Search results for: tumor suppressor gene

Authors: Ahmed M. Hjazi, Bader M. Hjazi

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Protein 4.1 is a crucial component of complex interactions between the cytoskeleton and other junctional complex proteins. When the gene encoding this protein is altered, resulting in reduced expression, or when the protein is absent, the red cell undergoes a significant structural change. This research aims to achieve a deeper comprehension of the biochemical effects of red cell protein deficiency. A Tandem Mass Spectrometry Analysis (TMT-MS/MS) of patient cells lacking protein 4.1 compared to three healthy controls was achieved by the Proteomics Institute of the University of Bristol. The SDS-PAGE and Western blotting were utilized on the original patient sample and controls to partially confirm TMT MS/MS data analysis of the protein-4.1-deficient cells. Compared to healthy controls, protein levels in samples lacking protein 4.1 had a significantly higher concentration of proteins that probably originated from reticulocytes. This could occur if the patient has an elevated reticulocyte count. The increase in chaperone and reticulocyte-associated proteins was most notable in this study. This may result from elevated quantities of reticulocytes in patients with hereditary elliptocytosis.

Keywords: hereditary elliptocytosis, protein 4.1, red cells, tandem mass spectrometry data.

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Authors: Billel Kenidra, Mohamed Benmohammed

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Data mining technique used in the field of clustering is a subject of active research and assists in biological pattern recognition and extraction of new knowledge from raw data. Clustering means the act of partitioning an unlabeled dataset into groups of similar objects. Each group, called a cluster, consists of objects that are similar between themselves and dissimilar to objects of other groups. Several clustering methods are based on partitional clustering. This category attempts to directly decompose the dataset into a set of disjoint clusters leading to an integer number of clusters that optimizes a given criterion function. The criterion function may emphasize a local or a global structure of the data, and its optimization is an iterative relocation procedure. The K-Means algorithm is one of the most widely used partitional clustering techniques. Since K-Means is extremely sensitive to the initial choice of centers and a poor choice of centers may lead to a local optimum that is quite inferior to the global optimum, we propose a strategy to initiate K-Means centers. The improved K-Means algorithm is compared with the original K-Means, and the results prove how the efficiency has been significantly improved.

Keywords: microarray data mining, biological pattern recognition, partitional clustering, k-means algorithm, centroid initialization

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Authors: Gaby Fahmy

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The last decades have seen a rise in metabolic disorders like diabetes, obesity, and fatty liver disease around the world. Environmental factors, especially nutrition, have contributed to this increase. Additionally, pre-conceptional parental nutritional choices have been shown to result in epigenetic modifications affecting gene expression during the developmental process in-utero. These epigenetic modifications have also been seen to extend to the following offspring in a trans-generational effect. This further highlights the significance and relevance of epigenetics and epigenetic tags, which were previously thought to be stripped in newly formed embryos. Suitable prenatal nutrition may partially counteract adverse outcomes caused by exposures to environmental contaminants, ultimately resulting in improved metabolic profiles like body weight and glucose homeostasis. This was seen in patients who were given dietary interventions like restrictive caloric intake, intermittent fasting, and time-restricted feeding. Changes in nutrition are pivotal in the regulation of epigenetic modifications that are transgenerational. For example, dietary choices such as fatty foods vs. vegetables and nuts in fathers were shown to significantly affect sperm motility and volume. This was pivotal in understanding the importance of paternal inheritance. Further research in the field is needed as it remains unclear how many generations are affected by these changes.

Keywords: epigenetics, transgenerational, diet, fasting

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Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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Authors: Humayun Kabir, Amirul Hasan, Yu Miyaoka, Makiko Yamaguchi, Chisaki Kadota, Kazuaki Takehara

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From field isolates of Newcastle disease virus (NDV) in Japan, one avirulent strain, APMV/northern pintail/Japan/Aomori/2003 (dk-Aomori/03, NDV 261), was selected for its excellent thermostability, and the strain was heat-treated at 56℃ temperatures for 30 min with each passage into Vero cells to maintain thermostability and to adapt Vero cells. After serial 20 passages in Vero cells, it was named NDV Vero20. When growth curves were tested in Vero cells, NDV Vero20 grew well to compare the original NDV261. The HN gene was sequenced, and found motifs that show thermostability. The intracerebral pathogenicity index (ICPI) test score was 0. The thermostability of the virus was confirmed by storing it at different temperatures, including at 37°C. When susceptible chicks were inoculated with NDV Vero20 through eye drops, induced adequate levels of antibody were measured using a serum neutralization test. The results showed that NDV Vero20, a vaccine candidate strain is thermostable, Vero cell adapted, and has immunogenic potential, which would make as an alternative to the traditional embryonated chicken eggs-based vaccine.

