No abstract

The hazardous effects of current nanoparticle synthesis methods have steered researchers to focus on developing newer eco-friendly methods for synthesizing nanoparticles using non-toxic chemicals. Owing to the diverse applications of nanoparticles in various fields such as catalysis, medicine, diagnostics, and sensors, several novel green approaches have been explored for synthesizing nanoparticles using different natural sources such as plants, algae, bacteria, and fungi. Hence, in the present work, a green method for the synthesis of gold nanoparticles (AuNPs) under ambient conditions using aqueous extracts of marine brown algae is reported and the synthesized AuNPs were evaluated for their catalytic efficiency. The aqueous extracts of algae comprise reducing as well as capping agents required for the formation of AuNPs. The Fourier transform infrared spectra of the extracts revealed the presence of compounds having hydroxyl groups that are largely responsible for the reduction of auric chloride to AuNPs at room temperature. Results from high-resolution transmission electron microscopy and dynamic light scattering studies suggested that most of the biosynthesized AuNPs are nearly spherical in shape with an average size in the range of 27-35 nm. High negative values of zeta potential measurement confirmed the stability of AuNPs. Moreover, the reduction kinetics of AuNPs studied by UV-visible spectrophotometry showed that they have good catalytic efficiency in the degradation of dyes as well as reduction of nitro compounds in the presence of sodium borohydride as reducing agent. This simple process for the biosynthesis of gold nanoparticles is rapid, cost-effective and eco-friendly. The formation of AuNPs was observed with the change of pale yellow gold solution to ruby red color of gold nanoparticles and confirmed by surface plasmon spectra using UV-visible spectroscopy. Nanoparticles synthesized through such environmentally benign routes can be used for synthesizing many other metal nanoparticles as well as for a wide range of biomedical applications, for commercial production on a large scale and also can be used as efficient catalysts for different organic reactions.

Methanolic extracts of cap and stipe of commercially obtained mushrooms Agaricus bisporus, Hypsizygus ulmarius, and Calocybe indica were analyzed for their antioxidant activity in different chemical systems including reducing power, free radical scavenging, ferric reducing antioxidant power (FRAP), superoxide scavenging, peroxide scavenging, metal chelating activities and electrochemical behavior. Scavenging effects on 2,2-diphenyl-1-picrylhydrazyl radicals were moderate (43.5-59.0%) at 1.5 mg/ml. Chelating effects on ferrous ions were moderate to excellent (40.6-96.1%) at 20 mg/ml. At 12 mg/ml, the reducing powers were excellent (2.54-1.71). FRAP results were in the range 2.15-0.98 at 16 mg/ml. The ability to scavenge H2O2 was moderate to excellent (48.9-97.7%) at 1.5 mg/ml. At 10 mg/ml, Agaricus bisporus cap proved to be better at scavenging superoxide radicals than others. Similar electrochemical responses of all extracts suggested similar electroactive chemical composition. The total phenols in the extracts ranged from 14.73-26.72 mg/g.The total flavonoid content ranged from 1.12-2.17 μg/g.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models. ADA activity differentiated patients into low and high ADA sets. The levels of the cytokines TNFα, IFNγ, IL-10, TGFβ and sRANKL were elevated in RA and more pronounced in high ADA sets. Serum metabolomic analysis shows altered metabolic pathways in RA which were distinct between low and high ADA sets. Comparative analysis with previous studies shows similar pathways are modulated by DMARDs and biologics. Random forest analysis distinguished RA from control by methyl-histidine and hydroxyisocaproic acid, while hexose-phosphate and fructose-6-phosphate distinguished high ADA from low ADA. The deregulated metabolic pathways of High ADA datasets significantly overlapped with high ADA expressing PBMCs GEO transcriptomics dataset. ADA induced the death of chondrocytes, synoviocyte proliferation, both inflammation in macrophages and their differentiation into osteoclasts and impaired differentiation of mesenchymal stem cells to osteoblasts and mineralization. PBMCs expressing elevated ADA had increased expression of cytokines and P2 receptors compared to synovial macrophages which has low expression of ADA. Our data demonstrates increased cytokine levels and distinct metabolic signatures of RA based on the ADA activity, suggests an important role for ADA in the pathophysiology of RA joints and as a potential marker and therapeutic target in RA patients.

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Glaucoma of which primary open angle glaucoma (POAG) constitutes 75%, is the second leading cause of blindness. Elevated intra ocular pressure and Nitric oxide synthase (NOS) dysfunction are hallmarks of POAG. We analyzed clinical data, cytokine profile, ATP level, metabolomics and GEO datasets to identify features unique to POAG. N9 microglial cells are used to gain mechanistic insights. Our POAG cohort showed elevated ATP in aqueous humor and cytokines in plasma. Metabolomic analysis showed changes in 21 metabolites including Dimethylarginine (DMAG) and activation of tryptophan metabolism in POAG. Analysis of GEO data sets and previously published proteomic data sets bins genes into signaling and metabolic pathways. Pathways from reanalyzed metabolomic data from literature significantly overlapped with those from our POAG data. DMAG modulated purinergic signaling, ATP secretion and cytokine expression were inhibited by N-Ethylmaleimide, NO donors, BAPTA and purinergic receptor inhibitors. ATP induced elevated intracellular calcium level and cytokines expression were inhibited by BAPTA. Metabolomics of cell culture supernatant from ATP treated sets showed metabolic deregulation and activation of tryptophan metabolism. DMAG and ATP induced IDO1/2 and TDO2 were inhibited by N-Ethylmaleimide, sodium nitroprusside and BAPTA. Our data obtained from clinical samples and cell culture studies reveal a strong association of elevated DMAG, ATP, cytokines and activation of tryptophan metabolism with POAG. DMAG mediated ATP signaling, inflammation and metabolic remodeling in microglia might have implications in management of POAG.

Methanolic extracts of four cultivated edible mushrooms of Pleurotus spp. namely Pleurotus florida, Pleurotus sajor-caju, Pleurotus cystidiosus and Pleurotus djamor along with the sporeless/low sporing mutants of Pleurotus florida, and Pleurotus sajor-caju were analyzed for their antioxidant activity using different chemical assays. The electrochemical behaviors of these extracts were also analyzed using cyclic voltammetry and differential pulse voltammetry. Results showed that scavenging effects on 2,2-diphenyl-1-picrylhydrazyl radicals were good (73.3-42.4 %) at 1.5 mg/ml. At 12 mg/ml, the reducing powers (2.54-1.71) and chelating effects on ferrous ions (56.0-78.5 %) were excellent. H 2 O 2 scavenging abilities at 1.5 mg/ml showed a wide range (20.0-85.4 %). Scavenging of superoxide radicals were excellent and were found to be in the range of 61.1-90.0 % at 16 mg/ml concentration. FRAP results were in the range of 1.20 -0.98 at 16 mg/ ml. Total phenolic and total flavonoid contents of the methanolic extracts ranged from 22.67 to 36.03 mg/g and 1.19-2.94 μg/g respectively. The study assessed the amount of variation in antioxidant activities exhibited by different cultivated species and their sporeless/low sporing mutants.

This study establishes the diarylidenecyclohexanones as good anti-inflammatory pharmacophores with selective high potency against PGE2 and 5-LOX without toxicity towards healthy human cells.