Search results for: Sertoli cell only syndrome (SCOS)

Authors: Sung-Hee Hwang, Michael Lee

Abstract:

Upregulated Src activity has been implicated in a variety of cancers. Thus, Src family tyrosine kinase (SFK) inhibitors are often effective cancer treatments. Here, we investigate the role of autophagy in ATG5 knockout cell lines generated by the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas mediated genome editing. The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA–DNA complementarity to identify target sites for sequence specific double-stranded DNA (dsDNA) cleavage. Interestingly, ATG5 KO cells clearly showed a greater proliferation rate than WT NIH 3T3 cells, implying that autophagy induction is cytotoxic. Also, the clonogenic survival of ATG5 KO cells was greater than WT cells. The MTT assay revealed that the cytotoxic effect of PP2 was weaker on ATG5 knockout cells than that WT cells. The conversion of non-autophagic LC3-I to autophagic LC3-II and RT-PCR confirmed the functional gene knockout. Furthermore, Cyto-ID autophagy assay also revealed that PP2 failed to induce autophagy in ATG5 knockout cells. Together, our findings suggest that the resistance to PP2 in ATG5 knockout cells is associated with defective autophagy.

Keywords: ATG5 knockout, Autophagy, CRISPR/Cas9, PP2

Procedia PDF Downloads 347

Authors: T. Büyüksırıt, H. Kuleaşan

Abstract:

Natural antimicrobials are used to preserve foods that can be found in plants, animals, and microorganisms. Antimicrobial substances are natural or artificial agents that produced by microorganisms or obtained semi/total chemical synthesis are used at low concentrations to inhibit the growth of other microorganisms. Food borne pathogens and spoilage microorganisms are inactivated by the use of antagonistic microorganisms and their metabolites. Yeasts can produce toxic proteins or glycoproteins (toxins) that cause inhibition of sensitive bacteria and yeast species. Antimicrobial substance producing phenotypes belonging different yeast genus were isolated from different sources. Toxins secreted by many yeast strains inhibiting the growth of other yeast strains. These strains show antimicrobial activity, inhibiting the growth of mold and bacteria. The effect of antimicrobial agents produced by yeasts can be extremely fast, and therefore may be used in various treatment procedures. Rapid inhibition of microorganisms is possibly caused by microbial cell membrane lipopolysaccharide binding and in activation (neutralization) effect. Antimicrobial agents inhibit the target cells via different mechanisms of action.

Keywords: antimicrobial agents, yeast, toxic protein, glycoprotein

Procedia PDF Downloads 363

Authors: Muhammad Arifur Rahman, Talukdar M. Waliullah, Takashi Ushimaru

Abstract:

Nucleophagy selectively degrades nuclear materials, especially nucleolus after nutrient starvation or inactivation of TORC1 kinase in budding yeast. Budding yeast phosphatidate (PA) phosphatase Pah1 that converts PA to diacylglycerol is essential for partitioning of lipid precursors between membrane and storage that is crucial for many aspects of cell growth and development. Pah1 is required for nuclear/ER membrane biogenesis and vacuole function, but whether Pah1 and its activator Nem1/Spo7 protein phosphatase complex are involved in autophagy is largely unknown. Loss of Pah1 causes expansion of the nucleus and fragmentation of the vacuole. Here we show that Pah1 is required for bulk autophagy and nucleophagy after TORC1 inactivation. Loss of Pah1 impaired nucleophagy severely and bulk autophagy to a lesser extent. Loss of the Pah1 activator Nem1-Spo7 protein phosphatase exhibited similar features.

