Search results for: pathway analysis.

Authors: Jma Hannan, Prawej Ansari, Yasser H. A. Abdel-Wahab, Peter R. Flatt

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Spirulina platensis (SP, Blue-green algae) have been accepted as a supplement for the treatment of pre and post-diabetes. The present study investigated the effects of butanol fraction from ethanol extract of S. platensis on insulin release from BRIN BD11 cells, isolated mouse islets, and perfused rat pancreas, as well as glucose homeostasis in type 2 diabetic rats and their molecular pathways. In a dose-dependent manner, S. platensis increased insulin release from mouse islets and pancreatic β-cells. The extract also elevated insulin release in perfused rat pancreas. Glucose, isobutylmethylxanthine, tolbutamide, and a depolarizing concentration of KCl significantly potentiated insulin release from BRIN BD11 cells. The effect of diazoxide and verapamil, as well as the absence of extracellular Ca2+ showed a reduction in insulin secretion. When administered orally together with glucose (2.5g/kg bw), S. platensis extract improved fasting and postprandial blood glucose in type 2 diabetes. These data suggest that the anti-diabetic activity of S. platensis is partly mediated by insulin secretion via the KATP channel-dependent pathway/the intracellular cAMP pathway.

Keywords: Insulin, glucose, S. platensis, type 2 diabetes, medicinal plants

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Authors: Kawsar Ahmed, Hong Wang

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The study's goal was to estimate the causal mediation impact of tobacco tax before and after price hikes among low-income male smokers, with a particular emphasis on the effect estimating pathways framework for continuous and dichotomous variables. From July to December 2021, a cross-sectional investigation of observational data (n=739) was collected from Bangladeshi low-wage smokers. The Quasi-Bayesian technique, binomial probit model, and sensitivity analysis using a simulation of the computational tools R mediation package had been used to estimate the effect. After a price rise for tobacco products, the average number of cigarettes or bidis sticks taken decreased from 6.7 to 4.56. Tobacco product rising prices have a direct effect on low-income people's decisions to quit or lessen their daily smoking habits of Average Causal Mediation Effect (ACME) [effect=2.31, 95 % confidence interval (C.I.) = (4.71-0.00), p<0.01], Average Direct Effect (ADE) [effect=8.6, 95 percent (C.I.) = (6.8-0.11), p<0.001], and overall significant effects (p<0.001). Tobacco smoking choice is described by the mediated proportion of income effect, which is 26.1% less of following price rise. The curve of ACME and ADE is based on observational figures of the coefficients of determination that asses the model of hypothesis as the substantial consequence after price rises in the sensitivity analysis. To reduce smoking product behaviors, price increases through taxation have a positive causal mediation with income that affects the decision to limit tobacco use and promote low-income men's healthcare policy.

Keywords: causal mediation analysis, directed acyclic graphs, tobacco price policy, sensitivity analysis, pathway estimation

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Authors: Kwame B. O. Amoah

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This paper focuses on retrofitting an old existing office building to a net-zero energy building (NZEB). An existing small office building in Melbourne, Florida, was chosen as a case study to integrate state-of-the-art design strategies and energy-efficient building systems to improve building performance and reduce energy consumption. The study aimed to explore possible ways to maximize energy savings and renewable energy generation sources to cover the building's remaining energy needs necessary to achieve net-zero energy goals. A series of retrofit options were reviewed and adopted with some significant additional decision considerations. Detailed processes and considerations leading to zero energy are well documented in this study, with lessons learned adequately outlined. Based on building energy simulations, multiple design considerations were investigated, such as emerging state-of-the-art technologies, material selection, improvements to the building envelope, optimization of the HVAC, lighting systems, and occupancy loads analysis, as well as the application of renewable energy sources. The comparative analysis of simulation results was used to determine how specific techniques led to energy saving and cost reductions. The research results indicate this small office building can meet net-zero energy use after appropriate design manipulations and renewable energy sources.

