Search results for: cardiac myosin binding protein-C

Authors: Mahdiyeh Gholaminezhad

Abstract:

Context: The study focuses on the potential impact of Sorafenib on SOAT1 protein in liver cancer treatment, addressing the need for more effective therapeutic options. Research aim: To explore the effects of Sorafenib on the activity of SOAT1 protein in liver cancer cells. Methodology: Molecular docking was employed to analyze the interaction between Sorafenib and SOAT1 protein. Findings: The study revealed a significant effect of Sorafenib on the stability and activity of SOAT1 protein, suggesting its potential as a treatment for liver cancer. Theoretical importance: This research highlights the molecular mechanism underlying Sorafenib's anti-cancer properties, contributing to the understanding of its therapeutic effects. Data collection: Data on the molecular structure of Sorafenib and SOAT1 protein were obtained from computational simulations and databases. Analysis procedures: Molecular docking simulations were performed to predict the binding interactions between Sorafenib and SOAT1 protein. Question addressed: How does Sorafenib influence the activity of SOAT1 protein and what are the implications for liver cancer treatment? Conclusion: The study demonstrates the potential of Sorafenib as a targeted therapy for liver cancer by affecting the activity of SOAT1 protein. Reviewers' Comments: The study provides valuable insights into the molecular basis of Sorafenib's action on SOAT1 protein, suggesting its therapeutic potential. To enhance the methodology, the authors could consider validating the docking results with experimental data for further validation.

Keywords: liver cancer, sorafenib, SOAT1, molecular docking

Procedia PDF Downloads 26

Authors: Herviyanti, Gusnidar, M. Harianti

Abstract:

The objective of this research were: a) using low-rank coal (subbituminous) as main humate material sources because this material will not be anthracite, and cannot using to be an energy sources b) to examine residual effects of humic matter from subbituminous which was combined with P fertilizers to adsorp Al and Fe metal, improving soil fertility, and increasing P fertilizing efficiency and Oxisol productivity. Therefore, optimalization crop productivity of upland rice can be achieved. The experiment was designed using a 3 x 4 factorial with 3 replications in randomly groups design. The 1st factor was 3 ways incubating humate material with P-fertilizer, which are: I1 = Incubation of humate material 1 week, then incubation P-fertilizers 1 week; I2 = Incubation of humate materials and P fertilizers directly into the soil for 2 weeks; and I3 = humate material and P fertilizer mixed for 1 week, then incubation to the soil for 1 week. The 2nd factor was residual effects of humate material and P-fertilizer combination which are 4 doses H1 = 400 ppm (0.8 Mg/ha) + 100% R; H2 = 400 ppm + 75% R; H3 = 800 ppm (1.6 Mg/ha) + 100% R,; and H4 = 800 ppm + 75% R. The 2nd year research results showed that the best treatment was founded residue effect of 800 ppm humate material and 100% R P-fertilizer doses in I3 way incubation that is equal to 6.19 t ha-1 upland rice yield. However, this result is almost the same as residual effects of 800 ppm humate material + 75% R P-fertilizer doses and upland rice yield the 1st year. It was concluded that addition of humate material can given the efficiency of P-fertilizer using up to 25% until the 2nd season planted.

Keywords: humate materials, P-fertilizer, subbituminous, upland rice

Procedia PDF Downloads 389

Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder

Abstract:

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.

Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands

Procedia PDF Downloads 388

Authors: Talakokula Visalakshi

Abstract:

Concrete is the most commonly used construction material across the globe, its usage is second only to water. It is prepared using ordinary Portland cement whose production contributes to 5-8% of total carbon emission in the world. On the other hand the fly ash by product from the power plants is produced in huge quantities is termed as waste and disposed in landfills. In order to address the above issues mentioned, it is essential that other forms of binding material must be developed in place of cement to make concrete. The geo polymer concrete is one such alternative developed by Davidovits in 1980’s. Geopolymer do not form calcium-silicate hydrates for matrix formation and strength but undergo polycondensation of silica and alumina precursors to attain structural strength. Its setting mechanism depends upon polymerization rather than hydration. As a result it is able to achieve its strength in 3-5 days whereas concrete requires about a month to do the same. The objective of this research is to assess the performance of geopolymer concrete under sulphate and acid attack. The assessment is done based on the experiments conducted on geopolymer concrete. The expected outcomes include that if geopolymer concrete is more durable than normal concrete, then it could be a competitive replacement option of concrete and can lead to significant reduction of carbon foot print and have a positive impact on the environment. Fly ash based geopolymer concrete offers an opportunity to completely remove the cement content from concrete thereby making the concrete a greener and future construction material.

