Search results for: biochemical pathway
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1538

Search results for: biochemical pathway

668 Spatial-Temporal Characteristics of Bacterioplankton in the Upper Part of Taktakorpu Water Complex

Authors: Fidan Z. Aliyeva

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In the presented article, the formation of the microbiological regime in the Takhtakorpu water complex, as well as spatial-temporal changes in the quantitative indicators of bacterioplankton, were studied. Taktakorpu water complex was built as a continuation of the reconstruction and expansion project of the Samur-Absheron irrigation system in Shabran on the northeastern slope of our republic. It should be noted that with the implementation of the project, the water supply of up to 150 thousand ha of useful land in the northern region has been improved, and the drinking, technical, and irrigation water needs of the population of Baku, Sumgayit and also the Absheron Peninsula, and industrial and agricultural areas, joining the agricultural circulation of new soil areas, Takhtakorpu reservoir with a volume of 238.4 million m³, connected with them -Valvalachay- Takhtakorpu and Takhtakorpu-Jeyranbatan canals have been created, conditions have been created to increase the resources of the Jeyranbatan reservoir. Special attention is paid to the study of saprophytic bacteria in order to determine the development dynamics and biochemical activity of the microbiological regime in the Takhtakorpu Water Complex, which is of great strategic importance for our republic, to evaluate changes under the influence of anthropogenic factors, as well as to evaluate the properties of self-cleaning, mineralization features of organic substances of allochthon and autochthonous origin. One of the main goals of our research is to determine the main structural indicators of bacterioplankton in the upper part of Takhtakorpu water complex in the first three stations and analyzing their quantitative values in a certain time aspect.

Keywords: water, irrigation, sewage, wastewater

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667 Action Potential of Lateral Geniculate Neurons at Low Threshold Currents: Simulation Study

Authors: Faris Tarlochan, Siva Mahesh Tangutooru

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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

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666 In silico Analysis towards Identification of Host-Microbe Interactions for Inflammatory Bowel Disease Linked to Reactive Arthritis

Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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665 Correlation between Copper Uptake and Decrease of Copper (Hypocupremia) in Burn Patients-Infected Pseudomonas aeruginosa

Authors: Khaled M. Khleifat

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Pseudomonas aeruginosa was isolated from infected burn patients and characterized by standard biochemical tests. The in vitro copper uptake was compared between this isolated pathogenic strain and two non-pathogenic control strains of Gram-positive bacteria Bacillusthuringiensis strain Israelisas well as Gram-negative bacteria Enterobacter aerogenes. Maximum copper uptake of 470 ppm/g biomass was obtained by P. aeruginosa strain, while the control strains B. thuringiensis and Enterobacter aerogenes had copper uptake of 350 and 383 ppm/g biomass, respectively. However, the lowest copper uptake (60 ppm/g biomass) was observed with another control the saprophytic strain Pseudomonas (Shewanella) putrefaciens. A further investigation regarding the effect of copper toxicity on bacterial growth, gave an MIC score of 600 ppm for P. aeruginosa strain compared to 460 and 300 ppm for the two Gram positive and Gram negative control strains, respectively. In tandem with these in vitro findings, blood analysis on burn patients infected with P. aeruginosa has indicated a selective decrease of copper (hypocupremia) and ceruloplasmin plasma levels. The iron metabolism was also affected by this copper deprivation leading to a similar decrease in plasma levels of PCV, iron, total iron-binding capacity, and transferrin. All these hematological changes were significantly different (P < 0.05) from the matched group of non-infected burn patients. The observed hypocupremia in infected burn patients was attributed to demanding scavenger ability by P. aeruginosa strain for the copper of plasma.

Keywords: Pseudomonas aeruginosa, hypocupremia, correlation, PCV

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664 Structural Protein-Protein Interactions Network of Breast Cancer Lung and Brain Metastasis Corroborates Conformational Changes of Proteins Lead to Different Signaling

Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

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663 Origanum vulgare as a Possible Modulator of Testicular Endocrine Function in Mice

Authors: Eva Tvrdá, Barbora Babečková, Michal Ďuračka, Róbert Kirchner, Július Árvay

