Search results for: factor VIII inhibitor

Authors: S. Yezli-Touiker, L. Kirane-Amrani, N. Soltani-Mazouni

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Ephestia kuehniella Zeller Lepidoptera, Pyralidae commonly called Mediterranean flour moth, is serious cosmopolitan pest of stored grain products, particularly flour Month. This species is also a source of allergen that causes asthma and rhinitis. Captopril is an inhibitor of angiotensin converting enzyme (ACE) it was tested in vivo by topical application on development of E. kuehniella. The compound is diluted in acetone and applied topically to newly emerged pupae (10mg/2ml). Report chitin protein of cuticule and ecdysteroid Amounts were determined in vivo. Results show that the captopril does not affect chitin protein of cuticule but traitment with captopril increase the hormonal production, the quantitative analysis reveals the presence of two peaks one at third and another at fifth day.

Keywords: Ephestia kuehniella, cuticule, hormone, captopril

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Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto

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Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.

Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone

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Authors: Khalil Khanafer

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The objective of this study is to determine if there is a correlation between the biological levels of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinase (TIMP) and the elastic moduli of the ascending aortic wall in patients with ascending thoracic aortic aneurysms (ATAA). Methods: Circumferential specimens from twelve patients with ATAA were obtained from the greater curvature, and their tensile properties (maximum elastic modulus) were tested uniaxially. The levels of MMP2, 3, and 9, as well as TIMP1, were determined in these aortic wall specimens using MMP/TIMP antibodies array. Direct relations were found between MMP2 and the elastic modulus of the ascending aorta wall and between MMP9 and TIMP1.

Keywords: elastic modulus, MMPs/TIMPs levels, Ascending Thoracic Aortic Aneurysm

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Authors: Sungsoo Na, Chanho Park

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Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.

Keywords: cancer DNA, resonance frequency, quartz crystal microbalance, lung cancer

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Authors: Sirikwan Ponprateep, Anchalee Tassanakajon, Vichien Rimphanitchayakit

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A Kazal-type serine proteinase inhibitor, SPIPm2, was abundantly expressed in the hemocytes and secreted into shrimp plasma has anti-viral property against white spot syndrome virus (WSSV). To discover the molecular mechanism of antiviral activity, the binding assay showed that SPIPm2 bind to the components of viral particle and shrimp hemocyte. From our previous report, viral target protein of SPIPm2 was identified, namely WSV477 using yeast two-hybrid screening. WSV477 is an early gene product of WSSV and involved in viral propagation. In this study, the co-immunoprecipitation technique and Tandem Mass Spectrometry (LC-MS/MS) was used to identify the target protein of SPIPm2 from shrimp hemocyte. The target protein of SPIPm2 was cyclophilin A. In vertebrate, cyclophilin A or peptidylprolyl isomerase A was reported to be the immune suppressor interacted with cyclosporin A involved in immune defense response. The recombinant cyclophilin A from Penaeus monodon (rPmCypA) was produced in E.coli system and purified using Ni-NTA column to confirm the protein-protein interaction. In vitro pull-down assay showed the interaction between rSPIPm2 and rPmCypA. To study the biological function of these proteins, the expression analysis of immune gene in shrimp defense pathways will be investigated after rPmCypA administration.

Keywords: cyclophilin A, protein-protein interaction, Kazal-type serine proteinase inhibitor, Penaeus monodon

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Jie Su, Zhenghua Zhou, Yushi Wang, Yongyi Li

