Search results for: in silico drug designing
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3638

Search results for: in silico drug designing

2498 Health Outcomes from Multidrug-Resistant Salmonella in High-Income Countries: A Systematic Review and Meta-Analysis

Authors: Andrea Parisi, Samantha Vilkins, Luis Furuya-Kanamori, John A. Crump, Benjamin P. Howden, Darren Gray, Kathryn Glass, Martyn Kirk

Abstract:

Objectives: Salmonella is a leading cause of foodborne enterocolitis worldwide. Nontyphoidal Salmonella (NTS) infections that are Multi-Drug Resistant (MDR) (non-susceptible to ≥1 agent in ≥3 antimicrobial categories) may result in more severe outcomes, although these effects have not been systematically examined. We conducted a systematic review and meta-analysis to examine impacts of MDR NTS on health in high-income settings. Methods: We systematically reviewed the literature from scientific databases, including PubMed, Scopus and grey literature sources, using PRISMA guidelines. We searched for data from case-control studies, cohorts, outbreaks, reports and theses, imposing no language restriction. We included only publications from January 1990 to September 2016 from high income countries as classified by World Bank. We extracted data from papers on duration of illness, hospitalisation rates, morbidity and mortality for MDR and non-MDR NTS strains. Results: After removing duplicates, the initial search revealed 4258 articles. After further screening, we identified 16 eligible studies for the systematic review, and 9 of these were included in meta-analysis. NTS serotypes differed among the reported studies but serotype Typhimurium, Enteritidis, Newport and Heidelberg were among the most often reported as MDR pathogens. Salmonella infections that were MDR were associated with excess bloodstream infections (OR 1.63; 95%CI 1.18-2.26), excess hospitalisations (OR 2.77; 95%CI 1.47-5.21) and higher mortality (OR 3.54; 95%CI 1.10-11.40). Conclusions: MDR NTS infections are a serious public health concern. With the emergence of MDR Salmonella strains in the high-income countries, it is crucial to restrict the use of antimicrobials both in animals and humans, and intervene to prevent foodborne infections.

Keywords: Antimicrobial Resistance, Bloodstream Infection, Health Outcomes, Hospitalisation, Invasive Disease, Multi-Drug Resistance (MDR), Mortality, Nontyphoidal Salmonella

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2497 Investigating the Antimicrobial Activity of Essential Oil Derived from Pistacia atlantica Gum against Extensively Drug-Resistant Gram-Negative Acinetobacter baumannii

Authors: Zhala Ahmad, Zainab Lazim, Haider Hamzah

Abstract:

Bacterial resistance is a pressing global health issue, with multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains to pose a serious threat. In this context, researchers are investigating effective, safe, and affordable metabolites to combat these pathogens. This study focuses on gum essential oil (GEO) extracted from Pistacia atlantica and its activity and the mechanism of action against XDR Gram-negative Acinetobacter baumannii. GEO was extracted by hydrodistillation and analyzed using GC-MS. Eleven A. baumannii isolates were collected from the ward environment of Burn and Plastic Surgery Hospital in Al Sulaymaniyah City, Iraq. They were identified using the VITEK 2 system, 16S rRNA gene, and confirmed with the blaₒₓₐ₋₅₁ gene; A. baumannii ATCC 19606 was used as a reference strain. The isolates were identified as resistant to twelve different antibiotics spanning six distinct antibiotic classes while showing susceptibility to tetracycline and trimethoprim. Over 40 chemical constituents were detected in the gum's essential oils, with α-pinene being the most abundant. GEO was found to inhibit the growth of A. baumannii isolates; the minimum inhibitory concentration (MIC) of GEO was 2.5 µl/ml. GEO induced protein leakage, phosphate, and potassium ion efflux, distorted cell morphology, and cell death in the tested bacteria. GEO exhibited bacterial clearance and anti-adhesion activity using Band-Aids. This study's findings suggest that GEO could be used as a potential alternative treatment for infectious diseases caused by XRD pathogens, shedding further light on the importance of GEO in biomedical applications. Future studies must focus on generating clinically feasible sources of GEO for testing in small animal models before proceeding to human trials, ensuring safe and effective translation from the laboratory to the clinic.

Keywords: antibiotic resistance, Acinetobacter baumannii, essential oils, Pistacia atlantica, alpha-pinene

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2496 Spectral Clustering for Manufacturing Cell Formation

Authors: Yessica Nataliani, Miin-Shen Yang

Abstract:

Cell formation (CF) is an important step in group technology. It is used in designing cellular manufacturing systems using similarities between parts in relation to machines so that it can identify part families and machine groups. There are many CF methods in the literature, but there is less spectral clustering used in CF. In this paper, we propose a spectral clustering algorithm for machine-part CF. Some experimental examples are used to illustrate its efficiency. Overall, the spectral clustering algorithm can be used in CF with a wide variety of machine/part matrices.

