Search results for: peptide inhibitors

Authors: Hawon Lee, Young-Pil Kim

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Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

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Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: T. Abohalkuma, J. Telegdi

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Preparation, characterization, and application of self-assembled monolayers (SAM) formed by fluorophosphonic and undecenyl phosphonic acids on carbon steel surfaces as anticorrosive nanocoatings were demonstrated. The anticorrosive efficacy of these SAM layers was followed by atomic force microscopy, as the change in the surface morphology caused by layer deposition and corrosion processes was monitored. The corrosion process was determined by electrochemical potentiodynamic polarization, whereas the surface wettability of the carbon steel samples was tested with the use of static and dynamic contact angle measurements. Results showed that both chemicals produced good protection against corrosion as they performed as anodic inhibitors, especially with increasing the time of layer formation, which results in a more compact molecular film. According to the atomic force microscope (AFM) images, the fluoro-phosphonic acid self-assembled molecular layer can control the general as well as the pitting corrosion, but the SAM layers of the undecenyl-phosphonic acid cannot inhibit the pitting corrosion. The AFM and the contact angle measurements confirmed the results achieved by electrochemical measurements.

Keywords: nanolayers, corrosion, phosphonic acids, coatings

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Authors: Ruth Leitch, Joanne Hughes

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This paper presents the findings of a three-year government-funded study (ILiAD) that aimed to understand the reasons for differential educational achievement within and between socially and economically deprived areas in Northern Ireland. Previous international studies have concluded that there is a positive correlation between deprivation and underachievement. Our preliminary secondary data analysis suggested that the factors involved in educational achievement within multiple deprived areas may be more complex than this, with some areas of high multiple deprivation having high levels of student attainment, whereas other less deprived areas demonstrated much lower levels of student attainment, as measured by outcomes on high stakes national tests. The study proposed that no single explanation or disparate set of explanations could easily account for the linkage between levels of deprivation and patterns of educational achievement. Using a social capital perspective that centralizes the connections within and between individuals and social networks in a community as a valuable resource for educational achievement, the ILiAD study involved a multi-level case study analysis of seven community sites in Northern Ireland, selected on the basis of religious composition (housing areas are largely segregated by religious affiliation), measures of multiple deprivation and differentials in educational achievement. The case study approach involved three (interconnecting) levels of qualitative data collection and analysis - what we have termed Micro (or community/grassroots level) understandings, Meso (or school level) explanations and Macro (or policy/structural) factors. The analysis combines a statistical mapping of factors with qualitative, in-depth data interpretation which, together, allow for deeper understandings of the dynamics and contributory factors within and between the case study sites. Thematic analysis of the qualitative data reveals both cross-cutting factors (e.g. demographic shifts and loss of community, place of the school in the community, parental capacity) and analytic case studies of explanatory factors associated with each of the community sites also permit a comparative element. Issues arising from the qualitative analysis are classified either as drivers or inhibitors of educational achievement within and between communities. Key issues that are emerging as inhibitors/drivers to attainment include: the legacy of the community conflict in Northern Ireland, not least in terms of inter-generational stress, related with substance abuse and mental health issues; differing discourses on notions of ‘community’ and ‘achievement’ within/between community sites; inter-agency and intra-agency levels of collaboration and joined-up working; relationship between the home/school/community triad and; school leadership and school ethos. At this stage, the balance of these factors can be conceptualized in terms of bonding social capital (or lack of it) within families, within schools, within each community, within agencies and also bridging social capital between the home/school/community, between different communities and between key statutory and voluntary organisations. The presentation will outline the study rationale, its methodology, present some cross-cutting findings and use an illustrative case study of the findings from a community site to underscore the importance of attending to community differences when trying to engage in research to understand and improve educational attainment for all.

