Search results for: hydrogen inhibition

Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Ouassila Bekkal Brikci Benhabib, Zahia Boucherit Otmani, Kebir Boucherit, A. Seghir

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The establishment of intravenous catheters in hospitalized patient is an act common in many clinical situations. These therapeutic tools, from their insertion in the body, represent gateways including fungal germs prone. The latter can generate the growth of biofilms, which can be the cause of fungal infection. Faced with this problem, we conducted a study at the University Hospital of Tlemcen in the neurosurgery unit and aims to isolate and identify Candida yeasts from intravenous catheters. Then test their ability to form biofilms. Materials and methods: 256 patient hospitalized in surgery of the hospital in west Algeria were submitted to this study. All samples were taken from peripheral venous catheters implanted for 72 hours or more days. A total of 31 isolates of Candida species were isolated. MIC and SMIC are determined at 80% inhibition by the test XTT tetrazolium measured at 490 nm. The final concentrations of antifungal agent being between 0.03 and 16 mg / ml for amphotericin B and from 0.015 to 8 mg / mL caspofungin. Results: 31 Candida species isolates from catheters including 14 Candida albicans and 17 Candida non albicans . 21 strains of all the isolates were able to form biofilms. In their form of Planktonic cells, all isolates are 100% susceptible to antifungal agents tested. However, in their state of biofilms, more isolates have become tolerant to the tested antifungals. Conclusion: Candida yeasts isolated from intravascular catheters are considered an important virulence factor in the pathogenesis of infections. Their involvement in catheter-related infections can be disastrous for their potential to generate biofilms. They survive high concentrations of antifungal where treatment failure. Pending the development of a therapeutic approach antibiofilm related to catheters, their mastery is going through: -The risk of infection prevention based on the training and awareness of medical staff, -Strict hygiene and maximum asepsis, and -The choice of material limiting microbial colonization.

Keywords: candida, biofilm, hospital, infection, amphotericin B, caspofungin

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: T. Kuchukhidze, N. Jalagonia, Z. Phachulia, R. Chedia

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Ceramic obtained on the base of aluminum oxide has wide application range, because it has unique properties, for example, wear-resistance, dielectric characteristics, exploitation ability at high temperatures and in corrosive atmosphere. Low temperature synthesis of α-Al2O3 is energo-economical process and it is actual for developing technologies of corundum ceramics fabrication. In the present work possibilities of low temperature transformation of oxyhydroxides in α-Al2O3, during a presence of small amount of rare–earth elements compounds (also Th, Re), have been discussed. Aluminium unstable oxyhydroxides have been obtained by hydrolysis of aluminium isopropoxide, nitrates, sulphate, chloride in alkaline environment at 80-90ºC tempertures. β-Al(OH)3 has been received from aluminium powder by ultrasonic development. Drying of oxyhydroxide sol has been conducted with presence of various types seeds, which amount reaches 0,1-0,2% (mas). Neodymium, holmium, thorium, lanthanum, cerium, gadolinium, disprosium nitrates and rhenium carbonyls have been used as seeds and they have been added to the sol specimens in amount of 0.1-0.2% (mas) calculated on metals. Annealing of obtained gels is carried out at 70 – 1100ºC for 2 hrs. The same specimen transforms in α-Al2O3 at 1100ºC. At this temperature in case of presence of lanthanum and gadolinium transformation takes place by 70-85%. In case of presence of thorium stabilization of γ-and θ-phases takes place. It is established, that thorium causes inhibition of α-phase generation at 1100ºC, at the time in all other doped specimens α-phase is generated at lower temperatures (1000-1050ºC). During the work the following devices have been used: X-ray difractometer DRON-3M (Cu-Kα, Ni filter, 2º/min), High temperature vacuum furnace OXY-GON, electronic scanning microscopes Nikon ECLIPSE LV 150, NMM-800TRF, planetary mill Pulverisette 7 premium line, SHIMADZU Dynamic Ultra Micro Hardness Tester, DUH-211S, Analysette 12 Dyna sizer.

Keywords: α-Alumina, combustion, phase transformation, seeding

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Authors: Shahindokht Bassiri-Jahromi, Mohammad Reza Pourshafie, Farzad Katiraee, Mannan Hajimahmoodi, Ehsan Mostafavi, Malihe Talebi

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Objective: Resistance of Candida species to antifungal agents has potentially serious implications for management of infections. Candida species are now fourth common organisms isolated from hospitalized patients. It is important to increase effective therapy. In the past decade, numerous reports of treatment failures were reported. Prevention and control of these infections will require new antimicrobial agents. Plant-derived antifungal have always been a source of novel therapeutics. The aim of this study was to investigate the antifungal effect of methanolic extract of pomegranate peel and pulp against Candida species. Material and Methods: Eight cultivars of Punica granatum L. were collected from Saveh Agricultural Investigation Center in Iran. Both pomegranate pulp and peel were dried and powdered separately. The dried powders were extracted by using a soxhlet extractor. The antifungal effect of methanolic extract of pomegranate peel and pulp were determined in vitro by minimum inhibitory concentration (MIC) against five standard species of (ATCC 10231), C. parapsilosis (ATCC 22019), C. tropicalis (ATCC 750), C. glabrata (PTCC 5297), and C. kroseii (PTCC 5295). Results: Maximum inhibitions of antifungal effect were attributed to peel extract pomegranate cultivar and Candida species. The most potential antifungal inhibition among 8 different cultivars observed by sour malas, sour white peel, and sour summer extracts respectively, against five Candida strains. The antifungal activity of pulp extracts against Candida species was approximately negative. Conclusion: The use of Punica granatum peel extract has been shown to possess antifungal activities. The phytochemistry and pharmacological actions of Punica granatum peel components suggest a wide range of clinical applications for the treatment and prevention of candidiasis.