Keywords: autophagy, Nem1/Spo7 phosphatase, Pah1, nucleophagy, TORC1

Procedia PDF Downloads 229

Authors: E. Marei, A. Hammad, S. Ismail, A. El-Gindy

Abstract:

This study aims to investigate the ability of different formula of mixed bacteria as a biological treatments of wastewater after primary treatment as a bio-treatment and bio-removal and bio-adsorbent of different heavy metals in natural circumstances. The wastewater was collected from Sarpium forest site-Ismailia Governorate, Egypt. These treatments were mixture of free cells and mixture of immobilized cells of different bacteria. These different formulas of mixed bacteria were prepared under Lab. condition. The obtained data indicated that, as a result of wastewater bio-treatment, the removal rate was found to be 76.92 and 76.70% for biological oxygen demand, 79.78 and 71.07% for chemical oxygen demand, 32.45 and 36.84 % for ammonia nitrogen as well as 91.67 and 50.0% for phosphate after 24 and 28 hrs with mixed free cells and mixed immobilized cells, respectively. Moreover, the bio-removals of different heavy metals were found to reach 90.0 and 50. 0% for Cu ion, 98.0 and 98.5% for Fe ion, 97.0 and 99.3% for Mn ion, 90.0 and 90.0% Pb, 80.0% and 75.0% for Zn ion after 24 and 28 hrs with mixed free cells and mixed immobilized cells, respectively. The results indicated that 13.86 and 17.43% of removal efficiency and reduction of total dissolved solids were achieved after 24 and 28 hrs with mixed free cells and mixed immobilized cells, respectively.

Keywords: wastewater bio-treatment , bio-sorption heavy metals, biological desalination, immobilized bacteria, free cell bacteria

Procedia PDF Downloads 202

Authors: Prabhu Thangaraju, Manoj Deepak, A. Sivakumar

Abstract:

Removal of inter vertebral disc along with spinal fusion has many disadvantages such as causing stress fractures. If it is possible regenerate the spine it would be possible avoid the complications of the surgery and achieve better results. Our study involves the use of mesenchymal stem cells in regenerating the discs. Our study involved 10 patients who presented with degenerative disc disease between 2008-2011 in our hospital. After adequate pre-operative check prepared mesenchymal stem cells were injected into the disc spaces. These patients were subjected to conservative therapy for a minimum of six weeks before they were accepted into the study. They were followed up regularly for a minimum of 2years with serial radiographs and MRI. 8 out of the 10 patients had completed reduction in the pain. The T2 weighted MRI images in 9 out of the 10 patients showed a bright signal compared the previous Images which indicated that there was improvement in the hydration levels. From the case study of 10 patients who were subjected to mesenchymal cell therapy in our hospital, we can conclude that the use of mesenchymal cells in treatment of intervertebral disc degeneration in a safe and effective option.

Keywords: mesenchymal stem cells, intervertebral disc, the spine, disc degeneration

Procedia PDF Downloads 372

Authors: Ashish Mahalle, Kishore Borakhade

Abstract:

High porosity metal foams are excellent for heat dissipation. There use has been widened to include heat removal from high density microelectronics circuits. Other important applications have been found in compact heat exchangers for airborne equipment, regenerative and dissipative air cooled condenser towers, and compact heat sinks for power electronic. The low relative density, open porosity and high thermal conductivity of the cell edges, large accessible surface area per unit volume, and the ability to mix the cooling fluid make metal foam heat exchangers efficient, compact and light weight. This paper reports the thermal performance of metal foam for high heat dissipation. In experimentation metal foam samples of different pore diameters i.e. 35 µ, 20 µ, 12 µ, are analyzed for varying velocities and heat inputs. The study investigate the effect of various dimensionless no. like Re,Nu, Pr and heat transfer characteristics of basic flow configuration.

Keywords: pores, foam, effective thermal conductivity, permeability

Procedia PDF Downloads 311

Authors: S. Alotaibi, S. Omer, Y. Su

Abstract:

The conventional Internal Combustion Engine (ICE) based vehicles are a threat to the environment as they account for a large proportion of the overall greenhouse gas (GHG) emissions in the world. Hence, it is required to replace these vehicles with more environment-friendly vehicles. Electric Vehicles (EVs) are promising technologies which offer both human comfort “noise, pollution” as well as reduced (or no) emissions of GHGs. In this paper, different types of EVs are reviewed and their advantages and disadvantages are identified. It is found that in terms of fuel economy, Plug-in Hybrid EVs (PHEVs) have the best fuel economy, followed by Hybrid EVs (HEVs) and ICE vehicles. Since Battery EVs (BEVs) do not use any fuel, their fuel economy is estimated as price per kilometer. Similarly, in terms of GHG emissions, BEVs are the most environmentally friendly since they do not result in any emissions while HEVs and PHEVs produce less emissions compared to the conventional ICE based vehicles. Fuel Cell EVs (FCEVs) are also zero-emission vehicles, but they have large costs associated with them. Finally, if the electricity is provided by using the renewable energy technologies through grid connection, then BEVs could be considered as zero emission vehicles.

