Search results for: pro-inflammatory molecules

Authors: Ginger Egberts, Fred Vermolen, Paul van Zuijlen

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One of the common complications in post-burn scars is contractions. Depending on the extent of contraction and the wound dimensions, the contracture can cause a limited range-of-motion of joints. A one-dimensional morphoelastic continuum hypothesis-based model describing post-burn scar contractions is considered. The beauty of the one-dimensional model is the speed; hence it quickly yields new results and, therefore, insight. This model describes the movement of the skin and the development of the strain present. Besides these mechanical components, the model also contains chemical components that play a major role in the wound healing process. These components are fibroblasts, myofibroblasts, the so-called signaling molecules, and collagen. The dermal layer is modeled as an isotropic morphoelastic solid, and pulling forces are generated by myofibroblasts. The solution to the model equations is approximated by the finite-element method using linear basis functions. One of the major challenges in biomechanical modeling is the estimation of parameter values. Therefore, this study provides a comprehensive description of skin mechanical parameter values and a sensitivity analysis. Further, since skin mechanical properties change with aging, it is important that the model is feasible for predicting the development of contraction in burn patients of different ages, and hence this study provides a feasibility study. The variability in the solutions is caused by varying the values for some parameters simultaneously over the domain of computation, for which the results of the sensitivity analysis are used. The sensitivity analysis shows that the most sensitive parameters are the equilibrium concentration of collagen, the apoptosis rate of fibroblasts and myofibroblasts, and the secretion rate of signaling molecules. This suggests that most of the variability in the evolution of contraction in burns in patients of different ages might be caused mostly by the decreasing equilibrium of collagen concentration. As expected, the feasibility study shows this model can be used to show distinct extents of contractions in burns in patients of different ages. Nevertheless, contraction formation in children differs from contraction formation in adults because of the growth. This factor has not been incorporated in the model yet, and therefore the feasibility results for children differ from what is seen in the clinic.

Keywords: biomechanics, burns, feasibility, fibroblasts, morphoelasticity, sensitivity analysis, skin mechanics, wound contraction

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Authors: Ahmad Sabry Mohamad, Kai F. Hoettges, Michael Pycraft Hughes

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This study investigates nanowires using Dielectrophoresis (DEP) in non-aqueous suspension of Tin (IV) Oxide (SnO2) nanoparticles dispersed in N,N-dimenthylformamide (DMF). The self assembly of nanowires in DEP impedance spectroscopy can be determined. In this work, dielectrophoretic method was used to measure non-organic molecules for estimating the permittivity and conductivity characteristic of the nanowires. As in aqueous such as salt solution has been dominating the transport of SnO2, which are the wire growth threshold, depend on applied voltage. While DEP assembly of nanowires depend on applied frequency, the applications of dielectrophoretic collection are measured using impedance spectroscopy.

Keywords: dielectrophoresis, impedance spectroscopy, nanowires, N, N-dimenthylformamide, SnO2

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Authors: Nitu Chhikaraa, S. B. Tyagia, Kiran Jainb, Mamta Kharkwala

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The I–III–VI2 semiconductor Nanocrystals such as AgInS2 have great interest for various applications such as optical devices (solar cell and LED), cellular Imaging and bio tagging etc. we synthesized the phase and shape controlled chalcopyrite AgInS2 (AIS) colloidal nanoparticles by thermal decomposition of metal xanthate at low temperature in an organic solvent’s containing surfactant molecules. Here we are focusing on enhancements of photoluminescence of AgInS2 Nps by coating of ZnS at low temperature for application of optical devices. The size of core shell Nps was less than 50nm.by increasing the time and temperature the emission of the wavelength of the Zn coated AgInS2 Nps could be adjusted from visible region to IR the QY of the AgInS2 Nps could be increased by coating of ZnS from 20 to 80% which was reasonably good as compared to those of the previously reported. The synthesized NPs were characterized by PL, UV, XRD and TEM.