Keywords: antifungal activity, Candida species, Punica granatum L., pharmacognosy

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Authors: Anjali Sidhu, Anju Bala, Amit Kumar

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Metal nanoparticles have the potential to revolutionize the agriculture owing to sizzling interdisciplinary nano-technological application domain. Numerous patents and products incorporating engineered nanoparticles (NPs) entered into agro-applications with the collective goal to promote proficiency as well as sustainability with lower input and generating meager waste than conventional products and approaches. Loose smut of wheat caused by Ustilago segetum tritici is an internally seed-borne pathogen. It is dormant in the seed unless the seed germinates and its symptoms are expressed at the reproductive stage of the plant only. Various seed treatment agents are recommended for this disease but due to the inappropriate methods of seed treatments used by farmers, each and every seed may not get treated, and the infected seeds escape the fungicidal action. The antimicrobial potential and small size of nanoparticles made them the material of choice as they could enter each seed and restrict the pathogen inside the seed due to the availability of more number of nanoparticles per unit volume of the nanoformulations. Nanoparticles of diverse nature known for their in vitro antimicrobial activity viz. ZnO, MgO, CuS and AgNPs were synthesized, surface modified and characterized by traditional methods. They were applied on infected wheat seeds which were then grown in pot conditions, and their mycelium was tracked in the shoot and leaf region of the seedlings by microscopic staining techniques. Mixed responses of inhibition of this internal mycelium were observed. The time and method of application concluded to be critical for application, which was optimised in the present work. The results implicated that there should be field trails to get final fate of these pot trails up to commercial level. The success of their field trials could be interpreted as a revolution to replace high dose organic fungicides of high residue behaviour.

Keywords: metal nanoparticles, nanopriming, seed borne pathogen, Ustilago segetum tritici

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Authors: Yatimah Alias, Tilagam Marimuthu, M. R. Mahmoudian, Sharifah Mohamad

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The rapid growth of science and technology in energy and environmental fields has enlightened the substantial importance of the conducting polymer and metal composite materials engineered at nano-scale. In this study, polypyrrole-cobalt composites (PPy-Co Cs) and polypyrrole-nickel oxide composites (PPy-NiO Cs) were prepared by a simple and facile chemical polymerization method with an aqueous solution of pyrrole monomer in the presence of metal salt. These composites then fabricated into non-enzymatic hydrogen peroxide (H2O2) and glucose sensor. The morphology and composition of the composites are characterized by the Field Emission Scanning Electron Microscope, Fourier Transform Infrared Spectrum and X-ray Powder Diffraction. The obtained results were compared with the pure PPy and metal oxide particles. The structural and morphology properties of synthesized composites are different from those of pure PPy and metal oxide particles, which were attributed to the strong interaction between the PPy and the metal particles. Besides, a favorable micro-environment for the electrochemical oxidation of H2O2 and glucose was achieved on the modified glassy carbon electrode (GCE) coated with PPy-Co Cs and PPy-NiO Cs respectively, resulting in an enhanced amperometric response. Both PPy-Co/GCE and PPy-NiO/GCE give high response towards target analyte at optimum condition of 500 μl pyrrole monomer content. Furthermore, the presence of pyrrole monomer greatly increases the sensitivity of the respective modified electrode. The PPy-Co/GCE could detect H2O2 in a linear range of 20 μM to 80 mM with two linear segments (low and high concentration of H2O2) and the detection limit for both ranges is 2.05 μM and 19.64 μM, respectively. Besides, PPy-NiO/GCE exhibited good electrocatalytic behavior towards glucose oxidation in alkaline medium and could detect glucose in linear ranges of 0.01 mM to 0.50 mM and 1 mM to 20 mM with detection limit of 0.33 and 5.77 μM, respectively. The ease of modifying and the long-term stability of this sensor have made it superior to enzymatic sensors, which must kept in a critical environment.

Keywords: metal oxide, composite, non-enzymatic sensor, polypyrrole

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Authors: N. Harun, E. E. Masiren, W. H. W. Ibrahim, F. Adam

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Amine absorption process is an approach for mitigation of CO2 from flue gas that produces from power plant. This process is the most common system used in chemical and oil industries for gas purification to remove acid gases. On the challenges of this process is high energy requirement for solvent regeneration to release CO2. In the past few years, mixed alkanolamines have received increasing attention. In most cases, the mixtures contain N-methyldiethanolamine (MDEA) as the base amine with the addition of one or two more reactive amines such as PZ. The reason for the application of such blend amine is to take advantage of high reaction rate of CO2 with the activator combined with the advantages of the low heat of regeneration of MDEA. Several experimental and simulation studies have been undertaken to understand this process using blend MDEA/PZ solvent. Despite those studies, the mechanism of CO2 absorption into the aqueous MDEA is not well understood and available knowledge within the open literature is limited. The aim of this study is to investigate the intermolecular interaction of the blend MDEA/PZ using Molecular Dynamics (MD) simulation. MD simulation was run under condition 313K and 1 atm using NVE ensemble at 200ps and NVT ensemble at 1ns. The results were interpreted in term of Radial Distribution Function (RDF) analysis through two system of interest i.e binary and tertiary. The binary system will explain the interaction between amine and water molecule while tertiary system used to determine the interaction between the amine and CO2 molecule. For the binary system, it was observed that the –OH group of MDEA is more attracted to water molecule compared to –NH group of MDEA. The –OH group of MDEA can form the hydrogen bond with water that will assist the solubility of MDEA in water. The intermolecular interaction probability of –OH and –NH group of MDEA with CO2 in blended MDEA/PZ is higher than using single MDEA. This findings show that PZ molecule act as an activator to promote the intermolecular interaction between MDEA and CO2.Thus, blend of MDEA with PZ is expecting to increase the absorption rate of CO2 and reduce the heat regeneration requirement.