Keywords: group technology, cell formation, spectral clustering, grouping efficiency

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2495 Development of All-in-One Solar Kit

Authors: Azhan Azhar, Mohammed Sakib, Zaurez Ahmad

Abstract:

The energy we receive from the sun is known as solar energy, and it is a reliable, long-lasting, eco-friendly and the most widely used energy source in the 21st century. It is. There are several techniques for harnessing solar energy, and we are all seeing large utility-scale projects to collect maximum amperes from the sun using current technologies. Solar PV is now on the rise as a means of harvesting energy from the sun. Moving a step further, our project is focused on designing an All-in-one portable Solar Energy based solution. We considered the minimum load conditions and evaluated the requirements of various devices utilized in this study to resolve the power requirements of small stores, hawkers, or travelers.

Keywords: DOD-depth of discharge, pulse width modulation charge controller, renewable energy, solar PV- solar photovoltaic

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2494 Optimal Energy Consumption with Semiconductor Lamps

Authors: Pejman Hosseiniun, Rose Shayeghi, Alireza Farzaneh, Abolghasem Ghasempour

Abstract:

Using LED lamps as lighting resources with new technology in designing lighting systems has been studied in this article. In this respect a history of LED emergence, its different manufacturing methods and technologies were revised, then their structure, light production line, its application and benefits in lighting industry has been evaluated. Finally, there is a comparison between these lamps and ordinary lamps to assess light parameters as well as energy consumption using DIALux software. Considering the results of analogies LED lamps have lower consumption and more lighting yield, therefore they are more economically feasible. Color variety, longer usage lap (circa 10 years) and compatibility with DC voltages are other LED lamps perquisites.

Keywords: LED, lighting efficiency, lighting intensity, luminance

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2493 Thatsana Nataya Chatri Dance: A Creative Conservation Process of Cultural Performing Arts for Competition

Authors: Dusittorn Ngamying

Abstract:

The research on Thatsana Nataya Chatri Dance: A Creative Conservation Process of Cultural Performing Arts for Competition was aimed at 1) studying the creative conservation process of cultural performing arts; 2) creating conservation process of cultural performing arts of Thatsana Nataya Chatri dance; and 3) utilizing the created performing arts for the competition. The study was conducted using the qualitative research method in the Central region provinces of Thailand through documentary study and data from field observations, interviews and focus group meetings. Data were collected from 50 informants consisting of 10 experts on the subject, 30 practitioners and 10 general information providers. The data collection instruments consisted of participatory and non-participatory forms, structured and non-structured interview schedules and focus group note forms. The data were verified by the triangulation technique and presented using the descriptive analysis. The results of the study reveal that the creative conservation process of cultural performing arts should be initiated by those who have experienced using a prior knowledge in the pursuit of new knowledge. The new knowledge is combined to generate creative work with the conservation process in 9 aspects: acquiring the related knowledge, creating theme and inspiration, designing the music and melody, designing costumes, inventing dance postures, selecting dancers, transferring the dance postures, preparing the stage and performance equipment, planning the performance event. Inventing the conservation process of cultural performing arts Thatsana Nataya Chatri dance consists of 33 dance postures and 14 transformed patterns. The performance requires 6 dancers, 3 males and 3 females. Costume features both male and female classical and modified dancer’s costumes. The duration of the show takes 5 minutes. As for the application for the competition, this creative work has been selected by Dramatic Works Association (Thailand) to represent Thailand at the Lombok International Dance Sports Festival 2015 held at Lombok, Indonesia. The team has been awarded the Second Place in the Traditional Dance category.

Keywords: creative conservation process, cultural performing arts, Thatsana Nataya Chatri dance, competition

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2492 Encoding the Design of the Memorial Park and the Family Network as the Icon of 9/11 in Amy Waldman's the Submission

Authors: Masami Usui

Abstract:

After 9/11, the American literary scene was confronted with new perspectives that enabled both writers and readers to recognize the hidden aspects of their political, economic, legal, social, and cultural phenomena. There appeared an argument over new and challenging multicultural aspects after 9/11 and this argument is presented by a tension of space related to 9/11. In Amy Waldman’s the Submission (2011), designing both the memorial park and the family network has a significant meaning in establishing the progress of understanding from multiple perspectives. The most intriguing and controversial topic of racism is reflected in the Submission, where one young architect’s blind entry to the competition for the memorial of Ground Zero is nominated, yet he is confronted with strong objections and hostility as soon as he turns out to be a Muslim named Mohammad Khan. This ‘Khan’ issue, immediately enlarged into a social controversial issue on American soil, causes repeated acts of hostility to Muslim women by ignorant citizens all over America. His idea of the park is to design a new concept of tracing the cultural background of the open space. Against his will, his name is identified as the ‘ingredient’ of the networking of the resistant community with his supporters: on the other hand, the post 9/11 hysteria and victimization is presented in such family associations as the Angry Family Members and Grieving Family Members. These rapidly expanding networks, whether political or not, constructed by the internet, embody the contemporary societal connection and representation. The contemporary quest for the significance of human relationships is recognized as a quest for global peace. Designing both the memorial park and the communication networks strengthens a process of facing the shared conflicts and healing the survivors’ trauma. The tension between the idea and networking of the Garden for the memorial site and the collapse of Ground Zero signifies the double mission of the site: to establish the space to ease the wounded and to remember the catastrophe. Reading the design of these icons of 9/11 in the Submission means that decoding the myth of globalization and its representations in this century.

