Search results for: circulating tumor cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3718

Search results for: circulating tumor cells

1378 Poly(N-Vinylcaprolactam) Based Degradable Microgels for Controlled Drug Delivery

Authors: G. Agrawal, R. Agrawal, A. Pich

Abstract:

The pH and temperature responsive biodegradable poly(N-vinylcaprolactam) (PVCL) based microgels functionalized with itaconic acid (IA) units are prepared via precipitation polymerization for drug delivery applications. Volume phase transition temperature (VPTT) of the obtained microgels is influenced by both IA content and pH of the surrounding medium. The developed microgels can be degraded under acidic conditions due to the presence of hydrazone based crosslinking points inside the microgel network. The microgel particles are able to effectively encapsulate doxorubicin (DOX) drug and exhibit low drug leakage under physiological conditions. At low pH, rapid DOX release is observed due to the changes in electrostatic interactions along with the degradation of particles. The results of the cytotoxicity assay further display that the DOX-loaded microgel exhibit effective antitumor activity against HeLa cells demonstrating their great potential as drug delivery carriers for cancer therapy.

Keywords: degradable, drug delivery, hydrazone linkages, microgels, responsive

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1377 Antimicrobial Efficacy of Some Antibiotics Combinations Tested against Some Molecular Characterized Multiresistant Staphylococcus Clinical Isolates, in Egypt

Authors: Nourhan Hussein Fanaki, Hoda Mohamed Gamal El-Din Omar, Nihal Kadry Moussa, Eva Adel Edward Farid

Abstract:

The resistance of staphylococci to various antibiotics has become a major concern for health care professionals. The efficacy of the combinations of selected glycopeptides (vancomycin and teicoplanin) with gentamicin or rifampicin, as well as that of gentamicin/rifampicin combination, was studied against selected pathogenic staphylococcus isolated from Egypt. The molecular distribution of genes conferring resistance to these four antibiotics was detected among tested clinical isolates. Antibiotic combinations were studied using the checkerboard technique and the time-kill assay (in both the stationary and log phases). Induction of resistance to glycopeptides in staphylococci was tried in the absence and presence of diclofenac sodium as inducer. Transmission electron microscopy was used to study the effect of glycopeptides on the ultrastructure of the cell wall of staphylococci. Attempts were made to cure gentamicin resistance plasmids and to study the transfer of these plasmids by conjugation. Trials for the transformation of the successfully isolated gentamicin resistance plasmid to competent cells were carried out. The detection of genes conferring resistance to the tested antibiotics was performed using the polymerase chain reaction. The studied antibiotic combinations proved their efficacy, especially when tested during the log phase. Induction of resistance to glycopeptides in staphylococci was more promising in presence of diclofenac sodium, compared to its absence. Transmission electron microscopy revealed the thickening of bacterial cell wall in staphylococcus clinical isolates due to the presence of tested glycopeptides. Curing of gentamicin resistance plasmids was only successful in 2 out of 9 tested isolates, with a curing rate of 1 percent for each. Both isolates, when used as donors in conjugation experiments, yielded promising conjugation frequencies ranging between 5.4 X 10-2 and 7.48 X 10-2 colony forming unit/donor cells. Plasmid isolation was only successful in one out of the two tested isolates. However, low transformation efficiency (59.7 transformants/microgram plasmid DNA) of such plasmids was obtained. Negative regulators of autolysis, such as arlR, lytR and lrgB, as well as cell-wall associated genes, such as pbp4 and/or pbp2, were detected in staphylococcus isolates with reduced susceptibility to the tested glycopeptides. Concerning rifampicin resistance genes, rpoBstaph was detected in 75 percent of the tested staphylococcus isolates. It could be concluded that in vitro studies emphasized the usefulness of the combination of vancomycin or teicoplanin with gentamicin or rifampicin, as well as that of gentamicin with rifampicin, against staphylococci showing varying resistance patterns. However, further in vivo studies are required to ensure the safety and efficacy of such combinations. Diclofenac sodium can act as an inducer of resistance to glycopeptides in staphylococci. Cell-wall thickness is a major contributor to such resistance among them. Gentamicin resistance in these strains could be chromosomally or plasmid mediated. Multiple mutations in the rpoB gene could mediate staphylococcus resistance to rifampicin.