Keywords: PL, UV, XRD, TEM

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Authors: Jichan Jang

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Mycobacterium abscessus is a rapidly growing life-threatening mycobacterium with multiple drug-resistance mechanisms. In this study, we screened the library to identify active molecules targeting Mycobacterium abscessus using resazurin live/dead assays. In this screening assay, the Z-factor was 0.7, as an indication of the statistical confidence of the assay. A cut-off of 80% growth inhibition in the screening resulted in the identification of four different compounds at a single concentration (20 μM). Dose-response curves identified three different hit candidates, which generated good inhibitory curves. All hit candidates were expected to have different molecular targets. Thus, we found that compound X, identified, may be a promising candidate in the M. abscessus drug discovery pipeline.

Keywords: Mycobacterium abscessus, antibiotics, drug discovery, emerging Pathogen

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Authors: Marwa Abida, Florian Gehring, Jamel Mars, Alexandre Vivet, Fakhreddine Dammak, Mohamed Haddar

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The demand for bio-based materials in semi-structural and structural applications is constantly growing to conform to new environmental policies. Among them, Plant Fiber Reinforced Composites (PFRC) are attractive for the scientific community as well as the industrial world. Due to their relatively low densities and low environmental impact, vegetal fibers appear to be suitable as reinforcing materials for polymers. However, the major issue of plant fibers and PFRC in general is their hydrophilic behavior (high affinity to water molecules). Indeed, when absorbed, water causes fiber swelling and a loss of mechanical properties. Thus, the environmental loadings (moisture, temperature, UV) can strongly affect their mechanical properties and therefore play a critical role in the service life of PFRC. In order to analyze the influence of conditioning at relative humidity on the behavior of flax fiber reinforced composites, a preliminary study on flax fabrics has been conducted. The conditioning of the fabrics in different humid atmospheres made it possible to study the influence of the water content on the hygro-mechanical behavior of flax reinforcement through mechanical tensile tests. This work shows that increasing the relative humidity of the atmosphere induces an increase of the water content in the samples. It also brings up the significant influence of water content on the stiffness and elongation at break of the fabric, while no significant change of the breaking load is detected. Non-linear decrease of flax fabric rigidity and increase of its elongation at maximal force with the increase of water content are observed. It is concluded that water molecules act as a softening agent on flax fabrics. Two kinds of typical tensile curves are identified. Most of the tensile curves of samples show one unique linear region where the behavior appears to be linear prior to the first yarn failure. For some samples in which water content is between 2.7 % and 3.7 % (regardless the conditioning atmosphere), the emergence of a two-linear region behavior is pointed out. This phenomenon could be explained by local heterogeneities of water content which could induce premature local plasticity in some regions of the flax fabric sample behavior.

Keywords: hygro-mechanical behavior, hygroscopy, flax fabric, relative humidity, mechanical properties

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Authors: Vishal Kumar, Soumitra Satapathi