Keywords: amine absorption process, blend MDEA/PZ, CO2 capture, molecular dynamic simulation, radial distribution function

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Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

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Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

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Authors: Pooja Kumari, Anandkumar Tengli

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Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Mohd Amran, Chan Yi Jing, Chong Chien Hwa

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Production of biogas from POME requires anaerobic digestion (AD), thus, anaerobic digester performance in biogas plants is crucial. As POME from different sources have varying characteristics due to different process flows in mills, there is no ideal treatment parameters for POME. Hence, different treatment plants alter different parameters in anaerobic digestion to achieve desired biogas production levels and to meet POME waste discharge limits. The objective of this study is to evaluate the performance of mesophilic anaerobic digestion in four different biogas plants in Malaysia. Aspects of POME pre-treatment efficiency, analysis of treated POME and AD’s bottom sludge characteristics, including several parameters like chemical oxygen demand (COD), biological oxygen demand (BOD), total solid (TS) removal in the effluent, pH and temperature changes, total biogas produced, the composition of biogas including methane (CH₄), carbon dioxide (CO₂), hydrogen sulfide (H₂S) and oxygen (O₂) were investigated. The effect of organic loading rate (OLR) and hydraulic retention time (HRT) on anaerobic digester performance is also evaluated. In pre-treatment, it is observed that BGP B has the lowest average outlet temperature of 40.41°C. All BGP shows a high-temperature fluctuation (36 to 49 0C) and good pH readings (minimum 6.7), leaving the pre-treatment facility before entering the AD.COD removal of POME is considered good, with an average of 78% and maximum removal of 85%. BGP C has the lowest average COD and TS content in treated POME, 13,313 mg/L, and 12,048 mg/L, respectively. However, it is observed that the treated POME leaving all ADs, still contains high-quality organic substances (COD between 12,000 to 19,000 mg/L) that might be able to digest further to produce more biogas. The biogas produced in all four BGPs varies due to different COD loads. BGP B has the highest amount of biogas produced, 378,874.7 Nm³/month, while BGP D has the lowest biogas production of 272,378.5 Nm³/month. Furthermore, the composition of biogas produced in all plants is well within literature values (CH4 between 55 to 65% and CO₂ between 32 to 36%).

Keywords: palm oil mill effluent, in-ground lagoon anaerobic digester, anaerobic digestion, biogas

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Authors: Daisy Biswas, Samar Kanti Bose, M. Mozaffar Hossain

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The development of value added composite products from bamboo with the application of gluing technology can play a vital role in economic development and also in forest resource conservation of any country. In this study, the gluability of Bambusa balcooa and Bambusa vulgaris, two locally grown bamboo species of Bangladesh was assessed. As the culm wall thickness of bamboos decreases from bottom to top, a culm portion of up to 5.4 m and 3.6 m were used from the base of B. balcooa and B. vulgaris, respectively, to get rectangular strips of uniform thickness. The color of the B. vulgaris strips was yellowish brown and that of B. balcooa was reddish brown. The strips were treated in borax-boric, bleaching and carbonization for extending the service life of the laminates. The preservative treatments changed the color of the strips. Borax–boric acid treated strips were reddish brown. When bleached with hydrogen peroxide, the color of the strips turned into whitish yellow. Carbonization produced dark brownish strips having coffee flavor. Chemical constituents for untreated and treated strips were determined. B. vulgaris was more acidic than B. balcooa. Then the treated strips were used to develop three-layered bamboo laminated panel. Urea formaldehyde (UF) and polyvinyl acetate (PVA) were used as binder. The shear strength and abrasive resistance of the panel were evaluated. It was found that the shear strength of the UF-panel was higher than the PVA-panel for all treatments. Between the species, gluability of B. vulgaris was better and in some cases better than hardwood species. The abrasive resistance of B. balcooa is slightly higher than B. vulgaris; however, the latter was preferred as it showed well gluability. The panels could be used as structural panel, floor tiles, flat pack furniture component, and wall panel etc. However, further research on durability and creep behavior of the product in service condition is warranted.