Keywords: educational achievement, multiple deprivation, community case studies, social capital

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Authors: Nirupama Dixit, Anyaa Mittal, Neeru Sood

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Alzheimer’s disease (AD) is a progressive form of dementia, contributing to up to 70% of cases, mostly observed in elderly but is not restricted to old age. The pathophysiology of the disease is characterized by specific pathological changes in brain. The changes (i.e. accumulation of metal ions in brain, formation of extracellular β-amyloid (Aβ) peptide aggregates and tangle of hyper phosphorylated Tau protein inside neurons) damage the neuronal connections irreversibly. The current issues in improvement of life quality of Alzheimer's patient lies in the fact that the diagnosis is made at a late stage of the disease and the medications do not treat the basic causes of Alzheimer's. The targeted delivery of drug through the blood brain barrier (BBB) poses several limitations via traditional approaches for treatment. To overcome these drug delivery limitation, nanoparticles provide a promising solution. This review focuses on current strategies for efficient targeted drug delivery using nanoparticles and improving the quality of therapy provided to the patient. Nanoparticles can be used to encapsulate drug (which is generally hydrophobic) to ensure its passage to brain; they can be conjugated to metal ion chelators to reduce the metal load in neural tissue thus lowering the harmful effects of oxidative damage; can be conjugated with drug and monoclonal antibodies against BBB endogenous receptors. Finally this review covers how the nanoparticles can play a role in diagnosing the disease.

Keywords: Alzheimer's disease, β-amyloid plaques, blood brain barrier, metal chelators, nanoparticles

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Authors: S. Ghalem, M. Mesmoudi, I. Daoudand, H. Allali

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The nitrogen-containing bisphosphonates (N-BPs) are well established as the treatments of choice for disorders of excessive bone resorption, myeloma and bone metastases, and osteoporosis. They inhibit farnesyl pyrophosphate synthase (FFPS), a key enzyme in the mevalonate pathway, resulting in inhibition of the prenylation of small GTP-binding proteins in osteoclasts and disruption of their cytoskeleton, adhesion/spreading, and invasion of cancer cells. A very few examples for synthesis of α-amino bisphosphonates based on several amino acids are known from the literature. In the present work, esters of aminoacid react with ketophsophonate (or their analog acid or acyl) to afford the desired products, α-iminophosphonates. The reaction of imine with dimethyl phosphate in the presence of catalytic amount of I2 give ester of α-aminobisphosphonate as sole product in good yield. Finally, we used computational docking methods to predict how several α-aminobisphosphonates bind to FPPS and how R and X influence. Pamidronate, β-aminobisphosphonate already marketed, was used as reference. These results are of interest since they represent a new and simple way to sythesize α-aminobisphosphonates with a free COOH group increased by R2 functionalisable and opening up the possibility of using the molecular docking to facilitate the design of other, novel FFPS inhibitors.

Keywords: drug research, cancer, α-amino bisphosphonates, molecular docking

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Authors: Jake Gonzalez, Tommy Dang

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This paper proposes a temporal graph approach to visualize and analyze the evolution of gene relationships and nomenclature over time. An interactive web-based tool implements this temporal graph, enabling researchers to traverse a timeline and observe coupled dynamics in network topology and naming conventions. Analysis of a real human genomic dataset reveals the emergence of densely interconnected functional modules over time, representing groups of genes involved in key biological processes. For example, the antimicrobial peptide DEFA1A3 shows increased connections to related alpha-defensins involved in infection response. Tracking degree and betweenness centrality shifts over timeline iterations also quantitatively highlight the reprioritization of certain genes’ topological importance as knowledge advances. Examination of the CNR1 gene encoding the cannabinoid receptor CB1 demonstrates changing synonymous relationships and consolidating naming patterns over time, reflecting its unique functional role discovery. The integrated framework interconnecting these topological and nomenclature dynamics provides richer contextual insights compared to isolated analysis methods. Overall, this temporal graph approach enables a more holistic study of knowledge evolution to elucidate complex biology.