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This study was designed to assess the in vitro effects of Origanum vulgare L. (oregano) extract on the testicular steroidogenesis. We focused on identifying major biomolecules present in the oregano extract, as well as to investigate its in vitro impact on the secretion of cholesterol, testosterone, dehydroepiandrosterone and androstenedione by murine testicular fragments. The extract was subjected to high performance liquid chromatography (HPLC) which identified cyranosid, daidzein, thymol, rosmarinic and trans-caffeic acid among the predominant biochemical components of oregano. For the in vitro experiments, testicular fragments from 20 sexually mature Institute of Cancer Research (ICR) mice were incubated in the absence (control group) or presence of the oregano extract at selected concentrations (10, 100 and 1000 μg/mL) for 24 h. Cholesterol levels were quantified using photometry and the hormones were assessed by ELISA (Enzyme-Linked Immunosorbent Assay). Our data revealed that the release of cholesterol and androstenedione (but not dehydroepiandrosterone and testosterone) by the testicular fragments was significantly impacted by the oregano extract in a dose-dependent fashion. Supplementation of the extract resulted in a significant decline of cholesterol (P < 0.05 in case of 100 μg/mL; P < 0.01 with respect 100 μg/mL extract), as well as androstenedione (P < 0.01 with respect to 100 and 1000 μg/mL extract). Our results suggest that the biomolecules present in Origanum vulgare L. could exhibit a dose-dependent impact on the secretion of male steroids, playing a role in the regulation of testicular steroidogenesis.

Keywords: mice, Origanum vulgare L., steroidogenesis, testes

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662 Apoptosis Inducing Potential of Onosma Bracteata Wall. in Mg-63 Human Osteosarcoma Cells via cdk2/Cyclin E Pathway

Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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661 Hepatoprotective Effects of Parsley, Basil, and Chicory Aqueous Extracts against Dexamethasone-Induced in Experimental Rats

Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

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Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

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660 MiR-200a/ZEB1 Pathway in Liver Fibrogenesis of Biliary Atresia

Authors: Hai-Ying Liu, Yi-Hao Chen, Shu-Yin Pang, Feng-Hua Wang, Xiao-Fang Peng, Li-Yuan Yang, Zheng-Rong Chen, Yi Chen, Bing Zhu

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Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

Keywords: biliary atresia, liver fibrosis, MicroRNA, epithelial-mesenchymal transition, zinc finger E-box-binding homeobox 1

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659 Traumatic Osteoarthritis Induces Mechanical Hyperalgesia through IL-1β/TNF-α-Mediated Upregulation of the Sema4D Gene Expression

Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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658 Characterization of White Spot Lesion Using Focused Ion Beam - Scanning Electron Microscopy

Authors: Malihe Moeinin, Robert Hill, Ferranti Wong

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Background: A white spot lesion (WSL) is defined as subsurface enamel porosity from carious demineralisation on the smooth surfaces of the tooth. It appears as a milky white opacity. Lesions shown an apparently intact surface layer, followed underneath by the more porous lesion body. The small pores within the body of the lesion act as diffusion pathway for both acids and minerals, so allowing the demineralisation of enamel to occur at the advancing front of the lesion. Objectives: The objective is to mapthe porosity and its size on WSL with Focused Ion Bean- Scanning Electron Microscopy (FIB-SEM) Method: The basic method used for FIB-SEM consisted of depositing a one micron thick layer of platinum over 25μmx 25μm of the interest region of enamel. Then, making a rough cut (25μmx 5μmx 20μm) with 3nA current and 30Kv was applied with the help of drift suppression (DS), using a standard “cross-sectional” cutting pattern, which ended at the front of the deposited platinum layer. Two adjacent areas (25μmx 5μmx 20μm) on the both sides of the platinum layer were milled under the same conditions. Subsequent, cleaning cross-sections were applied to polish the sub-surface edge of interest running perpendicular to the surface. The "slice and view" was carried out overnight for milling almost 700 slices with 2Kv and 4nA and taking backscattered (BS) images. Then, images were imported into imageJ and analysed. Results: The prism structure is clearly apparent on FIB-SEM slices of WSL with the dissolution of prism boundaries as well as internal porosity within the prism itself. Porosity scales roughly 100-400nm, which is comparable to the light wavelength (500nm). Conclusion: FIB-SEM is useful to characterize the porosity of WSL and it clearly shows the difference between WSL and normal enamel.