Keywords: Newcastle disease virus, thermostability, vaccine, Vero cell adaptability

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Authors: M. Helen

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Chemical graph serves as a convenient model for any real or abstract chemical system. Dendrimers are novel three dimensional hyper branched globular nanopolymeric architectures. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Dendrimers like poly L lysine (PLL), poly-propylene imine (PPI) and poly-amidoamine (PAMAM), etc., are used as gene carrier in drug delivery system because of their chemical characteristics. These characteristics of chemical compounds are analysed using topological indices (invariants under graph isomorphism) such as Wiener index, Zagreb index, etc., Prof. V. R. Kulli motivated by the application of Zagreb indices in finding the total π energy and derived Gourava indices which is an improved version over Zagreb indices. In this paper, we study the structure of PLL-Dendrimer that has the following applications: reduction in toxicity, colon delivery, and topical delivery. Also, we determine first and second Gourava indices, first and second hyper Gourava indices, product and sum connectivity Gourava indices for PLL-Dendrimer. Gourava Indices have found applications in Quantitative Structure-Property Relationship (QSPR)/ Quantitative Structure-Activity Relationship (QSAR) studies.

Keywords: connectivity Gourava indices, dendrimer, Gourava indices, hyper GouravaG indices

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Authors: Ravinder Singh, C Rajesh, Saroj Badhan, Shailendra Mishra, Ranjit Singh Kataria

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Heat shock protein 60 and 70 are crucial chaperones that guide appropriate folding of denatured proteins under heat stress conditions. HSP60 and HSP70 provide assistance in correct folding of a multitude of denatured proteins. The heat shock factors are the family of some transcription factors which controls the regulation of gene expression of proteins involved in folding of damaged or improper folded proteins during stress conditions. Under normal condition heat shock proteins bind with HSF-1 and act as its repressor as well as aids in maintaining the HSF-1’s nonactive and monomeric confirmation. The experimental protein structure for all these proteins in Bubalus bubalis is not known till date. Therefore computational approach was explored to identify three-dimensional structure analysis of all these proteins. In this study, an extensive in silico analysis has been performed including sequence comparison among species to comparative modeling of Bubalus bubalis HSP60, HSP70 and HSF-1 protein. The stereochemical properties of proteins were assessed by utilizing several scrutiny bioinformatics tools to ensure model accuracy. Further docking approach was used to study interactions between Heat shock proteins and HSF-1.

Keywords: Bubalus bubalis, comparative modelling, docking, heat shock protein

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Authors: A. Bahieldin, A. Atef, S. Edris, N. O. Gadalla, S. M. Hassan, M. A. Al-Kordy, A. M. Ramadan, A. S. M. Al- Hajar, F. M. El-Domyati

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The idea of this work is based on a natural exciting phenomenon suggesting that suppression of genes related to the program cell death (or PCD) mechanism might help the plant cells to efficiently tolerate abiotic stresses. The scope of this work was the detection of PCD-related transcription factors (TFs) that might also be related to salt stress tolerance in plant. Two model plants, e.g., tobacco and Arabidopsis, were utilized in order to investigate this phenomenon. Occurrence of PCD was first proven by Evans blue staining and DNA laddering after tobacco leaf discs were treated with oxalic acid (OA) treatment (20 mM) for 24 h. A number of 31 TFs up regulated after 2 h and co-expressed with genes harboring PCD-related domains were detected via RNA-Seq analysis and annotation. These TFs were knocked down via virus induced gene silencing (VIGS), an RNA interference (RNAi) approach, and tested for their influence on triggering PCD machinery. Then, Arabidopsis SALK knocked out T-DNA insertion mutants in selected TFs analogs to those in tobacco were tested under salt stress (up to 250 mM NaCl) in order to detect the influence of different TFs on conferring salt tolerance in Arabidopsis. Involvement of a number of candidate abiotic-stress related TFs was investigated.