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The ground motion characteristics, which are given by the analysis of acceleration records, underlie the formulation and revision of the seismic design code of structural engineering. China Digital Strong Motion Network had recorded a lot of accelerograms of main shock from 478 permanent seismic stations, during the Ms8.0 Wenchuan earthquake on 12th May, 2008. These accelerograms provided a large number of essential data for the analysis of ground motion characteristics of the event. The spatial distribution characteristics, rupture directivity effect, hanging-wall and footwall effect had been studied based on these acceleration records. The results showed that the contours of horizontal peak ground acceleration and peak velocity were approximately parallel to the seismogenic fault which demonstrated that the distribution of the ground motion intensity was obviously controlled by the spatial extension direction of the seismogenic fault. Compared with the peak ground acceleration (PGA) recorded on the sites away from which the front of the fault rupture propagates, the PGA recorded on the sites toward which the front of the fault rupture propagates had larger amplitude and shorter duration, which indicated a significant rupture directivity effect. With the similar fault distance, the PGA of the hanging-wall is apparently greater than that of the foot-wall, while the peak velocity fails to observe this rule. Taking account of the seismic intensity distribution of Wenchuan Ms8.0 earthquake, the shape of strong ground motion contours was significantly affected by the directional effect in the regions with Chinese seismic intensity level VI ~ VIII. However, in the regions whose Chinese seismic intensity level are equal or greater than VIII, the mutual positional relationship between the strong ground motion contours and the surface outcrop trace of the fault was evidently influenced by the hanging-wall and foot-wall effect.

Keywords: hanging-wall and foot-wall effect, peak ground acceleration, rupture directivity effect, strong ground motion

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Authors: Prescilla Lambert, Christophe Roos, Mounim Lebrini

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For several years, the Caribbean islands and West Africa have had to deal with the massive arrival of the brown seaweed Sargassum. Overall, this macroalgae, which constitutes a habitat for a great diversity of marine organisms, is also an additional stress factor for the marine environment (e.g., coral reefs). In addition, the accumulation followed by the significant decomposition of the Sargassum spp. biomass on the coast leads to the release of toxic gases (H₂S and NH₃), which calls into question the functioning of the economic, health and tourist life of the island and the other interested territories. Originally, these algae are formed by the eutrophication of the oceans accentuated by global warming. Unfortunately, scientists predict a significant recurrence of these Sargassum strandings for years to come. It is therefore more than necessary to find solutions by putting in place a sustainable management plan for this phenomenon. Martinique, a small island in the Caribbean arc, is one of the many areas impacted by Sargassum seaweed strandings. Since 2011, there has been a constant increase in the degradation of the materials present in this region, largely due to toxic/corrosive gases released by the algae decomposition. In order to protect the structures and the vulnerable building materials while limiting the use of synthetic/petroleum based molecules as much as possible, research is being conducted on molecules of natural origin. Thus, thanks to the chemical composition, which comprise molecules with interesting properties, algae such as Sargassum could potentially help to solve many issues. Therefore, this study focuses on the green extraction and characterization of molecules from the species Sargassum fluitans and Sargassum natans present in Martinique. The secondary metabolites found in these extracts showed variability in yield rates due to local climatic conditions. The tests carried out shed light on the anticorrosive and antibacterial potential of the algae. These extracts can thus be described as natural inhibitors. The effect of variation in inhibitor concentrations was tested in electrochemistry using electrochemical impedance spectroscopy and polarization curves. The analysis of electrochemical results obtained by direct immersion in the extracts and self-assembled molecular layers (SAMs) for Sargassum fluitans III, Sargassum natans I and VIII species was conclusive in acid and alkaline environments. The excellent results obtained reveal an inhibitory efficacy of 88% at 50mg/L for the crude extract of Sargassum fluitans III and efficacies greater than 97% for the chemical families of Sargassum fluitans III. Similarly, microbiological tests also suggest a bactericidal character. Results for Sargassum fluitans III crude extract show a minimum inhibitory concentration (MIC) of 0.005 mg/mL on Gram-negative bacteria and a MIC greater than 0.6 mg/mL on Gram-positive bacteria. These results make it possible to consider the management of local and international issues while valuing a biomass rich in biodegradable molecules. The next step in this study will therefore be the evaluation of the toxicity of Sargassum spp..

