Search results for: amyloid aggregation inhibition

Authors: Arvind Kumar

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The city of Kanpur is located in the terrestrial plain area on the bank of the river Ganges and is the second largest city in the state of Uttar Pradesh. The city generates approximately 1400-1600 tons per day of MSW. Kanpur has been known as a major point and non-points-based pollution hotspot for the river Ganges. The city has a major industrial hub, probably the largest in the state, catering to the manufacturing and recycling of plastic and other dry waste streams. There are 4 to 5 major drains flowing across the city, which receive a significant quantity of waste leakage, which subsequently adds to the Ganges flow and is carried to the Bay of Bengal. A river-to-sea flow approach has been established to account for leaked waste into urban drains, leading to the build-up of marine litter. Throughout its journey, the river accumulates plastic – macro, meso, and micro, from various sources and transports it towards the sea. The Ganges network forms the second-largest plastic-polluting catchment in the world, with over 0.12 million tonnes of plastic discharged into marine ecosystems per year and is among 14 continental rivers into which over a quarter of global waste is discarded 3.150 Kilo tons of plastic waste is generated in Kanpur, out of which 10%-13% of plastic is leaked into the local drains and water flow systems. With the Support of Kanpur Municipal Corporation, 1TPD capacity MRF for drain waste management was established at Krishna Nagar, Kanpur & A German startup- Plastic Fisher, was identified for providing a solution to capture the drain waste and achieve its recycling in a sustainable manner with a circular economy approach. The team at Plastic Fisher conducted joint surveys and identified locations on 3 drains at Kanpur using GIS maps developed during the survey. It suggested putting floating 'Boom Barriers' across the drains with a low-cost material, which reduced their cost to only 2000 INR per barrier. The project was built upon the self-sustaining financial model. The project includes activities where a cost-efficient model is developed and adopted for a socially self-inclusive model. The project has recommended the use of low-cost floating boom barriers for capturing waste from drains. This involves a one-time time cost and has no operational cost. Manpower is engaged in fishing and capturing immobilized waste, whose salaries are paid by the Plastic Fisher. The captured material is sun-dried and transported to the designated place, where the shed and power connection, which act as MRF, are provided by the city Municipal corporation. Material aggregation, baling, and transportation costs to end-users are borne by Plastic Fisher as well.

Keywords: Kanpur, marine environment, drain waste management, plastic fisher

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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

Procedia PDF Downloads 271

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: Min Han, Di Wu, Lin Yuan, Fei Liu

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Mechanical sensors have undergone a continuous evolution and have become an important part of many industries, ranging from manufacturing to process, chemicals, machinery, health-care, environmental monitoring, automotive, avionics, and household appliances. Concurrently, the microelectronics and microfabrication technology have provided us with the means of producing mechanical microsensors characterized by high sensitivity, small size, integrated electronics, on board calibration, and low cost. Here we report a new kind of mechanical sensors based on the quantum transport process of electrons in the closely spaced nanoparticle films covering a flexible polymer sheet. The nanoparticle films were fabricated by gas phase depositing of preformed metal nanoparticles with a controlled coverage on the electrodes. To amplify the conductance of the nanoparticle array, we fabricated silver interdigital electrodes on polyethylene terephthalate(PET) by mask evaporation deposition. The gaps of the electrodes ranged from 3 to 30μm. Metal nanoparticles were generated from a magnetron plasma gas aggregation cluster source and deposited on the interdigital electrodes. Closely spaced nanoparticle arrays with different coverage could be gained through real-time monitoring the conductance. In the film coulomb blockade and quantum, tunneling/hopping dominate the electronic conduction mechanism. The basic principle of the mechanical sensors relies on the mechanical deformation of the fabricated devices which are translated into electrical signals. Several kinds of sensing devices have been explored. As a strain sensor, the device showed a high sensitivity as well as a very wide dynamic range. A gauge factor as large as 100 or more was demonstrated, which can be at least one order of magnitude higher than that of the conventional metal foil gauges or even better than that of the semiconductor-based gauges with a workable maximum applied strain beyond 3%. And the strain sensors have a workable maximum applied strain larger than 3%. They provide the potential to be a new generation of strain sensors with performance superior to that of the currently existing strain sensors including metallic strain gauges and semiconductor strain gauges. When integrated into a pressure gauge, the devices demonstrated the ability to measure tiny pressure change as small as 20Pa near the atmospheric pressure. Quantitative vibration measurements were realized on a free-standing cantilever structure fabricated with closely-spaced nanoparticle array sensing element. What is more, the mechanical sensor elements can be easily scaled down, which is feasible for MEMS and NEMS applications.