Keywords: American literature, cultural studies, globalization, literature of catastrophe

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2491 Development and Validation of a Liquid Chromatographic Method for the Quantification of Related Substance in Gentamicin Drug Substances

Authors: Sofiqul Islam, V. Murugan, Prema Kumari, Hari

Abstract:

Gentamicin is a broad spectrum water-soluble aminoglycoside antibiotics produced by the fermentation process of microorganism known as Micromonospora purpurea. It is widely used for the treatment of infection caused by both gram positive and gram negative bacteria. Gentamicin consists of a mixture of aminoglycoside components like C1, C1a, C2a, and C2. The molecular structure of Gentamicin and its related substances showed that it has lack of presence of chromophore group in the molecule due to which the detection of such components were quite critical and challenging. In this study, a simple Reversed Phase-High Performance Liquid Chromatographic (RP-HPLC) method using ultraviolet (UV) detector was developed and validated for quantification of the related substances present in Gentamicin drug substances. The method was achieved by using Thermo Scientific Hypersil Gold analytical column (150 x 4.6 mm, 5 µm particle size) with isocratic elution composed of methanol: water: glacial acetic acid: sodium hexane sulfonate in the ratio 70:25:5:3 % v/v/v/w as a mobile phase at a flow rate of 0.5 mL/min, column temperature was maintained at 30 °C and detection wavelength of 330 nm. The four components of Gentamicin namely Gentamicin C1, C1a, C2a, and C2 were well separated along with the related substance present in Gentamicin. The Limit of Quantification (LOQ) values were found to be at 0.0075 mg/mL. The accuracy of the method was quite satisfactory in which the % recovery was resulted between 95-105% for the related substances. The correlation coefficient (≥ 0.995) shows the linearity response against concentration over the range of Limit of Quantification (LOQ). Precision studies showed the % Relative Standard Deviation (RSD) values less than 5% for its related substance. The method was validated in accordance with the International Conference of Harmonization (ICH) guideline with various parameters like system suitability, specificity, precision, linearity, accuracy, limit of quantification, and robustness. This proposed method was easy and suitable for use for the quantification of related substances in routine analysis of Gentamicin formulations.

Keywords: reversed phase-high performance liquid chromatographic (RP-HPLC), high performance liquid chromatography, gentamicin, isocratic, ultraviolet

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2490 Computational Screening of Secretory Proteins with Brain-Specific Expression in Glioblastoma Multiforme

Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

Abstract:

Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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2489 Exploring Simple Sequence Repeats within Conserved microRNA Precursors Identified from Tea Expressed Sequence Tag (EST) Database

Authors: Anjan Hazra, Nirjhar Dasgupta, Chandan Sengupta, Sauren Das

Abstract:

Tea (Camellia sinensis) has received substantial attention from the scientific world time to time, not only for its commercial importance, but also for its demand to the health-conscious people across the world for its extensive use as potential sources of antioxidant supplement. These health-benefit traits primarily rely on some regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions is being worthwhile for studying the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea the trait-specific Simple Sequence Repeats (SSRs) are yet to be identified, which can be used for marker assisted breeding technique. MicroRNAs are endogenous, noncoding, short RNAs directly involved in regulating gene expressions at the post-transcriptional level. It has been found that diversity in miRNA gene interferes the formation of its characteristic hair pin structure and the subsequent function. In the present study, the precursors of small regulatory RNAs (microRNAs) has been fished out from tea Expressed Sequence Tag (EST) database. Furthermore, the simple sequence repeat motifs within the putative miRNA precursor genes are also identified in order to experimentally validate their existence and function. It is already known that genic-SSR markers are very adept and breeder-friendly source for genetic diversity analysis. So, the potential outcome of this in-silico study would provide some novel clues in understanding the miRNA-triggered polymorphic genic expression controlling specific metabolic pathways, accountable for tea quality.