Keywords: white spot lesion, FIB-SEM, enamel porosity, porosity

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657 Differential Expression of Biomarkers in Cancer Stem Cells and Side Populations in Breast Cancer Cell Lines

Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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656 Protective Effect of Vitamin D on Cardiac Apoptosis in Obese Rats

Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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655 Molecular Design and Synthesis of Heterocycles Based Anticancer Agents

Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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654 Kinetics and Mechanism Study of Photocatalytic Degradation Using Heterojunction Semiconductors

Authors: Ksenija Milošević, Davor Lončarević, Tihana Mudrinić, Jasmina Dostanić

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Heterogeneous photocatalytic processes have gained growing interest as an efficient method to generate hydrogen by using clean energy sources and degrading various organic pollutants. The main obstacles that restrict efficient photoactivity are narrow light-response range and high rates of charge carrier recombination. The formation of heterojunction by combining a semiconductor with low VB and a semiconductor with high CB and a suitable band gap was found to be an efficient method to prepare more sensible materials with improved charge separation, appropriate oxidation and reduction ability, and enhanced visible-light harvesting. In our research, various binary heterojunction systems based on the wide-band gap (TiO₂) and narrow bandgap (g-C₃N₄, CuO, and Co₂O₃) photocatalyst were studied. The morphology, optical, and electrochemical properties of the photocatalysts were analyzed by X-ray diffraction (XRD), scanning electron microscopy (FE-SEM), N₂ physisorption, diffuse reflectance measurements (DRS), and Mott-Schottky analysis. The photocatalytic performance of the synthesized catalysts was tested in single and simultaneous systems. The synthesized photocatalysts displayed good adsorption capacity and enhanced visible-light photocatalytic performance. The mutual interactions of pollutants on their adsorption and degradation efficiency were investigated. The interfacial connection between photocatalyst constituents and the mechanism of the transport pathway of photogenerated charge species was discussed. A radical scavenger study revealed the interaction mechanisms of the photocatalyst constituents in single and multiple pollutant systems under solar and visible light irradiation, indicating the type of heterojunction system (Z scheme or type II).

Keywords: bandgap alignment, heterojunction, photocatalysis, reaction mechanism

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653 Interaction between NiCl2 and Selenium on Energy Profiles in Wistar albino Preimplanted Rats

Authors: O. Adjroud

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The present study was conducted to investigate the interaction between selenium (Se) and chloride nickel (NiCl2) on energy profiles in Wistar albino preimplanted rats. NiCl2 was given on day 3 of pregnancy either in distilled drinking water at a dose of 20 mg/L/day for 16 consecutive days or as a single subcutaneous (s.c.) dose of 25, 50, or 100 mg/kg. Se was given as a s.c. injection (0.3 mg/kg) together with the higher dose (100 mg/kg) of NiCl2. Changes in energy profiles were evaluated in treated and control groups on days 5 and 20 of gestation. NiCl2 s.c. induced a significant increase in plasma glucose on day 20 of pregnancy. NiCl2 s.c. induced on day 5 and 20 of gestation a significant decrease in plasma triglycerides, with the higher dose. This decrease was maintained at day 20 of gestation with doses of 50 mg /kg. In addition, NiCl2 s.c. caused on day 5 of gestation a significant decrease in plasma total cholesterol with the low and medium doses. The pretreatment with Se reversed the effects of NiCl2 on plasma glucose, total cholesterol and triglycerides levels. NiCl2 administered in the drinking water augmented significantly the plasma triglycerides and total cholesterol levels and slighty the plasma glucose on day 20 of gestation, while on day 5 of gestation NiCl2 s.c. Induced a significant decrease in cholesterol. Three doses of NiCl2 (sc) induced severe alterations in liver and architecture which are markedly improved by Selenium. These results suggested that selenium has protective effects on energy profiles against the toxicity induced by NiCl2 administered subcutaneously in preimplanted rats.