Keywords: fly ash, geo polymer, geopolymer concrete, construction material

Procedia PDF Downloads 488

Authors: Sheila R. Pai, Rekha D. Kini, Amrutha Mary

Abstract:

Objective: To assess and compare the cardiac autonomic activity after mental stress among the wards of normal and hypertensive parents. Methods: The study included 67 subjects, 30 of them had a parental history of hypertension and rest 37 had normotensive parents. Subjects were divided into control group (wards of normotensive parents) and Study group (wards of hypertensive parents). The height, weight were noted, and Body Mass Index (BMI) was also calculated. The mental stress test was carried out. Blood pressure (BP) and electro cardiogram (ECG) was recorded during normal breathing and after mental stress test. Heart rate variability (HRV) analysis was done by time domain method HRV was recorded and analyzed by the time-domain method. Analysis of HRV in the time-domain was done using the software version 1.1 AIIMS, New Delhi. The data obtained was analyzed using student’s t-test followed by Mann-Whitney U-test and P < 0.05 was considered significant. Results: There was no significant difference in systolic blood pressure and diastolic blood pressure (DBP) between study group and control group following mental stress. In the time domain analysis, the mean value of pNN50 and RMSSD of the study group was not significantly different from the control group after the mental stress test. Conclusion: The study thus concluded that there was no significant difference in HRV between study group and control group following mental stress.

Keywords: heart rate variability, time domain analysis, mental stress, hypertensive

Procedia PDF Downloads 273

Authors: Chandra Mukherjee

Abstract:

The prevalent knowledge of the biological systems is based on the standard scientific perception of natural equilibrium, determination and predictability. Recently, a rethinking of concepts was presented and a new scientific perspective emerged that involves complexity theory with deterministic chaos theory, nonlinear dynamics and theory of fractals. The unpredictability of the chaotic processes probably would change our understanding of diseases and their management. The mathematical definition of chaos is defined by deterministic behavior with irregular patterns that obey mathematical equations which are critically dependent on initial conditions. The chaos theory is the branch of sciences with an interest in nonlinear dynamics, fractals, bifurcations, periodic oscillations and complexity. Recently, the biomedical interest for this scientific field made these mathematical concepts available to medical researchers and practitioners. Any biological network system is considered to have a nominal state, which is recognized as a homeostatic state. In reality, the different physiological systems are not under normal conditions in a stable state of homeostatic balance, but they are in a dynamically stable state with a chaotic behavior and complexity. Biological systems like heart rhythm and brain electrical activity are dynamical systems that can be classified as chaotic systems with sensitive dependence on initial conditions. In biological systems, the state of a disease is characterized by a loss of the complexity and chaotic behavior, and by the presence of pathological periodicity and regulatory behavior. The failure or the collapse of nonlinear dynamics is an indication of disease rather than a characteristic of health.

Keywords: HRV, HRVI, LF, HF, DII

Procedia PDF Downloads 425

Authors: Shuafeng Yuan, Bojian Zheng

Abstract:

The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

Procedia PDF Downloads 245

Authors: Gizem Buldum, Alexander Bismarck, Athanasios Mantalaris

Abstract:

Cellulose is the most abundant biopolymer on earth and it is currently being utilised in a multitude of industrial applications. Over the last 30 years, attention has been paid to the bacterial cellulose (BC), since BC exhibits unique physical, chemical and mechanical properties when compared to plant-based cellulose, including high purity and biocompatibility. Although Acetobacter xylinum is the most efficient producer of BC, it’s long doubling time results in insufficient yields of the cellulose production. This limits widespread and continued use of BC. In this study, E. coli BL21 (DE3) or E. coli HMS cells are selected as host organisms for the expression of bacterial cellulose synthase operon (bcs) of A.xylinum. The expression system is created based on pET-Duet1 and pCDF plasmid vectors, which carry bcs operon. The results showed that all bcs genes were successfully transferred and expressed in E.coli strains. The expressions of bcs proteins were shown by SDS and Native page analyses. The functionality of the bcs operon was proved by congo red binding assay. The effect of culturing temperature and the inducer concentration (IPTG) on cell growth and plasmid stability were monitored. The percentage of plasmid harboring cells induced with 0.025 mM IPTG was obtained as 85% at 22˚C in the end of 10-hr culturing period. It was confirmed that the high output cellulose production machinery of A.xylinum can be transferred into other organisms.