Keywords: electric vehicles, zero emission car, fuel economy, CO₂ footprint

Procedia PDF Downloads 149

Authors: A. T. Adetunji, F. B. Lewu, R. Mundembe

Abstract:

Plants require nitrogen (N) to support desired production levels. Nitrogen is available to plants in the form of nitrate or ammonium, which are transported into the cell with the aid of various transport proteins. Ammonium transporters (AMTs) play a role in the uptake of ammonium, the form in which nitrogen is preferentially absorbed by plants. Solanum tuberosum AMT1 (StAMT1) was characterized using molecular biology and bioinformatics methods. Nucleotide database sequences were used to design AMT1-specific primers which were used to amplify the AMT1 internal regions. Nucleotide sequencing, alignment and phylogenetic analysis assigned StAMT1 to the AMT1 family. The deduced amino acid sequences showed that StAMT1 is 92%, 83% and 76% similar to Solanum lycopersicum LeAMT1.1, Lotus japonicus LjAMT1.1 and Solanum lycopersicum LeAMT1.2 respectively. StAMT1 fragments were shown to correspond to the 5th - 10th trans-membrane domains. Residue StAMT1 D15 is predicted to be essential for ammonium transport, while mutations of StAMT1 S76A may further enhance ammonium transport.

Keywords: ammonium transporter, bioinformatics, nitrogen, primers, Solanum tuberosum

Procedia PDF Downloads 250

Authors: Muhammad N. Khan, Syed O. Gillani, Mohsin Jamil, Tarbia Iftikhar

Abstract:

With the increasing demand of bandwidth and data rate, there is a dire need to implement antenna systems in mobile phones which are able to fulfill user requirements. A monopole antenna system with multi-antennas configurations is proposed considering the feasibility and user demand. The multi-antenna structure is referred to as multi-input multi-output (MIMO) antenna system. The multi-antenna system comprises of 4 antennas operating below 6 GHz frequency bands for 4G/LTE and 4 antenna for 5G applications at 28 GHz and the dimension of board is 120 × 70 × 0.8mm3. The suggested designs is feasible with a structure of low-profile planar-antenna and is adaptable to smart cell phones and handheld devices. To the best of our knowledge, this is the first design compared to the literature by having integrated antenna system for two standards, i.e., 4G and 5G. All MIMO antenna systems are simulated on commercially available software, which is high frequency structures simulator (HFSS).

Keywords: high frequency structures simulator (HFSS), mutli-input multi-output (MIMO), monopole antenna, slot antenna

Procedia PDF Downloads 250

Authors: Jun Sung Go, Jong Kang Park, Jong Tae Kim

Abstract:

As semi-conductor manufacturing technology evolves; the single event transient problem becomes more significant issue. Single event transient has a critical impact on both combinational and sequential logic circuits, so it is important to evaluate the soft error tolerance of the circuits at the design stage. In this paper, we present a soft error detecting simulation using scan chain. The simulation model generates a single event transient randomly in the circuit, and detects the soft error during the execution of the test patterns. We verified this model by inserting a scan chain in an 8051 microprocessor using 65 nm CMOS technology. While the test patterns generated by ATPG program are passing through the scan chain, we insert a single event transient and detect the number of soft errors per sub-module. The experiments show that the soft error rates per cell area of the SFR module is 277% larger than other modules.