Keywords: VIGS, PCD, RNA-Seq, transcription factors

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Authors: Alice Petzold, Alexandre Hassanin

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The number of giraffe species has been in focus of interest since the exploration of sub-Saharan Africa by European naturalists during the 18th and 19th centuries, as previous taxonomists, like Geoffroy Saint-Hilaire, Richard Owen or William Edward de Winton, recognized two or three species of Giraffa. For the last decades, giraffes were commonly considered as a single species subdivided into nine subspecies. In this study, we have re-examined available nuclear and mitochondrial data. Our genetic admixture analyses of seven introns support three species: G. camelopardalis (i.e., northern giraffes including reticulated giraffes), G. giraffa (southern giraffe) and G. tippelskirchi (Masai giraffe). However, the nuclear alignments show small variation and our phylogenetic analyses provide high support only for the monophyly of G. camelopardalis. Comparisons with the mitochondrial tree revealed a robust conflict for the position and monophyly of G. giraffa and G. tippelskirchi, which is explained firstly by a mitochondrial introgression from Masai giraffe to southeastern giraffe, and secondly, by gene flow mediated by male dispersal between southern populations (subspecies angolensis and giraffa). We conclude that current data gives only moderate support for three giraffe species and point out that additional nuclear data need to be studied to revise giraffe taxonomy.

Keywords: autosomal markers, Giraffidae, mitochondrial introgression, taxonomy

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Authors: Danni Cheng

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Purpose:Surgicallyinclusive treatment(SIT)isthemajor treatment fororopharyngealsquamouscellcarcinoma (OPSCC) in Eastern countries, while nonsurgical treatments(NSTs) are the priority treatment in Western countries. The preferred treatmentsforOPSCC patients remaindebated. Methods:Atotalof 153 consecutive OPSCC casesdiagnosed between 2009 and 2019inWCH, and 15,400 OPSCC cases from SEER database (2000-2017) were obtained. Clinical characteristics, treatments, and survival outcomes were retrospectively collected. We conductedKaplan-Meier curves univariate and multivariate analysis to compare the prognosis of OPSCC patients in WCH, SEER Asian, and SEER all ethnic population by different treatment modalities,HPVstatus, ages, and TNM stages. Results: The 5-year overall survival rate was 59% in WCH, 64% in the SEER all ethnic and 67% in SEER Asian group. In both univariate and multivariate analysis, SIT was observed as a consistent benefit factor for OPSCC patients in all three populations when classified by genders, tumor stages, and HPV status. Patients who underwent SIT had significantly better survival outcomes than those who received NSTsin WCH, SEER Asian, and SEER all ethnic groups. HPV positive status was the beneficial factor of OPSCC patients in all three groups. Besides, male patients had worse survival outcomes in both WCH and SEER Asian group, whereas male patients had better outcomes in the SEER all ethnic group. Conclusion: In contrast to nowadaysNSTs are the first-line therapiesfor OPSCC, our ten-year real-world data and SEER data indicated that OPSCC patients who underwent SIT had better prognosis than NSTs.

Keywords: OPSCC, survival outcome, SEER, treatment modalities

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Authors: Ilknur Tuncer, Nihayet Bizsel

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The scarcity of research in bacterial diversity and antimicrobial resistance in coastal environments as in Turkish coasts leads to difficulties in developing efficient monitoring and management programs. In the present study, biogeochemical analysis of sediments and antimicrobial susceptibility analysis of bacteria in Izmir Bay, eastern Aegean Sea under high anthropogenic pressure were aimed in summer period when anthropogenic input was maximum and at intertidal zone where the first terrigenious contact occurred for aquatic environment. Geochemical content of the intertidal zone of Izmir Bay was firstly illustrated such that total and organic carbon, nitrogen and phosphorus contents were high and the grain size distribution varied as sand and gravel. Bacterial diversity and antibiotic resistance were also firstly given for Izmir Bay. Antimicrobially assayed isolates underlined the multiple resistance in the inner, middle and outer bays with overall 19% high MAR (multiple antibiotic resistance) index. Phylogenetic analysis of 16S rRNA gene sequences indicated that 67 % of isolates belonged to the genus Bacillus and the rest included the families Alteromonadaceae, Bacillaceae, Exiguobacteriaceae, Halomonadaceae, Planococcaceae, and Staphylococcaceae.

