Search results for: cell uptake
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4211

Search results for: cell uptake

1361 Health Promoting Properties of Phytochemicals from Rosemary (Rosmarinus officinalis) for Cancer and Inflammatory Bowel Disease

Authors: Jeremy J. Johnson

Abstract:

Mediterranean herbs including rosemary (Rosmarinus officinalis) contain a variety of phytochemicals including diterpenes that possess extensive biological activity. Applications of diterpenes, including the more abundant forms carnosol and carnosic acid, have been shown to possess anti-cancer, anti-inflammatory, anti-oxidant, and anti-proliferation properties. To confirm these properties, we have evaluated rosemary extract and selected diterpenes for biological activity in cancer and inflammatory models. Our preliminary data have revealed that select diterpenes can disrupt androgen receptor functionality in prostate and breast cancer cells. This property is unique among natural products for hormone-responsive cancers. The second area of interest has been evaluating rosemary extract and selected diterpenes for activation of sestrin-2, an antioxidant protein, in colon cancer cells. A combination of in vitro and in vivo approaches have been utilized to characterize the activity of rosemary diterpenes in rosemary. Taken together, these results suggest that phytochemicals found in rosemary have distinct pharmacological actions for disrupting cell-signaling pathways in cancer and inflammatory bowel disease.

Keywords: rosemary, diterpene, cancer, inflammation

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1360 SnSₓ, Cu₂ZnSnS₄ Nanostructured Thin Layers for Thin-Film Solar Cells

Authors: Elena A. Outkina, Marina V. Meledina, Aliaksandr A. Khodin

Abstract:

Nanostructured thin films of SnSₓ, Cu₂ZnSnS₄ (CZTS) semiconductors were fabricated by chemical processing to produce thin-film photoactive layers for photocells as a prospective lowest-cost and environment-friendly alternative to Si, Cu(In, Ga)Se₂, and other traditional solar cells materials. To produce SnSₓ layers, the modified successive ionic layer adsorption and reaction (SILAR) technique were investigated, including successive cyclic dipping into Na₂S solution and SnCl₂, NaCl, triethanolamine solution. To fabricate CZTS layers, the cyclic dipping into CuSO₄ with ZnSO₄, SnCl₂, and Na₂S solutions was used with intermediate rinsing in distilled water. The nano-template aluminum/alumina substrate was used to control deposition processes. Micromorphology and optical characteristics of the fabricated layers have been investigated. Analysis of 2D-like layers deposition features using nano-template substrate is presented, including the effect of nanotips in a template on surface charge redistribution and transport.

Keywords: kesterite, nanotemplate, SILAR, solar cell, tin sulphide

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1359 Investigation of the Controversial Immunomodulatory Potential of Trichinella spiralis Excretory-Secretory Products versus Extracellular Vesicles Derived from These Products in vitro

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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1358 The “Buffer Layer” An Improved Electrode-Electrolyte Interface For Solid-State Batteries

Authors: Gregory Schmidt

Abstract:

Solid-state lithium batteries are broadly accepted as promising candidates for application in the next generation of EVs as they should offer safer and higher-energy-density batteries. Nonetheless, their development is impeded by many challenges, including the resistive electrode–electrolyte interface originating from the removal of the liquid electrolyte that normally permeates through the porous cathode and ensures efficient ionic conductivity through the cell. One way to tackle this challenge is by formulating composite cathodes containing solid ionic conductors in their structure, but this approach will require the conductors to exhibit chemical stability, electrochemical stability, flexibility, and adhesion and is, therefore, limited to some materials. Recently, Arkema developed a technology called buffering layer which allows the transformation of any conventional porous electrode into a catholyte. This organic layer has a very high ionic conductivity at room temperature, is compatible with all active materials, and can be processed with conventional Gigafactory equipment. Moreover, this layer helps protect the solid ionic conductor from the cathode and anode materials. During this presentation, the manufacture and the electrochemical performance of this layer for different systems of cathode and anode will be discussed.

Keywords: electrochemistry, all solid state battery, materials, interface

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1357 Fluoride-Induced Stress and Its Association with Bone Developmental Pathway in Osteosarcoma Cells

Authors: Deepa Gandhi, Pravin K. Naoghare, Amit Bafana, Krishnamurthi Kannan, Saravanadevi Sivanesana

Abstract:

Oxidative stress is known to depreciate normal functioning of osteoblast cells. Present study reports oxidative/inflammatory signatures in fluoride exposed human osteosarcoma (HOS) cells and its possible association with the genes involved in bone developmental pathway. Microarray analysis was performed to understand the possible molecular mechanisms of stress-mediated bone lose in HOS cells. Cells were chronically exposed with sub-lethal concentration of fluoride. Global gene expression is profiling revealed 34 up regulated and 2598 down-regulated genes, which were associated with several biological processes including bone development, osteoblast differentiation, stress response, inflammatory response, apoptosis, regulation of cell proliferation. Microarray data were further validated through qRT-PCR and western blot analyses using key representative genes. Based on these findings, it can be proposed that chronic exposure of fluoride may impair bone development via oxidative and inflammatory stress. The present finding also provides important biological clues, which will be helpful for the development of therapeutic targets against diseases related bone.