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Föster Resonance Energy Transfer (FRET) is a powerful technique used to probe close-range molecular interactions. Physically, the FRET phenomenon manifests as a dipole–dipole interaction between closely juxtaposed fluorescent molecules (10–100 Å). Our effort is to employ this FRET technique to make a prototype device for highly sensitive detection of environment pollutant. Among the most common environmental pollutants, nitroaromatic compounds (NACs) are of particular interest because of their durability and toxicity. That’s why, sensitive and selective detection of small amounts of nitroaromatic explosives, in particular, 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) has been a critical challenge due to the increasing threat of explosive-based terrorism and the need of environmental monitoring of drinking and waste water. In addition, the excessive utilization of TNP in several other areas such as burn ointment, pesticides, glass and the leather industry resulted in environmental accumulation, and is eventually contaminating the soil and aquatic systems. To the date, high number of elegant methods, including fluorimetry, gas chromatography, mass, ion-mobility and Raman spectrometry have been successfully applied for explosive detection. Among these efforts, fluorescence-quenching methods based on the mechanism of FRET show good assembly flexibility, high selectivity and sensitivity. Here, we report a FRET-based sensor system for the highly selective detection of NACs, such as TNP, DNT and TNT. The sensor system is composed of a copolymer Poly [(N,N-dimethylacrylamide)-co-(Boc-Trp-EMA)] (RP) bearing tryptophan derivative in the side chain as donor and dansyl tagged copolymer P(MMA-co-Dansyl-Ala-HEMA) (DCP) as an acceptor. Initially, the inherent fluorescence of RP copolymer is quenched by non-radiative energy transfer to DCP which only happens once the two molecules are within Förster critical distance (R0). The excellent spectral overlap (Jλ= 6.08×10¹⁴ nm⁴M⁻¹cm⁻¹) between donors’ (RP) emission profile and acceptors’ (DCP) absorption profile makes them an exciting and efficient FRET pair i.e. further confirmed by the high rate of energy transfer from RP to DCP i.e. 0.87 ns⁻¹ and lifetime measurement by time correlated single photon counting (TCSPC) to validate the 64% FRET efficiency. This FRET pair exhibited a specific fluorescence response to NACs such as DNT, TNT and TNP with 5.4, 2.3 and 0.4 µM LODs, respectively. The detection of NACs occurs with high sensitivity by photoluminescence quenching of FRET signal induced by photo-induced electron transfer (PET) from electron-rich FRET pair to electron-deficient NAC molecules. The estimated stern-volmer constant (KSV) values for DNT, TNT and TNP are 6.9 × 10³, 7.0 × 10³ and 1.6 × 104 M⁻¹, respectively. The mechanistic details of molecular interactions are established by time-resolved fluorescence, steady-state fluorescence and absorption spectroscopy confirmed that the sensing process is of mixed type, i.e. both dynamic and static quenching as lifetime of FRET system (0.73 ns) is reduced to 0.55, 0.57 and 0.61 ns DNT, TNT and TNP, respectively. In summary, the simplicity and sensitivity of this novel FRET sensor opens up the possibility of designing optical sensor of various NACs in one single platform for developing multimodal sensor for environmental monitoring and future field based study.

Keywords: FRET, nitroaromatic, stern-Volmer constant, tryptophan and dansyl tagged copolymer

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Authors: Esmat Mohammadinasab, Mostafa Sadeghi

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In this study are computed some thermodynamic properties such as entropy and specific heat capacity, enthalpy, entropy and gibbs free energy in 10 type different Aminoacids using Gaussian software with DFT method and 6-311G basis set. Then some topological indices such as Wiener, shultz are calculated for mentioned molecules. Finaly is showed relationship between thermodynamic peoperties and above topological indices and with different curves is represented that there is a good correlation between some of the quantum properties with topological indices of them. The instructive example is directed to the design of the structure-property model for predicting the thermodynamic properties of the amino acids which are discussed here.

Keywords: amino acids, DFT Method, molecular descriptor, thermodynamic properties

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Authors: Elham jassemi Zargani, Mohammad almasi

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Densities and viscosities for binary mixtures of diethylamine + 2 Alkanol (2 propanol up to 2 pentanol) were measured over the entire composition range and temperature interval of 293.15 to 323.15 K. Excess molar volumes V_m^E and viscosity deviations Δη were calculated and correlated by the Redlich−Kister type function to derive the coefficients and estimate the standard error. For mixtures of diethylamine with used 2-alkanols, V_m^E and Δη are negative over the entire range of mole fraction. The observed variations of these parameters, with alkanols chain length and temperature, are discussed in terms of the inter-molecular interactions between the unlike molecules of the binary mixtures.

Keywords: densities, viscosities, diethylamine, 2-alkanol, Redlich-Kister

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Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

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The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

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Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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Authors: Shilu Deepa Thomas, P. Jayaprakash, Dorota Łazewska, Katarzyna Kieć-Kononowicz, B. Sadek