Keywords: glycopeptides, combinations, induction, diclofenac, transmission electron microscopy, polymerase chain reaction

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1376 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

Abstract:

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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1375 Identification of Hub Genes in the Development of Atherosclerosis

Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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1374 Biodistribution of Fluorescence-Labelled Epidermal Growth Factor Protein from Slow Release Nanozolid Depots in Mouse

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

Abstract:

Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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1373 Study The Role Effect of Poly Pyrrole on LiFePO4 as Positive Electrode

Authors: Atef Youssef, Marwa Mostafa Moharam

Abstract:

The effects of poly pyrrole (PP) addition on LiFePO4 have been studied by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and galvanostatic measurements. PP was prepared with LiFePO₄ in different ways, such as chemically dispersion, insinuation polymerization, and electrochemically polymerization. The EIS results showed that the charge transfer resistance (Rct) of LiFePO₄ was decreased by adding 10% PP polymerized in a situation to 153 vs. 1660  for bare LiFePO₄. The CV curves show that 10% PP added LiFePO₄ had higher electrochemical reactivity for lithium insertion and extraction than the un-doped material. The mean redox potential is E1/2 = 3.45 V vs. Li+/Li. The first discharge curve of the 10% poly pyrrole doped LiFePO₄ showed a mainly flat voltage plateau over the 3.45–3.5 V range, indicating the lithium extraction and insertion reactions between LiFePO₄ and FePO₄. A specific discharge capacity of cells prepared from in-situ 10% PP added LiFePO4to was about 210 vs. 65 mAhg-1 for bare LiFePO₄.

Keywords: liFePO₄, poly pyrrole addition, positive electrode, lithium battery

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1372 A Review of Deep Learning Methods in Computer-Aided Detection and Diagnosis Systems based on Whole Mammogram and Ultrasound Scan Classification

Authors: Ian Omung'a

Abstract:

Breast cancer remains to be one of the deadliest cancers for women worldwide, with the risk of developing tumors being as high as 50 percent in Sub-Saharan African countries like Kenya. With as many as 42 percent of these cases set to be diagnosed late when cancer has metastasized and or the prognosis has become terminal, Full Field Digital [FFD] Mammography remains an effective screening technique that leads to early detection where in most cases, successful interventions can be made to control or eliminate the tumors altogether. FFD Mammograms have been proven to multiply more effective when used together with Computer-Aided Detection and Diagnosis [CADe] systems, relying on algorithmic implementations of Deep Learning techniques in Computer Vision to carry out deep pattern recognition that is comparable to the level of a human radiologist and decipher whether specific areas of interest in the mammogram scan image portray abnormalities if any and whether these abnormalities are indicative of a benign or malignant tumor. Within this paper, we review emergent Deep Learning techniques that will prove relevant to the development of State-of-The-Art FFD Mammogram CADe systems. These techniques will span self-supervised learning for context-encoded occlusion, self-supervised learning for pre-processing and labeling automation, as well as the creation of a standardized large-scale mammography dataset as a benchmark for CADe systems' evaluation. Finally, comparisons are drawn between existing practices that pre-date these techniques and how the development of CADe systems that incorporate them will be different.

Keywords: breast cancer diagnosis, computer aided detection and diagnosis, deep learning, whole mammogram classfication, ultrasound classification, computer vision

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1371 A New Tool for Global Optimization Problems: Cuttlefish Algorithm

Authors: Adel Sabry Eesa, Adnan Mohsin Abdulazeez Brifcani, Zeynep Orman

Abstract:

This paper presents a new meta-heuristic bio-inspired optimization algorithm which is called Cuttlefish Algorithm (CFA). The algorithm mimics the mechanism of color changing behavior of the cuttlefish to solve numerical global optimization problems. The colors and patterns of the cuttlefish are produced by reflected light from three different layers of cells. The proposed algorithm considers mainly two processes: reflection and visibility. Reflection process simulates light reflection mechanism used by these layers, while visibility process simulates visibility of matching patterns of the cuttlefish. To show the effectiveness of the algorithm, it is tested with some other popular bio-inspired optimization algorithms such as Genetic Algorithms (GA), Particle Swarm Optimization (PSO) and Bees Algorithm (BA) that have been previously proposed in the literature. Simulations and obtained results indicate that the proposed CFA is superior when compared with these algorithms.

Keywords: Cuttlefish Algorithm, bio-inspired algorithms, optimization, global optimization problems

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1370 Inhibitory Effect on TNF-Alpha Release of Dioscorea membranacea and Its Compounds

Authors: Arunporn Itharat, Srisopa Ruangnoo, Pakakrong Thongdeeying

Abstract:

The rhizomes of Dioscorea membranacea (DM) has long been used in Thai Traditional medicine to treat cancer and inflammatory conditions such as rheumatism. The objective of this study was to investigate anti-inflammatory activity by determining the inhibitory effect on LPS-induced TNF-α from RAW264.7 cells of crude extracts and pure isolated compounds from DM. Three known dihydrophenantrene compounds were isolated by a bioassay guided isolation method from DM ethanolic extract [2,4 dimethoxy-5,6-dihydroxy-9,10-dihydrophenanthrene (1) and 5-hydroxy-2,4,6-trimethoxy-9,10-dihydrophenanthrene(2) and 5,6,2 -trihydroxy 3,4-methoxy, 9,10- dihydrophenanthrene (3)]. 1 showed the highest inhibitory effect on PGE2, followed by 3 and 1 (IC50 = 2.26, 4.97 and >20 μg/ml or 8.31,17.25 and > 20 µM respectively). These findings suggest that this plant showed anti-inflamatory effects by displaying an inhibitory effect on TNF-α release, hence, this result supports the usage of Thai traditional medicine to treat inflammation related diseases.