Keywords: bone, HOS cells, microarray, stress

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1356 Small Molecule Inhibitors of PD1-PDL1 Interaction

Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

Abstract:

Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

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1355 Breast Cancer Early Recognition, New Methods of Screening, and Analysis

Authors: Sahar Heidary

Abstract:

Breast cancer is a main public common obstacle global. Additionally, it is the second top reason for tumor death across women. Considering breast cancer cure choices can aid private doctors in precaution for their patients through future cancer treatment. This article reviews usual management centered on stage, histology, and biomarkers. The growth of breast cancer is a multi-stage procedure including numerous cell kinds and its inhibition residues stimulating in the universe. Timely identification of breast cancer is one of the finest methods to stop this illness. Entirely chief therapeutic administrations mention screening mammography for women aged 40 years and older. Breast cancer metastasis interpretations for the mainstream of deaths from breast cancer. The discovery of breast cancer metastasis at the initial step is essential for managing and estimate of breast cancer development. Developing methods consuming the exploration of flowing cancer cells illustrate talented outcomes in forecasting and classifying the initial steps of breast cancer metastasis in patients. In public, mammography residues are the key screening implement though the efficiency of medical breast checks and self-checkup is less. Innovative screening methods are doubtful to exchange mammography in the close upcoming for screening the overall people.

Keywords: breast cancer, screening, metastasis, methods

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1354 Acute Toxic Effects of Zn(SO4) on Gill and Liver Tissues of Fresh Water Catfish Clarias batrachus (L.)

Authors: Muneesh Kumar, Rajesh Kumar, Sangeeta Devi

Abstract:

Heavy metals are a major problem because they are toxic and tend to accumulate in living organisms. This study was carried out with the aims of studying on histopathology of Zn(SO4) toxicity on gill and liver tissues of catfish (Clarias batrachus) within the period of 96 h. Totally, 140 fishes with mean weight 50±10 g were stocked in 12 aquariums with capacity of 200 L water and divided in to 3 trails including control, 4 ppm and 8 ppm of Zn with 3 replicates. Tissue samples were fixed by bouin’s solution and sectioned in 7 μm based on histological regular method and stained with Hematoxylin and Eosin (H&E) method for microscopic study within the period of 96 h. Results showed some damaged such as hyperplasia, telangiectasis and edema, necrosis of second filaments, jerky movement, aneurism, hyperemia and fusion of second filaments in gills; and cell atrophy, necrosis, fatty degeneration, hyperemia and bile stagnation at different treatments in comparison with control. Gill and liver tissue damages were severed with the increase of Zn concentration and days. Therefore, Zn had acute toxicity effects on gill and liver tissues in Catfish at 5 and 10 ppm concentrations.

Keywords: gill, liver, histopathology, zinc, Clarias batrachus

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1353 In vivo Spectroscopic Study on the Effects of Ionising and Non-Ionising Radiation on Some Biophysical Properties of Rat Blood

Authors: S. H. Allehyani, H. S. Ibrahim, F. M. Ali, E. Sayd, T. Abou Aiad

Abstract:

The present study aimed to analyse the radiation risk associated with the exposure of haemoglobin (Hb) of rat red blood cells (rbcs) exposed to a 50-Hz 6-kV/m electric field, a fast neutron dose of 1 mSv, and mixed radiation from fast neutrons and an electric field distributed over a period of three weeks at a rate of 5 days/week and 8 hours/day. The dielectric measurements and the absorption spectra for the haemoglobin molecule in the frequency range of 1 kHz to 5 MHz were measured for all of the samples. The dielectric relaxation results demonstrated an increase in the dielectric increment (∆ε) for the rbcs from all of the irradiated animals, which indicates an increase in the electric dipole. Moreover, the results revealed a decrease in the relaxation time (τ) and the molecular radius (r) of the irradiated molecules, which indicates that the increase in ∆ε is mainly due to a pronounced increase in the centre of mass of the charge on the electric dipole of the Hb molecule. The results from the absorption spectra indicate that the ratio of met-haemoglobin to oxy-haemoglobin is altered by irradiation. Moreover, the results from the delayed effect studies show that the structure and function of the newly generated Hb molecules are altered and dissimilar to that of healthy Hb.

Keywords: rat red blood cell haemoglobin, dielectric properties, absorption spectra, biochemical analysis

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1352 Industrial Waste Multi-Metal Ion Exchange

Authors: Thomas S. Abia II

Abstract:

Intel Chandler Site has internally developed its first-of-kind (FOK) facility-scale wastewater treatment system to achieve multi-metal ion exchange. The process was carried out using a serial process train of carbon filtration, pH / ORP adjustment, and cationic exchange purification to treat dilute metal wastewater (DMW) discharged from a substrate packaging factory. Spanning a trial period of 10 months, a total of 3,271 samples were collected and statistically analyzed (average baseline + standard deviation) to evaluate the performance of a 95-gpm, multi-reactor continuous copper ion exchange treatment system that was consequently retrofitted for manganese ion exchange to meet environmental regulations. The system is also equipped with an inline acid and hot caustic regeneration system to rejuvenate exhausted IX resins and occasionally remove surface crud. Data generated from lab-scale studies was transferred to system operating modifications following multiple trial-and-error experiments. Despite the DMW treatment system failing to meet internal performance specifications for manganese output, it was observed to remove the cation notwithstanding the prevalence of copper in the waste stream. Accordingly, the average manganese output declined from 6.5 + 5.6 mg¹L⁻¹ at pre-pilot to 1.1 + 1.2 mg¹L⁻¹ post-pilot (83% baseline reduction). This milestone was achieved regardless of the average influent manganese to DMW increasing from 1.0 + 13.7 mg¹L⁻¹ at pre-pilot to 2.1 + 0.2 mg¹L⁻¹ post-pilot (110% baseline uptick). Likewise, the pre-trial and post-trial average influent copper values to DMW were 22.4 + 10.2 mg¹L⁻¹ and 32.1 + 39.1 mg¹L⁻¹, respectively (43% baseline increase). As a result, the pre-trial and post-trial average copper output values were 0.1 + 0.5 mg¹L⁻¹ and 0.4 + 1.2 mg¹L⁻¹, respectively (300% baseline uptick). Conclusively, the operating pH range upstream of treatment (between 3.5 and 5) was shown to be the largest single point of influence for optimizing manganese uptake during multi-metal ion exchange. However, the high variability of the influent copper-to-manganese ratio was observed to adversely impact the system functionality. The journal herein intends to discuss the operating parameters such as pH and oxidation-reduction potential (ORP) that were shown to influence the functional versatility of the ion exchange system significantly. The literature also proposes to discuss limitations of the treatment system such as influent copper-to-manganese ratio variations, operational configuration, waste by-product management, and system recovery requirements to provide a balanced assessment of the multi-metal ion exchange process. The take-away from this literature is intended to analyze the overall feasibility of ion exchange for metals manufacturing facilities that lack the capability to expand hardware due to real estate restrictions, aggressive schedules, or budgetary constraints.