Keywords: Bambusa balcooa, Bambusa vulgaris, polyvinyl acetate, urea formaldehyde

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Authors: Kanika Kalra, Harmeet Kaur, Dinesh Goyal

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Total phenolics were extracted from waste orange peels by solvent extraction and alkali hydrolysis method. The most efficient solvents for extracting phenolic compounds from waste biomass were methanol (60%) > dimethyl sulfoxide > ethanol (60%) > distilled water. The extraction yields were significantly impacted by solvents (ethanol, methanol, and dimethyl sulfoxide) due to varying polarity and concentrations. Extraction of phenolics using 60% methanol yielded the highest phenolics (in terms of gallic acid equivalent (GAE) per gram of biomass) in orange peels. Alkali hydrolyzed extract from orange peels contained 7.58±0.33 mg GAE g⁻¹. By using the solvent extraction technique, it was observed that 60% methanol is comparatively the best-suited solvent for extracting polyphenolic compounds and gave the maximum yield of 4.68 ± 0.47 mg GAE g⁻¹ in orange peel extracts. DPPH radical scavenging activity and reducing the power of orange peel extract were checked, where 60% methanolic extract showed the highest antioxidant activity, 85.50±0.009% for DPPH, and dimethyl sulfoxide (DMSO) extract gave the highest yield of 1.75±0.01% for reducing power ability of the orange peels extract. Characterization of the polyphenolic compounds was done by using Fourier transformation infrared (FTIR) spectroscopy. Solvent and alkali hydrolysed extracts were evaluated for antibacterial activity using the agar well diffusion method against Gram-positive Bacillus subtilis MTCC441 and Gram-negative Escherichia coli MTCC729. Methanolic extract at 300µl concentration showed an inhibition zone of around 16.33±0.47 mm against Bacillus subtilis, whereas, for Escherichia coli, it was comparatively less. Broth-based turbidimetric assay revealed the antibacterial effect of different volumes of orange peel extracts against both organisms.

Keywords: orange peels, total phenolic content, antioxidant, antibacterial

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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Authors: Alma Ramić, Mirjana Skočibušić, Renata Odžak, Tomica Hrenar, Ines Primožič

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In an attempt to identify a new class of antimicrobial agents, the antimicrobial potential of Cinchona alkaloid derivatives was evaluated. The bark of the Cinchona trees is the source of a variety of alkaloids, among which the best known are quinine, quinidine, cinchonine and cinchonidine. They are very useful as organocatalysts in stereoselective synthesis. On the other hand, quinine is traditionally used in the treatment of malaria. Furthermore, Cinchona alkaloids possess various analgesic, anti-inflammatory and anti–arrhythmic properties as well. In this work we present the synthesis of twenty quaternary derivatives of pseudo−enantiomeric Cinchona alkaloid derivatives to evaluate their antibacterial activity. Quaternization of quinuclidine moiety was carried out with groups diverse in their size. The structures of compounds were systematically modified to obtain drug-like properties with proper physical and chemical properties and avoiding toxophore. All compounds were prepared in good yields and were characterized by standard analytical spectroscopy methods (1D and 2D NMR, IR, MS). The antibacterial activities of all compounds were evaluated against series of recent clinical isolates of antibiotic susceptible Gram-positive and resistant Gram-negative pathogens by determining their zone of inhibition and minimum inhibitory concentrations. All compounds showed good to strong broad-spectrum activity, equivalent or better in comparison with standard antibiotics used. Furthermore, seven compounds exhibited significant antibacterial efficiency against Gram-negative isolates. To visualize the results, principal component analysis was used as an additional classification tool. Cytotoxicity of compounds with different cell lines in human cell culture was determined. Based on these results, substituted quaternary Cinchona scaffold can be considered as promising new class of antimicrobials and further investigations should be performed. Supported by Croatian Science Foundation, Project No 3775 ADESIRE.

Keywords: antibacterial efficiency, cinchona alkaloids, cytotoxicity, pseudo‐enantiomers

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Authors: Madiha El Awamie, Catherine Rees

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Natural preservatives have been used as alternatives to traditional chemical preservatives; however, a limited number have been commercially developed and many remain to be investigated as sources of safer and effective antimicrobials. In this study, we have been investigating the antimicrobial activity of an extract of Glycyrrhiza glabra (liquorice) that was provided as a waste material from the production of liquorice flavourings for the food industry, and to investigate if this retained the expected antimicrobial activity so it could be used as a natural preservative. Antibacterial activity of liquorice extract was screened for evidence of growth inhibition against eight species of Gram-negative and Gram-positive bacteria, including Listeria monocytogenes, Listeria innocua, Staphylococcus aureus, Enterococcus faecalis and Bacillus subtilis. The Gram-negative bacteria tested include Pseudomonas aeruginosa, Escherichia coli and Salmonella typhimurium but none of these were affected by the extract. In contrast, for all of the Gram-positive bacteria tested, growth was inhibited as monitored using optical density. However parallel studies using viable count indicated that the cells were not killed meaning that the extract was bacteriostatic rather than bacteriocidal. The Minimum Inhibitory Concentration [MIC] and Minimum Bactericidal Concentration [MBC] of the extract was also determined and a concentration of 50 µg ml^-1 was found to have a strong bacteriostatic effect on Gram-positive bacteria. Microscopic analysis indicated that there were changes in cell shape suggesting the cell wall was affected. In addition, the use of a reporter strain of Listeria transformed with the bioluminescence genes luxABCDE indicated that cell energy levels were reduced when treated with either 12.5 or 50 µg ml^-1 of the extract, with the reduction in light output being proportional to the concentration of the extract used. Together these results suggest that the extract is inhibiting the growth of Gram-positive bacteria only by damaging the cell wall and/or membrane.

