Search results for: drug discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2461

Search results for: drug discovery

361 Comparison of 18F-FDG and 11C-Methionine PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

Abstract:

Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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360 Simulation of the FDA Centrifugal Blood Pump Using High Performance Computing

Authors: Mehdi Behbahani, Sebastian Rible, Charles Moulinec, Yvan Fournier, Mike Nicolai, Paolo Crosetto

Abstract:

Computational Fluid Dynamics blood-flow simulations are increasingly used to develop and validate blood-contacting medical devices. This study shows that numerical simulations can provide additional and accurate estimates of relevant hemodynamic indicators (e.g., recirculation zones or wall shear stresses), which may be difficult and expensive to obtain from in-vivo or in-vitro experiments. The most recent FDA (Food and Drug Administration) benchmark consisted of a simplified centrifugal blood pump model that contains fluid flow features as they are commonly found in these devices with a clear focus on highly turbulent phenomena. The FDA centrifugal blood pump study is composed of six test cases with different volumetric flow rates ranging from 2.5 to 7.0 liters per minute, pump speeds, and Reynolds numbers ranging from 210,000 to 293,000. Within the frame of this study different turbulence models were tested including RANS models, e.g. k-omega, k-epsilon and a Reynolds Stress Model (RSM) and, LES. The partitioners Hilbert, METIS, ParMETIS and SCOTCH were used to create an unstructured mesh of 76 million elements and compared in their efficiency. Computations were performed on the JUQUEEN BG/Q architecture applying the highly parallel flow solver Code SATURNE and typically using 32768 or more processors in parallel. Visualisations were performed by means of PARAVIEW. Different turbulence models including all six flow situations could be successfully analysed and validated against analytical considerations and from comparison to other data-bases. It showed that an RSM represents an appropriate choice with respect to modeling high-Reynolds number flow cases. Especially, the Rij-SSG (Speziale, Sarkar, Gatzki) variant turned out to be a good approach. Visualisation of complex flow features could be obtained and the flow situation inside the pump could be characterized.

Keywords: blood flow, centrifugal blood pump, high performance computing, scalability, turbulence

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359 In vitro and in vivo Potential Effect of the N-Acylsulfonamide Bis-oxazolidin-2-ones on Toxoplasma gondii

Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

Abstract:

Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

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358 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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357 Effect of Lowering the Proportion of Chlorella vulgaris in Fish Feed on Tilapia's Immune System

Authors: Hamza A. Pantami, Khozizah Shaari, Intan S. Ismail, Chong C. Min

Abstract:

Introduction: Tilapia is the second-highest harvested freshwater fish species in Malaysia, available in almost all fish farms and markets. Unfortunately, tilapia culture in Malaysia is highly affected by Aeromonas hydrophila and Streptococcus agalactiae, which affect the production rate and consequently pose a direct negative economic impact. Reliance on drugs to control or reduce bacterial infections has been led to contamination of water bodies and development of drug resistance, as well as gave rise to toxicity issues in downstream fish products. Resorting to vaccines have helped curb the problem to a certain extent, but a more effective solution is still required. Using microalgae-based feed to enhance the fish immunity against bacterial infection offers a promising alternative. Objectives: This study aims to evaluate the efficacy of Chlorella vulgaris at lower percentage incorporation in feeds for an immune boost of tilapia in a shorter time. Methods: The study was in two phases. The safety concentration studies at 500 mg/kg-1 and the administration of cultured C. vulgaris biomass via incorporation into fish feed for five different groups in three weeks. Group 1 was the control (0% incorporation), whereas group 2, 3, 4 and 5 received 0.625%, 1.25%, 2.5% and 5% incorporation respectively. The parameters evaluated were the blood profile, serum lysozyme activity (SLA), serum bactericidal activity (SBA), phagocytosis activity (PA), respiratory burst activity (RBA), and lymphoproliferation activity (LPA). The data were analyzed via ANOVA using SPSS (version 16). Further testing was done using Tukey’s test. All tests were performed at the 95% confidence interval (p < 0.05). Results: There were no toxic signs in tilapia fish at 500 mg/kg-1. Treated groups showed significantly better immune parameters compared to the control group (p < 0.05). Conclusions: C. vulgaris crude biomass in a fish meal at a lower incorporation level of 5% can increase specific and non-specific immunity in tilapia fish in a shorter time duration.