Keywords: copper, industrial wastewater treatment, multi-metal ion exchange, manganese

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1351 Study of Effective Parameters on Mechanical Properties of Toughened PP Compounds in Presence of Biofillers and Blowing Agents

Authors: Koosha Rezaei, Mehdi Moghri bidgoli, Mazyar Khakpour

Abstract:

Wood-plastic composites foam is one of the most used products were the industry today. In this study, composite foam polypropylene in the presence of different biofilers such as Spruce wood, wheat and rice husk as well as 3 different types toughening agents such as polyolefin elastomer, styrene butadiene styrene and styrene-ethylene butadiene styrene, and two types of cause blowing agents azodicarbonamide and sodium bicarbonate was prepared. For improving dispersion of biofilers, in the mixing process we used polypropylene coupling agent grafted with maleic anhydride. Due to the large number of variables, the statistical analysis of response surface to analyze the results of the impact test, tensile modulus and tensile strength and modeling were used. Co-rotating twine extruder was made composite melt mixing method and then to perform mechanical tests using injection molding, respectively.Images from electron microscopy showed cell sandwich structure in composite amply demonstrates.

Keywords: polypropylene, wood plastic composite foam, response surface analysis, morphology, mechanical properties

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1350 Chronic Impact of Silver Nanoparticle on Aerobic Wastewater Biofilm

Authors: Sanaz Alizadeh, Yves Comeau, Arshath Abdul Rahim, Sunhasis Ghoshal

Abstract:

The application of silver nanoparticles (AgNPs) in personal care products, various household and industrial products has resulted in an inevitable environmental exposure of such engineered nanoparticles (ENPs). Ag ENPs, released via household and industrial wastes, reach water resource recovery facilities (WRRFs), yet the fate and transport of ENPs in WRRFs and their potential risk in the biological wastewater processes are poorly understood. Accordingly, our main objective was to elucidate the impact of long-term continuous exposure to AgNPs on biological activity of aerobic wastewater biofilm. The fate, transport and toxicity of 10 μg.L-1and 100 μg.L-1 PVP-stabilized AgNPs (50 nm) were evaluated in an attached growth biological treatment process, using lab-scale moving bed bioreactors (MBBRs). Two MBBR systems for organic matter removal were fed with a synthetic influent and operated at a hydraulic retention time (HRT) of 180 min and 60% volumetric filling ratio of Anox-K5 carriers with specific surface area of 800 m2/m3. Both reactors were operated for 85 days after reaching steady state conditions to develop a mature biofilm. The impact of AgNPs on the biological performance of the MBBRs was characterized over a period of 64 days in terms of the filtered biodegradable COD (SCOD) removal efficiency, the biofilm viability and key enzymatic activities (α-glucosidase and protease). The AgNPs were quantitatively characterized using single-particle inductively coupled plasma mass spectroscopy (spICP-MS), determining simultaneously the particle size distribution, particle concentration and dissolved silver content in influent, bioreactor and effluent samples. The generation of reactive oxygen species and the oxidative stress were assessed as the proposed toxicity mechanism of AgNPs. Results indicated that a low concentration of AgNPs (10 μg.L-1) did not significantly affect the SCOD removal efficiency whereas a significant reduction in treatment efficiency (37%) was observed at 100 μg.L-1AgNPs. Neither the viability nor the enzymatic activities of biofilm were affected at 10 μg.L-1AgNPs but a higher concentration of AgNPs induced cell membrane integrity damage resulting in 31% loss of viability and reduced α-glucosidase and protease enzymatic activities by 31% and 29%, respectively, over the 64-day exposure period. The elevated intercellular ROS in biofilm at a higher AgNPs concentration over time was consistent with a reduced biological biofilm performance, confirming the occurrence of a nanoparticle-induced oxidative stress in the heterotrophic biofilm. The spICP-MS analysis demonstrated a decrease in the nanoparticles concentration over the first 25 days, indicating a significant partitioning of AgNPs into the biofilm matrix in both reactors. The concentration of nanoparticles increased in effluent of both reactors after 25 days, however, indicating a decreased retention capacity of AgNPs in biofilm. The observed significant detachment of biofilm also contributed to a higher release of nanoparticles due to cell-wall destabilizing properties of AgNPs as an antimicrobial agent. The removal efficiency of PVP-AgNPs and the biofilm biological responses were a function of nanoparticle concentration and exposure time. This study contributes to a better understanding of the fate and behavior of AgNPs in biological wastewater processes, providing key information that can be used to predict the environmental risks of ENPs in aquatic ecosystems.