Keywords: hepatotoxicity, nickel chloride, preimplanted rat, biochemical parameters

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652 Metabolome-based Profiling of African Baobab Fruit (Adansonia Digitata L.) Using a Multiplex Approach of MS and NMR Techniques in Relation to Its Biological Activity

Authors: Marwa T. Badawy, Alaa F. Bakr, Nesrine Hegazi, Mohamed A. Farag, Ahmed Abdellatif

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Diabetes Mellitus (DM) is a chronic disease affecting a large population worldwide. Africa is rich in native medicinal plants with myriad health benefits, though less explored towards the development of specific drug therapy as in diabetes. This study aims to determine the in vivo antidiabetic potential of the well-reported and traditionally used fruits of Baobab (Adansonia digitata L.) using STZ induced diabetic model. The in-vitro cytotoxic and antioxidant properties were examined using MTT assay on L-929 fibroblast cells and DPPH antioxidant assays, respectively. The extract showed minimal cytotoxicity with an IC50 value of 105.7 µg/mL. Histopathological and immunohistochemical investigations showed the hepatoprotective and the renoprotective effects of A. digitata fruits’ extract, implying its protective effects against diabetes complications. These findings were further supported by biochemical assays, which showed that i.p., injection of a low dose (150 mg/kg) of A. digitata twice a week lowered the fasting blood glucose levels, lipid profile, hepatic and renal markers. For a comprehensive overview of extract metabolites composition, ultrahigh performance (UHPLC) analysis coupled to high-resolution tandem mass spectrometry (HRMS/MS) in synchronization with molecular networks led to the annotation of 77 metabolites, among which 50% are reported for the first time in A. digitata fruits.

Keywords: adansonia digital, diabetes mellitus, metabolomics, streptozotocin, Sprague, dawley rats

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651 Enzymatic Saccharification of Dilute Alkaline Pre-treated Microalgal (Tetraselmis suecica) Biomass for Biobutanol Production

Authors: M. A. Kassim, R. Potumarthi, A. Tanksale, S. C. Srivatsa, S. Bhattacharya

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Enzymatic saccharification of biomass for reducing sugar production is one of the crucial processes in biofuel production through biochemical conversion. In this study, enzymatic saccharification of dilute potassium hydroxide (KOH) pre-treated Tetraselmis suecica biomass was carried out by using cellulase enzyme obtained from Trichoderma longibrachiatum. Initially, the pre-treatment conditions were optimised by changing alkali reagent concentration, retention time for reaction, and temperature. The T. suecica biomass after pre-treatment was also characterized using Fourier Transform Infrared Spectra and Scanning Electron Microscope. These analyses revealed that the functional group such as acetyl and hydroxyl groups, structure and surface of T. suecica biomass were changed through pre-treatment, which is favourable for enzymatic saccharification process. Comparison of enzymatic saccharification of untreated and pre-treated microalgal biomass indicated that higher level of reducing sugar can be obtained from pre-treated T. suecica. Enzymatic saccharification of pre-treated T. suecica biomass was optimised by changing temperature, pH, and enzyme concentration to solid ratio ([E]/[S]). Highest conversion of carbohydrate into reducing sugar of 95% amounted to reducing sugar yield of 20 (wt%) from pre-treated T. suecica was obtained from saccharification, at temperature: 40°C, pH: 4.5 and [E]/[S] of 0.1 after 72 h of incubation. Hydrolysate obtained from enzymatic saccharification of pretreated T. suecica biomass was further fermented into biobutanol using Clostridium saccharoperbutyliticum as biocatalyst. The results from this study demonstrate a positive prospect of application of dilute alkaline pre-treatment to enhance enzymatic saccharification and biobutanol production from microalgal biomass.

Keywords: microalgal biomass, enzymatic saccharification, biobutanol, fermentation

Procedia PDF Downloads 383
650 Two Years Retrospective Study of Body Fluid Cultures Obtained from Patients in the Intensive Care Unit of General Hospital of Ioannina

Authors: N. Varsamis, M. Gerasimou, P. Christodoulou, S. Mantzoukis, G. Kolliopoulou, N. Zotos

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Purpose: Body fluids (pleural, peritoneal, synovial, pericardial, cerebrospinal) are an important element in the detection of microorganisms. For this reason, it is important to examine them in the Intensive Care Unit (ICU) patients. Material and Method: Body fluids are transported through sterile containers and enriched as soon as possible with Tryptic Soy Broth (TSB). After one day of incubation, the broth is poured into selective media: Blood, Mac Conkey No. 2, Chocolate, Mueller Hinton, Chapman and Saboureaud agar. The above selective media are incubated directly for 2 days. After this period, if any number of microbial colonies are detected, gram staining is performed. After that, the isolated organisms are identified by biochemical techniques in the automated Microscan system (Siemens) and followed by a sensitivity test on the same system using the minimum inhibitory concentration MIC technique. The sensitivity test is verified by Kirby Bauer-based plate test. Results: In 2017 the Laboratory of Microbiology received 60 samples of body fluids from the ICU. More specifically the Microbiology Department received 6 peritoneal fluid specimens, 18 pleural fluid specimens and 36 cerebrospinal fluid specimens. 36 positive cultures were tested. S. epidermidis was identified in 18 specimens, S. haemolyticus in 6, and E. faecium in 12. Conclusions: The results show low detection of microorganisms in body fluid cultures.

