin inducer suggesting its future application for development of aflatoxin resistant herbal drug varieties through green transgenics. The combination also showed pronounced antioxidant activity as compared to SSEO and LA used separately. Interestingly, the combination showed significant in situ protection of Picrorhiza kurroa rhizomes against mould infestation.

Comparative Assessment of Antioxidant, Anti-Diabetic and Cytotoxic Effects of Three Peel/Shell Food Waste Extract-Mediated Silver Nanoparticles.

BACKGROUND: The natural food waste peels/shells discarded as waste materials are ample sources of natural bioactive compounds. The natural food waste mediated silver (Ag) nanoparticle (NPs) synthesis will be advantageous over chemical synthesis. MATERIALS AND METHODS: Using the various phytochemical-rich ripe P. americana peel (PAP), fresh Beta vulgaris peel (BVP), and rawArachis hypogaea shell (AHS) extracts, the bio-synthesis of PAP-AgNPs, BVP-AgNPs, and AHS-AgNPs, respectively, were carried out and its characterization was completed by standard procedures. The three biosynthesized AgNP's multiple biological effects were accomplished by evaluating their cytotoxicity, antidiabetic, and antioxidant effects. RESULTS: The biosynthesis of the three generated Ag nanoparticles was confirmed through UV-vis spectrum analysis while the X-ray diffraction outlines revealed the generated AgNPs nature. The morphological structure and elemental information of the three AgNPs were obtained through SEM (scanning electron microscopy) and EDX (energy-dispersive X-ray) study. Multiple biological assays exhibited that the three generated AgNPs have significant cytotoxic, antidiabetic, and moderate antioxidant activity. In a comparative analysis, the PAP-AgNPs displayed higher anticancer potential than BVP and AHS-AgNPs, whereas AHS-AgNPs exhibited a higher antidiabetic effect with the lowest IC50 value (1.68 µg/mL) than PAP and BVP AgNPs. All three generated AgNPs displayed moderate antioxidant effects, among them BVP-AgNPs were more effective than PAP and AHS AgNPs. More than two effects of the three biosynthesized AgNPs specifies that they have ample perspective in therapeutic applications in pharmaceutical and other related industries in controlling cancer and diabetes.

Correlations on Phenolic Screening Related to In Vitro and In Ovo Assessment of Ocimum basilicum L. Hydro-Alcoholic Extracts Used as Skin Active Ingredient.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves' extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Assessment of Use and Safety of Edaravone for Amyotrophic Lateral Sclerosis in the Veterans Affairs Health Care System.

Importance: Using real-world data, the US Department of Veterans Affairs (VA) initiated a surveillance evaluation of edaravone after its approval for amyotrophic lateral sclerosis (ALS) in 2017. The use and safety of edaravone for patients with ALS in the VA health care system remain to be assessed. Objective: To describe a pharmacovigilance surveillance initiative with edaravone to monitor patient characteristics, utilization (edaravone cycles and riluzole use), and safety and to evaluate safety/effectiveness. Design, Setting, and Participants: This propensity score-matched cohort study used data on 369 patients with documented definite or probable ALS in the Veterans Health Administration (VHA) with at least 1 prescription for edaravone between August 1, 2017, and September 30, 2019. The analysis compared edaravone (alone or with riluzole) with riluzole only. For chronic users (≥6 months of drug), a time-to-event model evaluated ALS-related outcomes, with censoring at outcome, death, or end of evaluation. Patients with Parkinson disease, dementia, schizophrenia, or significant respiratory insufficiency per diagnosis codes within 2 years before prescription initiation were excluded. In overall matched cohorts, 223 patients treated with edaravone were 1:3 propensity score matched based on predefined confounders. For the chronic user subgroup analysis, 96 patients receiving edaravone and 424 patients receiving riluzole only were included. Exposures: Edaravone (alone or with riluzole) vs riluzole only. Main Outcomes and Measures: Patient characteristics, ALS drug use, and mortality. Acute outcomes (within 6 months of index) included proportion and mean time to event for death, discontinuation, or all-cause hospitalization, and outcomes for chronic users (receiving >6 months of treatment) included hazard ratios of outcomes related to disease-state progression. Results: Of 369 patients who received edaravone, most were older (mean [SD] age, 64.6 [11.3] years), male (346 [93.8%]), and White (261 [70.7%]). As of September 2019, 59.9% of edaravone patients had discontinued treatment; of those, 49.5% (108 of 218) received only 1 to 3 treatment cycles. Approximately 30% (110 patients) died. In a matched evaluation, significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole. Among chronic users, edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16). The death rate was lower with edaravone but the difference was not statistically significant. Conclusions and Relevance: Early edaravone discontinuation was common in the VA. Although outcomes favored use of riluzole only in the matched analysis, results should be interpreted with caution, as unmeasured bias in observational data is likely.

Highly efficient free radical-scavenging property of phenolic-functionalized chitosan derivatives: Chemical modification and activity assessment.