Keywords: biofilm, silver nanoparticle, single particle ICP-MS, toxicity, wastewater

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1349 A Clinical Cutoff to Identify Metabolically Unhealthy Obese and Normal-Weight Phenotype in Young Adults

Authors: Lívia Pinheiro Carvalho, Luciana Di Thommazo-Luporini, Rafael Luís Luporini, José Carlos Bonjorno Junior, Renata Pedrolongo Basso Vanelli, Manoel Carneiro de Oliveira Junior, Rodolfo de Paula Vieira, Renata Trimer, Renata G. Mendes, Mylène Aubertin-Leheudre, Audrey Borghi-Silva

Abstract:

Rationale: Cardiorespiratory fitness (CRF) and functional capacity in young obese and normal-weight people are associated with metabolic and cardiovascular diseases and mortality. However, it remains unclear whether their metabolically healthy (MH) or at risk (AR) phenotype influences cardiorespiratory fitness in this vulnerable population such as obese adults but also in normal-weight people. HOMA insulin resistance index (HI) and leptin-adiponectin ratio (LA) are strong markers for characterizing those phenotypes that we hypothesized to be associated with physical fitness. We also hypothesized that an easy and feasible exercise test could identify a subpopulation at risk to develop metabolic and related disorders. Methods: Thirty-nine sedentary men and women (20-45y; 18.530 kg.m-2) underwent a clinical evaluation, including the six-minute step test (ST), a well-validated and reliable test for young people. Body composition assessment was done by a tetrapolar bioimpedance in a fasting state and in the folicular phase for women. A maximal cardiopulmonary exercise testing, as well as the ST, evaluated the oxygen uptake at the peak of the test (VO2peak) by an ergospirometer Oxycon Mobile. Lipids, glucose, insulin were analysed and the ELISA method quantified the serum leptin and adiponectin from blood samples. Volunteers were divided in two groups: AR or MH according to a HI cutoff of 1.95, which was previously determined in the literature. T-test for comparison between groups, Pearson´s test to correlate main variables and ROC analysis for discriminating AR from up-and-down cycles in ST (SC) were applied (p<0.05). Results: Higher LA, fat mass (FM) and lower HDL, SC, leg lean mass (LM) and VO2peak were found in AR than in MH. Significant correlations were found between VO2peak and SC (r= 0.80) as well as between LA and FM (r=0.87), VO2peak (r=-0.73), and SC (r=-0.65). Area under de curve showed moderate accuracy (0.75) of SC <173 to discriminate AR phenotype. Conclusion: Our study found that at risk obese and normal-weight subjects showed an unhealthy metabolism as well as a poor CRF and functional daily activity capacity. Additionally, a simple and less costly functional test associated with above-mentioned aspects is able to identify ‘at risk’ subjects for primary intervention with important clinical and health implications.

Keywords: aerobic capacity, exercise, fitness, metabolism, obesity, 6MST

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1348 Protective Effect of Germinated Fenugreek Seeds on Keratoachantoma Cancer Skin

Authors: Zahra Sokar, Sara Oufquir, Brahim Eddafali, Abderrahman Chait

Abstract:

Fenugreek is one of the oldest plants used in traditional herbal medicine. Several studies have demonstrated the anticancer effects of seeds by inhibiting the proliferation, angiogenesis, invasion and metastasis of various cancers. While there is plenty of research demonstrating the antineoplastic effects of dormant seeds, little is known about the potential of sprouts in fighting cancer. Therefore, we propose to study the chemoprotective effect of germinating fenugreek seeds on keratoacanthoma skin cancer induced by cutaneous exposure to DMA/Croton oil in mice. The results obtained show that oral administration of 250 and 500 mg/kg aqueous sprout seed extract reduces the incidence, rate, volume, and tumor weight in a very significant manner. Histological examination revealed that mice treated with 250 mg/kg showed strong inhibition of squamous cell carcinoma formation with thickening of the epithelial layer and mild acanthosis and hyperkeratosis. A dose of 500 mg/kg prevented invasion and the occurrence of hyperkeratosis. Fenugreek sprouts appear to be a promising natural product for preventing keratoacanthoma skin cancer. Nevertheless, further studies in the same field need to be developed to evaluate the antineoplastic potential of germinated seeds.

Keywords: anticancer, fenugreek, keratoacanthoma, sprouts

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1347 Unearthing SRSF1’s Novel Function in Binding and Unfolding of RNA G-Quadruplexes

Authors: Naiduwadura Ivon Upekala De Silva, Nathan Lehman, Talia Fargason, Trenton Paul, Zihan Zhang, Jun Zhang

Abstract:

SRSF1 governs splicing of over 1,500 mRNA transcripts. SRSF1 contains two RNA-recognition motifs (RRMs) and a C-terminal Arg/Ser-rich region (RS). It has been thought that SRSF1 RRMs exclusively recognize single-stranded exonic splicing enhancers, while RS lacks RNA-binding specificity. With our success in solving the insolubility problem of SRSF1, we can explore the unknown RNA-binding landscape of SRSF1. We find that SRSF1 RS prefers purine over pyrimidine. Moreover, SRSF1 binds to the G-quadruplex (GQ) from the ARPC2 mRNA, with both RRMs and RS being crucial. Our binding assays show that the traditional RNA-binding sites on the RRM tandem and the Arg in RS are responsible for GQ binding. Interestingly, our FRET and circular dichroism data reveal that SRSF1 unfolds the ARPC2 GQ, with RS leading unfolding and RRMs aiding. Our saturation transfer difference NMR results discover that Arg residues in SRSF1 RS interact with the guanine base but with other nucleobases, underscoring the uniqueness of the Arg/guanine interaction. Our luciferase assays confirm that SRSF1 can alleviate the inhibitory effect of GQ on gene expression in the cell. Given the prevalence of RNA GQ and SR proteins, our findings unveil unexplored SR protein functions with broad implications in RNA splicing and translation.