Keywords: temporal graph, gene relationships, nomenclature evolution, interactive visualization, biological insights

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Authors: Olaitan Akanji, Cleophas Loto, Patricia Popoola, Andrei Kolesnikov

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Studies involving performance of corrosion inhibitors had been identified as one of the critical research needs for improving the durability of mild steel used in various industrial applications. This paper investigates the inhibiting effect of calcium gluconate against the corrosion of mild steel in 2.5M magnesium chloride using weight loss method and linear polarization technique, calculated corrosion rates from the obtained weight loss data, potentiodynamic polarization measurements are in good agreement. Results revealed calcium gluconate has strong inhibitory effects with inhibitor efficiency increasing with increase in inhibitor concentration at ambient temperature, the efficiency of the inhibitor increased in the following order of concentrations 2%g/vol,1.5%g/vol,1%g/vol,0.5%g/vol. Further results obtained from potentiodynamics experiments had good correlation with those of the gravimetric methods, the adsorption of the inhibitor on the mild steel surface from the chloride has been found to obey Langmuir, Frumkin and Freudlich adsorption isotherm. Scanning electron microscopy (SEM) observation confirmed the existence of an absorbed protective film on the metal surface.

Keywords: calcium gluconate, corrosion, magnesium chloride, mild steel

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Authors: Sehrish Iftikhar, Ahmad Ali Shahid, Kiran Nawaz, Waheed Anwar

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Discovery and development of new compounds require intense studies in chemistry, biochemistry. Numerous experiments under laboratory-, greenhouse- and field conditions can be performed to select suitable candidates and to understand their full potential. Novel fungicides are fundamental to combat plant diseases. Fusarium solani is important plant pathogen. New broad spectrum foliar fungicides against complex II were designed in this study. Complex II, namely succinate dehydrogenase (SDH), or succinate quinone oxidoreductase (SQR) is a multi-subunit enzyme at the crossroads of TCA and ETC at the inner mitochondrial membrane. The need for new and innovative fungicides is driven by resistance management, regulatory hurdles and increasing customer expectations amongst others. Fungicidal activity was assessed for the effect on mycelial growth and spore germination of the fungi using fungicide amended media assay. In mycelial growth assay compounds C10 and C6 were highly active against all the isolates. The compounds C1 and C10 were found most potent in spore germination test. It fully proved that the SDHIs designed in this paper displayed as good inhibitory effects against Fusarium solani.

Keywords: Wilt, Fusarium, SDH, antifungal

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Authors: A. Asselah, A. Khalfi, M. A.Toumi, A.Tazerouti

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The study of the corrosion inhibition of a standard carbon steel "API 5L grade X70" by two biodegradable anionic surfactants derived from fatty acids by photo sulfochlorination, called sodium lauryl methyl ester sulfonates and sodium palmityl methyl ester sulfonates was carried. A solution at 2.5 g/l NaCl saturated with carbon dioxide is used as a corrosive medium. The gravimetric and electrochemical technics (stationary and transient) were used in order to quantify the rate of corrosion and to evaluate the electrochemical inhibition efficiency, thus the nature of the mode of action of the inhibitor, in addition to a surface characterization by scanning electron microscopy (MEB) coupled to energy dispersive X-ray spectroscopy (EDX). The variation of the concentration and the temperature were examined, and the mode of adsorption of these inhibitors on the surface of the metal was established by assigning it the appropriate isotherm and determining the corresponding thermodynamic parameters. The MEB-EDX allowed the visualization of good adhesion of the protective film formed by the surfactants to the surface of the steel. The corrosion inhibition was evaluated at around 93% for sodium lauryl methyl ester sulfonate surfactant at 20 ppm and 87.2% at 50 ppm for sodium palmityl methyl ester sulfonate surfactant.

Keywords: carbon steel, oilfield, corrosion, anionic surfactants

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Authors: Nisrine Benzbiria, Abderrahmane Thoume, Mustapha Zertoubi

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The goal of this research is to investigate the corrosion inhibition potential of functionalized graphene oxide (GO) with oxime derivative on AA2024-T3 surface in synthetic seawater. The utilization of functionalized graphene oxide is creating a category of corrosion inhibitors known as organically modified nanomaterials. In our work, the functionalization of GO by chalcone oxime enables graphene oxide to have enhanced water solubility and a good corrosion mitigation capacity. Fourier-transform infrared (FT-IR) spectroscopy was utilized to evaluate the main functional groups of the inhibitor. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curves (PDP) showed that the inhibitor acts as a mixed-type inhibitor. The inhibitory efficiency (IE) improved as the concentration increased to a value of 96% after one hour of exposure to a medium containing 60 mg/L ppm of the inhibitor. According to thermodynamic calculations, the adsorption of the inhibitor on the AA2024-T3 surface in 3% NaCl followed the Langmuir isotherm. The formation of a barrier layer was further confirmed by surface analysis. The protective film prevented the alloy dissolution and limited the accessibility of attacking ions, as evinced by solution analysis techniques.