Keywords: Sargassum, secondary metabolites, anticorrosive, antibacterial, natural inhibitors

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Authors: Camilo A. Guerrero-Martin, Erik Montes Paez, Marcia C. K. Oliveira, Jonathan Campos, Elizabete F. Lucas

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Asphaltenes precipitation is considered as a formation damage problem, which can reduce the oil recovery factor. It fouls piping and surface installations, as well as cause serious flow assurance complications and decline oil well production. Therefore, researchers have shown an interest in chemical treatments to control this phenomenon. The aim of this paper is to assess the asphaltenes precipitation onset of crude oils in the presence of cardanol, by titrating the crude with n-heptane. Moreover, based on this results obtained at atmosphere pressure, the asphaltenes precipitation onset pressure were calculated to predict asphaltenes precipitation in the reservoir, by using differential liberation and refractive index data of the oils. The influence of cardanol concentrations in the asphaltenes stabilization of three Brazilian crude oils samples (with similar API densities) was studied. Therefore, four formulations of cardanol in toluene were prepared: 0, 3, 5, 10 and 15 m/m%. The formulations were added to the crude at 2:98 ratio. The petroleum samples were characterized by API density, elemental analysis and differential liberation test. The asphaltenes precipitation onset (APO) was determined by titrating with n-heptane and monitoring with near-infrared (NIR). UV-Vis spectroscopy experiments were also done to assess the precipitate asphaltenes content. The asphaltenes precipitation envelopes (APE) were also determined by numerical simulation (Multiflash). In addition, the adequate artificial lift systems (ALS) for the oils were selected. It was based on the downhole well profile and a screening methodology. Finally, the oil flowrates were modelling by NODAL analysis production system in the PIPESIM software. The results of this study show that the asphaltenes precipitation onset of the crude oils were 2.2, 2.3 and 6.0 mL of n-heptane/g of oil. The cardanol was an effective inhibitor of asphaltenes precipitation for the crude oils used in this study, since it displaces the precipitation pressure of the oil to lower values. This indicates that cardanol can increase the oil wells productivity.

Keywords: asphaltenes, NODAL analysis production system, precipitation pressure onset, inhibitory molecule

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Authors: Samira Ghizellaoui, Manel Boumagoura, Rayane Menzri

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The ground water Hamma rich in calcium and bicarbonate likely to deposit the tartar and subsequently lead to the obstruction of the pipes and the seizing of the stopping devices in addition to the financial losses resulting there from. It is therefore necessary to optimise an antiscaling treatment in order to avoid the risk of formation of tartar deposits in the various installations and to protect the equipment in contact with this water. MgCl2 is the chemical inhibitor which was tested. To optimise the effective concentration of this product, we used two electrochemical methods (chronoamperometry and impedancemetry) to identify the best method for optimizing antiscaling treatment. IR, RX, Raman spectroscopy and SEM indicate that the raw waters of Hamma give precipitates in the form of calcite (the most stable form), with the presence of a small amount of magnesian calcite and aragonite. In the presence of the inhibitor (MgCl2), calcium carbonate changes morphology to other forms that do not exist in the deposit obtained from the raw water (vaterite and calcium carbonate monohydrate).

Keywords: calcium carbonate, MgCl2, chronoamperometry, Impedancemetry

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Rahma Tibigui, Ikram Hadj Said, Rachid Belkada, Dalila Hammoutene

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The vulnerability of industrial facilities is highly concerned with multiple risks from corrosion. The commonly adopted solution is based on the use of organic inhibitors, which are gradually being replaced by environmentally friendly organic inhibitors. In our work, we carried out a quantum chemical study based on the Density Functional Theory (DFT) method at the B3LYP/6-311G (d,p) level of theory. The inhibitory performance of a derivative of the tetrazole molecule has been investigated and reported as a carbon steel-friendly corrosion inhibitor in hydrochloric acid (HCl) medium. The relationship is likely to exist between the molecular structure of this compound as well as its various global reactivity descriptors, and its corrosion inhibition efficiency, which was examined and then discussed. The results show low values of ΔE, which represent strong adsorption of the inhibitor on the steel surface. Moreover, the flat adsorption orientation confirmed the great ability to donate (accept) electrons to (from) steel, fabricating an anchored barrier to prevent steel from corrosion.

