Search results for: antimicrobial agents
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2162

Search results for: antimicrobial agents

572 Exploring 1,2,4-Triazine-3(2H)-One Derivatives as Anticancer Agents for Breast Cancer: A QSAR, Molecular Docking, ADMET, and Molecular Dynamics

Authors: Said Belaaouad

Abstract:

This study aimed to explore the quantitative structure-activity relationship (QSAR) of 1,2,4-Triazine-3(2H)-one derivative as a potential anticancer agent against breast cancer. The electronic descriptors were obtained using the Density Functional Theory (DFT) method, and a multiple linear regression techniques was employed to construct the QSAR model. The model exhibited favorable statistical parameters, including R2=0.849, R2adj=0.656, MSE=0.056, R2test=0.710, and Q2cv=0.542, indicating its reliability. Among the descriptors analyzed, absolute electronegativity (χ), total energy (TE), number of hydrogen bond donors (NHD), water solubility (LogS), and shape coefficient (I) were identified as influential factors. Furthermore, leveraging the validated QSAR model, new derivatives of 1,2,4-Triazine-3(2H)-one were designed, and their activity and pharmacokinetic properties were estimated. Subsequently, molecular docking (MD) and molecular dynamics (MD) simulations were employed to assess the binding affinity of the designed molecules. The Tubulin colchicine binding site, which plays a crucial role in cancer treatment, was chosen as the target protein. Through the simulation trajectory spanning 100 ns, the binding affinity was calculated using the MMPBSA script. As a result, fourteen novel Tubulin-colchicine inhibitors with promising pharmacokinetic characteristics were identified. Overall, this study provides valuable insights into the QSAR of 1,2,4-Triazine-3(2H)-one derivative as potential anticancer agent, along with the design of new compounds and their assessment through molecular docking and dynamics simulations targeting the Tubulin-colchicine binding site.

Keywords: QSAR, molecular docking, ADMET, 1, 2, 4-triazin-3(2H)-ones, breast cancer, anticancer, molecular dynamic simulations, MMPBSA calculation

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571 Chromosomal Damage in Human Lymphocytes by Ultraviolet Radiation

Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

Abstract:

Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios States and skin cancers. Objective: Identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for a groups 1 to 3 seconds (p<0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: ultraviolet rays, lymphocytes, chromosome breakpoints, photodamage

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570 Ultraviolet Radiation and Chromosomal Damage in Human Lymphocytes

Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

Abstract:

Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios states and skin cancers. Objective: To identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from the heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin, and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for groups 1 to 3 seconds (p < 0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: chromosome breakpoints, lymphocytes, photodamage, ultraviolet rays

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569 Surface Modified Polyamidoamine Dendrimer with Gallic Acid Overcomes Drug Resistance in Colon Cancer Cells HCT-116

Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

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568 Development and Evaluation of New Complementary Food from Maize, Soya Bean and Moringa for Young Children

Authors: Berhan Fikru

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The objective of this study was to develop new complementary food from maize, soybean and moringa for young children. The complementary foods were formulated with linear programming (LP Nutri-survey software) and Faffa (corn soya blend) use as control. Analysis were made for formulated blends and compared with the control and recommended daily intake (RDI). Three complementary foods composed of maize, soya bean, moringa and sugar with ratio of 65:20:15:0, 55:25:15:5 and 65:20:10:5 for blend 1, 2 and 3, respectively. The blends were formulated based on the protein, energy, mineral (iron, zinc an calcium) and vitamin (vitamin A and C) content of foods. The overall results indicated that nutrient content of faffa (control) was 16.32 % protein, 422.31 kcal energy, 64.47 mg calcium, 3.8 mg iron, 1.87mg zinc, 0.19 mg vitamin A and 1.19 vitamin C; blend 1 had 17.16 % protein, 429.84 kcal energy, 330.40 mg calcium, 6.19 mg iron, 1.62 mg zinc, 6.33 mg vitamin A and 4.05 mg vitamin C; blend 2 had 20.26 % protein, 418.79 kcal energy, 417.44 mg calcium, 9.26 mg iron, 2.16 mg zinc, 8.43 mg vitamin A and 4.19 mg vitamin C whereas blend 3 exhibited 16.44 % protein, 417.42 kcal energy, 242.4 mg calcium, 7.09 mg iron, 2.22 mg zinc, 3.69 mg vitamin A and 4.72 mg vitamin C, respectively. The difference was found between all means statically significance (P < 0.05). Sensory evaluation showed that the faffa control and blend 3 were preferred by semi-trained panelists. Blend 3 had better in terms of its mineral and vitamin content than FAFFA corn soya blend and comparable with WFP proprietary products CSB+, CSB++ and fulfills the WHO recommendation for protein, energy and calcium. The suggested formulation with Moringa powder can therefore be used as a complementary food to improve the nutritional status and also help solve problems associated with protein energy and micronutrient malnutrition for young children in developing countries, particularly in Ethiopia.