Keywords: SR, SRSF!, RNA G-quadruplex, unfolding, RNA binding

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1346 Optimization of Reliability and Communicability of a Random Two-Dimensional Point Patterns Using Delaunay Triangulation

Authors: Sopheak Sorn, Kwok Yip Szeto

Abstract:

Reliability is one of the important measures of how well the system meets its design objective, and mathematically is the probability that a complex system will perform satisfactorily. When the system is described by a network of N components (nodes) and their L connection (links), the reliability of the system becomes a network design problem that is an NP-hard combinatorial optimization problem. In this paper, we address the network design problem for a random point set’s pattern in two dimensions. We make use of a Voronoi construction with each cell containing exactly one point in the point pattern and compute the reliability of the Voronoi’s dual, i.e. the Delaunay graph. We further investigate the communicability of the Delaunay network. We find that there is a positive correlation and a negative correlation between the homogeneity of a Delaunay's degree distribution with its reliability and its communicability respectively. Based on the correlations, we alter the communicability and the reliability by performing random edge flips, which preserve the number of links and nodes in the network but can increase the communicability in a Delaunay network at the cost of its reliability. This transformation is later used to optimize a Delaunay network with the optimum geometric mean between communicability and reliability. We also discuss the importance of the edge flips in the evolution of real soap froth in two dimensions.

Keywords: Communicability, Delaunay triangulation, Edge Flip, Reliability, Two dimensional network, Voronio

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1345 Biological Activity of Mesenchymal Stem Cells in the Surface of Implants

Authors: Saimir Heta, Ilma Robo, Dhimiter Papakozma, Eduart Kapaj, Vera Ostreni

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Introduction: The biocompatible materials applied to the implant surfaces are the target of recent literature studies. Methodologies: Modification of implant surfaces in different ways such as application of additional ions, surface microstructure change, surface or laser ultrasound alteration, or application of various substances such as recombinant proteins are among the most affected by articles published in the literature. The study is of review type with the main aim of finding the different ways that the mesenchymal cell reaction to these materials is, according to the literature, in the same percentage positive to the osteointegration process. Results: It is emphasized in the literature that implant success as a key evaluation key has more to implement implant treatment protocol ranging from dental health amenity and subsequent of the choice of implant type depending on the alveolar shape of the ridge level. Conclusions: Osteointegration is a procedure that should initially be physiologically independent of the type of implant pile material. With this physiological process, it can not "boast" for implant success or implantation depending on the brand of the selected implant, as the breadth of synthetic or natural materials that promote osteointegration is relatively large.

Keywords: mesenchymal cells, implants, review, biocompatible materials

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1344 FTIR and AFM Properties of Doubly Doped Tin Oxide Thin Films Prepared by Spin Coating Technique

Authors: Bahattin Duzgun, Adem Kocyigit, Demet Tatar, Ahmet Battal

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Tin oxide thin films are semiconductor materials highly transparent and with high mechanical and chemical stability, except for their interactions with oxygen atoms at high temperature. Many dopants, such as antimony (Sb), arsenic (As), fluorine (F), indium (In), molybdenum and (Mo) etc. have been used to improve the electrical properties of tin oxide films. Among these, Sb and F are found to be the most commonly used dopants for solar cell layers. Also Tin oxide tin films investigated and characterized by researchers different film deposition and analysis method. In this study, tin oxide thin films are deposited on glass substrate by spin coating technique and characterized by FTIR and AFM. FTIR spectroscopy revealed that all films have O-Sn-O and Sn-OH vibration bonds not changing with layer effect. AFM analysis indicates that all films are homogeneity and uniform. It can be seen that all films have needle shape structure in their surfaces. Uniformity and homogeneity of the films generally increased for increasing layers. The results found in present study showed that doubly doped SnO2 thin films is a good candidate for solar cells and other optoelectronic and technological applications.

Keywords: doubly doped, spin coating, FTIR analysis, AFM analysis

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1343 Mass Production of Endemic Diatoms in Polk County, Florida Concomitant with Biofuel Extraction

Authors: Melba D. Horton

Abstract:

Algae are identified as an alternative source of biofuel because of their ubiquitous distribution in aquatic environments. Diatoms are unique forms of algae characterized by silicified cell walls which have gained prominence in various technological applications. Polk County is home to a multitude of ponds and lakes but has not been explored for the presence of diatoms. Considering the condition of the waters brought about by predominant phosphate mining activities in the area, this research was conducted to determine if endemic diatoms are present and explore their potential for low-cost mass production. Using custom-built photobioreactors, water samples from various lakes provided by the Polk County Parks and Recreation and from nearby ponds were used as the source of diatoms together with other algae obtained during collection. Results of the initial culture cycles were successful, but later an overgrowth of other algae crashed the diatom population. Experiments were conducted in the laboratory to tease out some factors possibly contributing to the die-off. Generally, the total biomass declines after two culture cycles and the causative factors need further investigation. The lipid yield is minimum; however, the high frustule production after die-off adds value to the overall benefit of the harvest.

