Search results for: aryl hydrocarbon receptor (AhR)

Authors: Perminderjit Singh, Randeep Singh

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The performance, emission and combustion characteristics of a single cylinder four stroke variable compression ratio multifuel engine when fueled with different blends of rice bran oil methyl ester and ethanol are investigated and compared with the results of standard diesel. Biodiesel produced from rice bran oil by transesterification process has been used in this study. The experiment has been conducted at a fixed engine speed of 1500 rpm, 50% load and at compression ratios of 16.5:1, 17:1, 17.5:1 and 18:1. The impact of compression ratio on fuel consumption, brake thermal efficiency and exhaust gas emissions has been investigated and presented. Optimum compression ratio which gives the best performance has been identified. The results indicate longer ignition delay, the maximum rate of pressure rise, lower heat release rate and higher mass fraction burnt at higher compression ratio for waste cooking oil methyl ester when compared to that of diesel. The brake thermal efficiency at 50% load for rice bran oil methyl ester blends and diesel has been calculated and the blend B40 is found to give maximum thermal efficiency. The blends when used as fuel results in the reduction of carbon monoxide, hydrocarbon and increase in nitrogen oxides emissions.

Keywords: biodiesel, rice bran oil, transesterification, ethanol, compression ratio

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Authors: Azhar Jabareen, Mahmoud Huleihel

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

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

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Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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Authors: Vladimir Ryabov, Mikhail Baryshevs, Mikhail Voskresenskey, Boris Popov

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The human prostate gland (PG) samples were obtained from patients who had undergone radical prostatectomy for prostate cancer (PC) and used to extract total RNA and prepare the prostate stromal cell cultures (PSCC) and patients-derived organoids (PDO). Growth of the cell cultures was accessed under microscopic evaluation in transmitted light and the marker expression by reverse polymerase chain reaction (RT-PCR), immunofluorescence, and immunoblotting. Some PCR products from prostate tissue, PSCC, and PDO were cloned and sequenced. We found that the cells of early and late passages of PSCC and corresponding PDO expressed luminal (androgen receptor, AR; cytokeratin 18, CK18) and basal (CK5, p63) epithelial markers, the production of which decreased or disappeared in late PSCC and PDO. The PSCC and PDO of early passages from cancer tissue additionally produced cancer markers AMACR, TMPRSS2-ERG, and Ezh2. The expression of TMPRSS2-ERG fusion transcripts was verified by cloning and sequencing the PCR products. The results obtained suggest that early passages of PSCC might be used as a pre-clinical model for the evaluation of early markers of prostate cancer.

Keywords: localized prostate cancer, prostate epithelial markers, prostate cancer markers, AMACR, TMPRSS2-ERG, prostate stromal cell cultures, PDO

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Authors: A. M. Iordache, S. M. Iordache, V. Barna, M. Elisa, I. C. Vasiliu, C. R. Stefan, I. Chilibon, I. Stamatin, S. Caramizoiu, C. E. A. Grigorescu

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The general objective of the presentation is the development of an e-tongue like sensor based on modified screen printed electrode (SPE) structures with a receptor part made of porphyrins/metalloporphyrins chemically bound to graphene (the sensitive assembly) to act as antennas and “capture” the histamine molecules. Using a single, ultra-sensitive electrochemical sensor, we measured the concentration of histamine, a compound which is strongly connected to the level of freshness in foods (the caution level of histamine is 50 ppm, whereas the maximum accepted levels range from 200 ppm to 500 ppm). Our approach for the chemical immobilization of the porphyrins onto the surface of the graphenes was via substitution reaction: a solution of graphene in SOCl2 was heated to 800C for 6 hours. Upon cooling, the metallo-porphyrins were added and ultrasonicated for 4 hours. The solution was then allowed to cool to room temperature and then centrifuged in order to separate the deposit. The sensitive assembly was drop casted onto the carbon SPE and cyclic voltammetry was performed in the presence of histamine. The reaction is quasi-reversible and the sensor showed an oxidation potential for histamine at 600 mV. The results indicate a linear dependence of concentration of histamine as function of intensity. The results are reproducible; however the chemical stability of the sensitive assembly is low.