Keywords: energy consumption, building energy analysis, energy retrofits, energy-efficiency

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Authors: S. K. Ashiquer Rahman

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The paper concentrates on the importance of Sustainable Campus Strategies, emphasizing the significance of mobilizing Innovative technological tools for constructing effectiveness of higher education strategy and institutional cooperation for sustainable campus at the university level and preparing the university’s authority to face the upcoming higher education strategy and institutional cooperation difficulties to the Sustainable Campus Plan. Within a framework of Sustainable Campus Strategies and institutional cooperation, the paper discusses the significance of a set of reference points that will lead to operational activities for multi-stakeholder multi-criteria evaluation of Higher Education and Research Institutions relative to the Sustainable Campus criteria and potential action plan for the University’s Strategy and Institutional Cooperation. It makes mention of the emergence of the effectiveness of Higher Education Strategy and Institutional Cooperation as well as the necessity of mobilizing innovative technological methods and tools for constructing the effectiveness of this Process. The paper outlines the conceptual framing of a Sustainable Campus Strategy, Institutional Cooperation and Action Plan for a sustainable campus. Optimistically, these will be a milestone in higher education, a pathway to meet the imminent Sustainable Campus Strategy and Institutional Cooperation of the completive world, and be able to manage the required criteria for a Sustainable University.

Keywords: higher education strategy, institutional cooperation, sustainable campus, multi-criteria evaluation, innovative method and tools

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Authors: Jeongyeob Hong, Myeonghoon Park, Taeson Yoon

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After the advent of Achaeans which utilize different metabolism pathway and contain conspicuously different cellular structure, they have been recognized as possible materials for developing quality of human beings. Among diverse Achaeans, in this paper, we compared 16s RNA Sequences of four different species of Thermococcus: Achaeans genus specialized in sulfur-dealing metabolism. Four Species, Barophilus, Kodakarensis, Hydrothermalis, and Onnurineus, live near the hydrothermal vent that emits extreme amount of sulfur and heat. By comparing ribosomal sequences of aforementioned four species, we found similarities in their sequences and expressed protein, enabling us to expect that certain ribosomal sequence or proteins are vital for their survival. Apriori algorithms and Decision Tree were used. for comparison.

Keywords: Achaeans, Thermococcus, apriori algorithm, decision tree

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Authors: Richard White, Anne Drabble, Maureen O’Neill

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The University of the Sunshine Coast (USC) offers secondary school students in the final two years of school (Years 11 and 12, 16 – 18 years of age) an opportunity to participate in a program which provides an accelerated pathway to tertiary studies. Whilst still at secondary school, the students undertake two first year university subjects that are required subjects in USC undergraduate degree programs. The program is called Integrated Learning Pathway (ILP) and offers a range of disciplines, including business, design, drama, education, and engineering. Between 2010 and 2014, 38% of secondary students who participated in an ILP program commenced undergraduate studies at USC following completion of secondary school studies. The research reported here considers “before and after” literacy and numeracy competencies of students to determine what impact participation in the ILP program has had on their academic skills. Qualitative and quantitative data has been gathered via numeracy and literacy testing of the students, and a survey asking the students to self-evaluate their numeracy and literacy skills, and reflect on their views of these academic skills. The research will enable improved targeting of teaching strategies so that students will acquire not only course-specific learning outcomes but also collateral academic skills. This enhancement of academic skills will improve undergraduate experience and improve student retention.

Keywords: academic skills enhancement, accelerated pathways, improved teaching, student retention

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Authors: Mingxi Zhou, Jiří Kubásek, Iva Mozgová

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In Arabidopsis thaliana, histone 3 lysine 27 tri-methylation catalysed byPRC2 is playing essential functions in the regulation of plant development, growth, and reproduction[1-2]. Despite numerous studies related to the role of PRC2 in developmental control, how PRC2 works in the operational control in plants is unknown. In the present, the evidence that PRC2 probably participates in the regulation of retrograde singalling pathway in Arabidopsisis found. Firstly, we observed that the rosette size and biomass in PRC2-depletion mutants (clf-29 and swn-3) is significantly higher than WTunder medium light condition (ML: 125 µmol m⁻² s⁻²), while under medium high light condition (MHL: 300 µmol m⁻² s-2), the increase was reverse. Under ML condition, the photosynthesis related parameters determined by fluorCam did not show significant differences between WT and mutants, while the pigments concentration increased in the leaf of PRC2-depletion mutants, especially in swn. The dynamic of light-responsive genes and circadian clock genes expression by RT-qPCRwithin 24 hours in the mutants were comparable to WT. However, we observed upregulation of photosynthesis-associated nuclear genes in the PRC2-depletion mutants under chloroplast damaging condition (treated by lincomycin), corresponding to the so-called genome uncoupled (gun) phenotype. Here, we will present our results describing these phenotypes and our suggestion and outlook for studying the involvement of PRC2 in chloroplast-to-nucleus retrograde signalling.