Keywords: AA2024-T3, NaCl, electrochemical methods, FT-IR, SEM/AFM, DFT, MC simulation

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Authors: Yan-Shiang Chiou, Yi-Huang Hsueh

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Bacillus cereus is a foodborne pathogen that causes two types of foodborne illness, the emetic and diarrheal syndromes. B. cereus consistently ranks among the top three among bacterial foodborne outbreaks in the ten years of 2001 to 2010 in Taiwan. Foodborne outbreak caused by B. cereus has been increased, and recently it ranks second foodborne pathogen after Vibrio parahaemolyticus. This pathogen is difficult to control due to its ubiquitousness in the environment, the psychrotrophic nature of many strains, and the heat resistance of their spores. Because complete elimination of biofilms is difficult, a better understanding of the molecular mechanisms of biofilm formation by B. cereus will help to develop better strategies to control this pathogen. Surface translocation can be an important factor in biofilm formation. In B. cereus, NprR is a quorum sensor, and its apo NprR is a dimer and changes to a tetramer in the presence of NprX. The small peptide NprX may induce conformational change allowing the apo dimer to switch to an active tetramer specifically recognizing target DNA sequences. Our result showed that mutation of nprRX causes surface spreading deficiency. Mutation of flagella, pili and surfactant genes (flgAB, bcpAB, krsABC), did not abolish spreading motility. Under nprRX mutant, mutation of spo0A restored the spreading deficiency. This suggests that spreading motility is not related surfactant, pili and flagella but other unknown mechanism and Spo0A, a sporulation initiation protein, inhibits spreading motility.

Keywords: Bacillus cereus, nprRX, spo0A, spreading motility

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Authors: Sally Shepherd, Richard De Boer, Craig Murphy

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Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

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Authors: Ali Driouiche, Abdallah Hadfi

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During this work on scaling phenomenon observed in the irrigation water pipes in the agricultural region of Greater Agadir, a follow-up was carried out during a year of the physico-chemical quality of these waters. Sampling was conducted from 120 sampling points, well distributed in the study area and involved 120 water samples. The parameters measured for each sample are temperature, pH, conductivity, total hardness and the concentrations of the ions HCO₃₋, Ca²⁺, Mg²⁺, Na⁺, K⁺, SO₄₋, NO₃₋, Cl₋ and OH₋. Indeed, the monitoring of the physico-chemical quality shows that the total hardness varies between 20 and 65 °F and the complete alkalimetric title varies from 14 °F to 42 °F. For the kinetic study of the scaling power, an object of this work, 6 samples which have high hardness were selected from the 120 samples analyzed. This study was carried out using the controlled degassing method Laboratoire de Chimie et de Génie de l’Environnement (LCGE) where it was developed) and showed that the studied waters are calcifying. The germination time Tg varies between 16 and 34 minutes. The highlighting of new scale inhibitors to prevent the formation of scale in the pipelines of the agricultural sector of Greater Agadir will also be discussed.

Keywords: agadir, clogging pipes, localized irrigation, scaling power

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Authors: Naveed Ahmad Fazili

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More than 20 human diseases involve the fibrillation of a specific protein/peptide which forms pathological deposits at various sites. Hereditary lysozyme amyloidosis is a systemic disorder which mostly affects liver, spleen and kidney. This conformational disorder is featured by lysozyme fibril formation. In vivo lysozyme fibrillation was simulated under in vitro conditions using a strong denaturant GdHCl at 3M concentration. Sharp decline in the ANS fluorescence intensity compared to the partially unfolded states, almost 20 fold increase in ThT fluorescence intensity, increase in absorbance at 450 nm suggesting turbidity, negative ellipticity peak in the far-UVCD at 217 nm, red shift of 50 nm compared to the native state in congo red assay and appearance of a network of long rope like fibrils in TEM analysis suggested HEWL fibrillation. Anti-fibrillation potency of baicalein against the preformed fibrils of HEWL was investigated following ThT assay in which there was a dose dependent decrease in ThT fluorescence intensity compared to the fibrillar state of HEWL with the maximum effect observed at 150 μM baicalein concentration, loss of negative ellipticity peak in the far-UVCD region, dip in the Rayleigh scattering intensity and absorbance at 350 nm and 450 nm respectively together with a reduction in the density of fibrillar structure in TEM imaging. Thus, it could be suggested that baicalein could prove to be a positive therapeutics for hereditary human lysozyme amyloidosis.