Keywords: diatoms, algae, biofuel, lipid, photobioreactor, frustule

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1342 Effects of Plasma Treatment on Seed Germination

Authors: Yong Ho Jeon, Youn Mi Lee, Yong Yoon Lee

Abstract:

Effects of cold plasma treatment on various plant seed germination were studied. The seeds of hot pepper, cucumber, tomato and arabidopsis were exposed to plasma and the plasma was generated in various devices. The germination speed was evaluated compared to an unexposed control. A positive effect on germination speed was observed in all tested seeds but the effects strongly depended on the type of the used plasma device (Argon-DBD, surface-DBD or MARX generator), time of exposure (6s~10min or 1~10shots) and kind of seeds. The SEM images showed that arrays of gold particles along the cell wall were observed on the surface of cucumber seeds showed a germination-accelerating effect by plasma treatment, which was the same as untreated. However, when treated with the high dose plasma, gold particles were not arrayed at the seed surface, it seems that due to the surface etching. This may suggest that the germination is not promoted by etching or damage of surface caused by the plasma treatment. Seedling growth improvement was also observed by indirect plasma treatment. These lead to an important conclusion that the effect of charged particles on plasma play the essential role in plant germination and indirect plasma treatment offers new perspectives for large scale application.

Keywords: cold plasma, cucumber, germination, SEM

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1341 Clinico-pathological Study of Xeroderma Pigmentosa: A Case Series of Eight Cases

Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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1340 Thidiazuron's Role in Murraya paniculata and Fortunella hindsii's in vitro Flowering

Authors: Hasan Basri Jumin, Mardaleni

Abstract:

Fortunella hindsii and Muraya paniculata are family members of Rutaceae and have potentially improved genetic diversity. Isolated protoplasts were cultured with media supplemented with 2.0 % glucose and 0.0, 0.001, 0.01, 0.1 or 1.0. 10.0 mg/1 thidiazuron (TDZ) and, thickened with 0.9% gelrite, and maintained under 16 h photoperiod at 52.9 μmol/m²/s light intensity. The media supplemented with 0.00 mg/l TDZ yielded the maximum plating efficiency, while 0.001 mg/l TDZ produced the highest percentage of shoot formation, approximately 80%. After being cultured on the same TDZ concentration for 12 days, the protoplasts that survived developed cell walls. Ninety days following the culture of protoplasts, Fortunella hindsii and Murraya paniculata underwent somatic embryogenesis to grow into plantlets. Thidiazuron has demonstrated efficacy in forming flower buds that grow normally. Fortunella hindsii and Murraya paniculata shoots that emerged from branch internodes flowered in vitro on half-strength MT basal media containing 0.001 to 0.01 mg/l TDZ and 2-3% sucrose after two months of culture, and they eventually went on to flower. Seventy five percent of the plants displayed flowering on medium supplemented with 0.001 mg/l TDZ. Among the segments of Fortunella hindsii and Murraya paniculata generated from branch internodes, a possible precocious and floral gradient was found.

Keywords: Fortunella-hindsii, in-vitro flowering, Murraya-paniculata, protoplast, thidiazuron

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1339 Synthesis and Evaluation of Antioxidant Behavior of Some Indole-Based Melatonin Derivatives

Authors: Eddy Neuhaus, Hanif Shirinzadeh, Cigdem Karaaslan, Elif Ince, Hande Gurer-Orhan, Sibel Suzen

Abstract:

Reactive oxygen species (ROS) and oxidative stress can cause fatal damage to essential cell structures, including DNA. It is known that use of antioxidants could be advantageous in the prevention of various diseases such as cancer, cardiovascular diseases and neurodegenerative disorders. Since antioxidant properties of the indole ring-containing melatonin (MLT) has been described and evaluated, MLT-related compounds such as MLT metabolites and synthetic analogues are under investigation to determine which exhibit the highest activity with the lowest side-effects. Owing to indole and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of indole-7-carbaldehyde hydrazone derivatives were synthesized, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all indole-based MLT analogues was investigated both by lactate dehydrogenase leakage assay and by MTT assay. This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) Research and Development Grant 112S599.

Keywords: melatonin, antioxidant activity, indole, hydrazone, oxidative stress

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1338 Increased Availability and Accessibility of Family Planning Services: An Approach Leading to Improved Contraceptive Uptake and Reproductive Behavior of Women Living in Pakistan

Authors: Lutaf Ali, Haris Ahmed, Hina Najmi

Abstract:

Background: Access, better counseling and quality in the provision of family planning services remain big challenges. Sukh Initiative (a project of three different foundations) is a multi-pronged approach, working in one million underserved population residing peri urban slums in Karachi and providing door to door services by lady health workers (LHWs) and community health workers (CHWs) linked with quality family planning and reproductive (FP/RH) services both at public and private health care facilities. Objective: To assess the improvement in family planning and reproductive health behavior among MWRAs by improving access in peri-urban-underserved population of Karachi. Methodology: Using cross sectional study design 3866 married women with reproductive age (MWRAs) were interviewed in peri urban region of Karachi during November 2016 to January 2017. All face to face structured interviews were conducted with women aged 15-49 currently living with their husbands. Based on the project intervention question on reproductive health were developed and questions on contraceptive use were adopted from PDHS- Pakistan 2013. Descriptive and inferential analysis was performed on SPSS version 22. Results: 65% of population sample are literate, 51% women were in young age group- 15–29. On the poverty index, 6% of the population sample living at national poverty line 1.25$ and 52% at 2.50$. During the project years 79% women opted for facility based delivery; private facilities are the priority choice. 61.7% women initiated the contraceptive use in last two years (after the project).Use of family planning was increased irrespective of education level and poverty index- about 55.5% women with no formal education are using any form of contraception and trend of current modern contraceptives across poverty scores strata equally distributed amongst all groups. Age specific modern contraceptive prevalence rate (mCPR)(between 25-34) was found to be 43.8%. About 23% of this contraceptive ascertained from door to door services- short acting, (pills and condoms) are common, 29.5% from public facilities and 47.6% are from public facilities in which long acting and permanent method most received methods. Conclusion: Strategy of expanding access and choice in the form of providing family planning information and supplies at door step and availability of quality family planning services in the peripheries of underserved may improve the behavior of women regarding FP/RH.