Keywords: eco-friendly, corrosion inhibitors, tetrazole, DFT

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Sook Ching Yee, Angela Siew Hoong Lee

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Big data technologies have become a trend to exploit business opportunities and provide valuable business insights through the analysis of big data. However, there are still many organizations that have yet to adopt big data technologies especially small and medium organizations (SME). This study uses the technology acceptance model (TAM) to look into several constructs in the TAM and other additional constructs which are positive affect, negative affect, organizational factor and motivational factor. The conceptual model proposed in the study will be tested on the relationship and influence of positive affect, negative affect, organizational factor and motivational factor towards the intention to use big data technologies to produce an outcome. Empirical research is used in this study by conducting a survey to collect data.

Keywords: big data technologies, motivational factor, negative affect, organizational factor, positive affect, technology acceptance model (TAM)

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Authors: Taher S. Ababneh, Taghreed M. A. Jazzazi, Tareq M. A. Alshboul

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The inhibiting action against aluminum corrosion by three derivatives of 1,8-bis (benzylideneamino) naphthalene (BN) Schiff base has been investigated by means of DFT quantum chemical calculations at the B3LYP/6-31G(d) level of theory. The derivatives (CBN, NBN and MBN) were prepared from the condensation reaction of 1,8-diaminonaphthalene with substituted benzaldehyde (4-CN, 3-NO₂ and 3,4-(OMe)₂, respectively). Calculations were conducted to study the adsorption of each Schiff base on aluminum surface to evaluate its potential as a corrosion inhibitor. The computational structural features and electronic properties of each derivative such as relative energies and energies of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) have been reported. Thermodynamic functions and quantum chemical parameters such as the hardness of the inhibitor, the softness and the electrophilicity index were calculated to determine the derivative of the highest inhibition efficiency.

Keywords: corrosion, aluminum, DFT calculation, 1, 8-diaminonaphthalene, benzaldehyde

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Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia

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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.

Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis

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Authors: Ali Sagiroglu, Sema Noyan Alacali, Guray Arslan

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This paper presents a study on the influence of the safety factor in the concrete contribution to shear strength of high-strength concrete (HSC) beams according to TS500. In TS500, the contribution of concrete to shear strength is obtained by reducing diagonal cracking strength with a safety factor of 0.8. It was investigated that the coefficient of 0.8 considered in determining the contribution of concrete to the shear strength corresponds to which value of failure probability. Also, the changes in the reduction factor depending on different coefficients of variation of concrete were examined.

Keywords: reinforced concrete, beam, shear strength, failure probability, safety factor

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Authors: Mohammed Al-Khadher

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Currently, we are witnessing rapid advancements in the field of information and communications technology, forcing us, as psychologists, to combat the psychological and social effects of such developments. It also drives us to continually look for the development and preparation of measurement tools compatible with the changes brought about by the digital revolution. In this context, the current study aimed to identify the factor analysis of the Smartphone Addiction Inventory (SPAI) in the Republic of Yemen. The sample consisted of (1920) university students (1136 males and 784 females) who answered the inventory, and the data was analyzed using the statistical software (AMOS V25). The factor analysis results showed a goodness-of-fit of the data five-factor model with excellent indicators, as RMSEA-(.052), CFI-(.910), GFI-(.931), AGFI-(.915), TLI-(.897), NFI-(.895), RFI-(.880), and RMR-(.032). All within the ideal range to prove the model's fit of the scale’s factor analysis. The confirmatory factor analysis results showed factor loading in (4) items on (Time Spent), (4) items on (Compulsivity), (8) items on (Daily Life Interference), (5) items on (Craving), and (3) items on (Sleep interference); and all standard values of factor loading were statistically significant at the significance level (>.001).