Chitosan is an abundant and renewable polysaccharide, and chemical modification can be used to enhance the biological properties of chitosan. In this study, monophenol and ortho-diphenol were introduced to chitosan through chemical modification to get chitosan derivatives owned high antioxidant activity. Their free radical-scavenging activity against three free radicals and reduction ability was tested. Based on the four antioxidant assay, the antioxidant ability of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. The IC50 of inhibition of DPPH, hydroxyl (OH), and superoxide (O2-) radical-scavenging was 41-172, 10-89, and 14-38 µg/mL, respectively. Meanwhile, ortho-diphenol was more efficient group than monophenol on the improvement of antioxidant ability of chitosan derivatives. The possible free radical-scavenging mechanism, including the number of the hydroxyl groups and the presence ortho-dihydroxy substitution for the antioxidant ability were discussed. In vitro studies demonstrated that the constructed chitosan derivatives have good biocompatibility, and good antioxidant capacity to reduce oxidative stress. Functionalization of chitosan with phenolic group allows the possible applications on the therapy of oxidative-related diseases.

Variation in contrast-associated acute kidney injury prophylaxis for percutaneous coronary intervention: insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) program.

BACKGROUND: Contrast-Associated Acute Kidney Injury (CA-AKI) is a serious complication associated with percutaneous coronary intervention (PCI). Patients with chronic kidney disease (CKD) have an elevated risk for developing this complication. Although CA-AKI prophylactic measures are available, the supporting literature is variable and inconsistent for periprocedural hydration and N-acetylcysteine (NAC), but is stronger for contrast minimization. METHODS: We assessed the prevalence and variability of CA-AKI prophylaxis among CKD patients undergoing PCI between October 2007 and September 2015 in any cardiac catheterization laboratory in the VA Healthcare System. Prophylaxis included periprocedural hydration with normal saline or sodium bicarbonate, NAC, and contrast minimization (contrast volume to glomerular filtration rate ratio ≤ 3). Multivariable hierarchical logistic regression models quantified site-specific prophylaxis variability. As secondary analyses, we also assessed CA-AKI prophylaxis measures in all PCI patients regardless of kidney function, periprocedural hydration in patients with comorbid CHF, and temporal trends in CA-AKI prophylaxis. RESULTS: From 2007 to 2015, 15,729 patients with CKD underwent PCI. 6928 (44.0%) received periprocedural hydration (practice-level median rate 45.3%, interquartile range (IQR) 35.5-56.7), 5107 (32.5%) received NAC (practice-level median rate 28.3%, IQR 22.8-36.9), and 4656 (36.0%) received contrast minimization (practice-level median rate 34.5, IQR 22.6-53.9). After adjustment for patient characteristics, there was significant site variability with a median odds ratio (MOR) of 1.80 (CI 1.56-2.08) for periprocedural hydration, 1.95 (CI 1.66-2.29) for periprocedural hydration or NAC, and 2.68 (CI 2.23-3.15) for contrast minimization. These trends were similar among all patients (with and without CKD) undergoing PCI. Among patients with comorbid CHF (n = 5893), 2629 (44.6%) received periprocedural hydration, and overall had less variability in hydration (MOR of 1.56 (CI 1.38-1.76)) compared to patients without comorbid CHF (1.89 (CI 1.65-2.18)). Temporal trend analysis showed a significant and clinically relevant decrease in NAC use (64.1% of cases in 2008 (N = 1059), 6.2% of cases in 2015 (N = 128, p = < 0.0001)) and no significant change in contrast-minimization (p = 0.3907). CONCLUSIONS: Among patients with CKD undergoing PCI, there was low utilization and significant site-level variability for periprocedural hydration and NAC independent of patient-specific risk. This low utilization and high variability, however, was also present for contrast minimization, a well-established measure. These findings suggest that a standardized approach to CA-AKI prophylaxis, along with continued development of the evidence base, is needed.

DNA Binding Characteristics and Protective Effects of Yellow Pigment from Freshly Cut Yam (Dioscorea opposita).

Yam yellow pigments (YP) are natural pigments formed during the storage of freshly cut yam (Dioscorea opposita) under certain conditions. The interaction of YP with calf thymus DNA (ctDNA) and its protective effect against DNA oxidative damage were investigated using multiple spectroscopic techniques, competitive binding experiments, viscosity measurements, and gel electrophoresis. Results showed that YP participated in intercalative binding with ctDNA. YP exhibited a protective effect against hydroxyl-induced DNA damage, which was attributed to the high hydroxyl radical scavenging activity of YP. Our findings improve our understanding of the mechanism of interaction between YP and ctDNA, and provide a theoretical basis for the application of YP in the food and drug industry.

