Search results for: cardiac toxicity
10 Musictherapy and Gardentherapy: A Systemic Approach for the Life Quality of the PsychoPhysical Disability
Authors: Adriana De Serio, Donato Forenza
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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.Keywords: musictherapy, gardentherapy, disability, life quality
Procedia PDF Downloads 629 Insights on Nitric Oxide Interaction with Phytohormones in Rice Root System Response to Metal Stress
Authors: Piacentini Diego, Della Rovere Federica, Fattorini Laura, Lanni Francesca, Cittadini Martina, Altamura Maria Maddalena, Falasca Giuseppina
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Plants have evolved sophisticated mechanisms to cope with environmental cues. Changes in intracellular content and distribution of phytohormones, such as the auxin indole-3-acetic acid (IAA), have been involved in morphogenic adaptation to environmental stresses. In addition to phytohormones, plants can rely on a plethora of small signal molecules able to promptly sense and transduce the stress signals, resulting in morpho/physiological responses thanks also to their capacity to modulate the levels/distribution/reception of most hormones. Among these signaling molecules, nitrogen monoxide (nitric oxide – NO) is a critical component in several plant acclimation strategies to both biotic and abiotic stresses. Depending on its levels, NO increases plant adaptation by enhancing the enzymatic or non-enzymatic antioxidant systems or by acting as a direct scavenger of reactive oxygen/nitrogen (ROS/RNS) species produced during the stress. In addition, exogenous applications of NO-specific donor compounds showed the involvement of the signal molecule in auxin metabolism, transport, and signaling, under both physiological and stress conditions. However, the complex mechanisms underlying NO action in interacting with phytohormones, such as auxins, during metal stress responses are still poorly understood and need to be better investigated. Emphasis must be placed on the response of the root system since it is the first plant organ system to be exposed to metal soil pollution. The monocot Oryza sativa L. (rice) has been chosen given its importance as a stable food for some 4 billion people worldwide. In addition, increasing evidence has shown that rice is often grown in contaminated paddy soils with high levels of heavy metal cadmium (Cd) and metalloid arsenic (As). The facility through which these metals are taken up by rice roots and transported to the aerial organs up to the edible caryopses makes rice one of the most relevant sources of these pollutants for humans. This study aimed to evaluate if NO has a mitigatory activity in the roots of rice seedlings against Cd or As toxicity and to understand if this activity requires interactions with auxin. Our results show that exogenous treatments with the NO-donor SNP alleviate the stress induced by Cd, but not by As, in in-vitro-grown rice seedlings through increased intracellular root NO levels. The damages induced by the pollutants include root growth inhibition, root histological alterations and ROS (H2O2, O2●ˉ), and RNS (ONOOˉ) production. Also, SNP treatments mitigate both the root increase in root IAA levels and the IAA alteration in distribution monitored by the OsDR5::GUS system due to the toxic metal exposure. Notably, the SNP-induced mitigation of the IAA homeostasis altered by the pollutants does not involve changes in the expression of OsYUCCA1 and ASA2 IAA-biosynthetic genes. Taken together, the results highlight a mitigating role of NO in the rice root system, which is pollutant-specific, and involves the interaction of the signal molecule with both IAA and brassinosteroids at different (i.e., transport, levels, distribution) and multiple levels (i.e., transcriptional/post-translational levels). The research is supported by Progetti Ateneo Sapienza University of Rome, grant number: RG120172B773D1FFKeywords: arsenic, auxin, cadmium, nitric oxide, rice, root system
Procedia PDF Downloads 748 Utilization of Functionalized Biochar from Water Hyacinth (Eichhornia crassipes) as Green Nano-Fertilizers
Authors: Adewale Tolulope Irewale, Elias Emeka Elemike, Christian O. Dimkpa, Emeka Emmanuel Oguzie