Keywords: bacterial cellulose, biopolymer, recombinant expression system, production

Procedia PDF Downloads 401

Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

Abstract:

Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

Procedia PDF Downloads 412

Authors: Khushboo Bhavsar, Nisha K. Shah, Neha Parekh

Abstract:

The status of wastewater treatment needs a novel and quick method for treating the wastewater containing ammoniacal nitrogen. Adsorption behavior of ammoniacal nitrogen from wastewater using the nanoparticles loaded coconut coir was investigated in the present work. Manganese Oxide (MnO2) and Zinc Oxide (ZnO) nanoparticles were prepared and used for the further adsorption study. Manganese nanoparticles loaded coconut coir (MNLCC) and Zinc nanoparticles loaded coconut coir (ZNLCC) were prepared via a simple method and was fully characterized. The properties of both MNLCC and ZNLCC were characterized by Scanning electron microscopy, Fourier Transform Infrared Spectroscopy and X-ray diffraction. Adsorption characteristics were studied using batch technique considering various parameters like pH, adsorbent dosage, time, temperature and agitation time. The NH3-N adsorption process for MNLCC and ZNLCC was thoroughly studied from both kinetic and equilibrium isotherm view-points. The results indicated that the adsorption efficiency of ZNLCC was better when compared to MNLCC. The adsorption kinetics at different experimental conditions showed that second order kinetic model best fits ensuring the monovalent binding sites existing in the present experimental system. The outcome of the entire study suggests that the ZNLCC can be a smart option for the treatment of the ammoniacal nitrogen containing wastewater.

Keywords: ammoniacal nitrogen, MnO2, Nanoparticles, ZnO

Procedia PDF Downloads 356

Authors: Wan Azuati Wan Omar, Selva Rani John Jasudass, Siti Rohaiza Md. Saad

Abstract:

Introduction & objective: The objectives of this study were to assess patient’s knowledge of appropriate sublingual glyceryl trinitrate (GTN) use as well as to investigate how patients commonly store and carry their sublingual GTN tablets. Methodology: This was a cross-sectional survey, using a validated researcher-administered questionnaire. The study involved cardiac patients receiving sublingual GTN attending the outpatient and inpatient departments of Taiping Hospital, a non-academic public care hospital. The minimum calculated sample size was 92, but 100 patients were conveniently sampled. Respondents were interviewed on 3 areas, including demographic data, knowledge and use of sublingual GTN. Eight items were used to calculate each subject’s knowledge score and six items were used to calculate use score. Results: Of the 96 patients who consented to participate, majority (96.9%) were well aware of the indication of sublingual GTN. With regards to the mechanism of action of sublingual GTN, 73 (76%) patients did not know how the medication works. Majority of the patients (66.7%) knew about the proper storage of the tablet. In relation to the maximum number of sublingual GTN tablets that can be taken during each angina episode, 36.5% did not know that up to 3 tablets of sublingual GTN can be taken during each episode of angina. Fifty four (56.2%) patients were not aware that they need to replace sublingual GTN every 8 weeks after receiving the tablets. Majority (69.8%) of the patients demonstrated lack of knowledge with regards to the use of sublingual GTN as prevention of chest pain. Conclusion: Overall, patients’ knowledge regarding the self administration of sublingual GTN is still inadequate. The findings support the need for more frequent reinforcement of patient education, especially in the areas of preventive use, storage and drug stability.

Keywords: glyceryl trinitrate, knowledge, adherence, patient education

Procedia PDF Downloads 397

Authors: Liu Xiaohan

Abstract:

Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

Procedia PDF Downloads 62

Authors: Sanja O. Podunavac-Kuzmanović, Lidija R. Jevrić, Strahinja Z. Kovačević

Abstract:

In last decade, metal-organic complexes have captured intensive attention because of their wide range of biological activities such as antibacterial, antifungal, anticancerous, antimicrobial and antiHIV. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In view of our studies, we reasoned that benzimidazoles complexed to metal ions could act as a potent antibacterial agents. Thus, we have bioassayed the inhibitory potency of benzimidazoles and their metal salts (Co or Ni) against Gram negative bacteria Escherichia coli. In order to validate our in vitro study, we performed in silico studies using molecular docking software’s. The investigated compounds and their metal complexes (Co, Ni) showed good antibacterial activity against Escherichia coli. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and enhanced antibacterial activity in comparison with noncomplexed ligands. In view of their enhanced inhibitory properties we propose that the studied complexes can be used as potential pharmaceuticals. This study is financially supported by COST action CM1306 and the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina.