Keywords: amyloid fibrils, baicalein, congo red, negative ellipticity, therapeutics

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Authors: Houria Hamitouche, Abdellah Khelifa

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Quaternary ammonium salts (QACs) are the most common cationic surfactants of natural or synthetic origin usually. They possess one or more hydrophobic hydrocarbon chains and hydrophilic cationic group. In fact, the hydrophobic groups are derived from three main sources: petrochemicals, vegetable oils, and animal fats. These QACs have attracted the attention of chemists for a long time, due to their general simple synthesis and their broad application in several fields. They are important as ingredients of cosmetic products and are also used as corrosion inhibitors, in emulsion polymerization and textile processing. Within biological applications, QACs show a good antimicrobial activity and can be used as medicines, gene delivery agents or in DNA extraction methods. The 2004 worldwide annual consumption of QACs was reported as 500,000 tons. The petroleum product is considered a true reservoir of a variety of chemical species, which can be used in the synthesis of quaternary ammonium salts. The purpose of the present contribution is to synthesize the quaternary ammonium salts by Menschutkin reaction, via chloromethylation/quaternization sequences, from Algerian petroleum products namely: reformate, light naphtha and kerosene and characterize.

Keywords: quaternary ammonium salts, reformate, light naphtha, kerosene

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Authors: Nety Trisnawaty, Mirna Febriani

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The use of stainless steel wires in the field of dentistry is widely used, especially for orthodontic and prosthodontic treatment using stainless steel wire. The oral cavity is the ideal environment for corrosion, which can be caused by saliva. Prevention of corrosion on stainless steel wires can be done by using an organic or non-organic corrosion inhibitor. One of the organic inhibitors that can be used to prevent corrosion is black tea leaves extracts. To explain the comparison of chromium ions release for stainlees steel between artificial saliva and black tea leaves extracts. In this research we used artificial saliva, black tea leaves extracts, stainless steel wire and using Atomic Absorption Spectrophometric testing machine. The samples were soaked for 1, 3, 7 and 14 days in the artificial saliva and black tea leaves extracts. The results showed the difference of chromium ion release soaked in artificial saliva and black tea leaves extracts on days 1, 3, 7 and 14. Statistically, calculation with independent T-test with p < 0,05 showed a significant difference. The longer the duration of days, the more ion chromium were released. The conclusion of this study shows that black tea leaves extracts can inhibit the corrosion rate of stainless steel wires.

Keywords: chromium ion, stainless steel, artificial saliva, black tea leaves extracts

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Authors: Mohammad Ahmad Ahmad Odah

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Aging is a complex biological process characterized by the progressive decline of physiological functions and increased vulnerability to age-related diseases. Epigenetic changes, particularly DNA methylation alterations, play a critical role in the aging process by influencing gene expression and genomic stability. This study explores the potential of epigenetic reprogramming as a strategy to reverse aging phenotypes in human fibroblasts. Using CRISPR-Cas9 gene editing and small molecule inhibitors targeting DNA methylation and histone acetylation, we successfully induced significant changes in DNA methylation and gene expression profiles. Our results demonstrate a global reduction in DNA methylation levels and the identification of differentially methylated regions (DMRs) associated with cellular senescence and DNA repair. Additionally, treated fibroblasts exhibited enhanced proliferative capacity, reduced cellular senescence, and improved differentiation potential. These findings suggest that epigenetic reprogramming could be a promising approach for regenerative medicine, offering potential therapeutic strategies to counteract age-related decline and extend healthy lifespan.