Keywords: antibacterial activity, bioluminescence, Glycyrrhiza glabra, natural preservative

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Authors: Uchenna Egwu, Paul Jonathan Sallis

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Perennial ryegrass is an abundant renewable lignocellulosic biofuel feedstock for biomethane production through anaerobic digestion (AD). In this study, six anaerobic continuously stirred tank reactors (CSTRs) were set up in three pairs. Each pair of the CSTRs was then used to study the effects of operating temperatures – psychrophilic, mesophilic, and thermophilic, and optimum pH on the specific methane production (SMP) of the ryegrass during AD under discontinuous daily feeding conditions. The reactors were fed at an organic loading rate (OLR) ranging from 1-1.5 kgVS.L⁻¹d⁻¹ and hydraulic residence time, HRT=20 days for 140 days. The pH of the digesters was maintained at the range of 6.8-7.2 using 1 M NH₄HCO₃ solution, but this was replaced with biomass ash-extracts from day 105-140. The results obtained showed that the mean SMP of ryegrass measured between HRT 3 and 4 were 318.4, 425.4 and 335 N L CH₄ kg⁻¹VS.d⁻¹ for the psychrophilic (25 ± 2°C), mesophilic (40 ± 1°C) and thermophilic (60 ± 1°C) temperatures respectively. It was also observed that the buffering ability of the reactors increased with operating temperature, probably due to an increase in the solubility of ammonium bicarbonate (NH₄HCO₃) with temperature. The reactors also achieved a mean VS destruction of 61.9, 68.5 and 63.5%, respectively, which signifies that the mesophilic reactors achieved the highest specific methane production (SMP), while the psychrophilic reactors achieved the lowest. None of the reactors attained steady-state condition due to the discontinuous daily feeding times, and therefore, such feeding practice may not be the most effective for maximum biogas production over long periods of time. The addition of NH₄HCO₃ as supplement provided a good buffering condition in these AD digesters, but the digesters failed in the long run due to inhibition from the accumulation of free ammonia, which later led to decrease in pH, acidification, and souring of the digesters. However, the addition of biomass ash extracts was shown to potentially revive failed AD reactors by providing an adequate buffering and essential trace nutrient supplements necessary for optimal bacterial growth.

Keywords: anaerobic digestion, discontinuous feeding, perennial ryegrass, specific methane production, supplements, temperature

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Authors: H. Sebai, M. A. Jabria, D. Wannes, H. Tounsi, L. Marzouki

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We aimed in the present study to investigate the protective effects of Tunisian Rosa canina aqueous extract (RCAE) against ethanol-induced gastric ulceration and oxidative stress in a rat model. In this respect, adult male Wistar rats were used and divided into six groups of ten each: control, EtOH, EtOH plus various doses of RCAE, EtOH plus famotidine and EtOH + gallic acid. Phytochemical and biochemical analysis were performed using colorimetric methods. We found that RCAE is rich in total polyphenols, total flavonoids, and condensed tannins, and exhibited an importance in vitro antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In vivo, the results showed that oral administration of EtOH caused macroscopic and histological changes in gastric mucosa. These injuries are accompanied by an oxidative stress status as assessed by an increase of lipid peroxidation as well as a decrease of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Alcohol intoxication also induced intracellular mediators deregulation as assessed by an increase of hydrogen peroxide (H2O2), calcium and free iron levels in gastric mucosa. More, importantly, RCAE pretreatment reversed all macroscopic, histological and biochemical changes induced by EtOH administration. In conclusion, we suggest that RCAE has potent protective effects on acute ethanol-induced gastric ulceration related in part in part its antioxidant properties and its opposite effect on intracellular mediators. Indeed, Rosa canina can be offered as a food additive to protect against alcohol consumption-induced gastric and oxidative damage.

Keywords: alcohol, antioxidant properties, food additive, gastric ulceration, rat model, Rosa canina

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Authors: Ferhat Mohamed Amine, Boukhatem Mohamed Nadjib, Chemat Farid

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The Lamiaceae family is widely spread in Algeria. Due to the application of Thymus species growing wild in Algeria as a culinary herb and in folk medicine, the purpose of the present work was to evaluate antimicrobial activities of their essential oils and relate them with their chemical composition, for further application in food and pharmaceutical industries as natural valuable products. The extraction of the Thymus vulgaris L. essential oil (TVEO) was obtained by steam distillation. Chemical composition of the TVEO was determined by Gas Chromatography. A total of thirteen compounds were identified. Carvacrol (83.8%) was the major component, followed by cymene (8.15%) and terpinene (4.96%). Antibacterial action of the TVEO against 23 clinically isolated bacterial strains was determined by using agar disc diffusion and vapour diffusion methods at different doses. By disc diffusion method, TVEO showed potent antimicrobial activity against gram-positive bacteria more than gram-negative strains and antibiotic discs. The Diameter of Inhibition Zone (DIZ) varied from 25 to 60 mm for S. aureus, B. subtilisand E. coli. However, the results obtained by both agar diffusion and vapour diffusion methods were different. Significantly higher antibacterial effect was observed in the vapour phase at lower doses. S. aureus and B. subtilis were the most susceptible strains to the oil vapour. Therefore, smaller doses of EO in the vapour phase can be inhibitory to pathogenic bacteria. There is growing evidence that TVEO in vapour phase are effective antiseptic systems and appears worthy to be considered for practical uses in the treatment of human infections oras air decontaminants in hospital. TVEO has considerable antibacterial activity deserving further investigation for clinical applications. Also whilst the mode of action remains mainly undetermined, this experimental approach will need to continue.