Keywords: gas phase deposition, mechanical sensors, metallic nanoparticle arrays, quantum conductance

Procedia PDF Downloads 257

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

Procedia PDF Downloads 49

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

Procedia PDF Downloads 124

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

Procedia PDF Downloads 66

Authors: Olanrewaju Aladeitan, Obiageli Phina Anaghara-Uzor

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Despite the abundance of natural gas deposits in Nigeria and the immense potential, this presents both for the domestic and export oriented revenue, there exists an imbalance in the preference for export as against the development and optimal utilization of natural gas for the domestic industry. Considerable amounts of gas are still being wasted by flaring in the country to this day. Although the government has set in place initiatives to harness gas at the flare and thereby reduce volumes flared, the gas producers would rather direct the gas produced to the export market whereas gas apportioned to the domestic market is often marred by the low domestic gas price which is often discouraging to the gas producers. The exported fraction of gas production no doubt yields healthy revenues for the government and an encouraging return on investment for the gas producers and for this reason export sales remain enticing and preferable to the domestic sale of gas. This export pull impacts negatively if left unchecked, on the domestic market which is in no position to match the price at the international markets. The issue of gas price remains critical to the optimal development of the domestic gas industry, in that it comprises the basis for investment decisions of the producers on the allocation of their scarce resources and to what project to channel their output in order to maximize profit. In order then to rebalance the domestic industry and streamline the market for gas, the Gas Aggregation Company of Nigeria, also known as the Strategic Aggregator was proposed under the Nigerian Gas Master Plan of 2008 and then established pursuant to the National Gas Supply and Pricing Regulations of 2008 to implement the domestic gas supply obligation which focuses on ramping-up gas volumes for domestic utilization by mandatorily requiring each gas producer to dedicate a portion of its gas production for domestic utilization before having recourse to the export market. The 2008 Regulations further stipulate penalties in the event of non-compliance. This study, in the main, assesses the adequacy of the legal framework for the Nigerian Gas Industry, given that the operational laws are structured more for oil than its gas counterpart; examine the legal basis for the Strategic Aggregator in the light of the Domestic Gas Supply and Pricing Policy 2008 and the National Domestic Gas Supply and Pricing Regulations 2008 and makes a case for a review of the pivotal role of the Aggregator in the Nigerian Gas market. In undertaking this assessment, the doctrinal research methodology was adopted. Findings from research conducted reveal the reawakening of the Federal Government to the immense potential of its gas industry as a critical sector of its economy and the need for a sustainable domestic natural gas market. A case for the review of the ownership structure of the Aggregator to comprise a balanced mix of the Federal Government, gas producers and other key stakeholders in order to ensure the effective implementation of the domestic supply obligations becomes all the more imperative.

Keywords: domestic supply obligations, natural gas, Nigerian gas sector, strategic gas aggregator

Procedia PDF Downloads 194

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

Procedia PDF Downloads 271

Authors: Fatih Gundogan, Fatih Kafali, Abdullah Karadag, Alper Baloglu, Ersoy Pehlivan, Mustafa Eruyar, Osman Bayram, Orhan Karademiroglu, Wasim Shoman

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Nowadays many cities around the world are investing their efforts and resources for the purpose of facilitating their citizen’s life and making cities more livable and sustainable by implementing newly emerged phenomena of smart city. For this purpose, related research institutions prepare and publish smart city indices or benchmarking reports aiming to measure the city’s current ‘smartness’ status. Several functional domains, various indicators along different selection and calculation methods are found within such indices and reports. The selection criteria varied for each institution resulting in inconsistency in the ranking and evaluating. This research aims to evaluate the impact of selecting such functional domains, indicators and calculation methods which may cause change in the rank. For that, six functional domains, i.e. Environment, Mobility, Economy, People, Living and governance, were selected covering 19 focus areas and 41 sub-focus (variable) areas. 60 out of 191 indicators were also selected according to several criteria. These were identified as a result of extensive literature review for 13 well known global indices and research and the ISO 37120 standards of sustainable development of communities. The values of the identified indicators were obtained from reliable sources for ten cities. The values of each indicator for the selected cities were normalized and standardized to objectively investigate the impact of the chosen indicators. Moreover, the effect of choosing an integration method to represent the values of indicators for each city is investigated by comparing the results of two of the most used methods i.e. geometric aggregation and fuzzy logic. The essence of these methods is assigning a weight to each indicator its relative significance. However, both methods resulted in different weights for the same indicator. As a result of this study, the alternation in city ranking resulting from each method was investigated and discussed separately. Generally, each method illustrated different ranking for the selected cities. However, it was observed that within certain functional areas the rank remained unchanged in both integration method. Based on the results of the study, it is recommended utilizing a common platform and method to objectively evaluate cities around the world. The common method should provide policymakers proper tools to evaluate their decisions and investments relative to other cities. Moreover, for smart cities indices, at least 481 different indicators were found, which is an immense number of indicators to be considered, especially for a smart city index. Further works should be devoted to finding mutual indicators representing the index purpose globally and objectively.