Keywords: access, family planning, underserved population, socio-demographic facts

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1337 Evaluation of Long Term Evolution Mobile Signal Propagation Models and Vegetation Attenuation in the Livestock Department at Escuela Superior Politécnica de Chimborazo

Authors: Cinthia Campoverde, Mateo Benavidez, Victor Arias, Milton Torres

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This article evaluates and compares three propagation models: the Okumura-Hata model, the Ericsson 9999 model, and the SUI model. The inclusion of vegetation attenuation in the area is also taken into account. These mathematical models aim to predict the power loss between a transmitting antenna (Tx) and a receiving antenna (Rx). The study was conducted in the open areas of the Livestock Department at the Escuela Superior Politécnica de Chimborazo (ESPOCH) University, located in the city of Riobamba, Ecuador. The necessary parameters for each model were calculated, considering LTE technology. The transmitting antenna belongs to the mobile phone company ”TUENTI” in Band 2, operating at a frequency of 1940 MHz. The reception power data in the area were empirically measured using the ”Network Cell Info” application. A total of 170 samples were collected, distributed across 19 radius, forming concentric circles around the transmitting antenna. The results demonstrate that the Okumura Hata urban model provides the best fit to the measured data.

Keywords: propagation models, reception power, LTE, power losses, correction factor

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1336 Silk Fibroin-PVP-Nanoparticles-Based Barrier Membranes for Tissue Regeneration

Authors: Ivone R. Oliveira, Isabela S. Gonçalves, Tiago M. B. Campos, Leandro J. Raniero, Luana M. R. Vasconcellos, João H. Lopes

Abstract:

Originally, the principles of guided tissue/bone regeneration (GTR/GBR) were followed to restore the architecture and functionality of the periodontal system. In essence, a biocompatible polymer-based occlusive membrane is used as a barrier to prevent migration of epithelial and connective tissue to the regenerating site. In this way, progenitor cells located in the remaining periodontal ligament can recolonize the root area and differentiate into new periodontal tissues, alveolar bone, and new connective attachment. The use of synthetic or collagen-derived membranes with or without calcium phosphate-based bone graft materials has been the treatment used. Ideally, these membranes need to exhibit sufficient initial mechanical strength to allow handling and implantation, withstand the various mechanical stresses suffered during surgery while maintaining their integrity, and support the process of bone tissue regeneration and repair by resisting cellular traction forces and wound contraction forces during tissue healing in vivo. Although different RTG/ROG products are available on the market, they have serious deficiencies in terms of mechanical strength. Aiming to improve the mechanical strength and osteogenic properties of the membrane, this work evaluated the production of membranes that integrate the biocompatibility of the natural polymer (silk fibroin - FS) and the synthetic polymer poly(vinyl pyrrolidone - PVP) with graphene nanoplates (NPG) and gold nanoparticles (AuNPs), using the electrospinning equipment (AeroSpinner L1.0 from Areka) which allows the execution of high voltage spinning and/or solution blowing and with a high production rate, enabling development on an industrial scale. Silk fibroin uniquely solved many of the problems presented by collagen and was used in this work because it has unique combined merits, such as programmable biodegradability, biocompatibility and sustainable large-scale production. Graphene has attracted considerable attention in recent years as a potential biomaterial for mechanical reinforcement because of its unique physicochemical properties and was added to improve the mechanical properties of the membranes associated or not with the presence of AuNPs, which have shown great potential in regulating osteoblast activity. The preparation of FS from silkworm cocoons involved cleaning, degumming, dissolution in lithium bromide, dialysis, lyophilization and dissolution in hexafluoroisopropanol (HFIP) to prepare the solution for electrospinning, and crosslinking tests were performed in methanol. The NPGs were characterized and underwent treatment in nitric acid for functionalization to improve the adhesion of the nanoplates to the PVP fibers. PVP-NPG membranes were produced with 0.5, 1.0 and 1.5 wt% functionalized or not and evaluated by SEM/FEG, FTIR, mechanical strength and cell culture assays. Functionalized GNP particles showed stronger binding, remaining adhered to the fibers. Increasing the graphene content resulted in higher mechanical strength of the membrane and greater biocompatibility. The production of FS-PVP-NPG-AuNPs hybrid membranes was performed by electrospinning in separate syringes and simultaneously the FS solution and the solution containing PVP-NPG 1.5 wt% in the presence or absence of AuNPs. After cross-linking, they were characterized by SEM/FEG, FTIR and behavior in cell culture. The presence of NPG-AuNPs increased the viability and the presence of mineralization nodules.

Keywords: barrier membranes, silk fibroin, nanoparticles, tissue regeneration.