Keywords: body fluids, culture, intensive care unit, microorganisms

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649 Case Study of Sexual Violence Victim Assessment in Semarang Regency

Authors: Sujana T, Kurniasari MD, Ayakeding AM

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Background: Sexual violence is one of the violence with high incidence in Indonesia. Purpose: This research aims to describe the implementation of sexual violence victim assessment in Semarang Regency. Method: This research is a qualitative research with embeded single case study design. Data is analized with two units of analysis. The first unit of analysis is victim’s examiner with minimum one year of work experience. Semi-structured interview method is used to obtain the data. The second unit of analysis is document related. The data is taken by observing the pathway and description of every document and how it supported each implementation of assessment. Results: This study is resulted with three themes, which are: The first theme is assessments of sexual violence in Semarang regency has been standardized. The laws of the Republic of Indonesia have regulated the handling of victims of sexual violence in outline. Victims of sexual violence can be dealt with by the police, the Integrated Service Center for Women and Children Empowerment and the Regional General Hospital. Each examination site has different operational procedures standards for dealing with victims of sexual violence. Cooperation with family and witnesses is also required in the review process to obtain accurate results and evidence; The second idea that resulted from this study is there are inhibits factors in the assessments process. Victims sometimes feel embarrassed and reluctant to recount the chronological events during reporting. The examining officer should be able to approach and build a trust to convince the victim to be able to cooperate. The third theme is there are other things to consider in the process of assessing victims of sexual violence. Ensuring implementation in accordance with applicable operational procedures standards, providing exclusive examination rooms, counseling and safeguarding the privacy of victims are important to be considered in the assessment.

Keywords: assessment, case study, Semarang regency, sexual violence

Procedia PDF Downloads 133
648 Stipagrostis ciliata (Desf.) De Winter: A Promising Pastoral Species for Ecological Restoration in North African Arid Bioclimate

Authors: Lobna Mnif Fakhfakh, Mohamed Chaieb

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Most ecological studies in North Africa reveal a process of continuous degradation of pastoral ecosystems as a result of overgrazing. This degradation appears across the depletion of perennial grass species. Indeed, the majority of steppic ecosystems are characterized by a low density of perennial grasses. This phenomenon reveals a drop in food value of rangelands, which is now estimated at less than 100 UF.ha -1. -1 Year in all North African steppes. However, for ecological restoration initiatives, some species such the genus of Stipagrostis and Stipa can be considered a good candidates species for effective pastoral improvement under arid bioclimate. The present work concerns Stipagrostis ciliata (Desf.) De Winter, perennial grasses, abundant in ecosystems characterized by the high content of gypsum (CaSO4)2H2O in the southern Tunisia. This tufted species with C4 biochemical photosynthesis type is able to grow and develop under high temperature and low annual rainfall, where the minimum water potential (ψmd), can reach -4 MPa during the summer season with a phenological growth maintained throughout the season unfavorable. At this point in the early autumn rains, S. ciliata begins its growth, especially with a heading which occurs 2-3 weeks after the first autumn rains. From the foregoing, it can be concluded that Stipagrostis ciliata is an excellent promising pastoral species for the ecological restoration, and enhancement of ecosystems biological productivity in arid bioclimate of North Africa.