Keywords: smartphone addiction inventory (SPAI), confirmatory factor analysis (CFA), yemeni students, people at risk of smartphone addiction

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Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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Authors: Cigdem Karaaslan, Yalcin Duydu, Aylin Ustundag, Can Ozgur Yalcın, Hakan Goker

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Benzazole nucleus is found in the structure of many compounds as anticancer agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), Glasdegib (SMO inhibitor) are clinically used as anticancer therapeutics which bearing benzimidazole moiety. Based on the principle of bioisosterism in the present work, 23 compounds belonging to 2-(3,4-dimethoxy-phenyl) benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer activities. N-(5-Chloro-2-hydroxyphenyl)-3,4-dimethoxybenzamide, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of benzamide derivative to benzoxazole, was achieved by p-toluenesulfonic acid. Other 1H-benz (or pyrido) azoles were prepared by the reaction between 2-aminothiophenol, o-phenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the Nuclear Overhauser Effect Spectroscopy. A compound named, 5(4),7(6)-Dichloro-2-(3,4-dimethoxy) phenyl-1H-benzimidazole, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue, against A549 cells with the GI50 value of 1.5 µg/mL. In addition, 2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-1H-benzimi-dazole showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI₅₀ values of 7 and 5.5 µg/mL, respectively. It could be concluded that introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increase significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized in this study. Unsubstituted 2-(3,4-dimethoxyphenyl) imidazopyridines also gave the good inhibitory profile against A549 and HeLa cells.

Keywords: 3, 4-Dimethoxyphenyl, 1H-benzimidazole, benzazole, imidazopyridine

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Authors: Elham Rezaee, Sayyed Abbas Tabatabai

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Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.

Keywords: COX-2, dual inhibitors, sEH, synthesis

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Authors: Waleed Aly Sayed Ahmed, Eman Kishk, Tahani Shams

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Aim: To study the effects of co-administration of phosphodiesterase-5 inhibitor (PDE-5) and sodium selenite against the damage induced by ovarian ischemia-reperfusion in rats. Materials and Methods: A total of forty-two sexually mature, virgin, female rats were divided randomly into six groups of seven each: sham group (C), ischemia group (I), ischemia/reperfusion group (I/R), ischemia/reperfusion plus 1.4mg/kg sildenafil (I/R+S) group, ischemia/reperfusion plus 0.2mg/kg selenium (I/R+Se) group and ischemia/reperfusion plus combination of sildenafil and selenium (I/R+S+Se) group. In ischemia group (I), rats were exposed to ischemia for 3 hours (h). In ischemia/reperfusion group (I/R), rats were exposed to ischemia for 3 h followed by 6 h of reperfusion. Treated groups received 1.4mg/kg sildenafil or 0.2 mg/kg selenium or both 30 min before reperfusion. Both ovaries were surgically removed carefully. One ovary was examined for histopathological changes and the other was subject to biochemical analysis including malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx). Results: Assessment of ovarian tissue damage using a scoring system showed marked vascular congestion, interstitial edema, leukocyte infiltration, hemorrhage, and follicular degeneration in ischemia and ischemia/reperfusion groups. Tissue damage score for I, IR and all treated groups were significantly higher than those of the sham group (p<0.001), while tissue damage score decreased significantly in I/R+S and I/R+Se groups compared to I/R group (p<0.05), and notably, the difference was highly significant in I/R+S+Se group (p<0.001). There was significant increase in MDA levels and reduction in activities of CAT and GPx in I/R group compared to the sham group (p < 0.05). In I/R+S and I/R+Se groups, MDA was significantly decreased compared to the I/R group (p<0.05) and the difference was highly significant with co-administration of sildenafil and selenium (p<0.001). CAT and GPx were higher in all treated groups compared to I/R group (p<0.05). Conclusion: The co-administration of sildenafil citrate and selenium are highly protective against damage induced by ovarian ischemia/reperfusion in rats.