Keywords: corn soya blend, proximate composition, micronutrient, mineral chelating agents, complementary foods

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567 Isolation and Identification of Microorganisms from Marine-Associated Samples under Laboratory Conditions

Authors: Sameen Tariq, Saira Bano, Sayyada Ghufrana Nadeem

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The Ocean, which covers over 70% of the world's surface, is wealthy in biodiversity as well as a rich wellspring of microorganisms with huge potential. The oceanic climate is home to an expansive scope of plants, creatures, and microorganisms. Marine microbial networks, which incorporate microscopic organisms, infections, and different microorganisms, enjoy different benefits in biotechnological processes. Samples were collected from marine environments, including soil and water samples, to cultivate the uncultured marine organisms by using Zobell’s medium, Sabouraud’s dextrose agar, and casein media for this purpose. Following isolation, we conduct microscopy and biochemical tests, including gelatin, starch, glucose, casein, catalase, and carbohydrate hydrolysis for further identification. The results show that more gram-positive and gram-negative bacteria. The isolation process of marine organisms is essential for understanding their ecological roles, unraveling their biological secrets, and harnessing their potential for various applications. Marine organisms exhibit remarkable adaptations to thrive in the diverse and challenging marine environment, offering vast potential for scientific, medical, and industrial applications. The isolation process plays a crucial role in unlocking the secrets of marine organisms, understanding their biological functions, and harnessing their valuable properties. They offer a rich source of bioactive compounds with pharmaceutical potential, including antibiotics, anticancer agents, and novel therapeutics. This study is an attempt to explore the diversity and dynamics related to marine microflora and their role in biofilm formation.

Keywords: marine microorganisms, ecosystem, fungi, biofilm, gram-positive, gram-negative

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566 In Vitro Propagation in Barleria prionitis L. Via Callus Organogenesis

Authors: Rashmi Ranade, Neelu Joshi

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Barleria prionitis L. is a well explored Indian medicinal plant valued for its stem and leaf which forms an important ingredient of many Ayurvedic formulations. It is used for the treatment of various disorders like toothache, bleeding gums, strengthening gums, whooping cough, inflammation, arthritis, enlargement of scrotum and sciatica etc. The plant is propagated vegetatively through stem cuttings. Frequent harvesting of this plant has led to the shortage of planting material, and it has acquired the status of vulnerable plant species. Plant tissue culture technology offers a very good alternative for propagation and conservation of such plant species. The present investigation was undertaken to develop in vitro regeneration protocol for B. prionitis L. via callus organogenesis pathway. Stem and leaf explants were used for this purpose. Different media and plant growth regulators were optimized to develop the protocol. The problem of phenol secretion and browning and in vitro cultures at the establishment phase was successfully curbed with the usage of antibrowning agents such as ascorbic acid and activated charcoal. Optimum shoot multiplication was achieved by the use of liquid media and incorporation of silver nitrate and TIBA (triiodobenzoic acid) into the media. High percent rooting (76%) was observed on WPM media supplemented with IBA (2.0 mg/l), IAA (0.5 mg/l), GA3(0.5) and activated charcoal(500 mg/l). The rooted plantlets were subjected to in vitro hardening on sterile potting mix (soil:farmyard manure:compost; 1:2:1) and acclimatized under greenhouse conditions. Around 85% survival of plantlets was recorded upon acclimatization. This lab scale protocol would be tested for in vitro scaling up production of B. prionitis L.

Keywords: explant browning, liquid culture, micropropagation, shoot multiplication, phenolic secretion

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565 Methylene Blue Removal Using NiO nanoparticles-Sand Adsorption Packed Bed

Authors: Nedal N. Marei, Nashaat Nassar

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Many treatment techniques have been used to remove the soluble pollutants from wastewater as; dyes and metal ions which could be found in rich amount in the used water of the textile and tanneries industry. The effluents from these industries are complex, containing a wide variety of dyes and other contaminants, such as dispersants, acids, bases, salts, detergents, humectants, oxidants, and others. These techniques can be divided into physical, chemical, and biological methods. Adsorption has been developed as an efficient method for the removal of heavy metals from contaminated water and soil. It is now recognized as an effective method for the removal of both organic and inorganic pollutants from wastewaters. Nanosize materials are new functional materials, which offer high surface area and have come up as effective adsorbents. Nano alumina is one of the most important ceramic materials widely used as an electrical insulator, presenting exceptionally high resistance to chemical agents, as well as giving excellent performance as a catalyst for many chemical reactions, in microelectronic, membrane applications, and water and wastewater treatment. In this study, methylene blue (MB) dye has been used as model dye of textile wastewater in order to synthesize a synthetic MB wastewater. NiO nanoparticles were added in small percentage in the sand packed bed adsorption columns to remove the MB from the synthetic textile wastewater. Moreover, different parameters have been evaluated; flow of the synthetic wastewater, pH, height of the bed, percentage of the NiO to the sand in the packed material. Different mathematical models where employed to find the proper model which describe the experimental data and help to analyze the mechanism of the MB adsorption. This study will provide good understanding of the dyes adsorption using metal oxide nanoparticles in the classical sand bed.