Keywords: bacterial phylogeny, multiple antibiotic resistance, 16S rRNA genes, Izmir Bay, Aegean Sea

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Authors: Naso Isaiah Thanavisuth, Patompong Satapornpong

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Introduction: Covid-19 has been a global pandemic for some time now, causing severe symptoms to patients that received the virus. However, there has been no report on this gene in the Thai population. Objective: Our aim in this study is to explore and compare the frequency of HLA-C allele that is associated with severe COVID-19 symptoms in Thais and other populations. Method: 200 general Thai population were enrolled in this study. The genotyping of HLA -C alleles were determined by the polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP) and Luminex®IS 100 system (Luminex Corporation, Austin, Texas, USA). Results: We found that the frequency of alleles HLA-C* 01:02 (16.00%), HLA-C* 08:01(10.50%), HLA-C* 03:04 (10.25%),HLA-C* 07:02 (10.00%), HLA-C* 03:02 (9.25%), HLA-C* 07:01 (6.75%), HLA-C* 04:01 (5.00%), HLA-C* 06:02 (4.00%), HLA-C* 04:03 (4.00%), and HLA-C* 07:04 (3.75%) were more common in the Thai population. HLA-C* 01:02 (16.00%) allele was the highest frequency in the North, Center, and North East groups in Thailand, but there was the South region that was not significantly different when compared with the other groups of the region. Additionally, HLA-C∗14:02 allele was similarly distributed in Thais (3.00%), African Americans (1.98%), Caucasians (2.08%), Hispanics (1.71%), North American Natives (1.34%) and Asians (5.01%) by p-value = 0.6506, 0.6506, 0.6506, 0.6135 and 0.7182, respectively. Conclusion: Genetic variation database is important to identify HLA can be a risk factor for severe COVID-19 in many populations. In this study, we will support the research of the HLA markers for screening severe COVID-19 in many populations.

Keywords: HLA-C * 14:02, COVID-19, allele frequency, Thailand

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Authors: Ali Oztuna, Meral Sarper, Deniz Torun, Fatma Bayrakdar, Selcuk Kilic, Mehmet Baysallar

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Bacillus anthracis is one of the biological agents most likely to be used in case of bioterrorist attack as well as being the cause of anthrax. The bacterium's major virulence factors are the anthrax toxins and an antiphagocytic polyglutamic capsule. TEM8 (ANTXR1) and CMG2 (ANTXR2) are ubiquitously expressed type I transmembrane proteins, and ANTXR2 is the major receptor for anthrax toxins. MicroRNAs are 21-24 bp small noncoding RNAs that regulate gene expression by base pairing with the 3' UTR (untranslated regions) of their target mRNAs resulting in mRNA degradation and/or translational repression. MicroRNAs contribute to regulation of most biological processes and influence numerous pathological states like infectious disease. In this study, post-exposure (toxins) protective effect of the hsa-miR-124-3p against Bacillus anthracis was examined. In this context, i) THP-1 and U937 cells were differentiated to MΦ macrophage, ii) miRNA transfection efficiencies were evaluated by flow cytometry and qPCR, iii) protection against Bacillus anthracis toxins were investigated by XTT, cAMP ELISA and MEK2 cleavage assays. Acknowledgements: This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Grant SBAG-218S467.

Keywords: ANTXR2, hsa-miR-124-3p, MΦ macrophage, THP-1, U937

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Authors: Shalini Menon, K. Girish Kumar

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Norepinephrine (NE) is one of the naturally occurring catecholamines which act both as a neurotransmitter and a hormone. Catecholamine levels are used for the diagnosis and regulation of phaeochromocytoma, a neuroendocrine tumor of the adrenal medulla. The development of simple, rapid and cost-effective sensors for NE still remains a great challenge. Herein, a dual-channel sensor has been developed for the determination of NE. A mixture of AgNO₃, NaOH, NH₃.H₂O and cetrimonium bromide in appropriate concentrations was taken as the working solution. To the thoroughly vortexed mixture, an appropriate volume of NE solution was added. After a particular time, the fluorescence and absorbance were measured. Fluorescence measurements were made by exciting at a wavelength of 400 nm. A dual-channel optical sensor has been developed for the colorimetric as well as the fluorimetric determination of NE. Metal enhanced fluorescence property of nanoparticles forms the basis of the fluorimetric detection of this assay, whereas the appearance of brown color in the presence of NE leads to colorimetric detection. Wide linear ranges and sub-micromolar detection limits were obtained using both the techniques. Moreover, the colorimetric approach was applied for the determination of NE in synthetic blood serum and the results obtained were compared with the classic high-performance liquid chromatography (HPLC) method. Recoveries between 97% and 104% were obtained using the proposed method. Based on five replicate measurements, relative standard deviation (RSD) for NE determination in the examined synthetic blood serum was found to be 2.3%. This indicates the reliability of the proposed sensor for real sample analysis.