Keywords: phosphodiesterase-5 inhibitor, sildenafil, antioxidant, selenium, ovarian ischemia

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Authors: Kwanchai Ratanamanee, Pattra Ahmadi Pirshahid, Yaowaluk Khamphan, Sirinan Thubthimthad

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Obesity is a main global health problem. The obesity rated has continued to be higher and higher. It causes to serious systems, diabetes, coronary artery disease, stroke, and some types of cancer. Oristat is one of the best drugs worldwide used as a pancreatic lipase inhibitor. To develop the new therapeutic drugs from medicinal plant always explored. In this study, 24 medicinal plants were investigated for their pancreatic lipase and cholesterol esterase inhibitory effects with Fluorometer assay and oristat as a positive control. It showed that the ethanolic extract of pods of Acacia concinna (Willd.) D.C., possess pancreatic lipase and cholesterol esterase inhibitory activities of IC50 at 2.73 and 3.77 mg/ml respectively as well as oral acute toxicity of the extract (LD50) was 6,300 mg/kg body weight. The extract of A.concinna should be further investigated in animal testing. The results of pancreatic lipase and cholesterol esterase inhibitor of the extracts will lead us to utilize A.concinna for developing as obesity dietary supplement from a medicinal plant.

Keywords: Acacia concinna (Willd.) D. C., cholesterol esterase, obesity, pancreatic lipase

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Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen

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Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation

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Authors: Hamed Alipour-Banaei, Farhad Mehdizadeh

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We report the design and characterization of ultra high quality factor filter based on one-dimensional photonic-crystal Thue-Morse sequence structure. The behavior of aperiodic array of photonic crystal structure is numerically investigated and we show that by changing the angle of incident wave, desired wavelengths could be tuned and a tunable filter is realized. Also it is shown that high quality factor filter be achieved in the telecommunication window around 1550 nm, with a device based on Thue-Morse structure. Simulation results show that the proposed structure has a quality factor more than 100000 and it is suitable for DWDM communication applications.

Keywords: Thue-Morse, filter, quality factor, photonic

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Authors: Roikhan Mochamad Aziz

Abstract:

This study aims to analze the interdependence of several variables simultaneously in order to simplify the form of the relationship between some of the variables studied a number of factors less than the variable studied which means it can also describe the data structure of a research. Based 100 respondents from the public, such as the people of South Tangerang, this study used factor analysis tool. The results of this study indicate that the studied variables being formed into nine factors, namely faith factors, community factors, factors of social care, confidence factor, factor income, educational factors, self-satisfaction factors, factors work, and knowledge factor. Total variance of the 9 factors is 67,30% means that all nine of these factors are factors that can contribute too paying zakat of muzakki consciousness of 67,30% while the remaining 32,70% is supported by other factors outside the 9 factors.

Keywords: zakat, analysis factor, faith, education, knowledge

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Authors: E. G. Zaki, M. A. Migahed, A. M. Al-Sabagh, E. A. Khamis

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Inhibition effect of four novel nonionic surfactants based on sulphonamide, of linear alkyl benzene sulphonic acid (LABS), was reacted with 1 mole triethylenetetramine, tetraethylenepentamine then Ethoxylation of amide X 65 type carbon steel in oil wells formation water under H2S environment was investigated by electrochemical measurements. Scanning electron microscopy (SEM) and energy dispersion X-ray (EDX) were used to characterize the steel surface. The results showed that these surfactants act as a corrosion inhibitor in and their inhibition efficiencies depend on the ethylene oxide content in the system. The obtained results showed that the percentage inhibition efficiency (η%) was increased by increasing the inhibitor concentration until the critical micelle concentration (CMC) reached The quantum chemistry calculations were carried out to study the molecular geometry and electronic structure of obtained derivatives. The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital has been calculated using the theoretical computations to reflect the chemical reactivity and kinetic stability of compounds.

Keywords: corrosion, surfactants, steel surface, quantum

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Authors: Souhir Ben Amor, Heni Boubaker, Lotfi Belkacem

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This aims of this paper is to forecast the electricity spot prices. First, we focus on modeling the conditional mean of the series so we adopt a generalized fractional -factor Gegenbauer process (k-factor GARMA). Secondly, the residual from the -factor GARMA model has used as a proxy for the conditional variance; these residuals were predicted using two different approaches. In the first approach, a local linear wavelet neural network model (LLWNN) has developed to predict the conditional variance using the Back Propagation learning algorithms. In the second approach, the Gegenbauer generalized autoregressive conditional heteroscedasticity process (G-GARCH) has adopted, and the parameters of the k-factor GARMA-G-GARCH model has estimated using the wavelet methodology based on the discrete wavelet packet transform (DWPT) approach. The empirical results have shown that the k-factor GARMA-G-GARCH model outperform the hybrid k-factor GARMA-LLWNN model, and find it is more appropriate for forecasts.