Keywords: micro RNA, simple sequence repeats, tea quality, trait specific marker

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2488 Development of R³ UV Exposure for the UV Dose-Insensitive and Cost-Effective Fabrication of Biodegradable Polymer Microneedles

Authors: Sungmin Park, Gyungmok Nam, Seungpyo Woo, Young Choi, Sangheon Park, Sang-Hee Yoon

Abstract:

Puncturing human skin with microneedles is critically important for microneedle-mediate drug delivery. Despite of extensive efforts in the past decades, the scale-up fabrication of sharp-tipped and high-aspect-ratio microneedles, especially made of biodegradable polymers, is still a long way off. Here, we present a UV dose insensitive and cost-effective microfabrication method for the biodegradable polymer microneedles with sharp tips and long lengths which can pierce human skin with low insertion force. The biodegradable polymer microneedles are fabricated with the polymer solution casting where a poly(lactic-co-glycolic acid) (PLGA, 50:50) solution is coated onto a SU-8 mold prepared with a reverse, ramped, and rotational (R3) UV exposure. The R3 UV exposure is modified from the multidirectional UV exposure both to suppress UV reflection from the bottom surface without anti-reflection layers and to optimize solvent concentration in the SU-8 photoresist, therefore achieving robust (i.e., highly insensitive to UV dose) and cost-effective fabrication of biodegradable polymer microneedles. An optical model for describing the spatial distribution of UV irradiation dose of the R3 UV exposure is also developed to theoretically predict the microneedle geometry fabricated with the R3 UV exposure and also to demonstrate the insensitiveness of microneedle geometry to UV dose. In the experimental characterization, the microneedles fabricated with the R3 UV exposure are compared with those fabricated with a conventional method (i.e., multidirectional UV exposure). The R3 UV exposure-based microfabrication reduces the end-tip radius by a factor of 5.8 and the deviation from ideal aspect ratio by 74.8%, compared with conventional method-based microfabrication. The PLGA microneedles fabricated with the R3 UV exposure pierce full-thickness porcine skins successfully and are demonstrated to completely dissolve in PBS (phosphate-buffered saline). The findings of this study will lead to an explosive growth of the microneedle-mediated drug delivery market.

Keywords: R³ UV exposure, optical model, UV dose, reflection, solvent concentration, biodegradable polymer microneedle

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2487 Evolution of DNA-Binding With-One-Finger Transcriptional Factor Family in Diploid Cotton Gossypium raimondii

Authors: Waqas Shafqat Chattha, Muhammad Iqbal, Amir Shakeel

Abstract:

Transcriptional factors are proteins that play a vital role in regulating the transcription of target genes in different biological processes and are being widely studied in different plant species. In the current era of genomics, plant genomes sequencing has directed to the genome-wide identification, analyses and categorization of diverse transcription factor families and hence provide key insights into their structural as well as functional diversity. The DNA-binding with One Finger (DOF) proteins belongs to C2-C2-type zinc finger protein family. DOF proteins are plant-specific transcription factors implicated in diverse functions including seed maturation and germination, phytohormone signalling, light-mediated gene regulation, cotton-fiber elongation and responses of the plant to biotic as well as abiotic stresses. In this context, a genome-wide in-silico analysis of DOF TF family in diploid cotton species i.e. Gossypium raimondii has enabled us to identify 55 non-redundant genes encoding DOF proteins renamed as GrDofs (Gossypium raimondii Dof). Gene distribution studies have shown that all of the GrDof genes are unevenly distributed across 12 out of 13 G. raimondii chromosomes. The gene structure analysis illustrated that 34 out of 55 GrDof genes are intron-less while remaining 21 genes have a single intron. Protein sequence-based phylogenetic analysis of putative 55 GrDOFs has divided these proteins into 5 major groups with various paralogous gene pairs. Molecular evolutionary studies aided with the conserved domain as well as gene structure analysis suggested that segmental duplications were the principal contributors for the expansion of Dof genes in G. raimondii.

Keywords: diploid cotton , G. raimondii, phylogenetic analysis, transcription factor

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2486 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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2485 Prevalence of Seropositivity for Cytomegalovirus in Patients with Hereditary Bleeding Diseases in West Azerbaijan of Iran

Authors: Zakieh Rostamzadeh, Zahra Shirmohammadi

Abstract:

Human cytomegalovirus is a species of the cytomegalovirus family of viruses, which in turn is a member of the viral family known as herpesviridae or herpesviruses. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised such as HIV-infected persons, organ transplant recipients, or newborn infants. After infection, HCMV has an ability to remain latent within the body over long periods. Cytomegalovirus (CMV) causes infection in immunocompromised, hemophilia patients and those who received blood transfusion frequently. This study aimed at determining the prevalence of cytomegalovirus (CMV) antibodies in hemophilia patients. Materials and Methods: A retrospective observational study was carried out in Urmia, North West of Iran. The study population comprised a sample of 50 hemophilic patients born after 1985 and have received blood factors in West Azerbaijan. The exclusion criteria include: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling. All samples were evaluated with the method of ELISA, with a certain kind of kit and by a certain laboratory. Results: Fifty hemophiliacs from 250 patients registered with Urmia Hemophilia Society were enrolled in the study including 43 (86%) male, and 7 (14%) female. The mean age of patients was 10.3 years, range 3 to 25 years. None of patients had risk factors mentioned above. Among our studied population, 34(68%) had hemophilia A, 1 (2%) hemophilia B, 8 (16%) VWF, 3(6%) factor VII deficiency, 1 (2%) factor V deficiency, 1 (2%) factor X deficiency, 1 (2%). Sera of 50 Hemodialysis patients were investigated for CMV-specific immunoglobulin G (IgG) and IgM. % 91.89 patients were anti-CMV IgG positive and %40.54 was seropositive for anti-CMV IgM. 37.8% patient had serological evidence of reactivation and 2.7% of patients had the primary infection. Discussion: There was no relationship between the antibody titer and: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling.