Keywords: histamine, cyclic voltammetry, metallo-porphyrin, food freshness

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Authors: Ghazi Chabchoub, Mouna Feki, Mohamed Abid, Hammadi Ayadi

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Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are inherited as complex traits. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We analysed three intragenic microsatellite markers in the thyroid hormone receptor associated protein 2 gene (THRAP2), mapped near D12S79 marker, which have a potential role in immune function and inflammation [THRAP2-1(TG)n, THRAP2-2 (AC)n and THRAP2-3 (AC)n]. Our study population concerned 12 patients affected with AITDs belonging to a multiplex Tunisian family with high prevalence of AITDs. Fluorescent genotyping was carried out on ABI 3100 sequencers (Applied Biosystems USA) with the use of GENESCAN for semi-automated fragment sizing and GENOTYPER peak-calling software. Statistical analysis was performed using the non parametric Lod score (NPL) by Merlin software. Merlin outputs non-parametric NPLall (Z) and LOD scores and their corresponding asymptotic P values. The analysis for three intragenic markers in the THRAP2 gene revealed strong evidence for linkage (NPL=3.68, P=0.00012). Our results suggested the possible role of THRAP2 gene in AITDs susceptibility in this family.

Keywords: autoimmunity, autoimmune disease, genetic, linkage analysis

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Authors: Thanida Sritangthong, Suksun Amornraksa

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By-product upgrading is crucial in hydrocarbon industries as it can increase overall profit margin of the business. Microwave-assisted pyrolysis is relatively new technique which induces heat directly to raw materials. This results in a more energy saving and more energy-efficient process. It is also a promising method to enhance and accelerate chemical reactions, thus reducing the pyrolysis reaction time and increasing the quality of value-added products from different kinds of feedstocks. In this study, upgrading opportunity of fuel oil by-product from an olefins plant is investigated by means of microwave pyrolysis. The experiment was conducted in a lab-scale quartz reactor placed inside a 1,100 watts household microwave oven. Operating temperature was varied from 500 to 900C to observe the consequence on the quality of pyrolysis products. Several microwave receptors i.e. activated carbon, silicon carbide (SiC) and copper oxide (CuO) were used as a material to enhance the heating and reaction in the reactor. The effect of residence time was determined by adjusting flow rate of N2 carrier gas. The chemical composition and product yield were analyzed by using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The results showed that hydrogen, methane, ethylene, and ethane were obtained as the main gaseous products from all operating temperatures while the main liquid products were alkane, cycloalkane and polycyclic aromatic groups. The results indicated that microwave pyrolysis has a potential to upgrade low value hydrocarbons to high value products.

Keywords: fuel oil, heavy hydrocarbons, microwave pyrolysis, pyrolysis

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Authors: Serkan Tezgel

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The two qualities of the sea, as a medium of transportation and as a resource, necessitate maritime security for economic stability and good order at sea. The borderless nature of the sea makes it one of the best platforms to contribute to regional peace and international order. For this reason, the establishment of maritime security in East Mediterranean will enhance the security-peace-democracy triangle in the region. This paper proposes the application of the Smart Security Concept in the East Mediterranean. Smart Security aims to secure critical infrastructure, such as hydrocarbon platforms, against asymmetrical threats. The concept is based on Anti Asymmetrical Area Denial (A3D) which necessitates limiting freedom of action of maritime terrorists and piracy by founding safe and secure maritime areas through sea lines of communication using short range capabilities. Smart Security is a regional maritime cooperation concept for the narrow seas. Cooperation and interoperability are essential attributes of this regional security concept. Therefore, multinational excellence centers such as Multinational Maritime Security Center of Excellence-Aksaz in Turkey, which will determine necessary capabilities and plan/coordinate workshops, training and exercises, are bound to be the principal characteristic of Smart Security concept and similar regional concepts. Smart Security, a crucial enabler of energy and regional security, can provide an enduring approach for operating in the challenging environment of narrow seas and for countering asymmetrical threats.