Keywords: electricity price, k-factor GARMA, LLWNN, G-GARCH, forecasting

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Authors: Jelena Nedeljković Trailović, Marko Vasiljević, Jog Raj, Hunor Farkaš, Branko Petrujkić, Stamen Radulović, Gorana Popvić

Abstract:

The experiment was performed on a total of 99 one-day-old broilers of Cob 500 provenance, which were divided into IX equal groups. Broilers of the E-I group were fed 0.25 mg T-2 toxin/kg feed, E-II and E-III groups 0.25 mg T-2 toxin/kg feed with the addition of 1 kg/t and 3 kg/t of the mycotoxin detoxification agent MDA, respectively. The E-IV group received 1 mg of T-2 toxin/kg of feed, and the broilers of E-V and E-VI groups received 1 mg of T-2 toxin/kg of feed with the addition of 1 kg/t and 3 kg/t of the MDA detoxification preparation, respectively. The E-VII group received commercial feed without toxins and additives, the E-VIII and E-IX groups received feed with 1kg/t and 3kg/t of the MDA detoxification preparation. The trial lasted 42 days. Observing the results obtained on the 42nd day of the experiment, we can conclude that the change in the absolute mass of the spleen occurred in the broilers of the E-IV group (1.66±0.14)g, which was statistically significantly lower compared to the broilers of the E-V and E-VI groups (2.58±0.15 and 2.68±0.23)g. Heart mass was significantly statistically lower in broilers of group E-IV (9.1±0.38)g compared to broilers of group E-V and E-VI (12.23±0.5 and 11.43±0.51)g. It can be concluded that the broilers that received 1 kg/t and 3 kg/t of the detoxification preparation had an absolute mass of organs within physiological limits. Broilers of the E-IV group achieved the lowest BM during the experiment (on the 42nd day of the experiment 1879±52.73)g, they were significantly statistically lower than the BW of broilers of all experimental groups. This trend is observed from the beginning to the end of the experiment. The protective effect of the detoxification preparation can be seen in broilers of the E-V group, that had a significantly statistically higher BM on the 42nd day of the experiment (2225±58.81)g compared to broilers of group E-IV. Broilers of E-VIII group (2452±46.71) g, which received commercial feed with the addition of 1 kg/t MDA preparation, had the highest BMI at the end of the experiment. At the end of the trial on the 42nd day, blood samples were collected from broilers of the experimental groups that received T-2 toxin and MR detoxification preparations in different concentrations. Also, liver and breast musculature samples were collected for testing for the presence and content of T-2 toxin, HT-2 toxin, T-2 tetraol and T-2 triol. Due to very rapid elimination from the blood, no remains of T-2 toxin and its metabolites were detected in the blood of broilers of groups E-I to E-VI. In the breast muscles, T-2 toxin residues below LoQ < 0.2 (μg/kg) were detected in all groups that received T-2 toxin in food, the highest value was recorded in the E-IV group (0.122 μg/kg and the lowest in E -VI group 0.096 μg/kg). No T-2 toxin residues were detected in the liver. Remains of HT-2 were detected in the breast muscles and livers of broilers from E-IV, E-V and E-VI groups, LoQ < 1 (μg/kg); for the breast muscles: 0.054, 0.044 and 0.041 μg/kg, and for the liver: 0.473, 0.231 and 0.185 μg/kg. Summing up all the results, a partial protective effect of the detoxification preparation, added to food in the amount of 1kg/t, can be seen.

Keywords: T-2 toxin, bloiler, MDA, mycotoxuns

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