Keywords: PRC2, retrograde signalling, light acclimation, photosyntheis

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Authors: Rassoli Aisa, Abrishami Movahhed Arezu, Faturaee Nasser, Seddighi Amir Saeed, Shafigh Mohammad

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Cardiovascular diseases are one of the most common causes of mortality in developed countries. Coronary artery abnormalities and carotid artery stenosis, also known as silent death, are among these diseases. One of the treatment methods for these diseases is to create a deviatory pathway to conduct blood into the heart through a bypass surgery. The saphenous vein is usually used in this surgery to create the deviatory pathway. Unfortunately, a re-surgery will be necessary after some years due to ignoring the disagreement of mechanical properties of graft tissue and/or applied prostheses with those of host tissue. The objective of the present study is to clarify the viscoelastic behavior of human saphenous tissue. The stress relaxation tests in circumferential and longitudinal direction were done in this vein by exerting 20% and 50% strains. Considering the stress relaxation curves obtained from stress relaxation tests and the coefficients of the standard solid model, it was demonstrated that the saphenous vein has a non-linear viscoelastic behavior. Thereafter, the fitting with Fung’s quasilinear viscoelastic (QLV) model was performed based on stress relaxation time curves. Finally, the coefficients of Fung’s QLV model, which models the behavior of saphenous tissue very well, were presented.

Keywords: Viscoelastic behavior, stress relaxation test, uniaxial tensile test, Fung’s quasilinear viscoelastic (QLV) model, strain rate

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Farnaz Yusuf, Naseem A. Gaur

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The increase in environmental concerns, rapid depletion of fossil fuel reserves and intense interest in achieving energy security has led to a global research effort towards developing renewable sources of fuels. Second generation biofuels have attracted more attention recently as the use of lignocellulosic biomass can reduce fossil fuel dependence and is environment-friendly. Xylose is the main pentose and second most abundant sugar after glucose in lignocelluloses. Saccharomyces cerevisiae does not readily uptake and use pentose sugars. For an economically feasible biofuel production, both hexose and pentose sugars must be fermented to ethanol. Therefore, it is important to develop S. cerevisiae host platforms with more efficient xylose utilization. This work aims to construct a xylose fermenting yeast strains with engineered oxido-reductative pathway for xylose metabolism. Engineered strain was further improved by adaptive evolutionary engineering approach. The engineered strain is able to grow on xylose as sole carbon source with the maximum ethanol yield of 0.39g/g xylose and productivity of 0.139g/l/h at 96 hours. The further improvement in strain development involves over expression of pentose phosphate pathway and protein engineering of xylose reductase/xylitol dehydrogenase to change their cofactor specificity in order to reduce xylitol accumulation.

Keywords: biofuel, lignocellulosic biomass, saccharomyces cerevisiae, xylose

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Authors: Deepak Kumar, Ravi Rajwanshi, Mohd. Aslam Yusuf, Nisha Kant Pandey, Preeti Singh, Mukesh Saxena, Neera Bhalla Sarin

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Global issues are leading to concerns over food security. These include climate change, urbanization, increase in population subsequently leading to greater energy and water demand. Futuristic approach for crop improvement involves gene pyramiding for agronomic traits that empower the plants to withstand multiple stresses. In an earlier study from the laboratory, the efficacy of overexpressing γ-tocopherol methyl transferase (γ-TMT) gene from the vitamin E biosynthetic pathway has been shown to result in six-fold increase of the most biologically active form, the α-tocopherol in Brassica juncea which resulted in alleviation of salt, heavy metal and osmoticum induced stress by the transgenic plants. The glyoxalase I (gly I) gene from the glyoxalase pathway has also been earlier shown by us to impart tolerance against multiple abioitc stresses by detoxification of the cytotoxic compound methylglyoxal in Brassica juncea. Recently, both the transgenes were pyramided in Brassica juncea lines through sexual crosses involving two stable Brassica juncea lines overexpressing γ-TMT and gly I genes respectively. The transgene integration was confirmed by PCR analysis and their mRNA expression was evident by RT-PCR analysis. Preliminary physiological investigations showed ~55% increased seed germination under 200 mM NaCl stress in the pyramided line and 81% higher seed germination under 200 mM mannitol stress as compared to the WT control plants. The pyramided lines also retained more chlorophyll content when the leaf discs were floated on NaCl (200, 400 and 600 mM) or mannitol (200, 400 and 600 mM) compared to the WT control plants. These plants had higher Relative Water Content and greater solute accumulation under stress compared to the parental plants having γ-TMT or the glyI gene respectively. The studies revealed the synergy of two components from different metabolic pathways in enhancing stress hardiness of the transgenic B. juncea plants. It was concluded that pyramiding of genes (γ-TMT and glyI) from diverse pathways can lead to enhanced tolerance to salt and mannitol stress (simulating drought conditions). This strategy can prove useful in enhancing the crop yields under various abiotic stresses.