Keywords: benzimidazoles, complexes, antibacterial, Escherichia coli, metal

Procedia PDF Downloads 317

Authors: Mariana Sary Khalifa Rezk

Abstract:

The problem of respect for human rights in Southeast Asia has emerged as a main situation and is attracting the attention of the international network. Basically, the affiliation of Southeast Asian Nations (ASEAN) made human rights certainly one of its main troubles inside the ASEAN constitution in 2008. In the end, the Intergovernmental Fee on Human Rights ASEAN Human Rights (AICHR) was set up. AICHR is the Southeast Asia Human Rights Enforcement fee charged with the duties, functions and powers to sell and defend human rights. However, at the cease of 2016, the protecting feature assigned to the AICHR was no longer fulfilled. That is shown via several instances of human rights violations, which can be nonetheless ongoing and have not been solved. One case that has these days come to light is human rights violations against the Rohingya people in Myanmar. Using a felony-normative method, the study examines the urgency of setting up a human rights tribunal in Southeast Asia able to decide binding on ASEAN members or responsible parties. Information indicates ASEAN desires regional courts to cope with human rights abuses in the ASEAN region. Furthermore, the look also highlights 3 critical elements that ASEAN ought to take into account whilst establishing a human rights tribunal, particularly quantity. A good sized distinction in phrases of democracy and human rights improvement a few of the participants, a consistent implementation of the principle of non-interference and the economic trouble of the continuation of the court docket.

Keywords: politics, human rights, humanities, mankind, law human rights, Nigerian legal provisions, shariah law, comparative study, charter

Procedia PDF Downloads 29

Authors: Juliet Udoudom

Abstract:

Complement ordering principles of natural language phrases (XPs) stipulate that Head terms be consistently placed phrase initially or phrase-finally, yielding two basic theoretical orders – Head – Complement order or Complement – Head order. This paper examines the principles which determine complement ordering in English V- and N-bar structures. The aim is to determine the extent to which complement linearisations in the two phrase types are consistent with the two theoretical orders outlined above given the flexible and varied nature of natural language structures. The objective is to see whether there are variation(s) in the complement linearisations of the XPs studied and the implications which such variations hold for the inter-language syntax of English and Ibibio. A corpus-based approach was employed in obtaining the English data. V- and -N – bar structures containing complement structures were isolated for analysis. Data were examined from the perspective of the X-bar and Government – theories of Chomsky’s (1981) Government-Binding format. Findings from the analysis show that in V – bar structures in English, heads are consistently placed phrase – initially yielding a Head – Complement order; however, complement linearisation in the N – bar structures studied exhibited parametric variations. Thus, in some N – bar structures in English the nominal head is ordered to the left whereas in others, the head term occurs to the right. It may therefore be concluded that the principles which determine complement ordering are both Language – Particular and Phrase – specific following insights provided within Phrasal Syntax.

Keywords: complement order, complement–head order, head–complement order, language–particular principles

Procedia PDF Downloads 348

Authors: Hae-Jun Lee, Ji-Sun Shin, Kyung-Tae Lee

Abstract:

Potentilla species (Rosasease) have been used in traditional medicine to treat different ailment, disease or malady. In this study, we investigated the anti-inflammatory effects of ethanol extracts of NUTT (EPP) in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages and septic mice. EPP suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS-induced Raw 264.7 macrophages. Consistent with these observations, EPP reduced the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by downregulation of their promoter activities. EPP inhibited tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) at production and mRNA levels. Molecularly, EPP attenuated the LPS-induced transcriptional activity, and DNA-binding activity of nuclear factor-κB (NF-κB), and this was associated with a decrease of translocation and phosphorylation of p65 NF-κB by inhibiting the inhibitory κB-α (IκB-α) degradation and IκB kinase-α/β (IKK-α/β) phosphorylation. Furthermore, EPP suppressed the LPS-induced activation of activator protein-1 (AP-1) by reducing the expression of c-Fos and c-Jun in nuclear. EPP also reduced the phosphorylation of mitogen-activated protein kinase (MAPK), such as p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). In a sepsis model, pretreatment with EPP reduced the LPS-induced lethality. Collectively, these results suggest that the anti-inflammatory effects of EPP were associated with the suppression of NF-κB and AP-1 activation, and support its possible therapeutic role for the treatment of sepsis.