Keywords: bioinformatics, biomedicine, cytomegalovirus, immunocompromise

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2484 Development and Evaluation of Surgical Sutures Coated with Antibiotic Loaded Gold Nanoparticles

Authors: Sunitha Sampathi, Pankaj Kumar Tiriya, Sonia Gera, Sravanthi Reddy Pailla, V. Likhitha, A. J. Maruthi

Abstract:

Surgical site infections (SSIs) are the most common nosocomial infections localized at the incision site. With an estimated 27 million surgical procedures each year in USA, approximately 2-5% rate of SSIs are predicted to occur annually. SSIs are treated with antibiotic medication. Current trend suggest that the direct drug delivery from the suture to the scared tissue can improve patient comfort and wound recovery. For that reason coating the surface of the medical device such as suture and catguts with broad spectrum antibiotics can prevent the formation of bactierial colonies with out comprimising the mechanical properties of the sutures.Hence, the present study was aimed to develop and evaluate a surgical suture coated with an antibiotic Ciprofloxacin hydrochloride loaded on gold nanoparticles. Gold nanoparticles were synthesized by chemical reduction method and conjugated with ciprofloxacin using Polyvinylpyrolidone as stabilizer and gold as carrier. Ciprofloxacin conjugated gold nanoparticles were coated over an absorbable surgical suture made of Polyglactan using sodium alginate as an immobilising agent by slurry dipping technique. The average particle size and Polydispersity Index of drug conjugated gold NPs were found to be 129±2.35 nm and 0.243±0.36 respectively. Gold nanoparticles are characterized by UV-Vis absorption spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy and Transmission electron microscopy. FT-IR revealed that there is no chemical interaction between drug and polymer. Antimicrobial activity for coated sutures was evaluated by disc diffusion method on culture plates of both gram negative (E-coli) and gram positive bacteria (Staphylococcus aureus) and results found to be satisfactory. In vivo studies for coated sutures was performed on Swiss albino mice and histological evaluation of intestinal wound healing parameters such as wound edges in mucosa, muscularis, presence of necrosis, exudates, granulation tissue, granulocytes, macrophages, restoration, and repair of mucosal epithelium and muscularis propria on day 7 after surgery were studied. The control animal group, sutured with plain suture (uncoated suture) showed signs of restoration and repair, but presence of necrosis, heamorraghic infiltration and granulation tissue was still noticed. Whereas the animal group treated with ciprofloxacin and ciprofloxacin gold nanoparticle coated sutures has shown promising decrease in terms of haemorraghic infiltration, granulation tissue, necrosis and better repaired muscularis layers on comparision with plain coated sutures indicating faster rate of repair and less chance of sepsis. Hence coating of sutures with broad spectrum antibiotics can be an alternate technique to reduce SSIs.

Keywords: ciprofloxacin hydrochloride, gold nanoparticles, surgical site infections, sutures

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2483 Optimal Wheat Straw to Bioethanol Supply Chain Models

Authors: Abdul Halim Abdul Razik, Ali Elkamel, Leonardo Simon

Abstract:

Wheat straw is one of the alternative feedstocks that may be utilized for bioethanol production especially when sustainability criteria are the major concerns. To increase market competitiveness, optimal supply chain plays an important role since wheat straw is a seasonal agricultural residue. In designing the supply chain optimization model, economic profitability of the thermochemical and biochemical conversion routes options were considered. It was found that torrefied pelletization with gasification route to be the most profitable option to produce bioethanol from the lignocellulosic source of wheat straw.

Keywords: bio-ethanol, optimization, supply chain, wheat straw

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2482 Preparation and Evaluation of Gelatin-Hyaluronic Acid-Polycaprolactone Membrane Containing 0.5 % Atorvastatin Loaded Nanostructured Lipid Carriers as a Nanocomposite Scaffold for Skin Tissue Engineering

Authors: Mahsa Ahmadi, Mehdi Mehdikhani-Nahrkhalaji, Jaleh Varshosaz, Shadi Farsaei

Abstract:

Gelatin and hyaluronic acid are commonly used in skin tissue engineering scaffolds, but because of their low mechanical properties and high biodegradation rate, adding a synthetic polymer such as polycaprolactone could improve the scaffold properties. Therefore, we developed a gelatin-hyaluronic acid-polycaprolactone scaffold, containing 0.5 % atorvastatin loaded nanostructured lipid carriers (NLCs) for skin tissue engineering. The atorvastatin loaded NLCs solution was prepared by solvent evaporation method and freeze drying process. Synthesized atorvastatin loaded NLCs was added to the gelatin and hyaluronic acid solution, and a membrane was fabricated with solvent evaporation method. Thereafter it was coated by a thin layer of polycaprolactone via spine coating set. The resulting scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. Moreover, mechanical properties, in vitro degradation in 7 days period, and in vitro drug release of scaffolds were also evaluated. SEM images showed the uniform distributed NLCs with an average size of 100 nm in the scaffold structure. Mechanical test indicated that the scaffold had a 70.08 Mpa tensile modulus which was twofold of tensile modulus of normal human skin. A Franz-cell diffusion test was performed to investigate the scaffold drug release in phosphate buffered saline (pH=7.4) medium. Results showed that 72% of atorvastatin was released during 5 days. In vitro degradation test demonstrated that the membrane was degradated approximately 97%. In conclusion, suitable physicochemical and biological properties of membrane indicated that the developed gelatin-hyaluronic acid-polycaprolactone nanocomposite scaffold containing 0.5 % atorvastatin loaded NLCs could be used as a good candidate for skin tissue engineering applications.

Keywords: atorvastatin, gelatin, hyaluronic acid, nano lipid carriers (NLCs), polycaprolactone, skin tissue engineering, solvent casting, solvent evaporation

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2481 Hepatoprotective Effect of Ethyl Acetate Fraction of Ficus carica L. Leaves against Carbon Tetrachloride-Induced Toxicity in vitro and in vivo

Authors: Syeda Hira, Muhammad Gulfraz

Abstract:

Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

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2480 A Significant Clinical Role for the Capitalbio™ DNA Microarray in the Diagnosis of Multidrug-Resistant Tuberculosis in Patients with Tuberculous Spondylitis Simultaneous with Pulmonary Tuberculosis in High Prevalence Settings in China

Authors: Wenjie Wu, Peng Cheng, Zehua Zhang, Fei Luo, Feng Wu, Min Zhong, Jianzhong Xu

Abstract:

Background: There has been limited research into the therapeutic efficacy of rapid diagnosis of spinal tuberculosis complicated with pulmonary tuberculosis. We attempted to discover whether the utilization of a DNA microarray assay to detect multidrug-resistant spinal tuberculosis complicated with pulmonary tuberculosis can improve clinical outcomes. Methods: A prospective study was conducted from February 2006 to September 2015. One hundred and forty-three consecutive culture–confirmed, clinically and imaging diagnosed MDR-TB patients with spinal tuberculosis complicated by pulmonary tuberculosis were enrolled into the study. The initial time to treatment for MDR-TB, the method of infection control, radiological indicators of spinal tubercular infectious foci, culture conversion, and adverse drug reactions were compared with the standard culture methods. Results: Of the total of 143 MDR-TB patients, 68 (47.6%) were diagnosed by conventional culture methods and 75 (52.4%) following the implementation of detection using the DNA microarray. Patients in the microarray group began rational use of the second-line drugs schedule more speedily than sufferers in the culture group (17.3 vs. 74.1 days). Among patients were admitted to a general tuberculosis ward, those from the microarray group spent less time in the ward than those from the culture group (7.8 vs. 49.2 days). In those patients with six months follow-up (n=134), patients in the microarray group had a higher rate of sputum negativity conversion at six months (89% vs. 73%). In the microarray group, the rate of drug adverse reactions was significantly lower (22.2% vs. 67.7%). At the same time, they had a more obvious reduction of the area with spinal tuberculous lesions in radiological examinations (77% vs. 108%). Conclusions: The application of the CapitalBio™ DNA Microarray assay caused noteworthy clinical advances including an earlier time to begin MDR-TB treatment, increased sputum culture conversion, improved infection control measures and better radiographical results

Keywords: tuberculosis, multidrug-resistant, tuberculous spondylitis, DNA microarray, clinical outcomes

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2479 Ordered Mesoporous Carbons of Different Morphology for Loading and Controlled Release of Active Pharmaceutical Ingredients

Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

Abstract:

Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

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2478 PSS and SVC Controller Design by BFA to Enhance the Power System Stability

Authors: Saeid Jalilzadeh

Abstract:

Designing of PSS and SVC controller based on Bacterial Foraging Algorithm (BFA) to improve the stability of power system is proposed in this paper. Same controllers for PSS and SVC has been considered and Single machine infinite bus (SMIB) system with SVC located at the terminal of generator is used to evaluate the proposed controllers. BFA is used to optimize the coefficients of the controllers. Finally simulation for a special disturbance as an input power of generator with the proposed controllers in order to investigate the dynamic behavior of generator is done. The simulation results demonstrate that the system composed with optimized controllers has an outstanding operation in fast damping of oscillations of power system.