Keywords: adsorption, column, nanoparticles, methylene

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564 Formulation of Value Added Beff Meatballs with the Addition of Pomegranate (Punica granatum) Extract as a Source of Natural Antioxident

Authors: M. A. Hashem, I. Jahan

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The experiment was conducted to find out the effect of different levels of Pomegranate (Punica granatum) extract and synthetic antioxidant BHA (Beta Hydroxyl Anisole) on fresh and preserved beef meatballs in order to make functional food. For this purpose, ground beef samples were divided into five treatment groups. They were treated as control group, 0.1% synthetic antioxidant group, 0.1%, 0.2% and 0.3% pomegranate extract group as T1, T2, T3, T4 and T5 respectively. Proximate analysis, sensory tests (color, flavor, tenderness, juiciness, overall acceptability), cooking loss, pH value, free fatty acids (FFA), thiobarbituric acid values (TBARS), peroxide value (POV) and microbiological examination were determined in order to evaluate the effect of pomegranate extract as natural antioxidant and antimicrobial activities compared to BHA (Beta Hydroxyl Anisole) at first day before freezing and for maintaining meatballs qualities on the shelf life of beef meat balls stored for 60 days under frozen condition. Freezing temperature was -20˚C. Days of intervals of experiment were on 0, 15th, 30th and 60th days. Dry matter content of all the treatment groups differ significantly (p<0.05). On the contrary, DM content increased significantly (p<0.05) with the advancement of different days of intervals. CP content of all the treatments were increased significantly (p<0.05) among the different treatment groups. EE and Ash content were decreased significantly (p<0.05) at different treatment levels. FFA values, TBARS, POV were decreased significantly (p<0.05) at different treatment levels. Color, odor, tenderness, juiciness, overall acceptability decreased significantly (p<0.05) at different days of intervals. Raw PH, cooked pH were increased at different treatment levels significantly (p<0.05). The cooking loss (%) at different treatment levels were differ significantly (p<0.05). TVC (logCFU/g), TCC (logCFU/g) and TYMC (logCFU/g) was decreased significantly (p<0.05) at different treatment levels and at different days of intervals comparison to control. Considering CP, tenderness, juiciness, overall acceptability, cooking loss, FFA, POV, TBARS value and microbial analysis it can be concluded that pomegranate extract at 0.1%, 0.2% and 0.3% can be used instead of synthetic antioxidant BHA in beef meatballs. On the basis of sensory evaluation, nutrient quality, physicochemical properties, biochemical analysis and microbial analysis 0.3% Pomegranate extract can be recommended for formulation of value added beef meatball enriched with natural antioxidant.

Keywords: antioxidant, pomegranate, BHA, value added meat products

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563 An Investigation of the Use of Visible Spectrophotometric Analysis of Lead in an Herbal Tea Supplement

Authors: Salve Alessandria Alcantara, John Armand E. Aquino, Ma. Veronica Aranda, Nikki Francine Balde, Angeli Therese F. Cruz, Elise Danielle Garcia, Antonie Kyna Lim, Divina Gracia Lucero, Nikolai Thadeus Mappatao, Maylan N. Ocat, Jamille Dyanne L. Pajarillo, Jane Mierial A. Pesigan, Grace Kristin Viva, Jasmine Arielle C. Yap, Kathleen Michelle T. Yu, Joanna J. Orejola, Joanna V. Toralba

Abstract:

Lead is a neurotoxic metallic element that is slowly accumulated in bones and tissues especially if present in products taken in a regular basis such as herbal tea supplements. Although sensitive analytical instruments are already available, the USP limit test for lead is still widely used. However, because of its serious shortcomings, Lang Lang and his colleagues developed a spectrophotometric method for determination of lead in all types of samples. This method was the one adapted in this study. The actual procedure performed was divided into three parts: digestion, extraction and analysis. For digestion, HNO3 and CH3COOH were used. Afterwards, masking agents, 0.003% and 0.001% dithizone in CHCl3 were added and used for the extraction. For the analysis, standard addition method and colorimetry were performed. This was done in triplicates under two conditions. The 1st condition, using 25µg/mL of standard, resulted to very low absorbances with an r2 of 0.551. This led to the use of a higher concentration, 1mg/mL, for condition 2. Precipitation of lead cyanide was observed and the absorbance readings were relatively higher but between 0.15-0.25, resulting to a very low r2 of 0.429. LOQ and LOD were not computed due to the limitations of the Milton-Roy Spectrophotometer. The method performed has a shorter digestion time, and used less but more accessible reagents. However, the optimum ratio of dithizone-lead complex must be observed in order to obtain reliable results while exploring other concentration of standards.