Keywords: anti-inflammation, activator protein-1, nuclear factor κB, Potentilla paradoxa Nutt

Procedia PDF Downloads 334

Authors: Harish Rajak, Preeti Patel

Abstract:

HDAC inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. The 3D-QSAR and Pharmacophore modeling studies were performed to identify important pharmacophoric features and correlate 3D-chemical structure with biological activity. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with well-assigned HDAC inhibitory activity was used for 3D-QSAR model development. Best 3D-QSAR model, which is a five PLS factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811) and standard deviation (0.0952). Molecular docking were performed using Histone Deacetylase protein (PDB ID: 1t69) and prepared series of hydroxamic acid based HDAC inhibitors. Docking study of compound 43 show significant binding interactions Ser 276 and oxygen atom of dioxine cap region, Gly 151 and amino group and Asp 267 with carboxyl group of CONHOH, which are essential for anticancer activity. On docking, most of the compounds exhibited better glide score values between -8 to -10.5. We have established structure activity correlation using docking, energetic based pharmacophore modelling, pharmacophore and atom based 3D QSAR model. The results of these studies were further used for the design and testing of new HDAC analogs.

Keywords: Docking, e-pharmacophore, HDACIs, QSAR, Suberoylanilidehydroxamic acid.

Procedia PDF Downloads 301

Authors: Viktoriia Malinovska, Iryna Kuklina, Katerina Grabicova, Milos Buric, Pavel Kozak

Abstract:

Personal care products, including organic UV filters, are considered emerging contaminants and their toxic effects have been a concern for the last decades. Sunscreen compounds continually enter the surface waters via sewage water treatment due to incomplete removal and during human recreational and laundry activities. Despite the environmental occurrence of organic UV filters in the freshwater environment, little is known about their impacts on aquatic biota. In this study, environmentally relevant concentrations of 5-Benzoyl-4-hydroxy-2-methoxybenzenesulfonic acid (BP-4, 2.5 µg/L) and 2-Phenylbenzimidazole-5-sulfonic acid (PBSA, 3 µg/L) were used to evaluate the cardiac and locomotor responses of signal crayfish Pacifastacus leniusculus during a short time period. The effects of these compounds were evident in experimental animals. Specimens exposed to both tested compounds exhibited significantly bigger changes in distance moved and time movement than controls. Significant differences in changes in mean heart rate were detected in both PBSA and BP-4 experimental groups compared to control groups. Such behavioral and physiological alterations demonstrate the ecological effects of selected sunscreen compounds during a short time period. Since the evidence of the impacts of sunscreen compounds is scarce, the knowledge of how organic UV filters influence aquatic organisms is of key importance for future research.

Keywords: aquatic pollutants, behavior, freshwaters, heart rate, invertebrate

Procedia PDF Downloads 105

Authors: Liang Jiansheng, Zhu Wei

Abstract:

Light and brassinosteroids are essential external and internal cues for plant survival. Although the coordination of light with phytohormone signals is crucial for plant growth and development, the molecular connection between light and brassinosteroid signaling during root soil penetration remains elusive. Here, we reveal that light-stabilized RACK1 couples a brassinosteroid signaling cascade to drive cell division in root meristems. RACK1 family scaffold proteins positively regulate light-induced the promotion of root elongation during soil penetration. Under the light condition, RACK1A interacts with both phyB and SPA1, then reinforces the phyB-SPA1 association to accumulate its abundance in roots. In response to brassinosteroid signals, RACK1A competes with BKI1 to attenuate the BRI1-BKI1 interaction, thereby leading to activating BRI1 actions in root development. Furthermore, RACK1A binds to BES1 to repress its DNA binding activity toward the target gene CYCD3;1. This ultimately allows to release the inhibition of CYCD3;1 transcription, and promotes cell division during root growth. Our study illustrates a new mechanistic model of how plants engage scaffold proteins in transducing light information to facilitate brassinosteroid signaling for root growth in the soil.