Keywords: PSS, SVC, SMIB, optimize controller

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2477 CMMI Key Process Areas and FDD Practices

Authors: Rituraj Deka, Nomi Baruah

Abstract:

The development of information technology during the past few years resulted in designing of more and more complex software. The outsourcing of software development makes a higher requirement for the management of software development project. Various software enterprises follow various paths in their pursuit of excellence, applying various principles, methods and techniques along the way. The new research is proving that CMMI and Agile methodologies can benefit from using both methods within organizations with the potential to dramatically improve business performance. The paper describes a mapping between CMMI key process areas (KPAs) and Feature-Driven Development (FDD) communication perspective, so as to increase the understanding of how improvements can be made in the software development process.

Keywords: Agile, CMMI, FDD, KPAs

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2476 Design for Sustainability as a Key Driver for Exploring the Potential of Cork Material

Authors: Spase Janevski

Abstract:

We, as designers, should be aware of the consequences of our material selection, at the early stages of the design process. Some of the designer’s decisions can have a very significant impact on design for sustainability. The influence of this concept has led to years of research studies into eco-friendly materials and their potentials for creating new sustainable products. In order to answer the question, 'how cork has become a design trend', this paper will present an overview of the implications of the concept of design for sustainability on the potential uses of cork material. A decade ago, cork as a material had an association with wine stoppers, but with the evolution of sustainable product design as part of the concept of design for sustainability, cork now offers product designers a wide range of new materials and applications. The purpose of this paper is to show how the phenomenon of sustainability has had an impact on the progress of the material which is currently not being an integral component of the design material palette. At the beginning, the nature of the relationship between cork and sustainability will be explained through the following stages: 1) fundamental understanding of the concept of Design for Sustainability and the importance of material selection for sustainable product design, and 2) the importance of cork oak trees for the environment and the environmental impacts of cork products. In order to examine and present the influence of the sustainability on the innovation in cork applications, the paper will provide a historical overview of designing with cork. The overview will consist of four stages: 1) pre-industrial period - the period when ancient nations used cork and amphoras to store their wine; 2) industrial period - emergence and industrialization of well-known wine stoppers; 3) post-industrial period - commercializing cork products in the area of floors and coverings and first developments in industrial research; and 4) the period when large cork realized the importance of sustainability and started to focus more markedly on research and development. The existence of new cork materials, the investigation in new applications and the investment in new innovations have proved that the sustainability approach has had a great influence on the revival of this material. In addition, the paper will present some of the new cork innovative materials and applications and their potentials for designing promising and sustainable solutions with additive manufacturing technologies, such as 3D printing. Lastly, the paper will introduce some questions for further study, such as the environmental impacts of the new hybrid materials and the gap between cork industry and cork research and development teams. The paper concludes by stating that cork is not only a material for wine stoppers anymore, thanks to the awareness of the concept of design for sustainability.

Keywords: cork, design for sustainability, innovation, sustainable materials

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2475 Creating Emotional Brand Attachment through Immersive Worlds in Brick-and-Mortar Stores

Authors: Sanne Dollerup

Abstract:

This paper is an analysis of the store Tarina Tarantino through an exploration of different perspectives of play. It is based on Yelp reviews where customers disclose a very positive emotional reaction toward the store. The paper proposes some general principles for designing immersive stores based on ‘possible world’ theory. The aim is to disclose essential condition for customer engagement is an overall cohesiveness in all elements in a store. The most significant contribution in this paper is that products become props for role-playing in a store, hence making them central for maintaining that role outside the store.

Keywords: experience design, emotional brand attachment, retail design, case study

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2474 New Drug Discoveries and Packaging Challenges

Authors: Anupam Chanda

Abstract:

Presently Packaging plays a significant role for drug discoveries. The process of selecting materials and the type of packaging also offers an opportunity for the Packaging scientist to look for biological delivery choices. Most injectable protein products were supplied in some sort of glass vial, prefilled syringe, cartridge. Those product having high Ph content there is a chance of “delamination “from inner surface of glass vial. With protein-based drugs, the biggest issue is the effect of packaging derivatives on the protein’s threedimensional and surface structure. These are any effects that relate to denaturation or aggregation of the protein due to oxidation or interactions from contaminants or impurities in the preparation. The potential for these effects needs to be carefully considered in choosing the container and the container closure system to avoid putting patients in jeopardy. Cause of Delamination : -Formulations with a high pH include phosphate and citrate buffers increase the risk of glass delamination. -High alkali content in glass could accelerate erosion. -High temperature during the vial-forming process increase the risk of glass delamination. -Terminal sterilization (irradiated at 20-40 kGy for 150 min) also is a risk factor for specific products(veterinary parenteral administration),could cause delamination. -High product-storage temperatures and long exposure times can increase the rate and severity of glass delamination. How to prevent Delamination -Treating the surface of the glass vials with materials, such as ammonium sulfate or siliconization can reduce the rate of glass erosion. -Consider alternative sterilization methods only in rare cases. -The correct specification for the glass to ensure its suitability for the pH of the product. -Use Cyclic olefin copolymer(COC)/Cyclic olefin Polymer(COP) Adsorption of protein and Solutions: Option#1 Coat with linear methoxylated polyglycerol and hyperbranchedmethoxylated polyglycerol. Option#2 Thehyperbranched non-methoxylated coating performed best. Option#3 Coat with hyperbranched polyglycerol Option#4 Right selection of Sterilization of glass vial/syringe.