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As the global population steadily approaches the 10billion mark, the world is currently faced with two major challenges among others – accessing sustainable and clean energy, and food security. Accessing cleaner and sustainable energy sources to drive global economy and technological advancement, and feeding the teeming human population require sustainable, innovative, and smart solutions. To solve the food production problem, producers have relied on fertilizers as a way of improving crop productivity. Commercial inorganic fertilizers, which is employed to boost agricultural food production, however, pose significant ecological sustainability and economic problems including soil and water pollution, reduced input efficiency, development of highly resistant weeds, micronutrient deficiency, soil degradation, and increased soil toxicity. These ecological and sustainability concerns have raised uncertainties about the continued effectiveness of conventional fertilizers. With the application of nanotechnology, plant biomass upcycling offers several advantages in greener energy production and sustainable agriculture through reduction of environmental pollution, increasing soil microbial activity, recycling carbon thereby reducing GHG emission, and so forth. This innovative technology has the potential for a circular economy and creating a sustainable agricultural practice. Nanomaterials have the potential to greatly enhance the quality and nutrient composition of organic biomass which in turn, allows for the conversion of biomass into nanofertilizers that are potentially more efficient. Water hyacinth plant harvested from an inland water at Warri, Delta State Nigeria were air-dried and milled into powder form. The dry biomass were used to prepare biochar at a pre-determined temperature in an oxygen deficient atmosphere. Physicochemical analysis of the resulting biochar was carried out to determine its porosity and general morphology using the Scanning Transmission Electron Microscopy (STEM). The functional groups (-COOH, -OH, -NH2, -CN, -C=O) were assessed using the Fourier Transform InfraRed Spectroscopy (FTIR) while the heavy metals (Cr, Cu, Fe, Pb, Mg, Mn) were analyzed using Inductively Coupled Plasma – Optical Emission Spectrometry (ICP-OES). Impregnation of the biochar with nanonutrients were achieved under varied conditions of pH, temperature, nanonutrient concentrations and resident time to achieve optimum adsorption. Adsorption and desorption studies were carried out on the resulting nanofertilizer to determine kinetics for the potential nutrients’ bio-availability to plants when used as green fertilizers. Water hyacinth (Eichhornia crassipes) which is an aggressively invasive aquatic plant known for its rapid growth and profusion is being examined in this research to harness its biomass as a sustainable feedstock to formulate functionalized nano-biochar fertilizers, offering various benefits including water hyacinth biomass upcycling, improved nutrient delivery to crops and aquatic ecosystem remediation. Altogether, this work aims to create output values in the three dimensions of environmental, economic, and social benefits.Keywords: biochar-based nanofertilizers, eichhornia crassipes, greener agriculture, sustainable ecosystem, water hyacinth
Procedia PDF Downloads 607 Amphiphilic Compounds as Potential Non-Toxic Antifouling Agents: A Study of Biofilm Formation Assessed by Micro-titer Assays with Marine Bacteria and Eco-toxicological Effect on Marine Algae
Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres
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Biofilm is a predominant lifestyle chosen by bacteria. Whether it is developed on an immerged surface or a mobile biofilm known as flocs, the bacteria within this form of life show properties different from its planktonic ones. Within the biofilm, the self-formed matrix of Extracellular Polymeric Substances (EPS) offers hydration, resources capture, enhanced resistance to antimicrobial agents, and allows cell-communication. Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint6 (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation7, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids9 to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge (BSV36, KLN47) or a zwitterionic polar-head group (SL386, MB2871) to prevent microfouling with marine bacteria. We also study the toxicity of these compounds in order to identify the most promising compound that must feature high anti-adhesive properties and a low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.Keywords: amphiphilic phospholipids, bacterial biofilm, marine microfouling, non-toxic antifouling
Procedia PDF Downloads 1436 Biomedical Application of Green Biosynthesis Magnetic Iron Oxide (Fe3O4) Nanoparticles Using Seaweed (Sargassum muticum) Aqueous Extract
Authors: Farideh Namvar, Rosfarizan Mohamed
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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed
Procedia PDF Downloads 3085 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent
Authors: Kuladip Jana