Keywords: security, cooperation, asymmetrical, area denial

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Authors: Leila Anoosheh

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Aim: The aim of this study was to assess The effects of aerobic training on microRNA let-7a expression and levels of tumor tissue IL-6 in mice with breast cancer. Method: Twenty BALB/c c mice (4-5 weeks,17 gr mass) were cancerous by injection of estrogen-dependent receptor breast cancer cells MC4-L2 and divided into two groups: tumor-training(TT) and tumor-control(TC) group. Then TT group completed aerobic training for 6 weeks, 5 days per week (14-18 m/min). After tumor emersion, tumor width and length were measured by digital caliper every week. 48 hours after the last exercise subjects were killed. Tissue sampling were collected and stored in -70ᵒ. Tumor tissue was homogenized and let-7a expression and IL-6 levels were accounted with Real time-PCR and ELISA Kit respectively. Statistical analysis of let-7a was conducted by the REST software. Repeated measures and independent tests were used to assess tumor size and IL-6, respectively. Results: Tumor size and IL-6 levels were significantly decreased in TT group compare with TC group (p<0.05). microRNA let-7a was increased significantly in TT against control group respectively (p=0/000). Conclusion: Reduction in tumor size, followed by aerobic exercise can be attributed to the loss of inflammatory factors such as IL-6; It seems that regarding to up regulation effects of aerobic exercise training on let-7a and down regulation effects of that on IL-6 in mice with breast cancer, This type of training can be used as adjuvant therapy in conjunction with other therapies for breast cancer.

Keywords: breast cancer, aerobic training, microRNA let-7a, IL-6

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Authors: F. S. Kadhim, A. Samsuri, H. Alwan

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Well logging records can help to answer many questions from a wide range of special interested information and basic petrophysical properties to formation evaluation of oil and gas reservoirs. The accurate calculations of porosity in carbonate reservoirs are the most challenging aspects of well log analysis. Many equations have been developed over the years based on known physical principles or on empirically derived relationships, which are used to calculate porosity, estimate lithology and water saturation; however these parameters are calculated from well logs by using modern technique in a current study. Nasiriya (NS) oilfield is one of giant oilfields in the Middle East, and the formation under study is the Mishrif carbonate formation which is the shallowest hydrocarbon bearing zone in the NS oilfield. Neurolog software (V5, 2008) was used to digitize the scanned copies of the available logs. Environmental corrections had been made as per Schlumberger charts 2005, which supplied in the Interactive Petrophysics software (IP, V3.5, 2008). Three saturation models have been used to calculate water saturation of carbonate formations, which are simple Archie equation, Dual water model, and Indonesia model. Results indicate that the Mishrif formation consists mainly of limestone, some dolomite and shale. The porosity interpretation shows that the logging tools have a good quality after making the environmental corrections. The average formation water saturation for Mishrif formation is around 0.4-0.6.This study is provided accurate behavior of petrophysical properties with depth for this formation by using modern software.

Keywords: lithology, porosity, water saturation, carbonate formation, mishrif formation

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Authors: Julius Ilawe Osayi, Peter Osifo

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Solid waste disposal, such as used tires is a global challenge as well as energy crisis due to rising energy demand amidst price uncertainty and depleting fossil fuel reserves. Therefore, the effectiveness of pyrolysis as a disposal method that can transform used tires into liquid fuel and other end-products has made the process attractive to researchers. Although used tires have been converted to liquid fuel using pyrolysis, there is the need to improve on the liquid fuel properties. Hence, this paper reports the investigation of zeolite NaY synthesized from kaolin, a locally abundant soil material in the Benin metropolis as a suitable catalyst and its effect on the properties of pyrolytic oil produced from used tires. The pyrolysis process was conducted for a range of 1 to 10 wt.% of catalyst concentration to used tire at a temperature of 600 oC, a heating rate of 15oC/min and particle size of 6mm. Although no significant increase in pyrolytic oil yield was observed compared to the previously investigated non-catalytic pyrolysis of a used tire. However, the Fourier transform infrared (FTIR), Nuclear Magnetic Resonance (NMR); and Gas chromatography-mass spectrometry (GC-MS) characterization results revealed the pyrolytic oil to possess an improved physicochemical and fuel properties alongside valuable industrial chemical species. This confirms the possibility of transforming kaolin into a catalyst suitable for improved fuel properties of the liquid fraction obtainable from thermal cracking of hydrocarbon materials.