Keywords: norepinephrine, colorimetry, fluorescence, silver nanoparticles

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Authors: Xiran Wang, Johanna Trinkl, Thomas Hoffmann, Wilfried Schwab

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Malonyltransferases (MATs) are enzymes that play a key role in the biosynthesis of secondary metabolites in plants, such as flavonoids and anthocyanins. As a kind of flavonoid-rich fruit, strawberries are an ideal model to study MATs. From Goodberry metabolome data, in the hybrid generation of 2 strawberries various, Fragaria × ananassa cv. 'Senga Sengana' and 'Candonga', we found the malonylated flavonoid concentration is significantly higher in 'Senga Sengana' compared with 'Candonga'. Therefore, we aimed to identify and characterize the malonyltransferases responsible for the different malonylated flavonoid concentrations in two different strawberry cultivars. In this study, we have found 6 MATs via genome mapping, metabolome analysis, gene cloning, and enzyme assay from strawberries, which catalyzed the malonylation of flavonoid substrates: quercetin-3-glucoside, kaempferol-3-glucoside, pelargonidin-3-glucoside, and cyanidin-3-glucoside. All four compounds reacted with FaMATs to varying degrees. These MATs have important implication into strawberries’ flavonoid biosynthesis, and also provide insights into insights into flavonoid biosynthesis, potential applications in agriculture, plant science, and pharmacy, and information on the regulation of secondary metabolism in plants.

Keywords: malonyltransferase, strawberry, flavonoid biosynthesis, enzyme assay

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Authors: Yasser Mahmoudi, Nader Karimi

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The present work examines analytically the effect internal heat generation on temperature fields in a channel partially-filled with a porous under local thermal non-equilibrium condition. The Darcy-Brinkman model is used to represent the fluid transport through the porous material. Two fundamental models (models A and B) represent the thermal boundary conditions at the interface between the porous medium and the clear region. The governing equations of the problem are manipulated, and for each interface model, exact solutions for the solid and fluid temperature fields are developed. These solutions incorporate the porous material thickness, Biot number, fluid to solid thermal conductivity ratio Darcy number, as the non-dimensional energy terms in fluid and solid as parameters. Results show that considering any of the two models and under zero or negative heat generation (heat sink) and for any Darcy number, an increase in the porous thickness increases the amount of heat flux transferred to the porous region. The obtained results are applicable to the analysis of complex porous media incorporating internal heat generation, such as heat transfer enhancement (THE), tumor ablation in biological tissues and porous radiant burners (PRBs).

Keywords: porous media, local thermal non-equilibrium, forced convection, heat transfer, exact solution, internal heat generation

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Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

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Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

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Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

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Authors: Patsarawadee Paojinda, Waranya Imprasittichai, Sudaratana R. Krungkrai, Nirianne Marie Q. Palacpac, Toshihiro Horii, Jerapan Krungkrai

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Fusion of the last two enzymes in the pyrimidine biosynthetic pathway in the inversed order by having COOH-terminal orotate phosphoribosyltransferase (OPRT) and NH2-terminal orotidine 5'-monophosphate decarboxylase (OMPDC), as OMPDC-OPRT, are described in many organisms. Here, we produced gene fusions of Plasmodium falciparum OMPDC-OPRT and expressed the bifunctional protein in Escherichia coli. The enzyme was purified to homogeneity using affinity and anion-exchange chromatography, exhibited enzymatic activities and functioned as a dimer. The activities, although unstable, can be stabilized by its substrate and product during purification and long-term storage. Furthermore, the enzyme expressed a perfect catalytic efficiency (kcat/Km). The kcat was selectively enhanced up to 3 orders of magnitude, while the Km was not much affected and remained at low µM levels when compared to the monofunctional enzymes. The fusion of the two enzymes, creating a “super-enzyme” with perfect catalytic power and more flexibility, reflects cryptic relationship of enzymatic reactivaties and metabolic functions on molecular evolution.