Keywords: scan chain, single event transient, soft error, 8051 processor

Procedia PDF Downloads 347

Authors: H. Farokhi, A. Bahadoran

Abstract:

This paper is focused on the absorbance and magnetic properties of a novel nanocomposite based on conducting polymer, carbon black and barium hexaferrite in epoxy resin on the E-glass fibre substrate. The highly conductive nanocomposite was provided by in-situ polymerization of aniline in the presence of carbon black (C) and barium hexaferrite (BaFe12O19) as electromagnetic absorbance material. The structure, morphology, and magnetic properties of samples were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM). SEM images showed the uniformly coated PAni on the surface of carbon black and barium hexaferrite. XRD peaks also verified the presence of carbon black and barium hexaferrite in the nanocomposite. The microwave characteristics determined from the magnetic and dielectric properties of the elastomeric composites obtained from scattering data by fitting the samples in a waveguide, where measured in the frequency in X-band frequency range, the range of 8 to 12 GHz. The reflection losses were evaluated to be less than −5dB over the whole X-band frequency (8–12 GHz) for the thickness of 1.4mm.

Keywords: conductive polymer, magnetic materials, capacitance, electrochemical cell

Procedia PDF Downloads 249

Authors: J. Nyenhuis, J. Drelich

Abstract:

This research study was designed to determine if food crops could be bio-fortified with micro-nutrients by growing sprouts on mineral fortified fiber mats. Diets high in processed foods have been found to lack essential micro-nutrients for optimum human development and overall health. Some micro-nutrients such as copper (Cu) have been found to enhance the inflammatory response through its oxidative functions, thereby having a role in cardiovascular disease (CVD), metabolic syndrome (MetS), diabetes and related complications. Recycled cellulose fibers and clay saturated with micro-nutrient ions can be converted to a novel mineral-metal hybrid material in which the fiber mat becomes a carrier of essential micro-nutrients. The reduction of ionic to metallic copper was accomplished using hydrogen at temperatures ranging from 400o to 600oC. Copper particles with diameters ranging from ~1 to 400-500 nm reside on the recycled fibers that make up the mats. Seeds purchased from a commercial, organic supplier were germinated on the specially engineered cellulose fiber mats that incorporated w10 wt% clay fillers saturated with either copper particles or ionic copper. After the appearance of the first leaves, the sprouts were dehydrated and analyzed for Cu content. Nutrient analysis showed 1.5 to 1.6 increase in Cu of the sprouts grown on the fiber mats with copper particles, and 2.3 to 2.5 increase on mats with ionic copper as compared to the control samples. The antibacterial properties of materials saturated with copper ions at room temperature and at temperatures up to 400°C have been verified with halo method tests against Escherichia Coli in previous studies. E. coli is a known pathogenic risk in sprout production. Copper exhibits excellent antibacterial properties when tested on S. aureus, a pathogenic gram-positive bacterium. This has also been confirmed for the fiber-copper hybrid material in this study. This study illustrates the potential for the use of engineered mats as a viable way to increase the micro-nutrient composition of locally-grown food crops and the need for additional research to determine the uptake, nutritional implications and risks of micro-nutrient bio-fortification.

Keywords: bio-fortification, copper nutrient analysis, micro-nutrient uptake, sprouts and mineral-fortified mats

Procedia PDF Downloads 354

Authors: Burak Dik, Oguzhan Avci, Irmak Dik, Emre Bahcivan

Abstract:

The objective of this study was to evaluate the effects of alone and combined administration of Peste des petits ruminants (PPR) vaccine with Corynebacterium cutis lysate (CCL) on the hematology and biochemistry parameters levels in sheep. CCL and PPR vaccine changes cell and organ activity. In this study, 12 ewes were divided into equal groups; first group; PPR vaccine was applied only one time 1 mL subcutan of armpit on 6 sheep, and the second group; CCL (1 mL) and PPR vaccine (1 mL) combination were applied only one time subcutan of armpit on 6 sheep. Blood samples were collected before treatment (0. hour, control) and after treatment (1, 3, 7, 14, 21 and 28 days) from the sheep. Plasma and serum samples were evaluated for hematology and biochemistry parameters and there were statistically significant in sheep. In conclusion, combined usage of PPR vaccine with CCL may not influence cells and organs. Repeated CCL treatment with vaccine can create hepatotoxic, renal and bone marrow effects in sheep.