Keywords: catalytic pyrolysis, fossil fuel, kaolin, pyrolytic oil, used tyres, Zeolite NaY

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Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

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Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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Authors: Aslanova Aida Ramiz

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One of the important aspects of rheophysical problems in oil and gas extraction is the regulation of thermohydrodynamic properties of liquid systems using physical and physicochemical methods. It is known that the constituent parts of real fluid systems in oil and gas production are practically non-conducting, non-magnetically active components. Real heterogeneous hydrocarbon systems, from the structural point of view, consist of an infinite number of microscopic local ion-electrostatic cores distributed in the volume of the dispersion medium. According to Cohen's rule, double electric layers are formed at the contact boundaries of components in contact (oil-gas, oil-water, water-condensate, etc.) in a heterogeneous system, and as a result, each real fluid system can be represented as a complex composition of a set of local electrostatic fields. The electrokinetic properties of this structure are characterized by a certain electrode potential. Prof. F.H. Valiyev called this potential the α-factor and came up with the idea that many natural and technological rheophysical processes (effects) are essentially electrokinetic in nature, and by changing the α-factor, it is possible to adjust the physical properties of real hydraulic systems, including thermohydrodynamic parameters. Based on this idea, extensive research work was conducted, and the possibility of reducing hydraulic resistances and improving rheological properties was experimentally discovered in real liquid systems by reducing the electrical potential with various physical and chemical methods.

Keywords: microcracked, electrode potential, hydraulic resistance, Newtonian fluid, rheophysical properties

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Sdiqeh Jalali, M. R. Khazdair

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Liver X receptors (LXR) have an essential role in the regulation of cholesterol metabolism, and their activation increase ABCG5 and ABCG8 genes expression for the improvement of cholesterol excretion from the body during reverse cholesterol transport (RCT). The aim of this study was to investigate the effects of high-intensity interval (HIT) and low intensity continuous (LIT) trainings on gene expression of these substances after a high-fat diet in Wistar rats. Materials and Methods: Fifteen male Wistar rats were divided into 3 groups: control group (n = 5), HIT exercise group (n = 5) and LIT exercise group (n = 5). All groups used a high-fat diet for 13 weeks, and the HIT and LIT groups performed the specific training program. The expression of LXRβ, ABCG5, and ABCG8 genes was measured after the training period. Findings: Data analysis showed significantly higher levels of LXRβ, ABCG5, and ABCG8 gene expression in HIT and LIT groups compared to the control group (P ≤ 0.05). Conclusion: HIT and LIT trainings after a high-fat diet have beneficial effects on RCT that prevent heart attack. Also, HIT training may have a greater effect on cholesterol excretion during the reverse cholesterol transport mechanism than LIT.

Keywords: liver X receptor, atherosclerosis, interval training, endurance training

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: Balram Panjwani, Bernd Wittgens, Jan Erik Olsen, Stein Tore Johansen

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The Norwegian ferroalloy industry is a world leader in sustainable production of ferrosilicon, silicon and manganese alloys with the lowest global specific energy consumption. One of the byproducts during the metal reduction process is energy rich off-gas and usually this energy is not harnessed. A novel concept for sustainable energy recovery from ferroalloy off-gas is discussed. The concept is founded on the idea of introducing a combustion chamber in the off-gas section in which energy rich off-gas mainly consisting of CO will be combusted. This will provide an additional degree of freedom for optimizing energy recovery. A well-controlled and high off-gas temperature will assure a significant increase in energy recovery and reduction of emissions to the atmosphere. Design and operation of the combustion chamber depend on many parameters, including the total power capacity of the combustion chamber, sufficient residence time for combusting the complex Poly Aromatic Hydrocarbon (PAH), NOx, as well as converting other potential pollutants. The design criteria for the combustion chamber have been identified and discussed and sizing of the combustion chamber has been carried out considering these design criteria. Computational Fluid Dynamics (CFD) has been utilized extensively for sizing the combustion chamber. The results from our CFD simulations of the flow in the combustion chamber and exploring different off-gas fuel composition are presented. In brief, the paper covers all aspect which impacts the sizing of the combustion chamber, including insulation thickness, choice of insulating material, heat transfer through extended surfaces, multi-staging and secondary air injection.