Keywords: herbal tea supplement, lead-dithizone complex, standard addition, visible spectroscopy

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562 Biorisk Management Education for Undergraduates Studying Clinical Microbiology at University in Japan

Authors: Shuji Fujimoto, Fumiko Kojima, Mika Shigematsu

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Biorisk management (Biosafety/Biosecurity) is required for anyone working in a clinical laboratory (including medical/clinical research laboratories) where infectious agents and potentially hazardous biological materials are examined/stored. Proper education and training based on international standards of biorisk management should be provided not only as a part of laboratory safety program in work place but also as a part of introductory training at educational institutions for continuity and to elevate overall baseline of the biorisk management. We reported results of the pilot study of biorisk management education for graduate students majored in laboratory diagnostics previously. However, postgraduate education is still late in their profession and the participants’ interview also revealed importance and demands of earlier biorisk management education for undergraduates. The aim of this study is to identify the need for biosafety/biosecurity education and training program which is designed for undergraduate students who are entering the profession in clinical microbiology. We modified the previous program to include more basic topics and explanations (risk management, principles of safe clinical lab practices, personal protective equipment, disinfection, disposal of biological substances) and provided incorporating in the routine educational system for faculty of medical sciences in Kyushu University. The results of the pre and post examinations showed that the knowledge of the students on biorisk control had developed effectively as a proof of effectiveness of the program even in the undergraduate students. Our study indicates that administrating the basic biorisk management program in the earlier stage of learning will add positive impact to the understanding of biosafety to the health professional education.

Keywords: biorisk management, biosafety, biosecurity, clinical microbiology, education for undergraduates

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561 Development of Generally Applicable Intravenous to Oral Antibiotic Switch Therapy Criteria

Authors: H. Akhloufi, M. Hulscher, J. M. Prins, I. H. Van Der Sijs, D. Melles, A. Verbon

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Background: A timely switch from intravenous to oral antibiotic therapy has many advantages, such as reduced incidence of IV-line related infections, a decreased hospital length of stay and less workload for healthcare professionals with equivalent patient safety. Additionally, numerous studies have demonstrated significant decreases in costs of a timely intravenous to oral antibiotic therapy switch, while maintaining efficacy and safety. However, a considerable variation in iv to oral antibiotic switch therapy criteria has been described in literature. Here, we report the development of a set of iv to oral switch criteria that are generally applicable in all hospitals. Material/methods: A RAND-modified Delphi procedure, which was composed of 3 rounds, was used. This Delphi procedure is a widely used structured process to develop consensus using multiple rounds of questionnaires within a qualified panel of selected experts. The international expert panel was multidisciplinary and composed out of clinical microbiologists, infectious disease consultants and clinical pharmacists. This panel of 19 experts appraised 6 major intravenous to oral antibiotic switch therapy criteria and operationalized these criteria using 41 measurable conditions extracted from the literature. The procedure to select a concise set of iv to oral switch criteria included 2 questionnaire rounds and a face-to-face meeting. Results: The procedure resulted in the selection of 16 measurable conditions, which operationalize 6 major intravenous to oral antibiotic switch therapy criteria. The following 6 major switch therapy criteria were selected: (1) Vital signs should be good or improving when bad. (2) Signs and symptoms related to the infection have to be resolved or improved. (3) The gastrointestinal tract has to be intact and functioning. (4) The oral route should not be compromised. (5) Absence of contra-indicated infections. (6) An oral variant of the antibiotic with good bioavailability has to exist. Conclusions: This systematic stepwise method which combined evidence and expert opinion resulted in a feasible set of 6 major intravenous to oral antibiotic switch therapy criteria operationalized by 16 measurable conditions. This set of early antibiotic iv to oral switch criteria can be used in daily practice in all adult hospital patients. Future use in audits and as rules in computer assisted decision support systems will lead to improvement of antimicrobial steward ship programs.

Keywords: antibiotic resistance, antibiotic stewardship, intravenous to oral, switch therapy

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560 Bilingual Siblings and Dynamic Family Language Policies in Italian/English Families

Authors: Daniela Panico

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Framed by language socialization and family language policy theories, the present study explores the ways the language choice patterns of bilingual siblings contribute to the shaping of the language environment and the language practices of Italian/English families residing in Sydney. The main source of data is video recordings of naturally occurring parent-children and child-to-child interactions during everyday routines (i.e., family mealtimes and siblings playtime) in the home environment. Recurrent interactional practices are analyzed in detail through a conversational analytical approach. This presentation focuses on the interactional trajectories developing during the negotiation of language choices between all family members and between siblings in face-to-face interactions. Fine-grained analysis is performed on language negotiation sequences of multiparty bilingual conversations in order to uncover the sequential patterns through which a) the children respond to the parental strategies aiming to minority language maintenance, and b) the siblings influence each other’s language use and choice (e.g., older siblings positioning themselves as language teachers and language brokers, younger siblings accepting the role of apprentices). The findings show that, along with the parents, children are active socializing agents in the family and, with their linguistic behavior, they contribute to the establishment of a bilingual or a monolingual context in the home. Moreover, by orienting themselves towards the use of one or the other language in family talk, bilingual siblings are a major internal micro force in the language ecology of a bilingual family and can strongly support language maintenance or language shift processes in such domain. Overall, the study provides insights into the dynamic ways in which family language policy is interactionally negotiated and instantiated in bilingual homes as well as the challenges of intergenerational language transmission.