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A large body of evidence suggests the involvement of cognitive impairment, increased levels of inflammation and oxidative stress in the pathogenesis of autism spectrum disorder (ASD). ASD commonly coexists with psychiatric conditions like anxiety and cognitive challenges, and individuals with ASD exhibit significant levels of inflammation and immune system dysregulation. Previous Studies have identified elevated levels of pro-inflammatory markers such as IL-1β, IL-6, IL-2 and TNF-α, particularly in young children with ASD. The current therapeutic options for ASD show limited effectiveness, signifying the importance of exploring an efficient drugs to address the core symptoms. The role of histamine H3 receptors (H3Rs) in memory and the prospective role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., ASD, is well-accepted. Hence, the effects of chronic systemic administration of H3R antagonist E159 on autistic-like repetitive behaviors, social deficits, memory and anxiety parameters, as well as neuroinflammation in Black and Tan BRachyury (BTBR) mice, were evaluated using Y maze, Barnes maze, self-grooming, open field and three chamber social test. E159 (2.5, 5 and 10 mg/kg, i.p.) dose-dependently ameliorated repetitive and compulsive behaviors by reducing the increased time spent in self-grooming and improved reduced spontaneous alternation in BTBR mice. Moreover, treatment with E159 attenuated disturbed anxiety levels and social deficits in tested male BTBR mice. Furthermore, E159 attenuated oxidative stress by significantly increasing GSH, CAT, and SOD and decreasing the increased levels of MDA in the cerebellum as well as the hippocampus. In addition, E159 decreased the elevated levels of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6). The observed results show that H3R antagonists like E159 may represent a promising novel pharmacological strategy for the future treatment of ASD.

Keywords: histamine H3 receptors, antagonist E159, autism, behaviors, mice

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Authors: Sandrine Delpeux-Ouldriane, Min Cai, Laurent Duclaux, Laurence Reinert, Fabrice Muller

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A novel hybrid adsorbent, based on chitosan biopolymer, clays and activated carbon was prepared. Hybrid chitosan beads containing dispersed clays and activated carbons were prepared by precipitation in basic medium. Such a composite material is still very porous and presents a wide adsorption spectrum. The obtained composite adsorbent is able to handle all the pollution types including heavy metals, polar and hydrophobic organic molecules and nitrates. It could find a place of choice in tertiary water treatment processes or for an ‘at source’ treatment concerning chemical or pharmaceutical industries.

Keywords: adsorption, chitosan, clay mineral, activated carbon

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Authors: Yunha Ryu, Kyoungsik Kim

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Raman spectroscopy is one of the most powerful techniques for chemical detection, but the low sensitivity originated from the extremely small cross-section of the Raman scattering limits the practical use of Raman spectroscopy. To overcome this problem, Surface Enhanced Raman Scattering (SERS) has been intensively studied for several decades. Because the SERS effect is mainly induced from strong electromagnetic near-field enhancement as a result of localized surface plasmon resonance of metallic nanostructures, it is important to design the plasmonic structures with high density of electromagnetic hot spots for SERS substrate. One of the useful fabrication methods is using porous nanomaterial as a template for metallic structure. Internal pores on a scale of tens of nanometers can be strong EM hotspots by confining the incident light. Also, porous structures can capture more target molecules than non-porous structures in a same detection spot thanks to the large surface area. Herein we report the facile fabrication method of porous SERS substrate by integrating solvent-assisted nanoimprint lithography and selective etching of block copolymer. We obtained nanostructures with high porosity via simple selective etching of the one microdomain of the diblock copolymer. Furthermore, we imprinted of the nanocone patterns into the spin-coated flat block copolymer film to make three-dimensional SERS substrate for the high density of SERS hot spots as well as large surface area. We used solvent-assisted nanoimprint lithography (SAIL) to reduce the fabrication time and cost for patterning BCP film by taking advantage of a solvent which dissolves both polystyrenre and poly(methyl methacrylate) domain of the block copolymer, and thus block copolymer film was molded under the low temperature and atmospheric pressure in a short time. After Ag deposition, we measured Raman intensity of dye molecules adsorbed on the fabricated structure. Compared to the Raman signals of Ag coated solid nanocone, porous nanocone showed 10 times higher Raman intensity at 1510 cm(-1) band. In conclusion, we fabricated porous metallic nanocone arrays with high density electromagnetic hotspots by templating nanoimprinted diblock copolymer with selective etching and demonstrated its capability as an effective SERS substrate.