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin
Procedia PDF Downloads 2534 The Study of Adsorption of RuP onto TiO₂ (110) Surface Using Photoemission Deposited by Electrospray
Authors: Tahani Mashikhi
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Countries worldwide rely on electric power as a critical economic growth and progress factor. Renewable energy sources, often referred to as alternative energy sources, such as wind, solar energy, geothermal energy, biomass, and hydropower, have garnered significant interest in response to the rising consumption of fossil fuels. Dye-sensitized solar cells (DSSCs) are a highly promising alternative for energy production as they possess numerous advantages compared to traditional silicon solar cells and thin-film solar cells. These include their low cost, high flexibility, straightforward preparation methodology, ease of production, low toxicity, different colors, semi-transparent quality, and high power conversion efficiency. A solar cell, also known as a photovoltaic cell, is a device that converts the energy of light from the sun into electrical energy through the photovoltaic effect. The Gratzel cell is the initial dye-sensitized solar cell made from colloidal titanium dioxide. The operational mechanism of DSSCs relies on various key elements, such as a layer composed of wide band gap semiconducting oxide materials (e.g. titanium dioxide [TiO₂]), as well as a photosensitizer or dye that absorbs sunlight to inject electrons into the conduction band, the electrolyte utilizes the triiodide/iodide redox pair (I− /I₃−) to regenerate dye molecules and a counter electrode made of carbon or platinum facilitates the movement of electrons across the circuit. Electrospray deposition permits the deposition of fragile, non-volatile molecules in a vacuum environment, including dye sensitizers, complex molecules, nanoparticles, and biomolecules. Surface science techniques, particularly X-ray photoelectron spectroscopy, are employed to examine dye-sensitized solar cells. This study investigates the possible application of electrospray deposition to build high-quality layers in situ in a vacuum. Two distinct categories of dyes can be employed as sensitizers in DSSCs: organometallic semiconductor sensitizers and purely organic dyes. Most organometallic dyes, including Ru533, RuC, and RuP, contain a ruthenium atom, which is a rare element. This ruthenium atom enhances the efficiency of dye-sensitized solar cells (DSSCs). These dyes are characterized by their high cost and typically appear as dark purple powders. On the other hand, organic dyes, such as SQ2, RK1, D5, SC4, and R6, exhibit reduced efficacy due to the lack of a ruthenium atom. These dyes appear in green, red, orange, and blue powder-colored. This study will specifically concentrate on metal-organic dyes. The adsorption of dye molecules onto the rutile TiO₂ (110) surface has been deposited in situ under ultra-high vacuum conditions by combining an electrospray deposition method with X-ray photoelectron spectroscopy. The X-ray photoelectron spectroscopy (XPS) technique examines chemical bonds and interactions between molecules and TiO₂ surfaces. The dyes were deposited at varying times, from 5 minutes to 40 minutes, to achieve distinct layers of coverage categorized as sub-monolayer, monolayer, few layers, or multilayer. Based on the O 1s photoelectron spectra data, it can be observed that the monolayer establishes a strong chemical bond with the Ti atoms of the oxide substrate by deprotonating the carboxylic acid groups through 2M-bidentate bridging anchors. The C 1s and N 1s photoelectron spectra indicate that the molecule remains intact at the surface. This can be due to the existence of all functional groups and a ruthenium atom, where the binding energy of Ru 3d is consistent with Ru2+.Keywords: deposit, dye, electrospray, TiO₂, XPS
Procedia PDF Downloads 353 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors
Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan
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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha
Procedia PDF Downloads 2072 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents
Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair
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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae
Procedia PDF Downloads 2951 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice
Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath
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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.Keywords: amifostine, fibrosis, inflammation, lung injury radiation
Procedia PDF Downloads 505