Keywords: antimicrobial drugs, carvacrol, disc diffusion, Thymus vulgaris, vapour diffusion

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Authors: Thilini Kananke

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Culinary herbs have long been considered as significant dietary sources of many potential health-promoting compounds. The present research focused on analysis of antimicrobial, antioxidant and physicochemical properties in selected four culinary herbs namely Murraya koenigii (Curry leaves), Pandanus amaryllifolius (Pandan leaves), Cymbopogon citrates (Lemon grass leaves), and Mentha Piperita (Minchi leaves) obtained from several market sites in Ratnapura District, Sri Lanka. The antimicrobial activity of ethanolic, chloroform and distilled water extracts of culinary herbs were evaluated against the strains of Staphylococcus aureus, Salmonella typhi and Shigella spp. Total phenolic content and the radical scavenging activity (using DPPH assay) of culinary herbs were determined. Four heavy metals (Cu, Cd, Pb and Fe) were analyzed in the selected culinary herbs using the atomic absorption spectroscopy (AAS). Proximate compositions of the selected herbs were analyzed using AOAC official methods. Antimicrobial activity of all selected culinary herbs showed relativity high inhibition zones against S. aureus. Pandan leaves showed the least antimicrobial activity against selected bacterial strains compared with other culinary herbs. Both the highest radical scavenging activity (lower IC50 value) and the total phenolic content (25.57 ±3.54µg GAE/100g) were reported in Mentha piperita extract. The highest concentrations of Cu, Fe and Cd were reported in Curry leaves (29.15 mg/kg), Lemon grass leaves (257.98 mg/kg) and Pandan leaves (6.05 mg/kg) respectively. The heavy metal contents detected in all culinary herbs were below the permitted limits set by WHO/FAO, except Cd. The highest moisture (85.00±0.00%) and fiber (10.66± 2.00%) contents were found in Pandan leaves, while the highest protein (8.94±0.29%), fat (12.3± 2.52%) and ash (3.50± 0.17%) contents were reported in curry leaves. The information obtained from this study highlights the importance of further investigation of other antioxidant, antimicrobial and health promoting compounds of culinary herbs available in Sri Lanka for a detailed comparison.

Keywords: antimicrobial, antioxidant, culinary herbs, proximate analysis

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Authors: H. M. Zakir Hossain

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Cenozoic mudstone samples, obtained from drilled cored and outcrop in northeastern Bengal Basin of Bangladesh were organic geochemically analyzed to identify vertical variations of organic facies, thermal maturity, hydrocarbon potential and depositional environments. Total organic carbon (TOC) content ranges from 0.11 to 1.56 wt% with an average of 0.43 wt%, indicating a good source rock potential. Total sulphur content is variable with values ranging from ~0.001 to 1.75 wt% with an average of 0.065 wt%. Rock-Eval S1 and S2 yields range from 0.03 to 0.14 mg HC/g rock and 0.01 to 0.66 mg HC/g rock, respectively. The hydrogen index values range from 2.71 to 56.09 mg HC/g TOC. These results revealed that the samples are dominated by type III kerogene. Tmax values of 426 to 453 °C and vitrinite reflectance of 0.51 to 0.66% indicate the organic matter is immature to mature. Saturated hydrocarbon ratios such as pristane, phytane, steranes, and hopanes, indicate mostly terrigenous organic matter with small influence of marine organic matter. Organic matter in the succession was accumulated in three different environmental conditions based on the integration of biomarker proxies. First phase (late Eocene to early Miocene): Deposition occurred entirely in seawater-dominated oxic conditions, with high inputs of land plants organic matter including angiosperms. Second phase (middle to late Miocene): Deposition occurred in freshwater-dominated anoxic conditions, with phytoplanktonic organic matter and a small influence of land plants. Third phase (late Miocene to Pleistocene): Deposition occurred in oxygen-poor freshwater conditions, with abundant input of planktonic organic matter and high influx of angiosperms. The lower part (middle Eocene to early Miocene) of the succession with moderate TOC contents and primarily terrestrial organic matter could have generated some condensates and oils in and around the study area.

Keywords: Bangladesh, geochemistry, hydrocarbon potential, mudstone

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Authors: Stephanie Hernández-Carreón, Judith Virginia Ríos-Arana