Keywords: abiotic stress, brassica juncea, glyoxalase I, α-tocopherol

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Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

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COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

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Authors: Hakam Alkhateeb

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Oleuropein, the main constituent of leaves and fruits of the olive tree, has been demonstrated to exert beneficial effects on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. However, the antidiabetic effect of oleuropein, to our knowledge, has not been examined. Therefore, in this study, we examined whether oleuropein ameliorated palmitate-induced insulin resistance in skeletal muscle. To examine this question, insulin resistance was rapidly induced by incubating (12h) soleus muscle with a high concentration of palmitate(2mM). Subsequently, we attempted to restore insulin sensitivity by incubating (12h) muscles with oleuropien (1.5mM), while maintaining high concentrations of palmitate. Palmitate treatment for 12 h reduced insulin-stimulated glucose transport, GLUT4 translocationandAS160 phosphorylation. Oleuropein treatment (12 h) fully restoredinsulin-stimulated glucose transport, GLUT4translocationandAS160 phosphorylation. Inhibition of PI3K phosphorylation with wortmannin (1µM)did not affect the oleuropein-induced improvements in insulin-stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation. These results suggested that the improvements in these parameters cannot account for activating PI3K pathway. Taken altogether, it appears that oleuropein, through activation of another pathway like activated protein kinase (AMPK), may provide a possible strategy by which they ameliorate palmitate-induced insulin resistance in skeletal muscles.

Keywords: AS160, diabetes, GLUT4, oleuropein

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

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In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi

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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.

Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites

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Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

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Authors: F. Javier Benitez, Francisco J. Real, Juan Luis Acero, Francisco Casas

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Three emerging contaminants (amitriptyline hydrochloride, methyl salicylate and 2-phenoxyethanol) frequently found in waste-waters were selected to be individually degraded in ultra-pure water by the combined advanced oxidation process constituted by UV radiation and chlorine. The influence of pH, initial chlorine concentration and nature of the contaminants was firstly explored. The trend for the reactivity of the selected compounds was deduced: amitriptyline hydrochloride > methyl salicylate > 2-phenoxyethanol. A later kinetic study was carried out and focused on the specific evaluation of the first-order rate constants and the determination of the partial contribution to the global reaction of the direct photochemical pathway and the radical pathway. A comparison between the rate constant values among photochemical experiments without and with the presence of Cl₂ reveals a clear increase in the oxidation efficiency of the combined process with respect to the photochemical reaction alone. In a second stage, the simultaneous oxidation of mixtures of the selected contaminants in several types of water (ultrapure water, surface water from a reservoir, and two secondary effluents) was also performed by the same combination UV/Cl₂ under more realistic operating conditions. The efficiency of this combined system UV/Cl₂ was compared to other oxidants such as the UV/S₂O₈^2- and UV/H₂O₂ AOPs. Results confirmed that the UV/Cl₂ system provides higher elimination efficiencies among the AOPs tested.

Keywords: emerging contaminants, UV/chlorine advanced oxidation process, amitriptyline, methyl salicylate, 2-phenoxyethanol, chlorination, photolysis

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Authors: Ayuko Itsuki, Sachiyo Aburatani

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In recent years, pollutions of the environment by toxic substances become a serious problem. While there are many methods of environmental clean-up, the methods by microorganisms are considered to be reasonable and safety for environment. Compost is known that it catabolize the meladorous substancess in its production process, however the mechanism of its catabolizing system is not known yet. In the catabolization process, organic matters turn into inorganic by the released enzymes from lots of microorganisms which live in compost. In other words, the cooperative of activated enzymes in the compost decomposes malodorous substances. Thus, clarifying the interaction among enzymes is important for revealing the catabolizing system of meladorous substance in compost. In this study, we utilized statistical method to infer the interaction among enzymes. We developed a method which combined partial correlation with cross correlation to estimate the relevance between enzymes especially from time series data of few variables. Because of using cross correlation, we can estimate not only the associative structure but also the reaction pathway. We applied the developed method to the enzyme measured data and estimated an interaction among the enzymes in decomposition mechanism of toluene.