Keywords: epigenetic reprogramming, aging, regenerative medicine, DNA methylation, cellular rejuvenation, CRISPR-Cas9, senescence

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Bendjazia Radia, Samira Kilani-Morakchi, Nadia Aribi

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Azadirachtin is a biorational insecticide commonly reported as selective to a range of beneficial insects. It is one of the most biologically active natural inhibitors of insect growth and development and it is known to be an antagonist of the juvenile hormone and 20-hydroxyecdysone (20E). However, its mechanism of action remains still unknown. In the present study, the toxicity of a commercial formulation of Azadirachtin (Neem Azal, 1% azadirachtine) was evaluated by topical application at various doses (0.1, 0.25, 0.5, 1 and 2 µg/insect) on the third instars larvae of D. melanogaster. Lethal doses (LD25: 0.28µg and LD50: 0.67µg), were evaluated by cumulated mortality at the immature stages. The effects of azadirachtin (LD25 and LD50) were then evaluated on the development (duration of the larval and pupal instars, the weight of larvae, pupa and adults) of Drosophila melanogaster. Results showed that the insecticide increased significantly the larval and pupal instar duration. A reduction of larval and pupal weight is noted under azadirachtin treatment as compared to controls. In addition, the weight of surviving adults at the two tested dose was also reduced. In conclusion, azadirachtin seemed to interfere with the functions of the endocrine system resulting in development defects.

Keywords: azadirachtin, d.melanogaster, toxicity, development

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Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

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Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

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Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu

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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.

Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition

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Authors: Dina Helmy El-Ghonemy, Thanaa Hamed Ali

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The aim of this study was to purify and characterize a keratinolytic enzyme produced by Aspergillus sp. DHE7 cultured in basal medium containing chicken feather as substrate. The enzyme was purified through ammonium sulfate saturation of 60%, followed by gel filtration chromatography in Sephadex G-100, with a 16.4-purification fold and recovery yield of 52.2%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the purified enzyme is a monomeric enzyme with an apparent molecular mass of 30 kDa — the purified keratinase of Aspergillus sp. DHE7 exhibited activity in a broad range of pH (7- 9) and temperature (40℃-60℃) profiles with an optimal activity at pH eight and 50℃. The keratinolytic activity was inhibited by protease inhibitors such as phenylmethylsulfonyl fluoride and ethylenediaminetetraacetate, while no reduction of activity was detected by the addition of dimethyl sulfoxide (DMSO). Bivalent cations, Ca²⁺ and Mn²⁺, were able to greatly enhance the activity of keratinase by 125.7% and 194.8%, respectively, when used at one mM final concentration. On the other hand, Cu²⁺ and Hg²⁺ inhibited the enzyme activity, which might be indicative of essential vicinal sulfhydryl groups of the enzyme for productive catalysis. Furthermore, the purified keratinase showed significant stability and compatibility against the tested commercial detergents at 37ºC. Therefore, these results suggested that the purified keratinase from Aspergillus sp. DHE7 may have potential use in the detergent industry and should be of interest in the processing of poultry feather waste.

Keywords: Aspergillus sp. DHE7, biochemical characterization, keratinase, purification, waste management

Procedia PDF Downloads 126

Authors: Gagan Dhawan

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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

Procedia PDF Downloads 371

Authors: Satya Eswari Jujjavarapu, Swast Dhagat

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Contagious diseases enact severe public health problems and have upsetting consequences. The cyclic lipopeptides explained by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very critical in confining the pathogens. As the degree of drug resistance upsurges in unparalleled manner, the perseverance of searching novel cyclic lipopeptides is being professed. The intense study has shown the implication of these bioactive compounds extending beyond antibacterial and antifungal. Lipopeptides, composed of single units of peptide and fatty acyl moiety, show broad spectrum antimicrobial effects. Among the surplus of cyclic lipopeptides, only few have materialized as strong antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin and bacillomycin have been integrated in mainstream healthcare. In our work daptomycin has been a major part of antimicrobial resource since the past decade. Daptomycin, a cyclic lipopeptide consists of 13-member amino acid with a decanoyl side-chain. This structure of daptomycin confers it the mechanism of action through which it forms pore in the bacterial cell membrane resulting in the death of cell. Daptomycin is produced by Streptococccus roseoporus and acts against Streptococcus pneumonia (PSRP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The PDB structure and ligands of daptomycin are available online. The molecular docking studies of these ligands with the lipopeptides were performed and their docking score and glide energy were recorded.