Keywords: CFD, combustion chamber, arc furnace, energy recovery

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Barbora Chmelova, Radek Sachl

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Gangliosides are amphipathic membrane lipids. Due to the composition of bulky oligosaccharide chains containing one or more sialic acids linked to the hydrophobic ceramide base, gangliosides are classified among glycosphingolipids. This unique structure induces a high self-aggregating tendency of gangliosides and, therefore, the formation of nanoscopic clusters called nanodomains. Gangliosides are preferentially present in an extracellular membrane leaflet of all human tissues and thus have an impact on a huge number of biological processes, such as intercellular communication, cell signalling, membrane trafficking, and regulation of receptor activity. Defects in their metabolism, impairment of proper ganglioside function, or changes in their organization lead to serious health conditions such as Alzheimer´s and Parkinson´s diseases, autoimmune diseases, tumour growth, etc. This work mainly focuses on ganglioside organization into nanodomains and their dynamics within the plasma membrane. Current research investigates static ganglioside nanodomains characterization; nevertheless, the information about their diffusion is missing. In our study, fluorescence correlation spectroscopy is implemented together with stimulated emission depletion (STED-FCS), which combines the diffraction-unlimited spatial resolution with high temporal resolution. By comparison of the experiments performed on model vesicles containing 4 % of either GM1, GM2, or GM3 and Monte Carlo simulations of diffusion on the plasma membrane, the description of ganglioside clustering, diffusion of nanodomains, and even diffusion of ganglioside molecules inside investigated nanodomains are described.

Keywords: gangliosides, nanodomains, STED-FCS, flourescence microscopy, membrane diffusion

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Authors: Luana N. Cardozo, Debora A. S. Coutinho, Fabiola Lagher, Bruno J. G. Silva, Ivonilce Venture, Mainara Tesser, Graciela Venera

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Ostrich oil is used as food in Brazil, and it has been the subject of scientific research because it contains essential fatty acids (Omega 3, 6, 7, and 9), which provide benefits to human health. Alkylglycerols are lipid ethers consisted of a saturated or unsaturated hydrocarbon chain joined by ether-type bonding to one of the glycerol hydroxyls. It is known that supplementation with alkylglycerols can act significantly on the functioning of immune system cells, both in pathological situations and in homeostasis. Objective: Analyze the presence of alkylglycerols in ostrich oil. Methods: The ostrich oil was bought from an industry that manufactures the product for sale as food, located in Mirante da Serra, northern Brazil. The samples were sent for analysis to the chemistry department of the Federal University of Paraná, where they were analyzed by the gas chromatography method. Results: The analysis of the ostrich oil presented alkylglycerols in area 514505154. Comparison, it is possible to observe that shark liver oil contains the area 26190196, and the difference between both is highly significant. Conclusion: The importance of alkylglycerol supplementation for the immune system is known. The analysis of the results made it possible to verify the presence of alkylglycerols in the ostrich oil, which is five times higher than in the shark liver oil, that would be the largest source food, but was surpassed by the ostrich oil until the present time. The present study emphasizes that ostrich oil can be considered a food source of alkylglycerols and may play a promising role in the immune system because it contains such substance, but further studies are needed to prove its performance in the body.