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1335 Physicochemical Properties, Antioxidant and Cytotoxic Activities of Extracts and Fractions from Phyllanthus amarus

Authors: Van Tang Nguyen, Jennette A. Sakoff, Christopher J. Scarlett

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Phyllanthus amarus (P. amarus) has been used as a traditional herbal plant for the treatment of chronic ailments such as hepatitis, diabetes and cancer. The objectives of this study were to determine the physicochemical properties, antioxidant and cytotoxic activities of crude P. amarus extracts and fractions using MTT and CCK-8 assays for cytotoxic evaluation. The outcomes indicated that P. amarus methanol (PAM) extract had lower residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents/g dried extract, respectively) than those of P. amarus water (PAW) extract, resulting antioxidant activity of PAM extract was significantly higher (P < 0.05) than that of PAW extract, PAM fractions and phyllanthin (a major compound in P. amarus). Cytotoxic activity of PAM extract for cancer cell lines of MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was higher than those of PAW extract and PAM fractions. Therefore, we can conclude that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs.

Keywords: antioxidant, cytotoxicity, Phyllanthus amarus, physicochemical

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1334 New Strategy for Breeding of Artemisia annua L. for a Sustainable Production of the Antimalarial Drug Artemisinin

Authors: Nadali Babaeian Jelodar, Chan Lai Keng, Arvind Bhatt, Laleh Bordbar, Leow E Shuen, Kamaruzaman Mohamed

Abstract:

Recently artemisinin (the endoperoxide sesquiterpene lactone) has received considerable attention because of its antimalarial activity. It is isolated from the aerial part of the Artemisia annua L. Artemisinin is very difficult to synthesise also its production by mean of cell, tissue or organ cultures is very low. Presently, only its extraction from A. annua L. plants remains the only source of the drug. The reported yield of artemisinin from leaves of A. annua L. is very low and unstable, with yields typically less than 1% of leaf dry weight. To increase the percentage of artemisinin, researchers have been engaged in developing new varieties. A review concerning the breeding of A. annua L. is presented. The aim of this review is to bring together most of the available scientific research papers about the breeding conducted on the genus A. annua L., which is currently scattered across various publications. Through this review the authors hope to attract the attention of breeders throughout the world to focus on the unexplored potential of A. annua L. species. Also the future scope of this plant has been emphasized with a view of the importance of breeding of A. annua L. for increasing of artemisinin content. By releasing of new cultivar of A. annua L. and cultivation of this plant offers the opportunity to optimize yield and achieve a uniform, high quality product.

Keywords: Artemisia annua L., breeding, artemisinin, cultivation, medicinal plant

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1333 Dexamethasone: Impact on Testicular Activity

Authors: Sadi-Guettaf Hassiba, Hadj-Bekkouche Fatima

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Dexamethasone (Dex) is a synthetic glucocorticoid that is used in therapy. However prolonged treatments with high doses are often required. This causes side effects that interfere with the activity of several endocrine systems, including the gonadotropic axis. The aim of our study is to determine the effect of Dex on testicular function in prepubertal Wistar rats. Newborn Wistar rats are submitted to intraperitoneal injection of Dex (1μg of Dex dissolved in NaCl 0.9% / 5g bw) for 20 days and then sacrificed at the age of 40days. A control group received NaCl 0.9%. The rat is weighed daily. The plasmatic levels of testosterone, LH and FSH were measured by radioimmunoassay. A histo-morphometric study was performed on sections of testis. Treated groups showed a significant decrease in body weight (p < 0.05), testis weight (p < 0.05) and plasma levels of testosterone (p < 0.05), of LH (P < .05) and FSH (p> 0.05). There is a reduction of seminiferous tubules average diameter and also of the seminiferous epithelium thickness with an increasing of lumen tubular. The diameter of the Leydig cells and Sertoli cell nucleus is also significantly reduced. Spermatogenesis is blocked at the stage round spermatid unlike witnesses or elongated spermatid stage is found. These results suggest that Dex administered during neonatal life influences testicular activity in the long term.

Keywords: dexamethasone, FSH, LH, rat, testis, testosterone

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1332 Synthesis, Characterization, and Biological Evaluation of 1,3,4-Mercaptooxadiazole Ether Derivatives Analogs as Antioxidant, Cytotoxic, and Molecular Docking Studies

Authors: Desta Gebretekle Shiferaw, Balakrishna Kalluraya

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Oxadiazoles and their derivatives with thioether functionalities represent a new and exciting class of physiologically active heterocyclic compounds. Several molecules with these moieties play a vital role in pharmaceuticals because of their diverse biological activities. This paper describes a new class of 1,3,4- oxadiazole-2-thioethers with acetophenone, coumarin, and N-phenyl acetamide residues (S-alkylation), with the hope that the addition of various biologically active molecules will have a synergistic effect on anticancer activity. The structure of the synthesized title compounds was determined by the combined methods of IR, proton-NMR, carbon-13-NMR, and mass spectrometry. Further, all the newly prepared molecules were assessed against their antioxidant activity. Furthermore, four compounds were assessed for their molecular docking interactions and cytotoxicity activity. The synthesized derivatives have shown moderate antioxidant activity compared to the standard BHA. The IC50 of the tilted molecules (11b, 11c, 13b, and 14b) observed for in vitro anti-cancer activities were 11.20, 15.73, 59.61, and 27.66 g/ml at 72-hour treatment time against the A549 cell lines, respectively. The tested compounds' biological evaluation showed that 11b is the most effective molecule in the series.

Keywords: antioxidant activity, cytotoxicity activity, molecular docking, 1, 3, 4-Oxadiazole-2 thioether derivatives

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