Keywords: Dioscorea membranacea, anti-inflammatory activity, TNF-Alpha , dihidrophenantrene compound

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1369 Role of Imaging in Predicting the Receptor Positivity Status in Lung Adenocarcinoma: A Chapter in Radiogenomics

Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

Abstract:

The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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1368 Bioremediation of Arsenic from Industrially Polluted Soil of Vatva, Ahmedabad, Gujarat, India

Authors: C. Makwana, S. R. Dave

Abstract:

Arsenic is toxic to almost all living cells. Its contamination in natural sources affects the growth of microorganisms. The presence of arsenic is associated with various human disorders also. The attempt of this sort of study provides information regarding the performance of our isolated microorganisms in the presence of Arsenic, which have ample scope for bioremediation. Six isolates were selected from the polluted sample of industrial zone Vatva, Ahmedabad, Gujarat, India, out of which two were Thermophilic organisms. The thermophilic exopolysaccharide (EPS) producing Bacillus was used for microbial enhance oil recovery (MEOR) and in the bio beneficiation. Inorganic arsenic primarily exists in the form of arsenate or arsenite. This arsenic resistance isolate was capable of transforming As +3 to As+5. This isolate would be useful for arsenic remediation standpoint from aquatic systems. The study revealed that the thermophilic microorganism was growing at 55 degree centigrade showed considerable remediation property. The results on the growth and enzyme catalysis would be discussed in response to Arsenic remediation.

Keywords: aquatic systems, thermophilic, exopolysacchride, arsenic

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1367 Investigation on Properties and Applications of Graphene as Single Layer of Carbon Atoms

Authors: Ali Ashjaran

Abstract:

Graphene is undoubtedly emerging as one of the most promising materials because of its unique combination of superb properties, which opens a way for its exploitation in a wide spectrum of applications ranging from electronics to optics, sensors, and biodevices. In addition, Graphene-based nanomaterials have many promising applications in energy-related areas. Graphene a single layer of carbon atoms, combines several exceptional properties, which makes it uniquely suited as a coating material: transparency, excellent mechanical stability, low chemical reactivity, Optical, impermeability to most gases, flexibility, and very high thermal and electrical conductivity. Graphene is a material that can be utilized in numerous disciplines including, but not limited to: bioengineering, composite materials, energy technology and nanotechnology, biological engineering, optical electronics, ultrafiltration, photovoltaic cells. This review aims to provide an overiew of graphene structure, properties and some applications.

Keywords: graphene, carbon, anti corrosion, optical and electrical properties, sensors

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1366 Predicting High-Risk Endometrioid Endometrial Carcinomas Using Protein Markers

Authors: Yuexin Liu, Gordon B. Mills, Russell R. Broaddus, John N. Weinstein

Abstract:

The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to the high-stage diseases. However, there are no available biomarkers that predict EEC patient staging at the time of diagnosis. We aim to develop a predictive scheme to help in this regards. Using reverse-phase protein array expression profiles for 210 EEC cases from The Cancer Genome Atlas (TCGA), we constructed a Protein Scoring of EEC Staging (PSES) scheme for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MD Anderson Cancer Center (MDACC) using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. PSES robustly distinguished high- from low-stage tumors in the TCGA cohort (area under the ROC curve [AUC]=0.74; 95% confidence interval [CI], 0.68 to 0.82) and in the validation cohort (AUC=0.67; 95% CI, 0.58 to 0.76). Even among grade 1 or 2 tumors, PSES was significantly higher in high- than in low-stage tumors in both the TCGA (P = 0.005) and MDACC (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in high-stage tumors. PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.