Keywords: ostrich oil, nutritional composition, alkylglycerols, food

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Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

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The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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Authors: Preet Singh, Kavitha Kongara, Dave Harding, Neil Ward, Paul Chambers

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The objective of this study was to compare the analgesic efficacy of opiorphin and its analogue with a mu-receptor agonist; morphine. Opiorphins (Gln-Arg-Phe-Ser-Arg) belong to the family of endogenous enkephalinase inhibitors, found in saliva of humans. They are inhibitors of two Zinc metal ectopeptidases (Neutral endopeptidase NEP, and amino-peptidase APN) which are responsible for the inactivation of the endogenous opioids; endorphins and enkephalins. Morphine and butorphanol exerts their analgesic effects by mimicking the actions of endorphins and enkephalins. The opiorphin analogue was synthesized based on the structure activity relationship of the amino acid sequence of opiorphin. The pharmacological profile of the analogue was tested by replacing Serine at position 4 with Proline. The hot plate and tail flick test were used to demonstrate the analgesic efficacy. There was a significant increase in the time for the tail flick response after an injection of opiorphin, which was similar to the morphine effect. There was no increase in time in the hot plate test after an injection of opiorphin. The results suggest that opiorphin works at spinal level only rather than both spinal and supraspinal. Further work is required to confirm our results. We did not find analgesic activity of the opiorphin analogue. Thus, Serine at position 4 is also important for its pharmacological action. Further work is required to illustrate the role of serine at position 4 in opiorphin.

Keywords: analgesic peptides, endogenous opioids, morphine, opiorphin

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Authors: Syed M. Shahid, Rozeena Shaikh, Syeda N. Nawab, Abid Azhar

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Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy and foot infections. Pathogenesis of diabetic nephropathy (DN) is implicated by the polymorphisms in genes encoding the specific components of renin angiotensin aldosterone system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and angiotensin converting enzyme (ACE) genes. This study was designed to explore the possible association of AG (M268T) polymorphism in the patients of diabetes and nephropathy in Pakistan. Study subjects included 100 controls, 260 diabetic patients without renal insufficiency and 190 diabetic nephropathy patients with persistent albuminuria. Fasting blood samples were collected from all the subjects after getting institutional ethical approval and informed consent. The biochemical estimations, PCR amplification and direct sequencing for the specific region of AGT gene was carried out. A significantly high frequency of TT genotype and T allele of AGT (M268T) was observed in the patients of diabetes with nephropathy as compared to controls and diabetic patients without any known renal impairment. The TT genotype and T allele of AGT (M268T) polymorphism may be considered as a genetic risk factor for the development and progression of nephropathy in diabetes. Further cross sectional population studies would be of help to establish and confirm the observed possible association of AGT gene variations with development of nephropathy in diabetes.

Keywords: RAAS, AGT (M268T), diabetes, nephropathy

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Authors: Anshu Siwach, Qianlai Zhuang, Ratul Baishya

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Context: This study focuses on the influence of moss cover and seasonality on soil microbial biomass and enzymatic activity in different Central Himalayan temperate forest types. Soil microbial biomass and enzymes are key indicators of microbial communities in soil and provide information on soil properties, microbial status, and organic matter dynamics. The activity of microorganisms in the soil varies depending on the vegetation type and environmental conditions. Therefore, this study aims to assess the effects of moss cover, seasons, and different forest types on soil microbial biomass carbon (SMBC), soil microbial biomass nitrogen (SMBN), and soil enzymatic activity in the Central Himalayas, Uttarakhand, India. Research Aim: The aim of this study is to evaluate the levels of SMBC, SMBN, and soil enzymatic activity in different temperate forest types under the influence of two ground covers (soil with and without moss cover) during the rainy and winter seasons. Question Addressed: This study addresses the following questions: 1. How does the presence of moss cover and seasonality affect soil microbial biomass and enzymatic activity? 2. What is the influence of different forest types on SMBC, SMBN, and enzymatic activity? Methodology: Soil samples were collected from different forest types during the rainy and winter seasons. The study utilizes the chloroform-fumigation extraction method to determine SMBC and SMBN. Standard methodologies are followed to measure enzymatic activities, including dehydrogenase, acid phosphatase, aryl sulfatase, β-glucosidase, phenol oxidase, and urease. Findings: The study reveals significant variations in SMBC, SMBN, and enzymatic activity under different ground covers, within the rainy and winter seasons, and among the forest types. Moss cover positively influences SMBC and enzymatic activity during the rainy season, while soil without moss cover shows higher values during the winter season. Quercus-dominated forests, as well as Cupressus torulosa forests, exhibit higher levels of SMBC and enzymatic activity, while Pinus roxburghii forests show lower levels. Theoretical Importance: The findings highlight the importance of considering mosses in forest management plans to improve soil microbial diversity, enzymatic activity, soil quality, and health. Additionally, this research contributes to understanding the role of lower plants, such as mosses, in influencing ecosystem dynamics. Conclusion: The study concludes that moss cover during the rainy season significantly influences soil microbial biomass and enzymatic activity. Quercus and Cupressus torulosa dominated forests demonstrate higher levels of SMBC and enzymatic activity, indicating the importance of these forest types in sustaining soil microbial diversity and soil health. Including mosses in forest management plans can improve soil quality and overall ecosystem dynamics.