Keywords: bifunctional enzyme, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase, plasmodium falciparum

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Authors: Eugene Stepanov, Arkadi Ponossov

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Ordinary differential equations with switching nonlinearities constitute a very useful tool in many applications. The solutions of such equations can usually be calculated analytically if they cross the discontinuities transversally. Otherwise, one has trajectories that slides along the discontinuity, and the calculations become less straightforward in this case. For instance, one of the problems one faces is non-uniqueness of the sliding modes. In the presentation, it is proposed to apply the theory of hybrid dynamical systems to calculate the solutions that are ‘hidden’ in the discontinuities. Roughly, one equips the underlying switched system with an explicitly designed discrete dynamical system (‘automaton’), which governs the dynamics of the switched system. This construction ‘splits’ the dynamics, which, as it is shown in the presentation, gives uniqueness of the resulting hybrid trajectories and at the same time provides explicit formulae for them. Projecting the hybrid trajectories back onto the original continuous system explains non-uniqueness of its trajectories. The automaton is designed with the help of the attractors of the specially constructed adjoint dynamical system. Several examples are provided in the presentation, which supports the efficiency of the suggested scheme. The method can be of interest in control theory, gene regulatory networks, neural field models and other fields, where switched dynamics is a part of the analysis.

Keywords: hybrid dynamical systems, singular perturbation analysis, sliding modes, switched dynamics

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Authors: Yonghwa Lee, Yoon Suk Kim, Yongsub Yi

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This study was to confirm the effects of anti-melanogenesis and anti-inflammatory effects from Opuntia humifusa fruit and stem extracts. A potent anti-oxidant activity was shown from the leaf extract at IC50 value of 38.33±1.07 μg/mL and fruit extract at IC50 value of 40.23±2.21 μg/mL by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, phenolic contents were confirmed total phenolic assay by high performance liquid chromatography (HPLC). Fraction of taxifolin from leaf extract was identified using HPLC and gas chromatography/mass spectrometry. The extracts of Opuntia humifusa fruit and stem were confirmed about toxicity effect in B16 F1 by cell viability. Melanin contents were decreased. Opuntia humifusa fruit and stem extracts had a positive effect of melanin synthesis inhibition for skin whitening. In investigating the anti-inflammatory activities of Opuntia humifusa, the results of cell viability indicated that taxifolin did not show cytotoxicity on RAW264.7 cells at 500 μM of concentration. The results show that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide (NO). In addition, taxifolin indicated the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) -α and interleukin (IL) -6 productions by cytokine assay and cyclooxygenase (COX)-2 expression by western blot analysis, meaning that taxifolin had a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa has anti-melanogenesis and anti-inflammatory activities.

Keywords: anti-melanogenesis, anti-inflammatory, Opuntia humifusa, taxifolin

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Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

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The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

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Authors: Y. Ruchi, A. Prerna, S. Deepshikha

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Amyotrophic lateral sclerosis (ALS), also known as “Lou Gehrig’s disease”. It is a neurodegenerative disease associated with degeneration of motor neurons in the cerebral cortex, brain stem, and spinal cord characterized by distal muscle weakness, atrophy, normal sensation, pyramidal signs and progressive muscular paralysis reflecting. ALS2 is a juvenile autosomal recessive disorder, slowly progressive, that maps to chromosome 2q33 and is associated with mutations in the alsin gene, a putative GTPase regulator. In this paper we have done homology modeling of alsin2 protein using multiple templates (3KCI_A, 4LIM_A, 402W_A, 4D9S_A, and 4DNV_A) designed using the Prime program in Schrödinger software. Further modeled structure is used to identify effective binding sites on the basis of structural and physical properties using sitemap program in Schrödinger software, structural and function analysis is done by using Prosite and ExPASy server that gives insight into conserved domains and motifs that can be used for protein classification. This paper summarizes the structural, functional and binding site property of alsin2 protein. These binding sites can be potential drug target sites and can be used for docking studies.