Keywords: bilingual siblings, family interactions, family language policy, language maintenance

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559 Oxidosqualene Cyclase: A Novel Inhibitor

Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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558 Anti-Aging Effects of Retinol and Alpha Hydroxy Acid on Elastin Fibers of Artificially Photo-Aged Human Dermal Fibroblast Cell Lines

Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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557 Molecular Epidemiology of Anthrax in Georgia

Authors: N. G. Vepkhvadze, T. Enukidze

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Anthrax is a fatal disease caused by strains of Bacillus anthracis, a spore-forming gram-positive bacillus that causes the disease anthrax in animals and humans. Anthrax is a zoonotic disease that is also well-recognized as a potential agent of bioterrorism. Infection in humans is extremely rare in the developed world and is generally due to contact with infected animals or contaminated animal products. Testing of this zoonotic disease began in 1907 in Georgia and is still being tested routinely to provide accurate information and efficient testing results at the State Laboratory of Agriculture of Georgia. Each clinical sample is analyzed by RT-PCR and bacteriology methods; this study used Real-Time PCR assays for the detection of B. anthracis that rely on plasmid-encoded targets with a chromosomal marker to correctly differentiate pathogenic strains from non-anthracis Bacillus species. During the period of 2015-2022, the State Laboratory of Agriculture (SLA) tested 250 clinical and environmental (soil) samples from several different regions in Georgia. In total, 61 out of the 250 samples were positive during this period. Based on the results, Anthrax cases are mostly present in Eastern Georgia, with a high density of the population of livestock, specifically in the regions of Kakheti and Kvemo Kartli. All laboratory activities are being performed in accordance with International Quality standards, adhering to biosafety and biosecurity rules by qualified and experienced personnel handling pathogenic agents. Laboratory testing plays the largest role in diagnosing animals with anthrax, which helps pertinent institutions to quickly confirm a diagnosis of anthrax and evaluate the epidemiological situation that generates important data for further responses.

Keywords: animal disease, baccilus anthracis, edp, laboratory molecular diagnostics

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556 Spectrum and Prevalence of Candida Infection in Diabetic Foot Ulcers

Authors: Seyed Reza Aghili, Tahereh Shokohi, Lotfollah Davoodi, Zahra Kashi, Azam Moslemi, Mahdi Abastabar, Iman Haghani, Sabah Mayahi, Asoudeh A.

Abstract:

Introduction: In diabetic foot ulcers, if fungal agents such as Candida species penetrate into the cutaneous or depth of ulcer, can increase the degree of the wound and cause Candia infection and make it more difficult to heal. Material & Methods: A cross-sectional study was performed on 100 diabetic foot ulcer patients in 2020 in Sari, Iran. patient's data and wound grade were recorded in a questionnaire. Candida infection was diagnosed with direct microscopic examination and culture of samples. Colony-PCR molecular method was used for ITS region of DNA and then PCR-RFLP with Msp1 enzyme and using HWP1 specific gene to determine species of Candida agent. Results: Of 100 patients, the mean age 62.1 ± 10.8 years, 95% type 2 diabetes, 83%>10 years duration diabetes, 59% male, 66%> poor education level, 99% married, 52% rural, 95% neuropathic symptoms, 88% using antibiotics, 69%HbA1C >9%, and mean ulcer degree 2.6±1.05 were. Candida infection was seen in 13% of the deep tissue of the wound and 7% cutaneous around the wound. The predominant Candida isolated was C. parapsilosis (71.5%), C .albicans (14.3%). Fungal infections caused by mold fungi were not detected. There was a statistically significant relationship between yeast infection and gender, rural, HbA1C and ulcer degree. Conclusion: Mycological evaluations often are ignored. Candida parapsilosis is the most common infectious agent in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections particularly, early diagnosis and effective treatment can help faster recovery and prevent amputation.