Keywords: Chlorella vulgaris, hematology profile, immune boost, lymphoproliferation

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356 Effect of Aquatic Seed Extract of (Cichorium intybus L.) and Metformin on Nitric Oxide in Type 2 Diabetic Rats

Authors: Lotfollah Rezagholizadeh

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Background and Aim: Diabetes mellitus is related to high mortality and morbidity caused by the early development of atherosclerosis correlated to diabetic macroangiopathy. The endothelium-derived vasodilator, nitric oxide (NO) has been implicated in the development of vascular complications via the regulation of blood flow, and various antiatherosclerotic actions. Patients with type 2 diabetes (T2D) have a decreased level of endothelial nitric oxide release. In this study we aimed to examine the effect of aquatic seed extract of Cichorium intybus L. (chicory) and metformin (a known prescription drug for diabetes) on NO levels in T2D rats. Methods: Five groups of adult male Wistar rats were used (n=6): Non-diabetic controls without extract treatment (Control), Non-diabetic controls with extract treatment (Chicory-control), T2D rats without extract treatment (NIA/STZ), T2D rats treated with the extract (Chicory-NIA/STZ), and T2D groups that received metformin (100 mg/kg) but no extract (Metformin-NIA/STZ). T2D was induced with intraperitoneal (i.p) injection of niacinamide (NIA, 200 mg/kg), 15 min after an i.p administration of streptozotocin (STZ, 55 mg/kg). Lyophilized chicory extract (125 mg/kg) was dissolved in 0.2 ml normal saline and administered one dose a day. The experiments lasted for 3 weeks after the diabetes induction. NO analysis was performed by assay based on the Griess reaction. Data were reported as the mean ± SD and statistical analysis was performed by ANOVA. Results: Serum nitric oxide levels decreased significantly in NIA/STZ group compared with Control and Chicory-control. Treatment with chicory extract caused a significant increase in serum levels of NO in Chicory-NIA/STZ group compare to NIA/STZ group (p<05). Metformin-NIA/STZ group did not show considerable difference when compared with NIA/STZ, with respect to NO levels. In a group of rats made diabetic by STZ alone (type 1 diabetic rats, T1D), chicory did not have a significant ameliorating effect. Conclusion: In this study, we clearly showed a relationship between low serum nitric oxide levels and diabetes mellitus in rats. The increase in serum nitric oxide by chicory extract is an indication of antiatherogenic effect of this plant. Chicory seed extract was more efficient than metformin in improving the NO levels in NO-deficient T2D diabetic rats.

Keywords: type 2 diabetes mellitus, nitric oxide, chicory, metformin

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355 Development of PVA/polypyrrole Scaffolds by Supercritical CO₂ for Its Application in Biomedicine

Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

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354 Impact of 99mTc-MDP Bone SPECT/CT Imaging in Failed Back Surgery Syndrome

Authors: Ching-Yuan Chen, Lung-Kwang Pan

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Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

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353 Hybrid Nanostructures of Acrylonitrile Copolymers

Authors: A. Sezai Sarac

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Acrylonitrile (AN) copolymers with typical comonomers of vinyl acetate (VAc) or methyl acrylate (MA) exhibit better mechanical behaviors than its homopolymer. To increase processability of conjugated polymer, and to obtain a hybrid nano-structure multi-stepped emulsion polymerization was applied. Such products could be used in, i.e., drug-delivery systems, biosensors, gas-sensors, electronic compounds, etc. Incorporation of a number of flexible comonomers weakens the dipolar interactions among CN and thereby decreases melting point or increases decomposition temperatures of the PAN based copolymers. Hence, it is important to consider the effect of comonomer on the properties of PAN-based copolymers. Acrylonitrile vinylacetate (AN–VAc ) copolymers have the significant effect to their thermal behavior and are also of interest as precursors in the production of high strength carbon fibers. AN is copolymerized with one or two comonomers, particularly with vinyl acetate The copolymer of AN and VAc can be used either as a plastic (VAc > 15 wt %) or as microfibers (VAc < 15 wt %). AN provides the copolymer with good processability, electrochemical and thermal stability; VAc provides the mechanical stability. The free radical copolymerization of AN and VAc copolymer and core Shell structure of polyprrole composites,and nanofibers of poly(m-anthranilic acid)/polyacrylonitrile blends were recently studied. Free radical copolymerization of acrylonitrile (AN) – with different comonomers, i.e. acrylates, and styrene was realized using ammonium persulfate (APS) in the presence of a surfactant and in-situ polymerization of conjugated polymers was performed in this reaction medium to obtain core-shell nano particles. Nanofibers of such nanoparticles were obtained by electrospinning. Morphological properties of nanofibers are investigated by scanning electron microscopy (SEM) and atomic force spectroscopy (AFM). Nanofibers are characterized using Fourier Transform Infrared - Attenuated Total Reflectance spectrometer (FTIR-ATR), Nuclear Magnetic Resonance Spectroscopy (1H-NMR), differential scanning calorimeter (DSC), thermal gravimetric analysis (TGA), and Electrochemical Impedance Spectroscopy. The electrochemical Impedance results of the nanofibers were fitted to an equivalent curcuit by modelling (ECM).