Keywords: Corynebacterium cutis lysate, hematology, peste des petits ruminants, vaccine

Procedia PDF Downloads 253

Authors: Danny Manuel Calvo Velasco, Robert Sanchez Cano

Abstract:

By using the transference matrix formalism, in this work, it is presented the study of the optical properties of the 1D graded structure, constructed by multiple bi-layers of dielectric and air, considering a redistribution of the material lengths following an arithmetic progression as a function of two parameters. It is presented a factorization for the transference matrices for the graded structure, which allows the interpretation of their optical properties in terms of the properties of simpler structures. It is shown that the graded structure presents new transmission peaks, which can be controlled by the parameter values located in frequencies for which a periodic system has a photonic bandgap. This result is extended to the case of a photonic crystal for which the unitary cell is the proposed graded structure, showing new transmission bands which are due to the multiple new sub-structures present in the system. Also, for the TE polarization, it is observed transmission bands' low frequencies which present low variation of its width and position with the incidence angle. It is expected that these results could guide a route in the design of new photonic devices.

Keywords: graded, material redistribution, photonic system, transference matrix

Procedia PDF Downloads 139

Authors: Manik Sharma, Ganapathy Krishnamurthi

Abstract:

The cost of some drugs and medical treatments has risen in recent years, that many patients are having to go without. A classification project could make researchers more efficient. One of the more surprising reasons behind the cost is how long it takes to bring new treatments to market. Despite improvements in technology and science, research and development continues to lag. In fact, finding new treatment takes, on average, more than 10 years and costs hundreds of millions of dollars. If successful, we could dramatically improve the industry's ability to model cellular images according to their relevant biology. In turn, greatly decreasing the cost of treatments and ensure these treatments get to patients faster. This work aims at solving a part of this problem by creating a cellular image classification model which can decipher the genetic perturbations in cell (occurring naturally or artificially). Another interesting question addressed is what makes the deep-learning model decide in a particular fashion, which can further help in demystifying the mechanism of action of certain perturbations and paves a way towards the explainability of the deep-learning model.

Keywords: cellular images, genetic perturbations, deep-learning, explainability

Procedia PDF Downloads 112

Authors: Reim A. Almotiri, Manal M. Alkhamisi

Abstract:

Ternary nanocomposites based on hydroxyapatite (HAP) and alumina (Al2O3) were embedded through graphene oxide (GO) nanosheets to be investigated for medical applications. The composition of the preparations has been confirmed by X-ray photoelectron spectroscopy, energy-dispersive X-ray analysis, and Fourier-Transform infrared spectroscopy. Scanning and transmission electron microscopy have shown the typical morphologies of the components of the nanocomposites with hydroxyapatite nanorods reaching an average diameter of 22.26±2 nm and an average length of 69.56±19.25 nm in the ternary nanocomposites. The ternary nanocomposite has a microhardness of 5.8±0.1 GPa and a higher average roughness of 6.5 nm compared to pure HAP preparation with an average roughness of 2.7 nm. All preparations have shown an acceptable cytotoxicity profile with a percent osteoblasts cell viability of 98.6±1.3% after culturing with the ternary nanocomposite. The TNC has also shown the highest antibacterial activity compared to preparations of each of its constituents and their nanocomposites, with a zone of inhibition’s diameter of 14.1±0.8 mm and 13.6±0.6 mm against Staphylococcus aureus and Escherichia coli, respectively, compared to no zone of inhibition for the pure hydroxyapatite preparation.