Keywords: block copolymer, porous nanostructure, solvent-assisted nanoimprint, surface-enhanced Raman spectroscopy

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Authors: Rania Hanafi Mahmoud Said, Rasha Mohamed Taha

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Background: The use of nanoparticles for medication delivery offers the possibility of avoiding the negative effects of systemic antibiotic dosing as well as antibiotic resistance in bacteria. Aim of the study: The goal of this study was to see the efficiency of local administration of tetracycline loaded on nano chitosan in the treatment of the induced infection of the albino rats gingiva with Porphyromonas gingivalis through Immunohistochemical localization of Interleukin-1beta (IL-1β) as a proinflammatory cytokine.Material and methods: Fifty adult male albino rats 150 - 180 grams body weight used in this investigation. Any changes in rats’ weights were detected. The male albino rats were divided haphazardly into five groups as Group I involved ten rats; they served as a normal negative control group. Group II involved ten rats; they were infected once with P.gingivalis that was injected into the interdental gingiva. Group III involved ten rats; they were subjected to the same procedure as group II and then to daily injection at the site of infection with diluted tetracycline powder. Group IV involved ten rats; they were subjected to the same procedure as group II and then to daily injection of nano Chitosan at the site of injection. Group V involved ten rats; they were subjected to the same procedure as group II and then to daily injection of tetracycline loaded on nano Chitosan at the site of injection. After rats had been euthanized, the extraction and preparation of their gingiva were carried out in order to examine histologically and immunohistochemically. Results: The light microscopic results of groups II, III, and IV showed degeneration represented by swollen epithelial cells, collagen fibers dissociation of the connective tissue of lamina propria, and areas of basement membrane discontinuation, while groups I and V showed an almost normal histological picture of gingival tissue. Immunohistochemical results showed a significant difference in Group II and III when compared to control. No significant difference appears in group V when compared to the control (group I). Conclusion: Using nanochitosan as a carrier for tetracycline is a new technology to get over the increasing resistance of tetracycline.

Keywords: immunohistochemistry, P.gingivalis, nano-chitosan, tetracycline, periodontitis

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Authors: Silvia Gastaldello, Maria Grillo, Luca Tassoni, Claudio Maran, Stefano Balbo

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Antioxidants are nowadays attractive not only for the countless benefits to the human and animal health, but also for the perspective of use as food preservative instead of synthetic chemical molecules. In this study, the radical scavenging activity of six protein extracts from pulse and oleaginous seeds was evaluated. The selected matrices are Pisum sativum (yellow pea from two different origins), Carthamus tinctorius (safflower), Helianthus annuus (sunflower), Lupinus luteus cv Mister (lupin) and Glycine max (soybean), since they are economically interesting for both human and animal nutrition. The seeds were grinded and proteins extracted from 20mg powder with a specific vegetal-extraction kit. Proteins have been quantified through Bradford protocol and scavenging activity was revealed using DPPH assay, based on radical DPPH (2,2-diphenyl-1-picrylhydrazyl) absorbance decrease in the presence of antioxidants molecules. Different concentrations of the protein extract (1, 5, 10, 50, 100, 500 µg/ml) were mixed with DPPH solution (DPPH 0,004% in ethanol 70% v/v). Ascorbic acid was used as a scavenging activity standard reference, at the same six concentrations of protein extracts, while DPPH solution was used as control. Samples and standard were prepared in triplicate and incubated for 30 minutes in dark at room temperature, the absorbance was read at 517nm (ABS30). Average and standard deviation of absorbance values were calculated for each concentration of samples and standard. Statistical analysis using t-students and p-value were performed to assess the statistical significance of the scavenging activity difference between the samples (or standard) and control (ABSctrl). The percentage of antioxidant activity has been calculated using the formula [(ABSctrl-ABS30)/ABSctrl]*100. The obtained results demonstrate that all matrices showed antioxidant activity. Ascorbic acid, used as standard, exhibits a 96% scavenging activity at the concentration of 500 µg/ml. At the same conditions, sunflower, safflower and yellow peas revealed the highest antioxidant performance among the matrices analyzed, with an activity of 74%, 68% and 70% respectively (p < 0.005). Although lupin and soybean exhibit a lower antioxidant activity compared to the other matrices, they showed a percentage of 46 and 36 respectively. All these data suggest the possibility to use undervalued edible matrices as antioxidants source. However, further studies are necessary to investigate a possible synergic effect of several matrices as well as the impact of industrial processes for a large-scale approach.