Keywords: core shell nanoparticles, nanofibers, ascrylonitile copolymers, hybrid nanostructures

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352 A Study on Awareness and Attitude of First-Year Medical Students on Epilepsy in University of Khartoum 2020-2021

Authors: Mohammed E. Ibrahim, Baraa A. Taha, Kamil M. A. Shabban

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Background: Epilepsy is a common but widely misunderstood illness. Consequently, patients with epilepsy suffer from considerable stigmatization in society. This social stigma and discrimination often cause more suffering for the patients than the disease itself. Since very few studies have explored the misperceptions about epilepsy among university students in Sudan, it is not possible to provide focused intervention aimed at eliminating this discrimination. Methods: A cross-sectional study was applied among the first-year medical students at the University of Khartoum between December (2020) and February (2021). A 29-item standardized questionnaire was self-administered by 198 students (out of 320) who agreed to participate in this study. Google form was the tool used to collect the data. The data were analyzed using the Statistical Package for Social Science software version 26. Result: Overall, the results indicate a negative trend in knowledge and attitude toward epilepsy. The vast majority of the respondents (84.8%) have read or heard about epilepsy, while 43.9% had seen someone with epilepsy. Only 7.5% of the participants reported that epilepsy is contagious, whereas 43.4% of them think that epilepsy is a psychological disorder. About 62.2% of students think head/birth trauma is a cause of epilepsy. On the other side, about 15.7% and 5.1% believed that evil spirits and punishment from god can also be a possible cause of epilepsy; we found these false beliefs are more common in participants from rural areas (p-value < 0.05). In regard to attitude, 19.7% of students thought that it is inappropriate for a patient with epilepsy to have a child. This attitude correlates with the mother’s education as the percentage is higher for those who have lower mother’s education (through secondary school education and below) (p < 0.05). The majority of Our participant knew that some people with epilepsy need life-long drug treatment; this belief was found to be more common in females than their counterparts(p < 0.05). . Finally, most of the respondents (93.9%) thought that a child with epilepsy Can be successful in a normal class. This belief is four-time as common in participants whose mothers have higher education (through university education and above) compared with corresponding respondents (p < 0.05). Conclusion: This study concludes that students' knowledge about epilepsy is limited and requires immediate intervention through educational campaigns to develop a well-informed and tolerant community.

Keywords: epilepsy, awareness, attitude, university students, Sudan

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351 Design and Development of Bioactive a-Hydroxy Carboxylate Group Modified MnFe₂O₄ Nanoparticle: Comparative Fluorescence Study, Magnetism and DNA Nuclease Activity

Authors: Indranil Chakraborty, Kalyan Mandal

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Three new α-hydroxy carboxylate group functionalized MnFe₂O₄ nanoparticles (NPs) have been developed to explore the microscopic origin of ligand modified fluorescence and magnetic properties of nearly monodispersed MnFe₂O₄ NPs. The surface functionalization has been carried out with three small organic ligands (tartrate, malate, and citrate) having different number of α-hydroxy carboxylate functional group along with steric effect. Detailed study unveils that α-hydroxy carboxylate moiety of the ligands plays key role to generate intrinsic fluorescence in functionalized MnFe₂O₄ NPs through the activation of ligand to metal charge transfer transitions, associated with ligand-Mn²⁺/Fe³⁺ interactions along with d-d transition corresponding to d-orbital energy level splitting of Fe³⁺ ions on NP surface. Further, MnFe₂O₄ NPs show a maximum 140.88% increase in coercivity and 97.95% decrease in magnetization compared to its bare one upon functionalization. The ligands that induce smallest crystal field splitting of d-orbital energy level of transition metal ions are found to result in strongest ferromagnetic activation of the NPs. Finally, our developed tartrate functionalized MnFe₂O₄ (T-MnFe₂O₄) NPs have been utilized for studying DNA binding interaction and nuclease activity for stimulating their beneficial activities toward diverse biomedical applications. The spectroscopic measurements indicate that T-MnFe₂O₄ NPs bind calf thymus DNA by intercalative mode. The ability of T-MnFe₂O₄ NPs to induce DNA cleavage was studied by gel electrophoresis technique where the complex is found to promote the cleavage of pBR322 plasmid DNA from the super coiled form I to linear coiled form II and nicked coiled form III with good efficiency. This may be taken into account for designing new biomolecular detection agents and anti-cancer drug which can open up a new door toward diverse non-invasive biomedical applications.