Keywords: moss cover, seasons, soil enzymes, soil microbial biomass, temperate forest types

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Arash Esmaeili, Zhibang Liu, Yang Xiang, Jimmy Yun, Lei Shao

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A high-pressure carbon dioxide (CO₂) absorption from a specific off-gas in a conventional column has been evaluated for the environmental concerns by the Aspen HYSYS simulator using a wide range of single absorbents and piperazine (PZ) blended solutions to estimate the outlet CO₂ concentration, CO₂ loading, reboiler power supply, and regeneration heat duty to choose the most efficient solution in terms of CO₂ removal and required heat duty. The property package, which is compatible with all applied solutions for the simulation in this study, estimates the properties based on the electrolyte non-random two-liquid (E-NRTL) model for electrolyte thermodynamics and Peng-Robinson equation of state for vapor phase and liquid hydrocarbon phase properties. The results of the simulation indicate that piperazine, in addition to the mixture of piperazine and monoethanolamine (MEA), demands the highest regeneration heat duty compared with other studied single and blended amine solutions, respectively. The blended amine solutions with the lowest PZ concentrations (5wt% and 10wt%) were considered and compared to reduce the cost of the process, among which the blended solution of 10wt%PZ+35wt%MDEA (methyldiethanolamine) was found as the most appropriate solution in terms of CO₂ content in the outlet gas, rich-CO₂ loading, and regeneration heat duty.

Keywords: absorption, amine solutions, aspen HYSYS, CO₂ loading, piperazine, regeneration heat duty

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Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Olufunmilola A. Abiodun, Adegbola O. Dauda, Ayobami Ojo, Samson A. Oyeyinka

Abstract:

Serendipity berry (Dioscoreophyllum cumminsii diel) is a tropical dioecious rainforest vine and native to tropical Africa. The vine grows during the raining season and is used mainly as sweetener. The sweetener in the berry is known as monellin which is sweeter than sucrose. The sweetener is extracted from the fruits and the seed is discarded. The discarded seeds contain bitter principles but had high yield of oil. Serendipity oil was extracted using three methods (N-hexane, expression and expression/n-hexane). Fatty acids and physicochemical properties of the oil obtained were determined. The oil obtained was clear, liquid and have odour similar to hydrocarbon. The percentage oil yield was 38.59, 12.34 and 49.57% for hexane, expression and expression-hexane method respectively. The seed contained high percentage of oil especially using combination of expression and hexane. Low percentage of oil was obtained using expression method. The refractive index values obtained were 1.443, 1.442 and 1.478 for hexane, expression and expression-hexane methods respectively. Peroxide value obtained for expression-hexane was higher than those for hexane and expression. The viscosities of the oil were 125.8, 128.76 and 126.87 cm³/s for hexane, expression and expression-hexane methods respectively which showed that the oil from expression method was more viscous than the other oils. The major fatty acids in serendipity seed oil were oleic acid (62.81%), linoleic acid (22.65%), linolenic (6.11%), palmitic acid (5.67%), stearic acid (2.21%) in decreasing order. Oleic acid which is monounsaturated fatty acid had the highest value. Total unsaturated fatty acids were 91.574, 92.256 and 90.426% for hexane, expression, and expression-hexane respectively. Combination of expression and hexane for extraction of serendipity oil produced high yield of oil. The oil could be refined for food and non-food application.

Keywords: serendipity seed oil, expression method, fatty acid, hexane

Procedia PDF Downloads 273