Keywords: ALS, binding site, homology modeling, neuronal degeneration

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Authors: Janis Zarins, Kristaps Blums, Oskars Radzins, Renars Deksnis, Atis Svare, Santa Salaka

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Wide tumor resection remains the first choice method for tumors of the oral cavity. Nevertheless, remained tissue defect impacts patients functional and aesthetical outcome, which could be improved using microvascular tissue transfers. Mandibular reconstruction is challenging due to the complexity of composite tissue defects and occlusal relationships for normal eating, chewing, and pain free jaw motions. Individual 3-D virtual planning would provide better symmetry and functional outcome. The main goal of preoperative planning is to develop a customized surgical approach with patient specific cutting guides of the mandible, osteotomy guides of the fibula, pre-bended osteosynthesis plates to perform more precise reconstruction, to decrease the surgery time and reach the best outcome. Our study is based on the analysis of 32 patients operated on between 2019 to 2021. All patients underwent mandible reconstruction with vascularized fibula flaps. Patients characteristics, surgery profile, survival, functional outcome, and quality of life was evaluated. Preoperative planning provided a significant decrease of surgery time and the best arrangement of bone closely similar as before the surgery. In cases of bone asymmetry, deformity and malposition, a new mandible was created using 3D planning to restore the appearance of lower jaw anatomy and functionality.

Keywords: mandibular, 3D planning, cutting guides, fibula flap, reconstruction

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Authors: S. Zith Dey Babu, S. Kour, S. Verma, C. Verma, V. Pathania, A. Agrawal, V. Chaudhary, A. Manoj Puthur, R. Goyal, A. Pal, T. Danti Dey, A. Kumar, K. Wadhwa, O. Ved

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Background: Skin cancer is now is the buzzing button in the field of medical science. The cyst's pandemic is drastically calibrating the body and well-being of the global village. Methods: The extracted image of the skin tumor cannot be used in one way for diagnosis. The stored image contains anarchies like the center. This approach will locate the forepart of an extracted appearance of skin. Partitioning image models has been presented to sort out the disturbance in the picture. Results: After completing partitioning, feature extraction has been formed by using genetic algorithm and finally, classification can be performed between the trained and test data to evaluate a large scale of an image that helps the doctors for the right prediction. To bring the improvisation of the existing system, we have set our objectives with an analysis. The efficiency of the natural selection process and the enriching histogram is essential in that respect. To reduce the false-positive rate or output, GA is performed with its accuracy. Conclusions: The objective of this task is to bring improvisation of effectiveness. GA is accomplishing its task with perfection to bring down the invalid-positive rate or outcome. The paper's mergeable portion conflicts with the composition of deep learning and medical image processing, which provides superior accuracy. Proportional types of handling create the reusability without any errors.

Keywords: computer-aided system, detection, image segmentation, morphology

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Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

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Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Ihab Saad Ahmed

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Background For Siewert type I and II gastroesophageal junction tumor (GEJ) laparoscopic proximal gastrectomy can be performed. It is associated with several perioperative benefits compared with open proximal gastrectomy. The use of laparoscopic proximal gastrectomy (LPG) has become an increasingly popular approach for select tumors Methods We describe our technique for LPG, including the preoperative work-up, illustrated images of the main principle steps of the surgery, and our postoperative course. Results Thirteen pts (nine males, four female) with type I, II (GEJ) adenocarcinoma had laparoscopic radical proximal gastrectomy and D2 lymphadenectomy. All of our patient received neoadjuvant chemotherapy, eleven patients had intrathoracic anastomosis through mini thoracotomy (two hand sewn end to end anastomoses and the other 9 patient end to side using circular stapler), two patients with intrathoracic anastomosis had flap and wrap technique, two patients had thoracoscopic esophageal and mediastinal lymph node dissection with cervical anastomosis The mean blood loss 80ml, no cases were converted to open. The mean operative time 250 minute Average LN retrieved 19-25, No sever complication such as leakage, stenosis, pancreatic fistula ,or intra-abdominal abscess were reported. Only One patient presented with empyema 1.5 month after discharge that was managed conservatively. Conclusion For carefully selected patients, LPG in GEJ tumour type I and II is a safe and reasonable alternative for open technique , which is associated with similar oncologic outcomes and low morbidity. It showed less blood loss, respiratory infections, with similar 1- and 3-year survival rates.

Keywords: LPG(laparoscopic proximal gastrectomy, GEJ( gastroesophageal junction tumour), d2 lymphadenectomy, neoadjuvant cth

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Authors: Farideh Namvar, Rosfarizan Mohamed

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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: Gagan Dhawan

Abstract:

Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

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