Keywords: antioxidants, DPPH assay, natural matrices, vegetal proteins

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Authors: Young June Yoon

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We will present four different topics in estimating the mechanical properties of biological tissues. First we elucidate the viscoelastic behavior of collagen molecules whose diameter is a couple of nanometers. By using the molecular dynamics simulation, we observed the viscoelastic behavior in different pulling velocity. Second, the protein layer, so called ‘sheath’ in enamel microstructure reduces the stress concentration in enamel minerals. We examined the result by using the finite element methods. Third, the anisotropic elastic constants of dentin are estimated by micromechanical analysis and estimated results are close to the experimentally measured data. Last, new formulation between the fabric tensor and the wave velocity is established for calcaneus by employing the poroelasticity. This formulation can be simply used for future experiments.

Keywords: tissues, mechanics, mechanical properties, wave propagation

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Authors: Ziani Borhane Eddine Cherif, Hazzi Mohamed, Mouhouche Fazia

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The vegetal extracts of aromatic and medicinal plants start to have much of interest like potential sources of natural bioactive molecules. Many features are conferred by the nature of the chemical function of their major constituents (phenol, alcohol, aldehyde, cetone). This biopotential lets us to focalize on the study of three main biological activities, the antioxidant, antibiotic and insecticidal activities of six Algerian aromatic plants in the aim of making in evidence by the chromatographic analysis (CPG and CG/SM) the phytochemical compounds implicating in this effects. The contents of Oxygenated monoterpenes represented the most prominent group of constituents in the majority of plants. However, the α-Terpineol (28,3%), Carvacrol (47,3%), pulégone (39,5%), Chrysanthenone (27,4%), Thymol 23,9%, γ-Terpinene 23,9% and 2-Undecanone(94%) were the main components. The antioxyding activity of the Essential oils and no-volatils extracts was evaluated in vitro using four tests: inhibition of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) radical-scavenging activity (ABTS•+), the thiobarbituric acid reactive substances (TBARS) assays and the reducing power. The measures of the IC50 of these natural compounds revealed potent activity (between 254.64-462.76mg.l-1), almost similar to that of BHT, BHA, Tocopherol and Ascorbic acid (126,4-369,1 mg.l-1) and so far than the Trolox one (IC50= 2,82mg.l-1). Furthermore, three ethanol extracts were found to be remarkably effective toward DPPH and ABTS inhibition, compared to chemical antioxidant BHA and BHT (IC = 9.8±0.1 and 28±0.7 mg.l-1, respectively); for reducing power test it has also exhibited high activity. The study on the insecticidal activity effect by contact, inhalation, fecundity and fertility of Callosobruchus maculatus and Tribolium confusum showed a strong potential biocide reaching 95-100% mortality only after 24 hours. The antibiotic activity of our essential oils were evaluated by a qualitative study (aromatogramme) and quantitative (MIC, MBC and CML) on four bacteria (Gram+ and Gram-) and one strain of pathogenic yeast, the results of these tests showed very interesting action than that induced by the same reference antibiotics (Gentamycin, and Nystatin Ceftatidine) such that the inhibition diameters and MIC values for tested microorganisms were in the range of 23–58 mm and 0.015–0.25%(v/v) respectively.

Keywords: aromatic plants, essential oils, no-volatils extracts, bioactive molecules, antioxidant activity, insecticidal activity, antibiotic activity

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

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Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

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Authors: Shagufta Tabassum, V. P. Pawar, jr., G. N. Shinde

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The study of dielectric relaxation properties of polar liquids in the binary mixture has been carried out at 10, 15, 20 and 25 ºC temperatures for 11 different concentrations using time domain reflectometry technique. The dielectric properties of a solute-solvent mixture of polar liquids in the frequency range of 10 MHz to 30 GHz gives the information regarding formation of monomers and multimers and also an interaction between the molecules of the liquid mixture under study. The dielectric parameters have been obtained by the least squares fit method using the Debye equation characterized by a single relaxation time without relaxation time distribution.