Keywords: root growth, cell division, light signaling, brassinosteroid signaling, soil penetration, scaffold protein, RACK1

Procedia PDF Downloads 80

Authors: Feng Ji Mervin Goh, Edmund Chee Jian Pua, Stuart Alexander Cook

Abstract:

Dilated cardiomyopathy (DCM) is a common cause of heart failure. Genetic mutations account for 50% of DCM cases with TTN mutations being the most common, accounting for up to 25% of DCM cases. However, the genetic architecture underlying Asian DCM patients is unknown. We evaluated 68 patients (female= 17) with DCM who underwent follow-up at the National Heart Centre, Singapore from 2013 through 2014. Clinical data were obtained and analyzed retrospectively. Genomic DNA was subjected to next-generation targeted sequencing. Nextera Rapid Capture Enrichment was used to capture the exons of a panel of 169 cardiac genes. DNA libraries were sequenced as paired-end 150-bp reads on Illumina MiSeq. Raw sequence reads were processed and analysed using standard bioinformatics techniques. The average age of onset of DCM was 46.1±10.21 years old. The average left ventricular ejection fraction (LVEF), left ventricular diastolic internal diameter (LVIDd), left ventricular systolic internal diameter (LVIDs) were 26.1±11.2%, 6.20±0.83cm, and 5.23±0.92cm respectively. The frequencies of mutations in major DCM-associated genes were as follows TTN (5.88% vs published frequency of 20%), LMNA (4.41% vs 6%), MYH7 (5.88% vs 4%), MYH6 (5.88% vs 4%), and SCN5a (4.41% vs 3%). The average callability at 10 times coverage of each major gene were: TTN (99.7%), LMNA (87.1%), MYH7 (94.8%), MYH6 (95.5%), and SCN5a (94.3%). In conclusion, TTN mutations are not common in Singaporean DCM patients. The frequencies of other major DCM-associated genes are comparable to frequencies published in the current literature.

Keywords: heart failure, dilated cardiomyopathy, genetics, next-generation sequencing

Procedia PDF Downloads 243

Authors: Jarel Elgin Tolentino, Arby Denise Nera, Mary Rose Roco, Angela Vianca Aspa, Nikko Beltran, Else Dapat

Abstract:

Drug resistance by cells has been the problem in the medical field for decades now. The use of medicinal plants as a source of creating powerful drugs has been nowadays recognized worldwide to treat such resistant diseases. In the present study, the potential for Diospyros philippinensis A. DC. to inhibit growth of both bacteria and cancer cell line was conducted. The leaf crude extracts were screened for the presence of phytochemicals and examined for potential bioactivities by employing several assays like Kirby-Bauer disc diffusion method, DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay for the antibacterial, antioxidant and cytotoxic activities of the extract, respectively. Phytochemical test results of the extracts revealed the presence of alkaloids, flavonoids, saponins, phenols, quinones, cardiac glycosides, phlobatannins, carbohydrate, cardenolides and proteins. The leaf extracts were found to exhibit antibacterial activity against gram-positive bacteria, high antioxidant activity (99.22% ± 0.005) but did not show any sign of cytotoxicity towards HCT116 (ATCC CCL-247). The study therefore concludes that D. philippinensis A. DC. leaf extract can be a source of antibacterial and chemopreventive agents. This claim may be used as basis for future investigation.

Keywords: bioassay, medicinal plants, plant crude extracts, phytochemical screening

Procedia PDF Downloads 281

Authors: Kolja Them, Priyal Chikhaliwala, Sudeshna Chandra

Abstract:

Purpose: The purpose of this work is to examine possibilities for noninvasive imaging and identification of tumor markers for cancer diagnosis. The proposed method uses antibody conjugated iron oxide nanoparticles and multicolor Magnetic Particle Imaging (mMPI). The method has the potential for radiation exposure free real-time estimation of local tumor marker concentrations in vivo. In this study, the method is applied to human Alpha-1-Fetoprotein. Materials and Methods: As tracer material AFP antibody-conjugated Dendrimer-Fe3O4 nanoparticles were used. The nanoparticle bioconjugates were then incubated with bovine serum albumin (BSA) to block any possible nonspecific binding sites. Parts of the resulting solution were then incubated with AFP antigen. MPI measurements were done using the preclinical MPI scanner (Bruker Biospin MRI GmbH) and the multicolor method was used for image reconstruction. Results: In multicolor MPI images the nanoparticles incubated only with BSA were clearly distinguished from nanoparticles incubated with BSA and AFP antigens. Conclusion: Tomographic imaging of human tumor marker Alpha-1-Fetoprotein is possible using AFP antibody conjugated iron oxide nanoparticles in presence of BSA. This opens interesting perspectives for cancer diagnosis.