Keywords: MnFe₂O₄ nanoparticle, α-hydroxy carboxylic acid, comparative fluorescence, magnetism study, DNA interaction, nuclease activity

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350 3D Interpenetrated Network Based on 1,3-Benzenedicarboxylate and 1,2-Bis(4-Pyridyl) Ethane

Authors: Laura Bravo-García, Gotzone Barandika, Begoña Bazán, M. Karmele Urtiaga, Luis M. Lezama, María I. Arriortua

Abstract:

Solid coordination networks (SCNs) are materials consisting of metal ions or clusters that are linked by polyfunctional organic ligands and can be designed to form tridimensional frameworks. Their structural features, as for example high surface areas, thermal stability, and in other cases large cavities, have opened a wide range of applications in fields like drug delivery, host-guest chemistry, biomedical imaging, chemical sensing, heterogeneous catalysis and others referred to greenhouse gases storage or even separation. In this sense, the use of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce extended structures with the needed characteristics for these applications. In this context, a novel compound, [Cu4(m-BDC)4(bpa)2DMF]•DMF has been obtained by microwave synthesis, where m-BDC is 1,3-benzenedicarboxylate and bpa 1,2-bis(4-pyridyl)ethane. The crystal structure can be described as a three dimensional framework formed by two equal, interpenetrated networks. Each network consists of two different CuII dimers. Dimer 1 have two coppers with a square pyramidal coordination, and dimer 2 have one with a square pyramidal coordination and other with octahedral one, the last dimer is unique in literature. Therefore, the combination of both type of dimers is unprecedented. Thus, benzenedicarboxylate ligands form sinusoidal chains between the same type of dimers, and also connect both chains forming these layers in the (100) plane. These layers are connected along the [100] direction through the bpa ligand, giving rise to a 3D network with 10 Å2 voids in average. However, the fact that there are two interpenetrated networks results in a significant reduction of the available volume. Structural analysis was carried out by means of single crystal X-ray diffraction and IR spectroscopy. Thermal and magnetic properties have been measured by means of thermogravimetry (TG), X-ray thermodiffractometry (TDX), and electron paramagnetic resonance (EPR). Additionally, CO2 and CH4 high pressure adsorption measurements have been carried out for this compound.

Keywords: gas adsorption, interpenetrated networks, magnetic measurements, solid coordination network (SCN), thermal stability

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349 Integrative Omics-Portrayal Disentangles Molecular Heterogeneity and Progression Mechanisms of Cancer

Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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348 Isolation and Characterization of a Narrow-Host Range Aeromonas hydrophila Lytic Bacteriophage

Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

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347 Enhancement in Antimicrobial and Antioxidant Activity of Cuminum cyminum L. through Niosome Nanocarries

Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

Abstract:

Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

Procedia PDF Downloads 494
346 Dipeptide Functionalized Nanoporous Anodic Aluminium Oxide Membrane for Capturing Small Molecules

Authors: Abdul Mutalib Md Jani, Abdul Hadi Mahmud, Mohd Tajuddin Mohd Ali

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The rapid growth of interest in surface modification of nanostructures materials that exhibit improved structural and functional properties is attracting more researchers. The unique properties of highly ordered nanoporous anodic aluminium oxide (NAAO) membrane have been proposed as a platform for biosensing applications. They exhibit excellent physical and chemical properties with high porosity, high surface area, tunable pore sizes and excellent chemical resistance. In this study, NAAO was functionalized with 3-aminopropyltriethoxysilane (APTES) to prepared silane-modified NAAO. Amine functional groups are formed on the surface of NAAO during silanization and were characterized using Fourier Transform Infrared spectroscopy (FTIR). The synthesis of multi segment of peptide on NAAO surfaces can be realized by changing the surface chemistry of the NAAO membrane via click chemistry. By click reactions, utilizing alkyne terminated with amino group, various peptides tagged on NAAO can be envisioned from chiral natural or unnatural amino acids using standard coupling methods (HOBt, EDCI and HBTU). This strategy seemly versatile since coupling strategy of dipeptide with another amino acids, leading to tripeptide, tetrapeptide or pentapeptide, can be synthesized without purification. When an appropriate terminus is selected, multiple segments of amino acids can be successfully synthesized on the surfaces. The immobilized NAAO should be easily separated from the reaction medium by conventional filtration, thus avoiding complicated purification methods. Herein, we proposed to synthesize multi fragment peptide as a model for capturing and attaching various small biomolecules on NAAO surfaces and can be also applied as biosensing device, drug delivery systems and biocatalyst.