Metabolomic analysis of Cyrtopodium glutiniferum extract by UHPLC-MS/MS and in vitro antiproliferative and genotoxicity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of orchids have been traditionally used as human phytotherapeutics. Cyrtopodium flavum, for example, due to the analgesic and anti-inflammatory properties, beside the capacity of heal skin lesions has been focus of research. Also Cyrtopodium glutiniferum, an orchid found in the Brazilian southeastern rainforest, is known to synthesize anti-inflammatory glucomannans in the pseudobulbs, as other potentially therapeutic compounds. AIM OF THE STUDY: We have reported the first metabolomic analysis focused on the phenols expression of the neotropical orchid Cyrtopodium glutiniferum Raddi, besides free radical scavenging, anti-inflammatory and antiproliferative activities, and the genotoxicity properties of the aqueous extract. MATERIAL AND METHODS: The metabolomics of C. glutiniferum aqueous extract was performed through UHPLC-MSn acquisition. We have detected the scavenging potential of the extract using DPPH assay. The genotoxic potential was performed by Ames Test (0-5000 µg mL-1) and micronucleous assay (0-5000 µg mL-1) in RAW264.7 cells. The cytotoxic potential of the extract against RAW264.7 was tested by WST-1 assay (0-500 µg mL-1). And after all, the RAW264.7 cells were treated with non-cytotoxic concentrations of C. glutiniferum (0-50 µg mL-1) to evaluate the antiproliferative and anti-inflammatory potential, besides the mitochondrial activity. RESULTS: From the 55 molecules identified, 45.5% belonged to the phenolic compounds database from Phenol Explorer, 29% to an in-house Orchidaceae molecules database, and 25.5% to both. Among the identified phenolic compounds, 18 subclasses were discriminated, being phenanthrenes the most abundant. Doses-dependent of C. glutiniferum extracts were able to induce DPPH free radicals scavenging and also to increase TA100 His+ revertants, in metabolic environment, showing mutagenicity just in the highest concentration, of 5 mg/plate. On Eukaryotic cell models, the extract also has induced dose-response and time-response cytotoxicity against RAW264.7 macrophages, mainly after 48 h and 72 h, even though the extract has not been able to induce the increase of micronucleated cells and mitotic index alteration on Micronucleus assay. The activation and proliferation of macrophages cultures were downregulated after 24 h and 48 h by the non-cytotoxic concentrations of the extract in a dose-dependent manner. CONCLUSIONS: The Cyrtopodium glutiniferum metabolomics, anti-inflammatory and anti-proliferative properties observed in this study suggest a therapeutic efficacy of the orchid extract applied in folk medicine.

Adsorptive interaction of peroxymonosulfate with graphene and catalytic assessment via non-radical pathway for the removal of aqueous pharmaceuticals.

Graphene has been applied as a catalyst in peroxymonosulfate (PMS) activation for the removal of pharmaceuticals in water. Firstly, a kinetic adsorption study of PMS was developed, fitting the results to the Elovich's equation. Moreover, the influence of the main variables in the adsorptive process such as pH, initial PMS concentration, and graphene dose were assessed. Secondly, the degradation of diclofenac as a target compound was studied comparing PMS-catalytic versus adsorption processes. PMS-catalytic process enhanced the removal of the micropollutant if compared to adsorption when using a low dose of graphene (less than 50 mg L-1) or after surface saturation. Studies using radical scavengers suggested the lack of radicals in the process, suggesting the non-radical activation of PMS. Thirdly, the adsorption versus PMS-catalytic processes were also compared for the oxidation of a mixture of three antibiotics (norfloxacin, tetracycline and sulfamethoxazole) with different chemical structure. PMS-catalytic activation was more effective for the removal of those compounds that presented less affinity towards adsorption onto the graphene surface. Finally, characterization of the fresh and PMS-treated material was performed. Graphene demonstrated to be stable after its use as catalysts in PMS activation, suffering only slight transformation of the surface oxidation groups.

In vitro and in vivo biocompatibility assessment of free radical scavenging nanocomposite scaffolds for bone tissue regeneration.

Bone is the second most transplanted tissue in the world, resulting in increased demand for bone grafts leading to the fabrication of synthetic scaffold grafting alternatives. Fracture sites are under increased oxidative stress after injuries, affecting osteoblast function and hindering fracture healing and remodeling. To counter oxidative stress, free radical scavenging agents, such as cerium oxide nanoparticles, have gained traction in tissue engineering. Toward the goal of developing a functional synthetic system for bone tissue engineering, we characterized the biocompatibility of a porous, bioactive, free radical scavenging nanocomposite scaffold composed of poly(1,8 octanediol-co-citrate), beta-tricalcium phosphate, and cerium oxide nanoparticles. We studied cellular and tissue compatibility utilizing in vitro and in vivo models to assess nanocomposite interactions with both human osteoblast cells and rat subcutaneous tissue. We found the scaffolds were biocompatible in both models and supported cell attachment, proliferation, mineralization, and infiltration. Using hydrogen peroxide, we simulated oxidative stress to study the protective properties of the nanocomposite scaffolds via a reduction in cytotoxicity and recovered mineralization of osteoblast cells in vitro. We also found after implantation in vivo the scaffolds exhibited biocompatible properties essential for successful scaffolds for bone tissue engineering. Cells were able to infiltrate through the scaffolds, the surrounding tissues elicited a minimal immune response, and there were signs of scaffold degradation after 30 days of implantation. After the array of biological characterization, we had confirmed the development of a nanocomposite scaffold system capable of supporting bone-remodeling processes while providing a protective free radical scavenging effect.