Keywords: functional domain, urban city index, indicator, smart city

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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: 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

Abstract:

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: 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: Mia Bahar, Özlem Bozkurt

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Obsessive-compulsive disorder (OCD) is a typical, persistent, and long-lasting mental health condition in which a person experiences uncontrollable, recurrent thoughts (or "obsessions") and/or activities (or "compulsions") that they feel compelled to engage in repeatedly. Obsessive-compulsive disorder is both underdiagnosed and undertreated. It frequently manifests in a variety of medical settings and is persistent, expensive, and burdensome. Obsessive-compulsive neurosis was long believed to be a condition that offered valuable insight into the inner workings of the unconscious mind. Obsessive-compulsive disorder is now recognized as a prime example of a neuropsychiatric condition susceptible to particular pharmacotherapeutic and psychotherapy therapies and mediated by pathology in particular neural circuits. An obsessive-compulsive disorder which is called OCD, usually has two components, one cognitive and the other behavioral, although either can occur alone. Obsessions are often repetitive and intrusive thoughts that invade consciousness. These obsessions are incredibly hard to control or dismiss. People who have OCD often engage in rituals to reduce anxiety associated with intrusive thoughts. Once the ritual is formed, the person may feel extreme relief and be free from anxiety until the thoughts of contamination intrude once again. These thoughts are strengthened through a manifestation of negative reinforcement because they allow the person to avoid anxiety and obscurity. These thoughts are described as autogenous, meaning they most likely come from nowhere. These unwelcome thoughts are related to actions which we can describe as Thought Action Fusion. The thought becomes equated with an action, such as if they refuse to perform the ritual, something bad might happen, and so people perform the ritual to escape the intrusive thought. In almost all cases of OCD, the person's life gets extremely disturbed by compulsions and obsessions. Studies show OCD is an estimated 1.1% prevalence, making it a challenging issue with high co-morbidities with other issues like depressive episodes, panic disorders, and specific phobias. The first to reveal brain anomalies in OCD were numerous CT investigations, although the results were inconsistent. A few studies have focused on the orbitofrontal cortex (OFC), anterior cingulate gyrus (AC), and thalamus, structures also implicated in the pathophysiology of OCD by functional neuroimaging studies, but few have found consistent results. However, some studies have found abnormalities in the basal ganglion. There have also been some discussions that OCD might be genetic. OCD has been linked to families in studies of family aggregation, and findings from twin studies show that this relationship is somewhat influenced by genetic variables. Some Research has shown that OCD is a heritable, polygenic condition that can result from de novo harmful mutations as well as common and unusual variants. Numerous studies have also presented solid evidence in favor of a significant additive genetic component to OCD risk, with distinct OCD symptom dimensions showing both common and individual genetic risks.

Keywords: compulsions, obsessions, neuropsychiatric, genetic

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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: 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: Parminder Kaur Heer, Alexei Lapkin