Keywords: diabetic foot ulcer, candida infection, risk factors, c. parapsilosis

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555 The Science of Successful Intimate Relationship in China: A Discourse Analytic Examination of Sex and Relationships Advice in Ayawawa’s Book

Authors: Hanlei Yang

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As a kind of popular culture in modern China, advice book on intimate relationship is turning into an important and controversial site with conflicts among neoliberalism, authoritative socialism, market-oriented principles, the science of successful sex and relationship, cosmopolitan notions of nuclear families, and the revitalization of Confucian conservatism and patriarchy. Accelerated modernization and marketization has contributed to great changes in China’s culture and social relations, which accordingly reconceptualizes and reconstructs family structures and moral ethics, particularly urban middle-class nuclear families. To comprehend the meaning of advice book fad in moral and social order, this research proposes to (i) understand the implication of Ayawawa through discourse analysis and how she mobilizes rhetorical devices and cultural resources to present a persuasive and scientific method of managing intimate relationship, (ii) examine the critical role of neoliberalism, post-feminism, and Confucian patriarchy assumed by Ayawawa in her books, (iii) explore how Ayawawa and her fans engage in establishing a model of intimate relationship and sexual subjectivity ordered by neoliberalism, class identity and authoritative socialism. Finally, this research argues that such new fad of a cultural phenomenon is gradually completed in the process of cooperation and negotiation of the state, commercial institutions, and intellectual elite agents. It helps to further learn about (i) the routine life under the influence of neoliberalism and modern hegemony, (ii) the perplexing relationship between China's indigenous cultural forms, global socio-economic and cultural influences in the late modern era.

Keywords: cultural study, intimate relationship, culture sociology, gender study

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554 Effectively Improving Cognition, Behavior, and Attitude of Diabetes Inpatients through Nutritional Education

Authors: Han Chih Feng, Yi-Cheng Hou, Jing-Huei Wu

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Diabetes is a chronic disease. Nutrition knowledge and skills enable individuals with type 2 diabetes to optimize metabolic self-management and quality of life. This research studies the effect of nutritional education on diabetes inpatients in terms of their cognition, behavior, and attitude. The participants are inpatients diagnosed with diabetes at Taipei Tzu Chi Hospital. A total of 103 participants, 58 male, and 45 females, enrolled in the research between January 2018 and July 2018. The research evaluates cognition, behavior, and attitude level before and after nutritional education conducted by dietitians. The result shows significant improvement in actual consumption (2.5 ± 1.4 vs 3.8 ± 0.7; p<.001), diet control motivation (2.7 ± 0.8 vs 3.4 ± 0.6; p<.001), correct nutrition concept (1.2± 0.4 vs 2.4 ± 0.5; p<.001), learning willingness (2.7± 0.9 vs 3.4 ± 0.6; p<.001), cognitive behaviors (1.4 ± 0.5 vs 2.9 ± 0.7; p<.001). AC sugar (278.5 ± 321.5 vs 152.2 ± 49.1; p<.001) and HbA1C (10.3 ± 2.6 vs 8.6 ± 1.9; p<.001) are significant improvement after nutritional education. After nutritional education, participants oral hypoglycemic agents increased from 16 (9.2%) to 33 (19.0%), insulin decreased from 75 (43.1%) to 68 (39.1%), and hypoglycemic drugs combined with insulin decreased from 83 (47.7%) to 73 (42.0%).Further analysis shows that female inpatients have significant improvement in diet control motivation (3.91 ± 0.85 vs 4.44 ± 0.59; p<0.000), correct nutrition concept (3.24± 0.48 vs 4.47± 0.51; p<0.000), learning willingness (3.89 ± 0.86 vs 4.44 ± 0.59; p<0.000) and cognitive behaviors (2.42 ± 0.58 vs 4.02 ± 0.69; p<0.000); male inpatients have significant improvement in actual food intake (4.41± 0.92 vs 3.97 ± 0.42; p<0.000), diet control motivation (3.62 ± 0.86 vs 4.29 ± 0.62; p<0.000), correct nutrition concept (3.26 ± 0.44 vs 4.36 ± 0.49; p<0.000), learning willingness (3.72± 0.93 vs 4.33± 0.63; p<0.000) and cognitive behaviors (2.45± 0.54 vs 4.03± 0.77; p<0.000). In conclusion, nutritional education proves effective, regardless of gender, in improving an inpatient’s cognition, behavior, and attitude toward diabetes self-management.

Keywords: diabetes, nutrition education, actual consumption, diet control motivation, nutrition concept, learning willingness, cognitive behaviors

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553 Anticancer Lantadene Derivatives: Synthesis, Cytotoxic and Docking Studies

Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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552 The Role of Non-Native Plant Species in Enhancing Food Security in Sub-Saharan Africa

Authors: Thabiso Michael Mokotjomela, Jasper Knight

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Intensification of agricultural food production in sub-Saharan Africa is of paramount importance as a means of increasing the food security of communities that are already experiencing a range of environmental and socio-economic stresses. However, achieving this aim faces several challenges including ongoing climate change, increased resistance of diseases and pests, extreme environmental degradation partly due to biological invasions, land tenure and management practices, socio-economic developments of rural populations, and national population growth. In particular, non-native plant species tend to display greater adaptation capacity to environmental stress than native species that form important food resource base for human beings, thus suggesting a potential for usage to shift accordingly. Based on review of the historical benefits of non-native plant species in food production in sub-Saharan Africa, we propose that use of non-invasive, non-native plant species and/or the genetic modification of native species might be viable options for future agricultural sustainability in this region. Coupled with strategic foresight planning (e.g. use of biological control agents that suppress plant species’ invasions), the consumptive use of already-introduced non-native species might help in containment and control of possible negative environmental impacts of non-native species on native species, ecosystems and biodiversity, and soil fertility and hydrology. Use of non-native species in food production should be accompanied by low cost agroecology practices (e.g. conservation agriculture and agrobiodiversity) that may promote the gradual recovery of natural capital, ecosystem services, and promote conservation of the natural environment as well as enhance food security.