Keywords: hydroxypatite, cytotoxicity, nanocomposites, X-ray analysis

Procedia PDF Downloads 83

Authors: Rania Abdulkareem Aboubakr Mahdaly Ammar

Abstract:

The aortic valve (AV) is a complex mechanical environment that includes flexure, tension, pressure and shear stress forces to blood flow during cardiac cycle. This mechanical environment regulates AV tissue structure by constantly renewing and remodeling the phenotype. In vitro, ex vivo and in vivo studies have explained that pathological states such as hypertension and congenital defects like bicuspid AV ( BAV ) can potentially alter the AV’s mechanical environment, triggering a cascade of remodeling, inflammation and calcification activities in AV tissue. Changes in mechanical environments are first sent by the endothelium that induces changes in the extracellular matrix, and triggers cell differentiation and activation. However, the molecular mechanism of this process is not very well understood. Understanding these mechanisms is critical for the development of effective medical based therapies. Recently, there have been some interesting studies on characterizing the hemodynamics associated with AV, especially in pathologies like BAV, using different experimental and numerical methods. Here, we review the current knowledge of the local AV mechanical environment and its effect on valve biology, focusing on in vitro and ex vivo approaches.

Keywords: aortic valve mechanobiology, bicuspid calcification, pressure stretch, shear stress

Procedia PDF Downloads 365

Authors: Kumaran Narayanan, Andrew N. Osahor

Abstract:

E. coli has been engineered by our group and by others as a vector to deliver DNA into cultured human and animal cells. However, so far conditions to improve gene delivery using this vector have not been investigated, resulting in a major gap in our understanding of the requirements for this vector to function optimally. Our group recently published novel data showing that simple addition of the DNA transfection reagent Lipofectamine increased the efficiency of the E. coli vector by almost 3-fold, providing the first strong evidence that further optimization of bactofection is possible. This presentation will discuss advances that demonstrate the effects of several intracellular strategies that improve the efficiency of this vector. Conditions that promote endosomal escape of internalized bacteria to evade lysosomal destruction after entry in the cell, a known obstacle limiting this vector, are elucidated. Further, treatments that increase bacterial lysis so that the vector can release its transgene into the mammalian environment for expression will be discussed. These experiments will provide valuable new insight to advance this E. coli system as an important class of vector technology for genetic correction of human disease models in cells and whole animals.

Keywords: DNA, E. coli, gene expression, vector

Procedia PDF Downloads 358

Authors: Abdulrahman T. Essa, Ahmed Aied, Omar Hamid, Felicity R. A. J. Rose, Kevin M. Shakesheff

Abstract:

Biodegradable poly(ester amide)s are promising polymers for biomedical applications such as drug delivery and tissue engineering because of their optimized chemical and physical properties. In this study, we developed a biodegradable polyester amide elastomer poly(serinol sebacate) (PSS) composed of crosslinked networks based on serinol and sebacic acid. The synthesized polymers were characterized to evaluate their chemical structures, mechanical properties, degradation behaviors and in vitro cytocompatibility. Analysis of proton nuclear magnetic resonance and Fourier transform infrared spectroscopy revealed the structure of the polymer. The PSS exhibit excellent solubility in a variety of solvents such as methanol, dimethyl sulfoxide and dimethylformamide. More importantly, the mechanical properties of PSS could be tuned by changing the curing conditions. In addition, the 3T3 fibroblast cells cultured on the PSS demonstrated good cell attachment and high viability.

Keywords: biodegradable, biomaterial, elastomer, mechanical properties, poly(serinol sebacate)

Procedia PDF Downloads 354

Authors: Muneeb Ahmad, Ali Raza

Abstract:

A computational method inspired by the immune system (IS) is presented, leveraging its shared characteristics of robustness, fault tolerance, scalability, and adaptability with swarm intelligence. This method aims to showcase flocking behaviors in a swarm of robots (SR). The innate part of the IS offers a variety of reactive and probabilistic cell functions alongside its self-regulation mechanism which have been translated to enable swarming behaviors. Although, the research is specially focused on flocking behaviors in a variety of simulated environments using e-puck robots in a physics-based simulator (CoppeliaSim); the artificial innate immune system (AIIS) can exhibit other swarm behaviors as well. The effectiveness of the immuno-inspired approach has been established with extensive experimentations, for scalability and adaptability, using standard swarm benchmarks as well as the immunological regulatory functions (i.e., Dendritic Cells’ Maturity and Inflammation). The AIIS-based approach has proved to be a scalable and adaptive solution for emulating the flocking behavior of SR.