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Microplastics (MPs) are plastic particles smaller than 5 mm that has been detected in soil, air, organisms, and mostly water around the world. Most studies have focused on MPs detection in marine waters, and less so in freshwater, such is the case of Mexico, where studies about MPs in freshwaters are limited. One of the most important rivers in the country is The Rio Grande/Río Bravo, a natural border between Mexico and the United States. Its waters serve different purposes, such as fishing, habitat to endemic species, electricity generation, agriculture, and drinking water sources, among others. Despite its importance, the river’s waters have not been analyzed to determine the presence of MPs; therefore, the purpose of this research is to determine if the Rio Bravo/Rio Grande is polluted with microplastics. For doing so, three sites (Borderland, Casa de Adobe, and Guadalupe) along the El Paso-Juárez metroplex have been sampled: 30 L of water were filtered through a plankton net (64 µm) in each site and sediments-composed samples were collected. Water samples and sediments were 1) digested with a hydrogen peroxide solution (30%), 2) resuspended in a calcium chloride solution (1.5 g/cm3) to separate MPs, and 3) filtered through a 0.45 µm nitrocellulose membrane. Processed water samples were dyed with Nile Red (1 mg/ml ethanol) and analyzed by fluorescence microscopy. Two water samples have been analyzed until January 2023: Casa de Adobe and Borderland finding a concentration of 5.67 particles/L and 5.93 particles/L, respectively. Three types of particles were observed: fibers, fragments, and films, fibers being the most abundant. These data, as well as the data obtained from the rest of the samples, will be analyzed by an ANOVA (α=0.05). The concentrations and types of particles found in the Río Bravo correspond with other studies on rivers associated with urban environments and agricultural activities in China, where a range of 3.67—10.7 particles/L was reported in the Wei River. Even though we are in the early stages of the study, and three new sites will be sampled and analyzed in 2023 to provide more data about this issue in the river, this presents the first evidence of microplastic pollution in the Rio Grande.

Keywords: microplastics, fresh water, Rio Bravo, fluorescence microscopy

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Authors: Milad Pirali, Sohrab Keyhani, Mohhamad Ali Sanjari, Ali Ashraf Jamshidi

Abstract:

Purpose: The effect of hamstring antagonist activity on the knee extensors torque of the Anterior Cruciate Ligament reconstruction (ACLR) is not clear and persistent muscle weakness is common after ACLR. Hamstring activation when acting as antagonist is considered very important for knee strengths. Therefore the purpose of this study was to examine hamstring antagonist coactivation during maximal effort of the isokinetic knee extension in ACLR athletes with hamstring autograft. Materials and Methods: We enrolled 20 professional athletes who underwent primary ACLR (hamstring tendon autograft)with 6-24 months postoperative and 20 healthy subjects as control group. Each subjects performed maximal effort isokinetic knee extension and flexion in 60/˚ s and 180/˚ s velocities for the involved and uninvolved limb. Synchronously, surface electromyography (EMG) was recorded of vastus medialis (VM), vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF). The antagonist integrated EMG (IEMG) values were normalized to the IEMG of the same muscle during maximal isokinetic eccentric effort at the same velocities and ROM. Results: A one-way analysis of variance designs shows significantly greater IEMG coactivation of hamstring and decreased activation of Vm in ACLR when compared to uninvolved and control group leg in 60/˚ s and 180/˚ s velocities. Likewise peak torque to body weight was decreased in ACLR compared to uninvolved and control group during knee extension in both velocities (p < 0.05). Conclusions: Decreased extensors moment caused by decreased quadriceps inhibition and increased hamstring coactivation. In addition, these result indicated to decrease of motor unit recruitment in the VM (as a kinesiologicmonitore of the knee). It is appearing that strengthening of the quadriceps to be an important for rehabilitation program after ACLR for preparation in athletes endeavors. Therefore, we suggest that having more emphasis and focus on quadriceps strength and less emphasis on hamstring following ACLR.

Keywords: ACLR-coactivation, dynamometry, electromyography, isokinetic

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Authors: Husain Rajib, T. H. Sheikh, D. G. Jewel

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Background: Amblyopia is a frequent cause of monocular blindness in children. It can be unilateral or bilateral reduction of best corrected visual acuity associated with decrement in visual processing, accomodation, motility, spatial perception or spatial projection. Anisometropia is an important risk factor for amblyopia that develops when unequal refractive error causes the image to be blurred in the critical developmental period and central inhibition of the visual signal originating from the affected eye associated with significant visual problems including anisokonia, strabismus, and reduced stereopsis. Methods: It is a prospective hospital based study of newly diagnosed of amblyopia seen at the pediatric clinic of Chittagong Eye Infirmary & Training Complex. There were 50 anisometropic amblyopia subjects were examined & questionnaire was piloted. Included were all patients diagnosed with refractive amblyopia between 3 to 13 years, without previous amblyopia treatment, and whose parents were interested to participate in the study. Patients diagnosed with strabismic amblyopia were excluded. Patients were first corrected with the best correction for a month. When the VA in the amblyopic eye did not improve over month, then occlusion treatment was started. Occlusion was done daily for 6-8 hours (full time) together with vision therapy. The occlusion was carried out for 3 months. Results: In this study about 8% subjects had anisometropia from myopia, 18% from hyperopia, 74% from astigmatism. The initial mean visual acuity was 0.74 ± 0.39 Log MAR and after intervention of amblyopia therapy with active vision therapy mean visual acuity was 0.34 ± 0.26 Log MAR. About 94% of subjects were improving at least two lines. The depth of amblyopia associated with type of anisometropic refractive error and magnitude of Anisometropia (p<0.005). By doing this study 10% mild amblyopia, 64% moderate and 26% severe amblyopia were found. Binocular function also decreases with magnitude of Anisometropia. Conclusion: Anisometropic amblyopia is a most important factor in pediatric age group because it can lead to visual impairment. Occlusion therapy with at least one instructed hour of active visual activity practiced out of school hours was effective in anisometropic amblyopes who were diagnosed at the age of 8 years and older, and the patients complied well with the treatment.