Keywords: Stipagrostis ciliata, pastoral species, ecological restoration, arid bioclimate

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647 Advanced Lithium Recovery from Brine: 2D-Based Ion Selectivity Membranes

Authors: Nour S. Abdelrahman, Seunghyun Hong, Hassan A. Arafat, Daniel Choi, Faisal Al Marzooqi

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Abstract—The advancement of lithium extraction methods from water sources, particularly saltwater brine, is gaining prominence in the lithium recovery industry due to its cost-effectiveness. Traditional techniques like recrystallization, chemical precipitation, and solvent extraction for metal recovery from seawater or brine are energy-intensive and exhibit low efficiency. Moreover, the extensive use of organic solvents poses environmental concerns. As a result, there's a growing demand for environmentally friendly lithium recovery methods. Membrane-based separation technology has emerged as a promising alternative, offering high energy efficiency and ease of continuous operation. In our study, we explored the potential of lithium-selective sieve channels constructed from layers of 2D graphene oxide and MXene (transition metal carbides and nitrides), integrated with surface – SO₃₋ groups. The arrangement of these 2D sheets creates interplanar spacing ranging from 0.3 to 0.8 nm, which forms a barrier against multivalent ions while facilitating lithium-ion movement through nano capillaries. The introduction of the sulfonate group provides an effective pathway for Li⁺ ions, with a calculated binding energy of Li⁺ – SO³⁻ at – 0.77 eV, the lowest among monovalent species. These modified membranes demonstrated remarkably rapid transport of Li⁺ ions, efficiently distinguishing them from other monovalent and divalent species. This selectivity is achieved through a combination of size exclusion and varying binding affinities. The graphene oxide channels in these membranes showed exceptional inter-cation selectivity, with a Li⁺/Mg²⁺ selectivity ratio exceeding 104, surpassing commercial membranes. Additionally, these membranes achieved over 94% rejection of MgCl₂.

Keywords: ion permeation, lithium extraction, membrane-based separation, nanotechnology

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646 Extraction and Uses of Essential Oil

Authors: Ram Prasad Baral

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A large number of herb materials contain Essential Oils with extensive bioactivities. Acknowledging the importance of plants and its medicinal value, extraction of Essential Oil had been done using Steam Distillation method. In this project, Steam Distillation was used to extract oil from different plant materials like Chamomilla recutita (L.) Rauschert, Artemisia Vulgaris L, Rhododendron anthopogon D. Don, Cymbopogon nardus L, Andropogon nardus, Cinnamomum tamala, Juniperus spp, Cymbopohonflexuosus flexuous, Mantha Arvensia, Nardostachys Jatamansi, Wintergreen Essential Oil, and Valeriana Officinalis. Research has confirmed centuries of practical use of essential oils, and we now know that the 'fragrant pharmacy' contains compounds with an extremely broad range of biochemical effects. Essential oils are so termed as they are believed to represent the very essence of odor and flavor. The recovery of Essential Oil from the raw botanical starting material is very important since the quality of the oil is greatly influenced during this step. There is a variety of methods for obtaining volatile oils from plants. Steam distillation method was found to be one of the promising techniques for the extraction of essential oil from plants as reputable distiller will preserve the original qualities of the plant. The distillation was conducted in Clevenger apparatus in which boiling, condensing, and decantation was done. Analysis of essential oil was done using Gas Chromatography-Mass Spectrometer apparatus, which gives evaluates essential oil qualitatively and quantitatively. The volume of essential oil obtained was changing with respect to temperature and time of heating.

Keywords: Chamomilla recutita (L.) Rauschert, Artemisia Vulgaris L, Rhododendron anthopogon D. Don, Cymbopogon nardus L, Andropogon nardus, Cinnamomum tamala, Juniperus spp, Cymbopohonflexuosus flexuous, Mantha

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645 Orotic Acid-Induced Fatty Liver in Mink: Characterization and Testing of Bioactive Peptides for Prevention and Treatment

Authors: Don Buddika Oshadi Malaweera, Lora Harris, Bruce Rathgeber, Chibuike C. Udenigwe, Kirsti Rouvinen-Watt

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Fatty liver disease is among the three most severe health concerns for mink and believed to occur through the same mechanism as nursing sickness. In North America, nursing sickness affects about 45% of mink farms and in Canada, approximately 50,000 mink females is affected annually. Orotic acid (OA) plays a critical role in lipid metabolism and can increase hepatic lipids by enhancing Sterol regulatory element binding protein-1c expression and decreasing Carnitine palmitoyl transferase I activity. This study was conducted to identify particular pathways and regulatory control points involved in fatty liver development, and evaluate the effectiveness of arginine and bioactive peptides for prevention and treatment of fatty liver disease in mink. A total of 45 mink were used in 9 treatments. The experimental diets consisted of 1% OA, 2% L-arginine and 5% of whey protein hydrolysates. At the end of 10 days of experimental period, the mink were anaesthetized, sampled for blood and euthanized, samples were obtained for histological, biochemical and molecular assays. The blood samples will be analyzed for clinical chemistry and triacylglycerol. The liver samples will be analyzed for total lipid content and analyzed for 6 genes of interest involved in adipogenic transformation, ER stress, and liver inflammation.