Keywords: nanoporous anodic aluminium oxide, silanization, peptide synthesise, click chemistry

Procedia PDF Downloads 257
345 In-silico DFT Study, Molecular Docking, ADMET Predictions, and DMS of Isoxazolidine and Isoxazoline Analogs with Anticancer Properties

Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

Abstract:

This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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344 In vitro Modeling of Aniridia-Related Keratopathy by the Use of Crispr/Cas9 on Limbal Epithelial Cells and Rescue

Authors: Daniel Aberdam

Abstract:

Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

Procedia PDF Downloads 183
343 Hexahydropyrimidine-2,4-Diones: Synthesis and Cytotoxic Activity

Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

Abstract:

The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

Procedia PDF Downloads 131
342 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

Procedia PDF Downloads 184
341 D-Epi App: Mobile Application to Control Sodium Valproat Administration in Children with Idiopatic Epilepsy in Indonesia

Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

Procedia PDF Downloads 256
340 Impedimetric Phage-Based Sensor for the Rapid Detection of Staphylococcus aureus from Nasal Swab

Authors: Z. Yousefniayejahr, S. Bolognini, A. Bonini, C. Campobasso, N. Poma, F. Vivaldi, M. Di Luca, A. Tavanti, F. Di Francesco

Abstract:

Pathogenic bacteria represent a threat to healthcare systems and the food industry because their rapid detection remains challenging. Electrochemical biosensors are gaining prominence as a novel technology for the detection of pathogens due to intrinsic features such as low cost, rapid response time, and portability, which make them a valuable alternative to traditional methodologies. These sensors use biorecognition elements that are crucial for the identification of specific bacteria. In this context, bacteriophages are promising tools for their inherent high selectivity towards bacterial hosts, which is of fundamental importance when detecting bacterial pathogens in complex biological samples. In this study, we present the development of a low-cost and portable sensor based on the Zeno phage for the rapid detection of Staphylococcus aureus. Screen-printed gold electrodes functionalized with the Zeno phage were used, and electrochemical impedance spectroscopy was applied to evaluate the change of the charge transfer resistance (Rct) as a result of the interaction with S. aureus MRSA ATCC 43300. The phage-based biosensor showed a linear range from 101 to 104 CFU/mL with a 20-minute response time and a limit of detection (LOD) of 1.2 CFU/mL under physiological conditions. The biosensor’s ability to recognize various strains of staphylococci was also successfully demonstrated in the presence of clinical isolates collected from different geographic areas. Assays using S. epidermidis were also carried out to verify the species-specificity of the phage sensor. We only observed a remarkable change of the Rct in the presence of the target S. aureus bacteria, while no substantial binding to S. epidermidis occurred. This confirmed that the Zeno phage sensor only targets S. aureus species within the genus Staphylococcus. In addition, the biosensor's specificity with respect to other bacterial species, including gram-positive bacteria like Enterococcus faecium and the gram-negative bacterium Pseudomonas aeruginosa, was evaluated, and a non-significant impedimetric signal was observed. Notably, the biosensor successfully identified S. aureus bacterial cells in a complex matrix such as a nasal swab, opening the possibility of its use in a real-case scenario. We diluted different concentrations of S. aureus from 108 to 100 CFU/mL with a ratio of 1:10 in the nasal swap matrices collected from healthy donors. Three different sensors were applied to measure various concentrations of bacteria. Our sensor indicated high selectivity to detect S. aureus in biological matrices compared to time-consuming traditional methods, such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and radioimmunoassay (RIA), etc. With the aim to study the possibility to use this biosensor to address the challenge associated to pathogen detection, ongoing research is focused on the assessment of the biosensor’s analytical performances in different biological samples and the discovery of new phage bioreceptors.

Keywords: electrochemical impedance spectroscopy, bacteriophage, biosensor, Staphylococcus aureus

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339 Sacidava and Its Role of Military Outpost in the Moesian Sector of the Danube Limes: Animal Food Resources and Landscape Reconstruction

Authors: Margareta Simina Stanc, Aurel Mototolea, Tiberiu Potarniche

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Sacidava archeological site is located in Dobrudja region, Romania, on a hill on the right bank of the Danube - the Musait point, located at about 5 km north-east from Dunareni village. The place-name documents the fact that, prior to the Roman conquest, in the area, there was a Getic settlement. The location of the Sacidava was made possible by corroborating the data provided by the ancient sources with the epigraphic documents (the milial pillar during the time of Emperor Decius). The tegular findings attest that an infantry unit, cohors I Cilicum milliaria equitata, as well as detachments from Legio V Macedonica and Legio XI Claudia, were confined to Sacidava. During the period of the Dominion, the garrison of the fortification is the host of a cavalry unit: cuneus equitum scutariorum. In the immediate vicinity to the Roman fortress, to the east, were identified two other fortifications: a Getic settlement (4th-1st century B.C.) and an Early Medieval settlement (9th-10th century A.C.). The archaeological material recovered during the research is represented by ceramic forms such as amphoras, jugs, pots, cups, plates, to which are added oil lamps, some of them typologically new at the time of discovery. Local ceramic shapes were also founded, worked by hand or by wheel, considered un-Romanized or in the course of Romanization. During the time of the Principality, Sacidava it represented an important military outpost serving mainly the city of Tropaeum Traiani, controlling also the supply and transport on the Danube limes in the Moesic sector. This role will determine the development of the fortress and the appearance of extramuros civil structures, thus becoming an important landmark during the 5th-6th centuries A.C., becoming a representation of power of the Roman empire in an area of continuous conflict. During recent archaeological researches, faunal remains were recovered, and their analysis allowed to estimate the animal resources and subsistence practices (animal husbandry, hunting, fishing) in the settlement. The methodology was specific to archaeozoology, mainly consisting of anatomical, taxonomical, and taphonomical identifications, recording, and quantification of the data. The remains of domestic mammals have the highest proportion indicating the importance of animal husbandry; the predominant species are Bos taurus, Ovis aries/Capra hircus, and Sus domesticus. Fishing and hunting were of secondary importance in the subsistence economy of the community. Wild boar and the red deer were the most frequently hunted species. Just a few fish bones were recovered. Thus, the ancient city of Sacidava is proving to be an important element of cultural heritage of the south-eastern part of Romania, for whose conservation and enhancement efforts must be made, especially by landscape reconstruction.