Keywords: noninvasive imaging, tumor antigens, antibody conjugated iron oxide nanoparticles, multicolor magnetic particle imaging, cancer diagnosis

Procedia PDF Downloads 303

Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

Abstract:

Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

Procedia PDF Downloads 69

Authors: C. Bala Prashanth Reddy, B. Abhinay, C. Sreekar, D. V. Shobhana Priscilla

Abstract:

The project aims in designing an emergency pacemaker which is capable of giving shocks to a human heart which has stopped working suddenly. A pacemaker is a machine commonly used by cardiologists. This machine is used in order to shock a human’s heart back into usage. The way the heart works is that there are small cells called pacemakers sending electrical pulses to cardiac muscles that tell the heart when to pump blood. When these electrical pulses stop, the heart stops beating. When this happens, a pacemaker is used to shock the heart muscles and the pacemakers back into action. The way this is achieved is by rubbing the two panels of the pacemaker together to create an adequate electrical current, and then the heart gets back to the normal state. The project aims in designing a system which is capable of continuously displaying the heart beat and blood pressure of a person on LCD. The concerned doctor gets the heart beat and also the blood pressure details continuously through the GSM Modem in the form of SMS alerts. In case of abnormal condition, the doctor sends message format regarding the amount of electric shock needed. Automatically the microcontroller gives the input to the pacemaker which in turn gives the shock to the patient. Heart beat monitor and display system is a portable and a best replacement for the old model stethoscope which is less efficient. The heart beat rate is calculated manually using stethoscope where the probability of error is high because the heart beat rate lies in the range of 70 to 90 per minute whose occurrence is less than 1 sec, so this device can be considered as a very good alternative instead of a stethoscope.

Keywords: missing R wave, PWM, demand pacemaker, heart

Procedia PDF Downloads 482

Authors: Janneth Gonzalez, Marco Avila, George Barreto

Abstract:

GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

Procedia PDF Downloads 342

Authors: Ankit Kargeti, Ravikant Shrivastav, Tabish Rasheed

Abstract:

The electronic structure calculation for the nanoclusters of AsSiTeB/SiAsBTe quaternary semiconductor alloy belonging to the III-V Group elements was performed. Motivation for this research work was to look for accurate electronic and geometric data of small nanoclusters of AsSiTeB/SiAsBTe in the gaseous form. The two clusters, one in the linear form and the other in the bent form, were studied under the framework of Density Functional Theory (DFT) using the B3LYP functional and LANL2DZ basis set with the software packaged Gaussian 16. We have discussed the Optimized Energy, Frontier Orbital Energy Gap in terms of HOMO-LUMO, Dipole Moment, Ionization Potential, Electron Affinity, Binding Energy, Embedding Energy, Density of States (DoS) spectrum for both structures. The important findings of the predicted nanostructures are that these structures have wide band gap energy, where linear structure has band gap energy (Eg) value is 2.375 eV and bent structure (Eg) value is 2.778 eV. Therefore, these structures can be utilized as wide band gap semiconductors. These structures have high electron affinity value of 4.259 eV for the linear structure and electron affinity value of 3.387 eV for the bent structure form. It shows that electron acceptor capability is high for both forms. The widely known application of these compounds is in the light emitting diodes due to their wide band gap nature.