Keywords: artificial innate immune system, flocking swarm, immune system, swarm intelligence

Procedia PDF Downloads 105

Authors: Maymona Al-Husari, Craig Murdoch, Steven Webb

Abstract:

Some tumors are known to exhibit an extracellular pH that is more acidic than the intracellular, creating a 'reversed pH gradient' across the cell membrane and this has been shown to affect their invasive and metastatic potential. Tumour hypoxia also plays an important role in tumour development and has been directly linked to both tumour morphology and aggressiveness. In this paper, we present a hybrid mathematical model of intracellular pH regulation that examines the effect of oxygen and pH on tumour growth and morphology. In particular, we investigate the impact of pH regulatory mechanisms on the cellular pH gradient and tumour morphology. Analysis of the model shows that: low activity of the Na+/H+ exchanger or a high rate of anaerobic glycolysis can give rise to a 'fingering' tumour morphology; and a high activity of the lactate/H+ symporter can result in a reversed transmembrane pH gradient across a large portion of the tumour mass. Also, the reversed pH gradient is spatially heterogenous within the tumour, with a normal pH gradient observed within an intermediate growth layer, that is the layer between the proliferative inner and outermost layer of the tumour.

Keywords: acidic pH, cellular automaton, ebola, tumour growth

Procedia PDF Downloads 332

Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

Abstract:

Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

Procedia PDF Downloads 338

Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

Abstract:

Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

Procedia PDF Downloads 198

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

Procedia PDF Downloads 71

Authors: Sanjay M. Tailor, Urmila H. Patel

Abstract:

Phthalyl Sulfacetamide belongs to well-known member of antimicrobial sulfonamide family. It is a potent antitumor drug. Structural characteristics of 4-amino-N-(2quinoxalinyl) benzene-sulfonamides (Phthalyl Sulfacetamide), C14H12N4O2S has been studied by method of X-ray crystallography. The compound crystallizes in monoclinic space group P21/n with unit cell parameters a= 7.9841 Ǻ, b= 12.8208 Ǻ, c= 16.6607 Ǻ, α= 90˚, β= 93.23˚, γ= 90˚and Z=4. The X-ray based three-dimensional structure analysis has been carried out by direct methods and refined to an R-value of 0.0419. The crystal structure is stabilized by intermolecular N-H…N, N-H…O and π-π interactions. The Hirshfeld surfaces and consequently the fingerprint analysis have been performed to study the nature of interactions and their quantitative contributions towards the crystal packing. An analysis of Hirshfeld surfaces and fingerprint plots facilitates a comparison of intermolecular interactions, which are the key elements in building different supramolecular architectures. Docking is used for virtual screening for the prediction of the strongest binders based on various scoring functions. Docking studies are carried out on Phthalyl Sulfacetamide for better activity, which is important for the development of a new class of inhibitors.

Keywords: phthalyl sulfacetamide, crystal structure, hirshfeld surface analysis, docking

Procedia PDF Downloads 348

Authors: Shoaei Shahram, Rafiei Felora

Abstract:

To study the effects of using superabsorbent polymers on physiological of maize in deficit Irrigation condition .an experiment carried out in split plot factorial based on completely Randomized Block design (RCBD) with three replication in 2012years. Deficit Irrigation was applied by three different Irrigation amount. Super absorbent polymers in 3 levels were and two veriety of maize allocated in sub plots. there was significant difference between Irrigation levels in all experimental Traits by increasing in deficit irrigation. Results of this research showed water stress significantly decreased relative water content (RWC) LAI,Ash percentage in both hybrids, and increased Cell membrane percentage and SPAD,ADF percent.whereas the application of super absorbent polymer compensated the negative effect of drought stress, especially in high rates of polymer application .These mentioned rates of polymer had the best effect to all of the studied traits. These findings can be suggested that the irrigation intervals of corn could be increased by application of super absorbent polymer.