Keywords: fatty liver, L-arginine, mink, orotic acid, whey protein hydrolysates

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644 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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643 Criteria for Assessing Prostate Structure after Proton Radiotherapy for Prostate Cancer

Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

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After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

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642 Circulating Oxidized LDL and Insulin Resistance among Obese School Students

Authors: Nayera E. Hassan, Sahar A. El-Masry, Mones M. Abu Shady, Rokia A. El Banna, Muhammad Al-Tohamy, Mehrevan M. Abd El-Moniem, Mona Anwar

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Circulating oxidized LDL (ox-LDL) is associated with obesity, insulin resistance (HOMA), metabolic syndrome, and cardiovascular disease in adults. Little is known about relations in children. Aim: To assess association of ox-LDL with fat distribution and insulin resistance in a group of obese Egyptian children. Methods: Study is cross-sectional consisting of 68 obese children, with a mean age of 9.96 ± 1.32. Each underwent a complete physical examination; blood pressure (SBP, DBP) and anthropometric measurements (weight, height, BMI; waist, hip circumferences, waist/hip ratio), biochemical tests of fasting blood glucose (FBS), insulin levels; lipid profile (TC, LDL,HDL, TG) and ox-LDL; calculated HOMA. Sample was classified according to waist/hip ratio into: group I with and group II without central obesity. Results: ox-LDL showed significant positive correlation with LDL and TC in all groups of obesity. After adjustment for age and sex, significant positive correlation was detected between ox-LDL with SBP, DBP, TC, LDL, insulin, and HOMA in group II and with TC and FBS in group I. Insignificant association was detected between ox-LDL and other anthropometric parameters including BMI in any group of obese children (p > 0.05). Conclusions: ox-LDL, as a marker of oxidative stress is not correlated with BMI among all studied obese children (aged 6-12 years). Increased oxidative stress has causal effects on insulin resistance in obese children without central obesity and on fasting blood sugar in those with central obesity. These findings emphasize the importance of obesity during childhood and suggest that the metabolic complications of obesity and body fat distribution are detectable early in life.

Keywords: ox-LDL, obesity, insulin resistance, children

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641 Layer-by-Layer Coated Dexamethasone Microcrystals for Experimental Inflammatory Bowel Disease Therapy

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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640 Angiogenic and Immunomodulatory Properties and Phenotype of Mesenchymal Stromal Cells Can Be Regulated by Cytokine Treatment

Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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639 Effect of 10 Weeks of Aerobic Exercise Training on Serum Concentrations of Surfactant Protein D and Insulin Resistance in Women with Type 2 Diabetes

Authors: Sajjad Rezaei, Mahdieh Molanouri Shamsi, Azadeh Jamali

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Background and purpose: Surfactant protein D (SP-D) is a lung-specific protein that is detectable in human plasma. Effect of exercise training on SP-D levels as well as its relation to metabolic indices is not known. The present study then aimed to investigate the effects of 10 weeks of aerobic training on serum levels of SP-D and insulin resistance in women with type 2 diabetes. Materials and methods: Twenty-two overweight women with type 2 diabetes mellitus were recruited through deliberate sampling and randomly assigned to intervention and control groups (11 in each group). The intervention group underwent a progressive aerobic training program for 10 weeks, 3 days per week, 30-55 min/day at 50-75% heart rate reserve (HRR). Control group continued with its everyday routine. Blood samples were obtained before and after training for biochemical analysis. Within-group and between-group differences were analyzed with paired and independent t-tests in spss software, respectively, and the relation between variables was analyzed with Pearson’s correlation coefficient (all at P = 0.05). Results: Significant differences were observed between groups in leptin, glucose, waist circumference and VO2 max after training. SP-D was decreased and VO2 max was increased significantly in intervention group. However, no significant correlation was observed between SP-D and other variables. Conclusion: Since there was no corresponding decrease in insulin resistance with decreased levels of SP-D, it seems unlikely for SP-D to mediate the association between obesity and insulin resistance in type 2 diabetics.

Keywords: exercise training, SP-D, insulin resistance, type 2 diabetes

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