Keywords: enzyme activities, comparative analysis, compost, toluene

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Authors: Jafar Ahmadi, Zhohreh Asiaban, Sedigheh Fabriki Ourang

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Brassinosteroids (BRs) regulate cell elongation, vascular differentiation, senescence and stress responses. BRs signal through the BES1/BZR1 family of transcription factors, which regulate hundreds of target genes involved in this pathway. In this research a comprehensive genome-wide analysis was carried out in BES1/BZR1 gene family in Arabidopsis thaliana, Cucumis sativus, Vitis vinifera, Glycin max, and Brachypodium distachyon. Specifications of the desired sequences, dot plot and hydropathy plot were analyzed in the protein and genome sequences of five plant species. The maximum amino acid length was attributed to protein sequence Brdic3g with 374aa and the minimum amino acid length was attributed to protein sequence Gm7g with 163aa. The maximum Instability index was attributed to protein sequence AT1G19350 equal with 79.99 and the minimum Instability index was attributed to protein sequence Gm5g equal with 33.22. Aliphatic index of these protein sequences ranged from 47.82 to 78.79 in Arabidopsis thaliana, 49.91 to 57.50 in Vitis vinifera, 55.09 to 82.43 in Glycin max, 54.09 to 54.28 in Brachypodium distachyon 55.36 to 56.83 in Cucumis sativus. Overall, data obtained from our investigation contributes a better understanding of the complexity of the BES1/BZR1 gene family and provides the first step towards directing future experimental designs to perform systematic analysis of the functions of the BES1/BZR1 gene family.

Keywords: BES1/BZR1, brassinosteroids, phylogenetic analysis, transcription factor

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Authors: Fernanda T. Orsati, Julie Causton

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Discursive practices enacted by educators in kindergarten create a blueprint for how the educational trajectories of students with disabilities are constructed. This two-year ethnographic case study critically examine educators’ relationships with students considered to present challenging behaviors in one kindergarten classroom located in a predominantly White middle-class school district in the Northeast of the United States. Focusing on the language and practices used by one special education teacher and three teaching assistants, this paper analyzes how teacher responses to students’ behaviors constructs and positions students over one year of kindergarten education. Using a critical discourse analysis, it shows that educators understand students’ behaviors as a deficit and needing consequences. This study highlights how educators’ responses reflect students' individual characteristics including family background, socioeconomics and ability status. This paper offers in-depth analysis of two students’ stories, which evidenced that the language used by educators amplifies the social positioning of students within the classroom and creates a foundation for who they are constructed to be. Through exploring routine language and practices, this paper demonstrates that educators outlined a blueprint of kindergartners, which positioned students as learners in ways that became the ground for either a limited or a promising educational pathway for them.

Keywords: behavior, early education, special education, critical discourse analysis

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Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

Abstract:

Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Orish E. Orisakwe, Chinna N. Orish, Anthonet N. Ezejiofor

Abstract:

African mesquite has been recognized for its antimicrobial, anti-inflammatory, and potential anticarcinogenic activities. However, its neuroprotective benefits against heavy metal-induced neurotoxicity remain largely unexplored. Therefore, the objective of this study was to investigate the neuroprotective properties of African mesquite in the hippocampus and olfactory bulb against common environmental pollutants, including Cd, As, Hg, and Pb. Thirty-five albino Sprague Dawley rats were divided into five groups for the experiment. Group 1 served as the control and did not receive either the heavy metal mixture (HMM) or African mesquite. Group 2 was orally administered HMM, consisting of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 960 days. Meanwhile, groups 3, 4, and 5 were treated with HMM along with African mesquite at doses of 500 mg/kg, 1000 mg/kg, and 1500 mg/kg, respectively. African mesquite reduced heavy metal accumulation in the hippocampus and olfactory bulb. Additionally, Sprague Dawley rats exhibited improved performance in the Passive avoidance and Cincinnati Maze tests. Furthermore, treatment with African mesquite significantly alleviated inflammation macromolecules peroxidation. It also restored the concentrations of SOD, CAT, GSH, GPx, Hmox-1, and reduced the activity of AChE, NRF2 and NFkB and improved histopathological findings. African mesquite exhibits a multifaceted neuroprotective effect with the potential to mitigate various aspects of heavy metal-induced neurotoxicity.