Keywords: density functional theory, DFT, density functional theory, nanostructures, HOMO-LUMO, density of states

Procedia PDF Downloads 114

Authors: Olga Blagova, Yuliya Osipova, Evgeniya Kogan, Alexander Nedostup

Abstract:

Purpose: to quantify the value of various clinical, laboratory and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. Methods: in 100 patients (65 men, 44.7±12.5 years) with «idiopathic» arrhythmias (n = 20) and dilated cardiomyopathy (DCM, n = 80) were performed 71 endomyocardial biopsy (EMB), 13 intraoperative biopsy, 5 study of explanted hearts, 11 autopsy with virus investigation (real-time PCR) of the blood and myocardium. Anti-heart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), coronary angiography (n = 47). The comparison group included of 50 patients (25 men, 53.7±11.7 years) with non-inflammatory heart diseases who underwent open heart surgery. Results. Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients of the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients of comparison group than in study group (group (65.0% and 40.2%; p < 0.01. Evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of anti-heart antibodies had the greatest importance to identify myocarditis: sensitivity was 81.5%, positive and negative predictive value was 75.0 and 60.5%. It is defined diagnostic value of non-invasive markers of myocarditis and diagnostic algorithm providing an individual assessment of the likelihood of myocarditis is developed. Conclusion. The greatest significance in the diagnosis of latent myocarditis in patients with 'idiopathic' arrhythmias and DCM have AHA. The use of complex of noninvasive criteria allows estimate the probability of myocarditis and determine the indications for EMB.

Keywords: myocarditis, "idiopathic" arrhythmias, dilated cardiomyopathy, endomyocardial biopsy, viral genome, anti-heart antibodies

Procedia PDF Downloads 173

Authors: Shalini Rankawat, Mansi Rankawat, Rahul Dubey, Mazad Zaveri

Abstract:

Physiological signals such as electrocardiogram (ECG) and arterial blood pressure (ABP) in the intensive care unit (ICU) are often seriously corrupted by noise, artifacts, and missing data, which lead to errors in the estimation of heart rate (HR) and incidences of false alarm from ICU monitors. Clinical support in ICU requires most reliable heart rate estimation. Cardiac activity, because of its relatively high electrical energy, may introduce artifacts in Electroencephalogram (EEG), Electrooculogram (EOG), and Electromyogram (EMG) recordings. This paper presents a robust heart rate estimation method by detection of R-peaks of ECG artifacts in EEG, EMG & EOG signals, using energy-based function and a novel Signal Quality Index (SQI) assessment technique. SQIs of physiological signals (EEG, EMG, & EOG) were obtained by correlation of nonlinear energy operator (teager energy) of these signals with either ECG or ABP signal. HR is estimated from ECG, ABP, EEG, EMG, and EOG signals from separate Kalman filter based upon individual SQIs. Data fusion of each HR estimate was then performed by weighing each estimate by the Kalman filters’ SQI modified innovations. The fused signal HR estimate is more accurate and robust than any of the individual HR estimate. This method was evaluated on MIMIC II data base of PhysioNet from bedside monitors of ICU patients. The method provides an accurate HR estimate even in the presence of noise and artifacts.

Keywords: ECG, ABP, EEG, EMG, EOG, ECG artifacts, Teager-Kaiser energy, heart rate, signal quality index, Kalman filter, data fusion

Procedia PDF Downloads 696

Authors: Strahinja Kovačević, Lidija Jevrić, Miloš Kuzmanović, Sanja Podunavac-Kuzmanović

Abstract:

In this paper, various derivatives of benzimidazole have been evaluated against Gram-negative bacteria Escherichia coli. For all investigated compounds the minimum inhibitory concentration (MIC) was determined. Quantitative structure-activity relationships (QSAR) attempts to find consistent relationships between the variations in the values of molecular properties and the biological activity for a series of compounds so that these rules can be used to evaluate new chemical entities. The correlation between MIC and some absorption, distribution, metabolism and excretion (ADME) parameters was investigated, and the mathematical models for predicting the antibacterial activity of this class of compounds were developed. The quality of the multiple linear regression (MLR) models was validated by the leave-one-out (LOO) technique, as well as by the calculation of the statistical parameters for the developed models and the results are discussed on the basis of the statistical data. The results of this study indicate that ADME parameters have a significant effect on the antibacterial activity of this class of compounds. Principal component analysis (PCA) and agglomerative hierarchical clustering algorithms (HCA) confirmed that the investigated molecules can be classified into groups on the basis of the ADME parameters: Madin-Darby Canine Kidney cell permeability (MDCK), Plasma protein binding (PPB%), human intestinal absorption (HIA%) and human colon carcinoma cell permeability (Caco-2).

Keywords: benzimidazoles, QSAR, ADME, in silico

Procedia PDF Downloads 375

Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay

Abstract:

Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.

Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression

Procedia PDF Downloads 284