Keywords: refractive error, anisometropia, amblyopia, strabismic amblyopia

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Authors: Andi Ismanto

Abstract:

Indonesia is the largest palm oil producer in the world. The increasing number of palm oil extensification in Indonesia started on 2000-2011. Based on preliminary figures from the Directorate General of Plantation, palm oil area in Indonesia until 2011 is about 8.91 million hectares.On 2011 production of palm oil CPO reaches 22.51 million tons. In the other hands, the increasing palm oil production has impact to environment. The Empty Bunch of Palm Oil (EBPO)waste was increased to 20 million tons in 2009. Utilization of waste EBPO currently only used as an organic fertilizer for plants. But, it was not a good solution, because TKKS that used as organic compost has high content of carbon and hydrogen compound. The EBPO waste has potential used as fuel by gasification because it has short time of decomposition. So, the process will be more efficient in time. Utilization of urban wastehas been created using an incinerator used as a source of electrical energy for household.Usually, waste burning process by incinerator is using diesel fuel and kerosene. It is certainly less effective and not environment friendly, considering the waste incineration process using Incinerator tools are continuously. Considering biomass is a renewable source of energy and the world's energy system must be switch from an energy based on fossil resources into the energy based on renewable resources, the "Gurza Incinerator": Design Build Powerful Biomass Incinerator Empty Bunch of Palm Oil (EBPO) as Elecrical Biomass Base Development, a renewable future technology. The tools is using EBPO waste as source of burning to burn garbage inside the Incinerator hopper. EBPO waste will be processed by means of gasification. Gasification isa process to produce gases that can be used as fuel for electrical power. Hopefully, this technology could be a renewable future energy and also as starting point of electrical biomass base development.

Keywords: incinerator, biomass, empty bunch palm oil, electrical energy

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Leticia Leandro Rade, Amanda Silva de Sousa, Suman Das, Wesley Generoso, Mayara Chagas Ávila, Plinio Salmazo Vieira, Antonio Bonomi, Gabriela Persinoti, Mario Tyago Murakami, Thomas Michael Makris, Leticia Maria Zanphorlin

Abstract:

Alkenes have an economic appeal, especially in the biofuels field, since they are precursors for drop-in biofuels production, which have similar chemical and physical properties to the conventional fossil fuels, with no oxygen in their composition. After the discovery of the first P450 CYP152 OleTJE in 2011, reported with its unique property of decarboxylating fatty acids (FA), by using hydrogen peroxide as a cofactor and producing 1-alkenes as the main product, the scientific and technological interest in this family of enzymes vastly increased. In this context, the present work presents a new decarboxylase (OleTRN) with low similarity with OleTJE (32%), its biochemical characterization, and structure elucidation. As main results, OleTRN presented a high yield of expression and purity, optimum reaction conditions at 35 °C and pH from 6.5 to 8.0, and higher specificity for oleic acid. Besides that, structure-guided mutations were performed and according to the functional characterizations, it was observed that some mutations presented different specificity and chemoselectivity by varying the chain-length of FA substrates from 12 to 20 carbons. These results are extremely interesting from a biotechnological perspective as those characteristics could diversify the applications and contribute to designing better cytochrome P450 decarboxylases. Considering that peroxygenases have the potential activity of decarboxylating and hydroxylating fatty acids and that the elucidation of the intriguing mechanistic involved in the decarboxylation preferential from OleTJE is still a challenge, the elucidation of OleTRN structure and the functional characterizations of OleTRN and its mutants contribute to new information about CYP152. Besides that, the work also contributed to the discovery of a new decarboxylase with a different selectivity profile from OleTJE, which allows a wide range of applications.

Keywords: P450, decarboxylases, alkenes, biofuels

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Authors: Xiangjun Li, Huaiyuan Tian, Wujie Zhang, Dianhua Liu

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Polyoxymethylene dimethyl ethers (PODE_n) as clean diesel additive can improve the combustion efficiency and quality of diesel fuel and alleviate the problem of atmospheric pollution. Considering synthetic routes, PODE production from methanol and formaldehyde is regarded as the most economical and promising synthetic route. However, methanol used for synthesizing PODE can produce water, which causes the loss of active center of catalyst and hydrolysis of PODE_n in the production process. Macroporous strong acidic cation exchange resin catalyst was prepared, which has comparative advantages over other common solid acid catalysts in terms of stability and catalytic efficiency for synthesizing PODE. Catalytic reactions were carried out under 353 K, 1 MPa and 3mL·g_cat^-1·h^-1 in a fixed bed reactor. Methanol conversion and PODE_3-6 selectivity reached 49.91% and 23.43%, respectively. Catalyst lifetime evaluation showed that resin catalyst retained its catalytic activity for 20 days without significant changes and catalytic activity of completely deactivated resin catalyst can basically return to previous level by simple acid regeneration. The acid exchange capacities of original and deactivated catalyst were 2.5191 and 0.0979 mmol·g^-1, respectively, while regenerated catalyst reached 2.0430 mmol·g^-1, indicating that the main reason for resin catalyst deactivation is that Brønsted acid sites of original resin catalyst were temporarily replaced by non-hydrogen ion cations. A separation process consisting of extraction and distillation for PODE_3-6 product was designed for separation of water and unreacted formaldehyde from reactive mixture and purification of PODE_3-6, respectively. The concentration of PODE_3-6 in final product can reach up to 97%. These results indicate that the scale-up production of PODE_3-6 from methanol and formaldehyde solution is feasible.

Keywords: inactivation, polyoxymethylene dimethyl ethers, separation process, sulfonic cation exchange resin

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