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Due to global challenges of increased competition and demand for more sustainable products/processes, there is a rising pressure on the industry to develop innovative processes. Through Process Intensification (PI) the existing and new processes may be able to attain higher efficiency. However, very few PI options are generally considered. This is because processes are typically analysed at a unit operation level, thus limiting the search space for potential process options. PI performed at more detailed levels of a process can increase the size of the search space. The different levels at which PI can be achieved is unit operations, functional and phenomena level. Physical/chemical phenomena form the lowest level of aggregation and thus, are expected to give the highest impact because all the intensification options can be described by their enhancement. The objective of the current work is thus, generation of numerous process alternatives based on phenomena, and development of their corresponding computer aided models. The methodology comprises: a) automated generation of process options, and b) automated generation of process models. The process under investigation is disintegrated into functions viz. reaction, separation etc., and these functions are further broken down into the phenomena required to perform them. E.g., separation may be performed via vapour-liquid or liquid-liquid equilibrium. A list of phenomena for the process is formed and new phenomena, which can overcome the difficulties/drawbacks of the current process or can enhance the effectiveness of the process, are added to the list. For instance, catalyst separation issue can be handled by using solid catalysts; the corresponding phenomena are identified and added. The phenomena are then combined to generate all possible combinations. However, not all combinations make sense and, hence, screening is carried out to discard the combinations that are meaningless. For example, phase change phenomena need the co-presence of the energy transfer phenomena. Feasible combinations of phenomena are then assigned to the functions they execute. A combination may accomplish a single or multiple functions, i.e. it might perform reaction or reaction with separation. The combinations are then allotted to the functions needed for the process. This creates a series of options for carrying out each function. Combination of these options for different functions in the process leads to the generation of superstructure of process options. These process options, which are formed by a list of phenomena for each function, are passed to the model generation algorithm in the form of binaries (1, 0). The algorithm gathers the active phenomena and couples them to generate the model. A series of models is generated for the functions, which are combined to get the process model. The most promising process options are then chosen subjected to a performance criterion, for example purity of product, or via a multi-objective Pareto optimisation. The methodology was applied to a two-step process and the best route was determined based on the higher product yield. The current methodology can identify, produce and evaluate process intensification options from which the optimal process can be determined. It can be applied to any chemical/biochemical process because of its generic nature.

Keywords: Phenomena, Process intensification, Process models , Process options

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Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali

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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.

Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum

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Authors: S. Reshma Reghu, Shiburaj Sugathan, T. G. Nandu, K. B. Ramesh Kumar, Mathew Dan

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Bacterial diseases are considered to be one of the most prevalent health hazards in the developing world and many bacteria are becoming resistant to existing antibiotics making the treatment ineffective. Thus, it is necessary to find novel targets and develop new antibacterial drugs with a novel mechanism of action. The process of bacterial cell division is a novel and attractive target for new antibacterial drug discovery. FtsZ, a homolog of eukaryotic tubulin, is the major protein of the bacterial cell division machinery and is considered as an important antibacterial drug target. Zingiberaceae, the Ginger family consists of aromatic herbs with creeping rhizomes. Many of these plants have antimicrobial properties.This study aimed to determine the anti-bacterial activity of selected Zingiberaceous plants by targeting bacterial cell division protein, FtsZ. Essential oils and methanol extracts of Amomum ghaticum, Alpinia galanga, Kaempferia galanga, K. rotunda, and Zingiber officinale were tested to find its antibacterial efficiency using disc diffusion method against authentic bacterial strains obtained from MTCC (India). Essential oil isolated from A.galanga and Z.officinale were further assayed for FtsZ inhibition assay following non-radioactive malachite green-phosphomolybdate assay using E. coli FtsZ protein obtained from Cytoskelton Inc., USA. Z.officinale essential oil possess FtsZ inhibitory property. A molecular docking study was conducted with the known bioactive compounds of Z. officinale as ligands with the E. coli FtsZ protein homology model. Some of the major constituents of this plant like catechin, epicatechin, and gingerol possess agreeable docking scores. The results of this study revealed that several chemical constituents in Ginger plants can be utilised as potential source of antibacterial activity and it can warrant further investigation through drug discovery studies.

Keywords: antibacterial, FtsZ, zingiberaceae, docking

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Authors: Bipasa Dey, Varsha Panwar, Tanmay Dutta