Keywords: food security, invasive species, agroecology, agrobiodiversity, socio-economic stresses

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551 Cas9-Assisted Direct Cloning and Refactoring of a Silent Biosynthetic Gene Cluster

Authors: Peng Hou

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Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

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550 Design, Synthesis and Pharmacological Investigation of Novel 2-Phenazinamine Derivatives as a Mutant BCR-ABL (T315I) Inhibitor

Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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549 Synthesis and Anticancer Evaluation of Substituted 2-(3,4-Dimethoxyphenyl) Benzazoles

Authors: Cigdem Karaaslan, Yalcin Duydu, Aylin Ustundag, Can Ozgur Yalcın, Hakan Goker

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Benzazole nucleus is found in the structure of many compounds as anticancer agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), Glasdegib (SMO inhibitor) are clinically used as anticancer therapeutics which bearing benzimidazole moiety. Based on the principle of bioisosterism in the present work, 23 compounds belonging to 2-(3,4-dimethoxy-phenyl) benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer activities. N-(5-Chloro-2-hydroxyphenyl)-3,4-dimethoxybenzamide, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of benzamide derivative to benzoxazole, was achieved by p-toluenesulfonic acid. Other 1H-benz (or pyrido) azoles were prepared by the reaction between 2-aminothiophenol, o-phenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the Nuclear Overhauser Effect Spectroscopy. A compound named, 5(4),7(6)-Dichloro-2-(3,4-dimethoxy) phenyl-1H-benzimidazole, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue, against A549 cells with the GI50 value of 1.5 µg/mL. In addition, 2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-1H-benzimi-dazole showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI₅₀ values of 7 and 5.5 µg/mL, respectively. It could be concluded that introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increase significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized in this study. Unsubstituted 2-(3,4-dimethoxyphenyl) imidazopyridines also gave the good inhibitory profile against A549 and HeLa cells.

Keywords: 3, 4-Dimethoxyphenyl, 1H-benzimidazole, benzazole, imidazopyridine

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548 Lethal and Sub-Lethal Effects of Pyriproxyfen on Demography of Convergent Lady Beetle, Hippodamia convergens (Goeze) (Coccinellidae: Coleoptera)

Authors: Ayesha Iftikhar, Faisal Hafeez, Muhammad Jawad Saleem, Afifa Naeem, Muhammad Sohaib

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To further develop integrated pest management (IPM) tactics against insect pests, demographic toxicology is considered important and efficient to evaluate the long-term effects of pesticides on biological control agents. In this study, lethal and sub-lethal effects of Pyriproxyfen (insect growth regulator) two concentrations of LC10 and LC30 were tested on second instar larvae of convergent lady beetle, Hippodamia convergens (Goeze) in order to evaluate the effect of insecticide on demographic parameters of the predator under laboratory conditions. The life table parameters were analysed statistically by using age-stage, two sex life table procedure. The results of this study show that developmental time for immature was prolonged in treated population (LC30 and LC10) rather than in control. Similarly, male and female longevity was also longer in the control group as compared to the treated population. Adult pre-oviposition period and fecundity were also greater in control as compared to the treated population. In addition, population parameters such as net reproductive rate (R0), intrinsic rate of increase (r) and finite rate of increase (λ) were also greater in control group rather than treated population. However, mean generation time (T) was greater in the treated group. The results revealed that pyriproxyfen, even at low concentrations, has potential to greatly affect the population growth of predatory lady beetle, therefore care should be taken when insect growth regulators are used within an IPM framework.

Keywords: ladybird beetle, IGR, integrated pest management, population inhibition

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547 Complex Network Approach to International Trade of Fossil Fuel

Authors: Semanur Soyyigit Kaya, Ercan Eren

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Energy has a prominent role for development of nations. Countries which have energy resources also have strategic power in the international trade of energy since it is essential for all stages of production in the economy. Thus, it is important for countries to analyze the weakness and strength of the system. On the other side, it is commonly believed that international trade has complex network properties. Complex network is a tool for the analysis of complex systems with heterogeneous agents and interaction between them. A complex network consists of nodes and the interactions between these nodes. Total properties which emerge as a result of these interactions are distinct from the sum of small parts (more or less) in complex systems. Thus, standard approaches to international trade are superficial to analyze these systems. Network analysis provides a new approach to analyze international trade as a network. In this network countries constitute nodes and trade relations (export or import) constitute edges. It becomes possible to analyze international trade network in terms of high degree indicators which are specific to complex systems such as connectivity, clustering, assortativity/disassortativity, centrality, etc. In this analysis, international trade of crude oil and coal which are types of fossil fuel has been analyzed from 2005 to 2014 via network analysis. First, it has been analyzed in terms of some topological parameters such as density, transitivity, clustering etc. Afterwards, fitness to Pareto distribution has been analyzed. Finally, weighted HITS algorithm has been applied to the data as a centrality measure to determine the real prominence of countries in these trade networks. Weighted HITS algorithm is a strong tool to analyze the network by ranking countries with regards to prominence of their trade partners. We have calculated both an export centrality and an import centrality by applying w-HITS algorithm to data.