Keywords: archaeozoology, landscape reconstruction, limes, military outpost

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338 Microbial Load, Prevalence and Antibiotic Resistance of Microflora Isolated from the Ghanaian Paper Currency Note: A Potential Health Threat

Authors: Simon Nyarko

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This study examined the microbial flora contamination of the Ghanaian paper currency notes and antibiotic resistance in Ejura Municipal, Ashanti Region, Ghana. This is a descriptive cross-sectional study designed to assess the profile of microflora contamination of the Ghanaian paper currency notes and antibiotic-resistant in the Ejura Municipality. The research was conducted in Ejura, a town in the Ejura Sekyeredumase Municipal of the Ashanti region of Ghana. 70 paper currency notes which were freshly collected from the bank, consisting of 15 pieces of GH ¢1, GH ¢2, and GH ¢5, 10 pieces of GH ¢10 and GH ¢20, and 5 pieces of GH ¢50, were randomly sampled from people by exchanging their money in usage with those freshly secured from the bank. The surfaces of each GH¢ note were gently swabbed and sent to the lab immediately in sterile Zip Bags and sealed, and tenfold serial dilution was inoculated on plate count agar (PCA), MacConkey agar (MCA), mannitol salt agar (MSA), and deoxycholate citrate agar (DCA). For bacterial identification, the study used appropriate laboratory and biochemical tests. The data was analyzed using SPSS-IBM version 20.0. It was found that 95.2 % of the 70 GH¢ notes tested positive for one or more bacterial isolates. On each GH¢ note, mean counts on PCA ranged from 3.0 cfu/ml ×105 to 4.8 cfu/ml ×105. Of 124 bacteria isolated. 36 (29.03 %), 32 (25.81%), 16 (12.90 %), 20 (16.13%), 13 (10.48 %), and 7 (5.66 %) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively. Bacterial isolates were Escherichia coli (25.81%), Staphylococcus aureus (18.55%), coagulase-negative Staphylococcus (15.32%), Klebsiella species (12.10%), Salmonella species (9.68%), Shigella species (8.06%), Pseudomonas aeruginosa (7.26%), and Proteus species (3.23%). Meat shops, commercial drivers, canteens, grocery stores, and vegetable shops contributed 25.81 %, 20.16 %, 19.35 %, 17.74 %, and 16.94 % of GH¢ notes, respectively. There was 100% resistance of the isolates to Erythromycin (ERY), and Cotrimoxazole (COT). Amikacin (AMK) was the most effective among the antibiotics as 75% of the isolates were susceptible to it. This study has demonstrated that the Ghanaian paper currency notes are heavily contaminated with potentially pathogenic bacteria that are highly resistant to the most widely used antibiotics and are a threat to public health.

Keywords: microflora, antibiotic resistance, staphylococcus aureus, culture media, multi-drug resistance

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337 Comparative Functional Analysis of Two Major Sterol-Biosynthesis Regulating Transcription Factors, Hob1 and Sre1, in Pathogenic Cryptococcus Species Complex

Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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336 Fungal Profile and Antifungal Susceptibility Patterns among Symptomatic Pediatrics Patients Attending Aboozar Children’s Hospital, Ahvaz, Iran

Authors: Nasrin Amirrajab, Yasaman Razavi Ghahfarokhi, Zahra Tootak, Maryam Hadian, Fatemeh Abooali Shamshiri

Abstract:

Urinary tract infections (UTIs) have been reported in children with nephrotic syndrome. However, the only causes for the infection reported to date are bacteria, but not many prior reported occurrences of fungi or yeast as causative organisms. Hence, the present study aimed to describe the epidemiology of urinary tract fungal infections in a tertiary care pediatric. A single-center cross-sectional study was conducted at the nephrology ward of Aboozar Pediatric Hospital between March 21, 2021, and April 28, 2022. Urine was collected aseptically from children, inoculated onto culture media, and incubated at 37 °C for 18–48 hours. Yeast was identified following standard procedures. Antifungal susceptibility testing was determined by the disk diffusion method according to the CLSI guideline. Descriptive statistics and logistical regressions were used to estimate the crude ratio with a 95% confidence interval. P-value < 0.05 was considered significant. Among 68 individuals referred to the mycology lab, the result of direct examination and culture of all patients approved for C.albicans. Of these, 38 individuals (55.8%) were male, and 30 (44.2%) were female. The patients' age ranges were between one month and an 18-year-old. In the study of infection intensity, the patients were classified into three levels such as few (73.5%), moderate (20.6%), and many (5.9%). In the present study, all the patients were sensitive to Posaconazole. Also, the eagle effect was found in Amphotericin B, Voriconazole, and Fluconazole with frequencies of 91.7%, 91.7%, and 83%, respectively. In addition, just 8.3% of isolates were resistant to Itraconazole. It has not shown resistance in other mentioned medicine. The patients showed an intermediate response to Itraconazole (91.7%), Fluconazole (17%), Voriconazole (8.3%), and Amphotericin B (8.3%). There is a high prevalence of yeast infections in children with suspected UTIs. Also, boys are more likely to get yeast infections, and the severity of the infection is higher than girls. The present study demonstrated the importance of diagnosing and selecting the appropriate drug for urinary tract fungal infections in hospitalized children.

Keywords: urinary tract infections, children, fungal infections, yeast, antifungal susceptibility

Procedia PDF Downloads 68
335 Autophagy Defects That Modify Human Immune Cell Metabolism and Promote Aging-Associated Inflammation

Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

Abstract:

Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

Procedia PDF Downloads 131
334 Fort Conger: A Virtual Museum and Virtual Interactive World for Exploring Science in the 19th Century

Authors: Richard Levy, Peter Dawson

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Ft. Conger, located in the Canadian Arctic was one of the most remote 19th-century scientific stations. Established in 1881 on Ellesmere Island, a wood framed structure established a permanent base from which to conduct scientific research. Under the charge of Lt. Greely, Ft. Conger was one of 14 expeditions conducted during the First International Polar Year (FIPY). Our research project “From Science to Survival: Using Virtual Exhibits to Communicate the Significance of Polar Heritage Sites in the Canadian Arctic” focused on the creation of a virtual museum website dedicated to one of the most important polar heritage site in the Canadian Arctic. This website was developed under a grant from Virtual Museum of Canada and enables visitors to explore the fort’s site from 1875 to the present, http://fortconger.org. Heritage sites are often viewed as static places. A goal of this project was to present the change that occurred over time as each new group of explorers adapted the site to their needs. The site was first visited by British explorer George Nares in 1875 – 76. Only later did the United States government select this site for the Lady Franklin Bay Expedition (1881-84) with research to be conducted under the FIPY (1882 – 83). Still later Robert Peary and Matthew Henson attempted to reach the North Pole from Ft. Conger in 1899, 1905 and 1908. A central focus of this research is on the virtual reconstruction of the Ft. Conger. In the summer of 2010, a Zoller+Fröhlich Imager 5006i and Minolta Vivid 910 laser scanner were used to scan terrain and artifacts. Once the scanning was completed, the point clouds were registered and edited to form the basis of a virtual reconstruction. A goal of this project has been to allow visitors to step back in time and explore the interior of these buildings with all of its artifacts. Links to text, historic documents, animations, panorama images, computer games and virtual labs provide explanations of how science was conducted during the 19th century. A major feature of this virtual world is the timeline. Visitors to the website can begin to explore the site when George Nares, in his ship the HMS Discovery, appeared in the harbor in 1875. With the emergence of Lt Greely’s expedition in 1881, we can track the progress made in establishing a scientific outpost. Still later in 1901, with Peary’s presence, the site is transformed again, with the huts having been built from materials salvaged from Greely’s main building. Still later in 2010, we can visit the site during its present state of deterioration and learn about the laser scanning technology which was used to document the site. The Science and Survival at Fort Conger project represents one of the first attempts to use virtual worlds to communicate the historical and scientific significance of polar heritage sites where opportunities for first-hand visitor experiences are not possible because of remote location.