Keywords: delamination of glass, ptrotien adoptions inside the glass surface, extractable & leachable solutions, injectable designs for new drugs

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2473 Analytical Method Development and Validation of Stability Indicating Rp - Hplc Method for Detrmination of Atorvastatin and Methylcobalamine

Authors: Alkaben Patel

Abstract:

The proposed RP-HPLC method is easy, rapid, economical, precise and accurate stability indicating RP-HPLC method for simultaneous estimation of Astorvastatin and Methylcobalamine in their combined dosage form has been developed.The separation was achieved by LC-20 AT C18(250mm*4.6mm*2.6mm)Colum and water (pH 3.5): methanol 70:30 as mobile phase, at a flow rate of 1ml/min. wavelength of this dosage form is 215nm.The drug is related to stress condition of hydrolysis, oxidation, photolysis and thermal degradation.

Keywords: RP- HPLC, atorvastatin, methylcobalamine, method, development, validation

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2472 Canthin-6-One Alkaloid Inhibits NF-κB and AP-1 Activity: An Inhibitory Action At Transcriptional Level

Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

Abstract:

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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2471 Anti-proliferative Activity and HER2 Receptor Expression Analysis of MCF-7 (Breast Cancer Cell) Cells by Plant Extract Coleus Barbatus (Andrew)

Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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2470 Construction of Ovarian Cancer-on-Chip Model by 3D Bioprinting and Microfluidic Techniques

Authors: Zakaria Baka, Halima Alem

Abstract:

Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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2469 One Pot Synthesis of Cu–Ni–S/Ni Foam for the Simultaneous Removal and Detection of Norfloxacin

Authors: Xincheng Jiang, Yanyan An, Yaoyao Huang, Wei Ding, Manli Sun, Hong Li, Huaili Zheng

Abstract:

The residual antibiotics in the environment will pose a threat to the environment and human health. Thus, efficient removal and rapid detection of norfloxacin (NOR) in wastewater is very important. The main sources of NOR pollution are the agricultural, pharmaceutical industry and hospital wastewater. The total consumption of NOR in China can reach 5440 tons per year. It is found that neither animals nor humans can totally absorb and metabolize NOR, resulting in the excretion of NOR into the environment. Therefore, residual NOR has been detected in water bodies. The hazards of NOR in wastewater lie in three aspects: (1) the removal capacity of the wastewater treatment plant for NOR is limited (it is reported that the average removal efficiency of NOR in the wastewater treatment plant is only 68%); (2) NOR entering the environment will lead to the emergence of drug-resistant strains; (3) NOR is toxic to many aquatic species. At present, the removal and detection technologies of NOR are applied separately, which leads to a cumbersome operation process. The development of simultaneous adsorption-flocculation removal and FTIR detection of pollutants has three advantages: (1) Adsorption-flocculation technology promotes the detection technology (the enrichment effect on the material surface improves the detection ability); (2) The integration of adsorption-flocculation technology and detection technology reduces the material cost and makes the operation easier; (3) FTIR detection technology endows the water treatment agent with the ability of molecular recognition and semi-quantitative detection for pollutants. Thus, it is of great significance to develop a smart water treatment material with high removal capacity and detection ability for pollutants. This study explored the feasibility of combining NOR removal method with the semi-quantitative detection method. A magnetic Cu-Ni-S/Ni foam was synthesized by in-situ loading Cu-Ni-S nanostructures on the surface of Ni foam. The novelty of this material is the combination of adsorption-flocculation technology and semi-quantitative detection technology. Batch experiments showed that Cu-Ni-S/Ni foam has a high removal rate of NOR (96.92%), wide pH adaptability (pH=4.0-10.0) and strong ion interference resistance (0.1-100 mmol/L). According to the Langmuir fitting model, the removal capacity can reach 417.4 mg/g at 25 °C, which is much higher than that of other water treatment agents reported in most studies. Characterization analysis indicated that the main removal mechanisms are surface complexation, cation bridging, electrostatic attraction, precipitation and flocculation. Transmission FTIR detection experiments showed that NOR on Cu-Ni-S/Ni foam has easily recognizable FTIR fingerprints; the intensity of characteristic peaks roughly reflects the concentration information to some extent. This semi-quantitative detection method has a wide linear range (5-100 mg/L) and a low limit of detection (4.6 mg/L). These results show that Cu-Ni-S/Ni foam has excellent removal performance and semi-quantitative detection ability of NOR molecules. This paper provides a new idea for designing and preparing multi-functional water treatment materials to achieve simultaneous removal and semi-quantitative detection of organic pollutants in water.

Keywords: adsorption-flocculation, antibiotics detection, Cu-Ni-S/Ni foam, norfloxacin

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