Keywords: complex network approach, fossil fuel, international trade, network theory

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546 Antiproliferative Effect of Polyphenols from Crocus sativus L. Leaves on Human Colon Adenocarcinoma Cells (Caco-2)

Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle

Abstract:

Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.

Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells

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545 Acanthopanax koreanum and Major Ingredient, Impressic Acid, Possess Matrix Metalloproteinase-13 Down-Regulating Capacity and Protect Cartilage Destruction

Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim

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Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.

Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase

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544 Potentials and Challenges of Adventure Tourism Development: A Case Study of Kashmir Valley, India

Authors: Abdul Hamid Mir

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Tourism which is considered as the economic bonanza of Jammu and Kashmir plays an important role in the socio-economic development of Jammu and Kashmir. It is considered as a multi-segmented industry which provides different type of jobs like hotel managers, receptionists, guides, tour operators, travel agents, photographers, etc. Kashmir Valley which is one of the three meso regions (Jammu, Kashmir and Ladakh) of Jammu and Kashmir State is famous all over the world due to its natural beauty. It attracts tourists from the every corner of the globe that is why it has earned name as ‘Paradise on Earth’ and ‘Switzerland of Asia’. It is full of natural treasure and gratifies the several types of tourists. The tourists are experiences fun, thrilling events and safe experience in Kashmir valley, but on the other hand, the adventure tourists are experiencing the physical risks, dangers and losses (injuries, death etc) too. Kashmir valley has greater potential to become one of the best adventure tourism destinations in the world. It offers immense opportunities to the adventurists to explore the wonderful exotic Himalayan ranges and landscapes, in addition, to facing the challenges of fast flowing rivers. Adventure tourism is at the initial stage of development in Kashmir valley and virgin areas needs to be explored and develop which in result will increase not only tourist arrivals but also enhance the business opportunities and economy of local people in Kashmir. Thus the exploitation of virginity of adventure tourism potentials in Kashmir valley is need of the hour. Therefore the present study highlights the potentials of adventure tourism in Kashmir valley and also focuses on the problems in the development of adventure tourism. Furthermore, the study extends to give various recommendations and suggestions in order to develop adventure tourism and broaden the base of tourist arrivals on one hand and sustained the growth on the other hand.

Keywords: adventure, Kashmir, tourism, tourists, potential, rafting, skiing

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543 Comparative Electrochemical Studies of Enzyme-Based and Enzyme-less Graphene Oxide-Based Nanocomposite as Glucose Biosensor

Authors: Chetna Tyagi. G. B. V. S. Lakshmi, Ambuj Tripathi, D. K. Avasthi

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Graphene oxide provides a good host matrix for preparing nanocomposites due to the different functional groups attached to its edges and planes. Being biocompatible, it is used in therapeutic applications. As enzyme-based biosensor requires complicated enzyme purification procedure, high fabrication cost and special storage conditions, we need enzyme-less biosensors for use even in a harsh environment like high temperature, varying pH, etc. In this work, we have prepared both enzyme-based and enzyme-less graphene oxide-based biosensors for glucose detection using glucose-oxidase as enzyme and gold nanoparticles, respectively. These samples were characterized using X-ray diffraction, UV-visible spectroscopy, scanning electron microscopy, and transmission electron microscopy to confirm the successful synthesis of the working electrodes. Electrochemical measurements were performed for both the working electrodes using a 3-electrode electrochemical cell. Cyclic voltammetry curves showed the homogeneous transfer of electron on the electrodes in the scan range between -0.2V to 0.6V. The sensing measurements were performed using differential pulse voltammetry for the glucose concentration varying from 0.01 mM to 20 mM, and sensing was improved towards glucose in the presence of gold nanoparticles. Gold nanoparticles in graphene oxide nanocomposite played an important role in sensing glucose in the absence of enzyme, glucose oxidase, as evident from these measurements. The selectivity was tested by measuring the current response of the working electrode towards glucose in the presence of the other common interfering agents like cholesterol, ascorbic acid, citric acid, and urea. The enzyme-less working electrode also showed storage stability for up to 15 weeks, making it a suitable glucose biosensor.

Keywords: electrochemical, enzyme-less, glucose, gold nanoparticles, graphene oxide, nanocomposite

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