Keywords: African mesquite, heavy metal mixture;, neurotoxicity;, chemoprevention

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Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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Authors: Charles Q. Yu, Victoria H. Fan, Ahmed F. Al-Qahtani, Ibraim Viera

Abstract:

Introduction: Over 12 million people are blind due to opacity of the cornea, the clear tissue forming the front of the eye. Current methods use plastic implants to produce a clear optical pathway into the eye but are limited by a high rate of complications. New implants utilizing completely inside-the-eye projection technology can overcome blindness due to scarring of the eye by producing images on the retina without need for a clear optical pathway into the eye and may be free of the complications of traditional treatments. However, the interior of the eye is a challenging location for the design of optical focusing systems which can produce a sufficiently high quality image. No optical focusing systems have previously been characterized for this purpose. Methods: 3 optical focusing systems for intraocular (inside the eye) projection were designed and then modeled with ray tracing software, including a pinhole system, a planoconvex, and an achromatic system. These were then constructed using off-the-shelf components and tested in the laboratory. Weight, size, magnification, depth of focus, image quality and brightness were characterized. Results: Image quality increased with complexity of system design, as did weight and size. A dual achromatic doublet optical system produced the highest image quality. The visual acuity equivalent achieved with this system was better than 20/200. Its weight was less than that of the natural human crystalline lens. Conclusions: We demonstrate for the first time that high quality images can be produced by optical systems sufficiently small and light to be implanted within the eye.

Keywords: focusing, projection, blindness, cornea , achromatic, pinhole

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Authors: Ali Bahri Lubis

Abstract:

Tryptophan oxidation by Heme-dioxygenase enzyme is initial important stepTryptophan oxidation by Heme-dioxygenase enzyme is initial important step in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment upon abovementioned diseases. The mechanism has been debatable since no one has been yet proved the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR, and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment for the abovementioned diseases. The mechanism has been debatable since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction.

Keywords: heme-dioxygenase enzyme, tryptophan oxidation, kynurenine pathway, n-formyl kynurenine

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Authors: Chul Lee, Seoae Cho, Erich D. Jarvis, Heebal Kim

Abstract:

Vocal learning, the ability to imitate vocalizations based on auditory experience, is a homoplastic character state observed in different independent lineages of animals such as songbirds, parrots, hummingbirds and human. It has now become possible to perform genome-wide molecular analyses across vocal learners and vocal non-learners with the recent expansion of avian genome data. It was analyzed the whole genomes of human and 48 avian species including those belonging to the three avian vocal learning lineages, to determine if behavior and neural convergence are associated with molecular convergence in divergent species of vocal learners. Analyses of 8295 orthologous genes across bird species revealed 141 genes with amino acid substitutions specific to vocal learners. Out of these, 25 genes have vocal learner specific genetic homoplasies, and their functions were enriched for learning. Several sites in these genes are estimated under convergent evolution and positive selection. A potential role for a subset of these genes in vocal learning was supported by associations with gene expression profiles in vocal learning brain regions of songbirds and human disease that cause language dysfunctions. The key candidate gene with multiple independent lines of the evidences specific to vocal learners was DRD5. Our findings suggest cAMP-based learning pathway in avian vocal learners, indicating molecular homoplastic changes associated with a complex behavioral trait, vocal learning.

Keywords: amino acid substitutions, convergent evolution, positive selection, vocal learning

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

Abstract:

Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Sujeeta Karki, Jeeban Poudel, Ja Hyung Choi, Sea Cheon Oh

Abstract:

A lab-scale fluidized bed was used for the study of sewage sludge, a non-lignocellulosic biomass, torrefaction. The influence of torrefaction temperature ranging from 200–350 °C and residence time of 0–50 minutes on the physical and chemical properties of the torrefied product was investigated. Properties of the torrefied product were analyzed on the basis of degree of torrefaction, ultimate and proximate analysis, gas analysis and chemical exergy. The degree of torrefaction and chemical exergy had a positive influence on increasing the torrefaction temperature. Moreover, the effect of torrefaction temperature and residence time on the elemental variation of sewage sludge exhibited an increase in the weight percentage of carbon while the content of H/C and O/C molar ratios decreased. The product gas emitted during torrefaction was analyzed to study the pathway of hydrocarbons and oxygen-containing compounds. The compounds with oxygen were emitted at higher temperatures in contrast to hydrocarbon gases. An attempt was made to obtain the chemical exergy of sewage sludge. In addition, the study of various correlations for predicting the calorific value of torrefied sewage sludge was made.

Keywords: chemical exergy, degree of torrefaction, fluidized bed, higher heating value (HHV), O/C and H/C molar ratios, sewage sludge

Procedia PDF Downloads 145