Keywords: excess properties, relaxation time, static dielectric constant, and time domain reflectometry technique

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Authors: Fulwah Alqahtani, Jafar Mahdavi, Lee Weldon, Nick Holliday, Dlawer Ala'Aldeen

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There are two isoforms of laminin receptor; monomeric 37 kDa laminin receptor precursor (37 LRP) and mature 67 kDa laminin receptor (67 LR). The relationship between the 67 LR and its precursor 37 LRP is not completely understood, but previous observations have suggested that 37 LRP can undergo homo- and/or hetero- dimerization with Galectin-3 (Gal-3) to form mature 67 LR. Gal-3 is the only member of the chimera-type group of galectins, and has one C-terminal carbohydrate recognition domain (CRD) that is responsible for binding the ß-galactoside moieties of mono- or oligosaccharides on several host and microbial molecules. The aim of this work was to investigate homo- and hetero-dimerization among the 37 LRP and Gal-3 to form mature 67 LR in mammalian cells using bimolecular fluorescence complementation (BiFC).

Keywords: 37 LRP, 67 LR, Gal-3, BiFC

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Authors: Lali Shanshiashvili, Marika Chikviladze, Nino Mamulashvili, Maia Sepashvili, Nana Narmania, David Mikeladze

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Purpose: During demyelinating inflammatory diseases and after the damage of the myelin sheet, myelin-derived proteins, including myelin basic protein (MBP), are secreted into the extracellular space. MBP shows extensive post-translational modifications, including the deimination of arginine residues. Deiminated MBP is structurally less ordered, susceptible to proteolytic attack, and more immunogenic than the unmodified one. It is hypothesized that MBP could change the inflammatory response in astrocytes. Methods: MBP was isolated and purified from bovine brain white matter. Primary astrocyte cultures were prepared from whole brains of 2-day-old Wistar rats. For evaluation of glutamate uptake/release in astrocytes following treatment of cells with MBP charge isomers, Glutamate Assay Kit was used. The expression of EAAT-2 (excitatory amino acid transporters), peroxisome proliferator-activated receptor gamma (PPAR- γ), inhibitor of nuclear factor kappa B (IkB), and high mobility group protein B1 (HMGB1) in astrocytes were assayed by Western Blot analysis. Results: This study investigated the action of deiminated isomer (C8) on the cultured primary astrocytes and compared its effects with the effects of unmodified C1 isomers. The study found that C8 and C1 MBP differently act on the uptake and release of glutamate in astrocytes: nonmodified C1 MBP increases the uptake of glutamate and does not change the release, whereas C8 decreases the release of glutamate but does not alter the uptake. Nevertheless, both isomers increased the expression of PPAR-γ and EAAT2 in the same intensity. However, immunostaining and Western Blots of cell lysates showed a decrease of IkB and increased expression of HMGB1 after the treatment of astrocytes by C8. Moreover, in the presence of C8, astrocytes release more nitric oxide than unmodified C1 isomers. Conclusion: These data suggest that the deiminated isomer of MBP evokes an inflammatory response and enhances the ability of astrocytes to release proinflammatory mediators through activation of NF-kB after the breakdown of myelin sheets. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, glutamate, deimination, astrocytes, inflammation

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Authors: Laggoun Chouki

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In this paper we present the design and mechanisms of the physics process and discuss the performances of continuous gas laser dynamics, based on molecules N2(v=1)→C02(001)(v=3). The main objectives of work in this area are, obtaining the high laser energies in short time durations needed for the feasibility studies the physical principles that can be used to make laser sources capable of delivering high average powers. We note that, in order to reach both objectives, one has to convert electrical or chemical energy into laser energy, using gaseous media. The process generating the wave excited, on the basis of the excited level vibration, Theoretical predictions are compared with experimental results. The feasibility and effectiveness of the proposed method is demonstrated by computer simulation.