Keywords: daptomycin, molecular docking, structure-based drug design, lipopeptide

Procedia PDF Downloads 266

Authors: Farhat Sultana

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Originality: TQM principles are considered the tools to enhance organizational performance for most organizations. The paper contributes to the literature on the social enterprise because social organizations are still far behind in implementing TQM as compared to other private, public, and nonprofit organizations. Study design: The study is based on the data and information provided by two case studies and one focus group of social enterprises. Purpose: The purpose of the study is to get a deep understating of TQM implementation and to recognize the enablers of TQM in social enterprises that enhance the organizational performance of social enterprises located in UAE. Findings: As per the findings of the study, key enablers of Total Quality management in the case enterprises are leadership support, strategic approach for quality, continuous improvement, process improvement, employee empowerment and customer focus practices, though some inhibitors for TQM implementation such as managerial structure for quality assurance and performance appraisal mechanism are also pointed out by the study. Research limitations: The study findings are only based on two case studies and one focus group, which is not enough to generalize the findings to all social organizations. Practical Implications: Identified TQM enablers can help management to implement TQM successfully in social enterprises. Social implications: The study provides enabling path for Social enterprises to implement TQM to seek quality output to build a better society.

Keywords: TQM, social enterprise, enablers of TQM, UAE

Procedia PDF Downloads 113

Authors: Muhammad Arsalan Khan Sherwani

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The use of Volatile Corrosion Inhibitors (VCI) to protect Aboveground Storage Tank (AST) bottom plates against soil-side corrosion is one of the emerging corrosion prevention methods, specifically for tanks constructed on oily sand pad. Oily sand pad and the presence of air gaps underneath the bottom plates lead to severe corrosion and high metal thickness loss. In such cases, the cathodic protection cannot be fully considered as effective due to Cathodic Protection (CP) current shielding. These situations sometimes result in serious failures on multiple fronts, such as; containment losses, system shutdowns, extensive repairs, environmental impact and safety concerns in case of flammable fluids. Recently, East West Pipeline Department (EWPD) of Saudi Aramco has deployed this technology to one of the crude oil storage tanks, which showed high metal thickness loss during its out of service inspection. Soil-side corrosion rustled in major repairs of bottom plates and ultimately caused enormous unplanned activities in term of time as well as cost. This paper mainly focuses on the methodology of VCI installation, corrosion monitoring system and the expected results of protection.

Keywords: Vapor Corrosion Inhibitor, Soil Side Corrosion, External Corrosion, Above Grade Storage Tank

Procedia PDF Downloads 75

Authors: Neeraj Kumar Mishra, In Su Kim

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The isoindoline, indazole and indole heterocycles are ubiquitous structural motif found in heterocyclic compounds as they exhibit biological and medicinal applications. For example, isoindoline motif is present in molecules that act as endothelin-A receptor antagonists and dipeptidyl peptidase inhibitors. Moreover, isoindoline derivatives are very crucial constituents in the field of materials science as attractive candidates for organic light-emitting devices. However, compounds containing the indazole motif are known to exhibit to a variety of biological activities, such as estrogen receptor, HIV protease inhibition and anti-tumor activity. The prevalence of indazoles and indoles has led to the development of many useful methods for their preparation. Thus, isoindoline, indazole and indole heterocycles can be new candidates for the next generation of pharmaceuticals. Therefore, the development of highly efficient strategies for the formation of these heterocyclic architectures is an area of great interest in organic synthesis. The past years, transition-metal-catalyzed C−H activation followed by annulation reaction has been frequently used as a powerful tool to construct various heterocycles. Herein, we describe our recent achievements about the transition-metal-catalyzed tandem cyclization reactions of N-benzyltriflamides, 1,2-disubstituted arylhydrazines, acetanilides, etc. via C−H bond activation to access the corresponding bioactive heterocylic scaffolds.

Keywords: biologically active, C-H activation, heterocyclic compounds, transition-metal catalysts

Procedia PDF Downloads 309