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Laccase, a multicopper oxidase (EC 1.10.3.2) have been at the forefront as a superior industrial biocatalyst. They are versatile in terms of bestowing sustainable and ecological catalytic reactions such as polymerisation, xenobiotic degradation and bioremediation of phenolic and non-phenolic compounds. Regardless of the wide biotechnological applications, the critical limiting factors viz. reusability, retrieval, and storage stability still prevail. This can cause an impediment in their applicability. Crosslinked enzyme aggregates (CLEAs) have emerged as a promising technique that rehabilitates these essential facets, albeit at the expense of their enzymatic activity. The carrier free crosslinking method prevails over the carrier-bound immobilisation in conferring high productivity, low production cost owing to the absence of additional carrier and circumvent any non-catalytic ballast which could dilute the volumetric activity. To the best of our knowledge, the ε-amino group of lysyl residue is speculated as the best choice for forming Schiff’s base with glutaraldehyde. Despite being most preferrable, excess glutaraldehyde can bring about disproportionate and undesirable crosslinking within the catalytic site and hence could deliver undesirable catalytic losses. Moreover, the surface distribution of lysine residues in Trametes versicolor laccase is significantly less. Thus, to mitigate the adverse effect of glutaraldehyde in conjunction with scaling down the degradation or catalytic loss of the enzyme, crosslinking with inert substances like gelatine, collagen, Bovine serum albumin (BSA) or excess lysine is practiced. Analogous to these molecules, sugars have been well known as a protein stabiliser. It helps to retain the structural integrity, specifically secondary structure of the protein during aggregation by changing the solvent properties. They are comprehended to avert protein denaturation or enzyme deactivation during precipitation. We prepared crosslinked enzyme aggregates (CLEAs) of laccase from T. versicolor with the aid of sugars. The sugar CLEAs were compared with the classic BSA and glutaraldehyde laccase CLEAs concerning physico-chemical properties. The activity recovery for the fructose CLEAs were found to be ~20% higher than the non-sugar CLEA. Moreover, the 𝐾𝑐𝑎𝑡𝐾𝑚⁄ values of the CLEAs were two and three-fold higher than BSA-CLEA and GACLEA, respectively. The half-life (t1/2) deciphered by sugar-CLEA was higher than the t1/2 of GA-CLEAs and free enzyme, portraying more thermal stability. Besides, it demonstrated extraordinarily high pH stability, which was analogous to BSA-CLEA. The promising attributes of increased storage stability and recyclability (>80%) gives more edge to the sugar-CLEAs over conventional CLEAs of their corresponding free enzyme. Thus, sugar-CLEA prevails in furnishing the rudimentary properties required for a biocatalyst and holds many prospects.

Keywords: cross-linked enzyme aggregates, laccase immobilization, enzyme reusability, enzyme stability

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Authors: Anne M. Denton, Rahul Gomes, David W. Franzen

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High-resolution elevation data are becoming increasingly available, but typical approaches for computing topographic features, like slope and curvature, still assume small sliding windows, for example, of size 3x3. That means that the digital elevation model (DEM) has to be resampled to the scale of the landform features that are of interest. Any higher resolution is lost in this resampling. When the topographic features are computed through regression that is performed at the resolution of the original data, the accuracy can be much higher, and the reported result can be adjusted to the length scale that is relevant locally. Slope and variance are calculated for overlapping windows, meaning that one regression result is computed per raster point. The number of window centers per area is the same for the output as for the original DEM. Slope and variance are computed by performing regression on the points in the surrounding window. Such an approach is computationally feasible because of the additive nature of regression parameters and variance. Any doubling of window size in each direction only takes a single pass over the data, corresponding to a logarithmic scaling of the resulting algorithm as a function of the window size. Slope and variance are stored for each aggregation step, allowing the reported slope to be selected to minimize variance. The approach thereby adjusts the effective window size to the landform features that are characteristic to the area within the DEM. Starting with a window size of 2x2, each iteration aggregates 2x2 non-overlapping windows from the previous iteration. Regression results are stored for each iteration, and the slope at minimal variance is reported in the final result. As such, the reported slope is adjusted to the length scale that is characteristic of the landform locally. The length scale itself and the variance at that length scale are also visualized to aid in interpreting the results for slope. The relevant length scale is taken to be half of the window size of the window over which the minimum variance was achieved. The resulting process was evaluated for 1-meter DEM data and for artificial data that was constructed to have defined length scales and added noise. A comparison with ESRI ArcMap was performed and showed the potential of the proposed algorithm. The resolution of the resulting output is much higher and the slope and aspect much less affected by noise. Additionally, the algorithm adjusts to the scale of interest within the region of the image. These benefits are gained without additional computational cost in comparison with resampling the DEM and computing the slope over 3x3 images in ESRI ArcMap for each resolution. In summary, the proposed approach extracts slope and aspect of DEMs at the lengths scales that are characteristic locally. The result is of higher resolution and less affected by noise than existing techniques.

Keywords: high resolution digital elevation models, multi-scale analysis, slope calculation, window-based regression

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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