Keywords: modelling, lasers, gas, numerical, nozzle

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Sibashish Baksi, Ujjaini Sarkar, Sudeshna Saha

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In the present study, hydrolysis of Pinus roxburghi wood powder was carried out with Viscozyme, and kinetics of the hydrolysis has been investigated. Finely ground sawdust is submerged into 2% aqueous peroxide solution (pH=11.5) and pretreated through autoclaving, probe sonication, and alkaline peroxide pretreatment. Afterward, the pretreated material is subjected to hydrolysis. A chain of experiments was executed with delignified biomass (50 g/l) and varying enzyme concentrations (24.2–60.5 g/l). In the present study, 14.32 g/l of glucose, along with 7.35 g/l of xylose, have been recovered with a viscozyme concentration of 48.8 g/l and the same condition was treated as optimum condition. Additionally, thermal deactivation of viscozyme has been investigated and found to be gradually decreasing with escalated enzyme loading from 48.4 g/l (dissociation constant= 0.05 h⁻¹) to 60.5 g/l (dissociation constant= 0.02 h⁻¹). The hydrolysis reaction is a pseudo first-order reaction, and therefore, the rate of the hydrolysis can be expressed as a fractal-like kinetic equation that communicates between the product concentration and hydrolytic time t. It is seen that the value of rate constant (K) increases from 0.008 to 0.017 with augmented enzyme concentration from 24.2 g/l to 60.5 g/l. Greater value of K is associated with stronger enzyme binding capacity of the substrate mass. However, escalated concentration of supplied enzyme ensures improved interaction with more substrate molecules resulting in an enhanced de-polymerization of the polymeric sugar chains per unit time which eventually modifies the physiochemical structure of biomass. All fractal dimensions are in between 0 and 1. Lower the value of fractal dimension, more easily the biomass get hydrolyzed. It can be seen that with increased enzyme concentration from 24.2 g/l to 48.4 g/l, the values of fractal dimension go down from 0.1 to 0.044. This indicates that the presence of more enzyme molecules can more easily hydrolyze the substrate. However, an increased value has been observed with a further increment of enzyme concentration to 60.5g/l because of diffusional limitation. It is evident that the hydrolysis reaction system is a heterogeneous organization, and the product formation rate depends strongly on the enzyme diffusion resistances caused by the rate-limiting structures of the substrate-enzyme complex. Value of the rate constant increases from 1.061 to 2.610 with escalated enzyme concentration from 24.2 to 48.4 g/l. As the rate constant is proportional to Fick’s diffusion coefficient, it can be assumed that with a higher concentration of enzyme, a larger amount of enzyme mass dM diffuses into the substrate through the surface dF per unit time dt. Therefore, a higher rate constant value is associated with a faster diffusion of enzyme into the substrate. Regression analysis of time curves with various enzyme concentrations shows that diffusion resistant constant increases from 0.3 to 0.51 for the first two enzyme concentrations and again decreases with enzyme concentration of 60.5 g/l. During diffusion in a differential scale, the enzyme also experiences a greater resistance during diffusion of larger dM through dF in dt.

Keywords: viscozyme, glucose, fractal kinetics, thermal deactivation

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Authors: Mina Boroujerdi, Javad Tavakoli

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Hydrogels are extensively studied as matrices for the controlled release of drugs. To evaluate the mobility of embedded molecules, these drug delivery systems are usually characterized by release studies. In this contribution, an electronic device for swelling pressure measurement during drug release from hydrogel network was developed. Also, poly acrylic acid micro particles were prepared for prolonged and sustained controlled acetaminophen release. Effect of swelling pressure on drug release from micro particles studied under different environment pH in order to predict release profile in gastro-intestine medium. Swelling ratio and swelling pressure were measured in different pH.

Keywords: swelling pressure, drug delivery, hydrogel, polyelectrolyte

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Umut Kokbas, Mustafa Nisari

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Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

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Authors: S. Ghammamy, M. Mirzaabdollahiha

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Quantum mechanical calculations of energies, geometries, and vibrational wavenumbers of fluorous 1,3-dion compounds are carried out using density functional theory (DFT/B3LYP) method with LANL2DZ basis sets. The calculated HOMO and LUMO energies show that charge transfer occurs in the molecules. The thermodynamic functions of fluorous 1,3-dion compounds have been performed at B3LYP/LANL2DZ basis sets. The theoretical spectrograms for F NMR spectra of fluorous 1,3-dion compounds have also been constructed. The F NMR nuclear shieldings of fluoride ligands in fluorous 1,3-dion compounds have been studied quantum chemical.

Keywords: density function theory, natural bond orbital, HOMO, LOMO, fluorous

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