Keywords: 3D imaging, multimedia, virtual reality, arctic

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333 One Species into Five: Nucleo-Mito Barcoding Reveals Cryptic Species in 'Frankliniella Schultzei Complex': Vector for Tospoviruses

Authors: Vikas Kumar, Kailash Chandra, Kaomud Tyagi

Abstract:

The insect order Thysanoptera includes small insects commonly called thrips. As insect vectors, only thrips are capable of Tospoviruses transmission (genus Tospovirus, family Bunyaviridae) affecting various crops. Currently, fifteen species of subfamily Thripinae (Thripidae) have been reported as vectors for tospoviruses. Frankliniella schultzei, which is reported as act as a vector for at least five tospovirses, have been suspected to be a species complex with more than one species. It is one of the historical unresolved issues where, two species namely, F. schultzei Trybom and F. sulphurea Schmutz were erected from South Africa and Srilanaka respectively. These two species were considered to be valid until 1968 when sulphurea was treated as colour morph (pale form) and synonymised under schultzei (dark form) However, these two have been considered as valid species by some of the thrips workers. Parallel studies have indicated that brown form of schultzei is a vector for tospoviruses while yellow form is a non-vector. However, recent studies have shown that yellow populations have also been documented as vectors. In view of all these facts, it is highly important to have a clear understanding whether these colour forms represent true species or merely different populations with different vector carrying capacities and whether there is some hidden diversity in 'Frankliniella schultzei species complex'. In this study, we aim to study the 'Frankliniella schultzei species complex' with molecular spectacles with DNA data from India and Australia and Africa. A total of fifty-five specimens was collected from diverse locations in India and Australia. We generated molecular data using partial fragments of mitochondrial cytochrome c oxidase I gene (mtCOI) and 28S rRNA gene. For COI dataset, there were seventy-four sequences, out of which data on fifty-five was generated in the current study and others were retrieved from NCBI. All the four different tree construction methods: neighbor-joining, maximum parsimony, maximum likelihood and Bayesian analysis, yielded the same tree topology and produced five cryptic species with high genetic divergence. For, rDNA, there were forty-five sequences, out of which data on thirty-nine was generated in the current study and others were retrieved from NCBI. The four tree building methods yielded four cryptic species with high bootstrap support value/posterior probability. Here we could not retrieve one cryptic species from South Africa as we could not generate data on rDNA from South Africa and sequence for rDNA from African region were not available in the database. The results of multiple species delimitation methods (barcode index numbers, automatic barcode gap discovery, general mixed Yule-coalescent, and Poisson-tree-processes) also supported the phylogenetic data and produced 5 and 4 Molecular Operational Taxonomic Units (MOTUs) for mtCOI and 28S dataset respectively. These results of our study indicate the likelihood that F. sulphurea may be a valid species, however, more morphological and molecular data is required on specimens from type localities of these two species and comparison with type specimens.

Keywords: DNA barcoding, species complex, thrips, species delimitation

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332 Excavation of Phylogenetically Diverse Bioactive Actinobacteria from Unexplored Regions of Sundarbans Mangrove Ecosystem for Mining of Economically Important Antimicrobial Compounds

Authors: Sohan Sengupta, Arnab Pramanik, Abhrajyoti Ghosh, Maitree Bhattacharyya

Abstract:

Newly emerged phyto-pathogens and multi drug resistance have been threating the world for last few decades. Actinomycetes, the most endowed group of microorganisms isolated from unexplored regions of the world may be the ultimate solution to these problems. Thus the aim of this study was to isolate several bioactive actinomycetes strains capable of producing antimicrobial secondary metabolite from Sundarbans, the only mangrove tiger land of the world. Fifty four actinomycetes were isolated and analyzed for antimicrobial activity against fifteen test organisms including three phytopathogens. Nine morphologically distinct and biologically active isolates were subjected to polyphasic identification study. 16s rDNA sequencing indicated eight isolates to reveal maximum similarity to the genus streptomyces, whereas one isolate presented only 93.57% similarity with Streptomyces albogriseolus NRRL B-1305T. Seventy-one carbon sources and twenty-three chemical sources utilization assay revealed their metabolic relatedness. Among these nine isolates three specific strains were found to have notably higher degree of antimicrobial potential effective in a broader range including phyto-pathogenic fungus. PCR base whole genome screen for PKS and NRPS genes, confirmed the occurrence of bio-synthetic gene cluster in some of the isolates for novel antibiotic production. Finally the strain SMS_SU21, which showed antimicrobial activity with MIC value of 0.05 mg ml-1and antioxidant activity with IC50 value of 0.242±0.33 mg ml-1 was detected to be the most potential one. True prospective of this strain was evaluated utilizing GC-MS and the bioactive compound responsible for antimicrobial activity was purified and characterized. Rare bioactive actinomycetes were isolated from unexplored heritage site. Diversity of the biosynthetic gene cluster for antimicrobial compound production has also been evaluated. Antimicrobial compound SU21-C has been identified and purified which is active against a broad range of pathogens.

Keywords: actinomycetes, sundarbans, antimicrobial, pks nrps, phyto-pathogens, GC-MS

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