Keywords: super absorbent, p hysiological, water stress, zea maize

Procedia PDF Downloads 320

Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

Abstract:

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

Procedia PDF Downloads 453

Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

Abstract:

Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

Procedia PDF Downloads 196

Authors: Ruolan Zhang, Ryo Imai, Naoko Senda, Tomoyuki Sakai

Abstract:

Enzymes have attracted increasing attentions in industrial manufacturing for their applicability in catalyzing complex chemical reactions under mild conditions. Directed evolution has become a powerful approach to optimize enzymes and exploit their full potentials under the circumstance of insufficient structure-function knowledge. With the incorporation of cell-free synthetic biotechnology, rapid enzyme synthesis can be realized because no cloning procedure such as transfection is needed. Its open environment also enables direct enzyme measurement. These properties of cell-free biotechnology lead to excellent throughput of enzymes generation. However, the capabilities of current screening methods have limitations. Fluorescence-based assay needs applicable fluorescent label, and the reliability of acquired enzymatic activity is influenced by fluorescent label’s binding affinity and photostability. To acquire the natural activity of an enzyme, another method is to combine pre-screening step and high-performance liquid chromatography (HPLC) measurement. But its throughput is limited by necessary time investment. Hundreds of variants are selected from libraries, and their enzymatic activities are then identified one by one by HPLC. The turn-around-time is 30 minutes for one sample by HPLC, which limits the acquirable enzyme improvement within reasonable time. To achieve the real high-throughput enzyme screening, i.e., obtain reliable enzyme improvement within reasonable time, a widely applicable high-throughput measurement of enzymatic reactions is highly demanded. Here, a high-throughput screening method using broadband coherent anti-Stokes Raman spectroscopy (CARS) was proposed. CARS is one of coherent Raman spectroscopy, which can identify label-free chemical components specifically from their inherent molecular vibration. These characteristic vibrational signals are generated from different vibrational modes of chemical bonds. With the broadband CARS, chemicals in one sample can be identified from their signals in one broadband CARS spectrum. Moreover, it can magnify the signal levels to several orders of magnitude greater than spontaneous Raman systems, and therefore has the potential to evaluate chemical's concentration rapidly. As a demonstration of screening with CARS, alcohol dehydrogenase, which converts ethanol and nicotinamide adenine dinucleotide oxidized form (NAD+) to acetaldehyde and nicotinamide adenine dinucleotide reduced form (NADH), was used. The signal of NADH at 1660 cm⁻¹, which is generated from nicotinamide in NADH, was utilized to measure the concentration of it. The evaluation time for CARS signal of NADH was determined to be as short as 0.33 seconds while having a system sensitivity of 2.5 mM. The time course of alcohol dehydrogenase reaction was successfully measured from increasing signal intensity of NADH. This measurement result of CARS was consistent with the result of a conventional method, UV-Vis. CARS is expected to have application in high-throughput enzyme screening and realize more reliable enzyme improvement within reasonable time.

Keywords: Coherent Anti-Stokes Raman Spectroscopy, CARS, directed evolution, enzyme screening, Raman spectroscopy

Procedia PDF Downloads 141

Authors: Hairin Taha, Aditya Arya, M. A. Hapipah, A. M. Mustafa

Abstract:

Plants have been an important source of medicine since ancient times. Pseuduvaria monticola is a rare montane forest species from the Annonaceae family. Traditionally, the plant was used to cure symptoms of fever, inflammation, stomach-ache and also to reduce the elevated levels of blood glucose. Scientifically, we have evaluated the antidiabetic potential of the Pseuduvaria monticola bark methanolic extract on certain in vitro cell based assays, followed by in vivo study. Results from in vitro models displayed PMm upregulated glucose uptake and insulin secretion in mouse pancreatic β-cells. In vivo study demonstrated the PMm down-regulated hyperglycaemia, oxidative stress and elevated levels of pro-inflammatory cytokines in type 2 diabetic rat models. Altogether, the study revealed that Pseuduvaria monticola might be used as a potential candidate for the management of type 2 diabetes and its related complications.

Keywords: type 2 diabetes, Pseuduvaria monticola, insulin secretion, glucose uptake

Procedia PDF Downloads 439