Keywords: endometrial carcinoma, protein, protein scoring of EEC staging (PSES), stage

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1365 Laparoscopic Curative Resection for Right-Sided Colonic Tumours: Initial Experience from a Cancer Hospital of a Developing Country

Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

Abstract:

Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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1364 Repositioning Sodium Valproate for Amelioration of Bleomycin-induced Scleroderma: The Role of Oxidative Stress, Transforming Growth Factor Beta-1, and the Mammalian Target of Rapamycin

Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

Abstract:

Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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1363 New 5’-O- and 6-Substituted Purine Nucleoside Analogs: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines

Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

Abstract:

Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

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1362 Arbutin-loaded Butylglyceryl Dextran Nanoparticles for Topical Delivery

Authors: Mohammad F. Bostanudin, Tan S. Fei, Azwan M. Lazim

Abstract:

Toward the development of colloidal systems that are able to enhance permeation across the skin, a material combining the non-toxic and non-immunogenic of dextran with alkylglycerols permeation enhancing property has been designed. To this purpose, a range of butylglyceryl dextrans (DEX-OX4) were synthesized via functionalization with n-butylglycidyl ether and the successful functionalization was confirmed by NMR and FT-IR spectroscopies, along with GPC with a degree of modification in the range 6.3–35.7 %. A reduced viscosity and an increased molecular weight of DEX-OX4 were also recorded when compared to that of the native dextran. DEX-OX4 was further formulated into nanocarriers and loaded with α-arbutin prior to be investigated for their particle size, morphology, stability, loading ability, and release profiles. The resulting nanoparticles were found to be close-to-spherical and relatively stable at pH 5 and 7, with size 180–220 nm (ζ-potential -22 to -25 mV), and a loading degree of 11.7 %. Lack of toxicity at application-relevant concentrations and increased permeation across skin biological membrane model were demonstrated by nanoparticles in-vitro results against immortalized skin human keratinocytes cells (HaCaT).

Keywords: butylglycerols, dextran, nanoparticles, transdermal

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1361 Umbilical Epidermal Inclusion Cysts, a Rare Cause of Umbilical Mass: A Case Report and Review of Literature

Authors: Christine Li, Amanda Robertson

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Epidermal inclusion cysts occur when epidermal cells are implanted in the dermis following trauma, or surgery. They are a rare cause of an umbilical mass, with very few cases previously reported following abdominal surgery. These lesions can present with a range of symptoms, including palpable mass, pain, redness, or discharge. This paper reports a case of an umbilical epidermal inclusion cyst in a 52-year-old female presenting with a six-week history of a painful, red umbilical lump on a background of two previous diagnostic laparoscopies. Abdominal computed tomography (CT) scans revealed non-specific soft tissue thickening in the umbilical region. This was successfully treated with complete excision of the lesion. Umbilical lumps are a common presentation but can represent a diagnostic challenge. The differential diagnosis should include an epidermal inclusion cyst, particularly in a patient who has had previous abdominal surgery, including laparoscopic surgery.

Keywords: epidermal inclusion cyst, laparoscopy, umbilical mass, umbilicus

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1360 Review of Carbon Materials: Application in Alternative Energy Sources and Catalysis

Authors: Marita Pigłowska, Beata Kurc, Maciej Galiński

Abstract:

The application of carbon materials in the branches of the electrochemical industry shows an increasing tendency each year due to the many interesting properties they possess. These are, among others, a well-developed specific surface, porosity, high sorption capacity, good adsorption properties, low bulk density, electrical conductivity and chemical resistance. All these properties allow for their effective use, among others in supercapacitors, which can store electric charges of the order of 100 F due to carbon electrodes constituting the capacitor plates. Coals (including expanded graphite, carbon black, graphite carbon fibers, activated carbon) are commonly used in electrochemical methods of removing oil derivatives from water after tanker disasters, e.g. phenols and their derivatives by their electrochemical anodic oxidation. Phenol can occupy practically the entire surface of carbon material and leave the water clean of hydrophobic impurities. Regeneration of such electrodes is also not complicated, it is carried out by electrochemical methods consisting in unblocking the pores and reducing resistances, and thus their reactivation for subsequent adsorption processes. Graphite is commonly used as an anode material in lithium-ion cells, while due to the limited capacity it offers (372 mAh g-1), new solutions are sought that meet both capacitive, efficiency and economic criteria. Increasingly, biodegradable materials, green materials, biomass, waste (including agricultural waste) are used in order to reuse them and reduce greenhouse effects and, above all, to meet the biodegradability criterion necessary for the production of lithium-ion cells as chemical power sources. The most common of these materials are cellulose, starch, wheat, rice, and corn waste, e.g. from agricultural, paper and pharmaceutical production. Such products are subjected to appropriate treatments depending on the desired application (including chemical, thermal, electrochemical). Starch is a biodegradable polysaccharide that consists of polymeric units such as amylose and amylopectin that build an ordered (linear) and amorphous (branched) structure of the polymer. Carbon is also used as a catalyst. Elemental carbon has become available in many nano-structured forms representing the hybridization combinations found in the primary carbon allotropes, and the materials can be enriched with a large number of surface functional groups. There are many examples of catalytic applications of coal in the literature, but the development of this field has been hampered by the lack of a conceptual approach combining structure and function and a lack of understanding of material synthesis. In the context of catalytic applications, the integrity of carbon environmental management properties and parameters such as metal conductivity range and bond sequence management should be characterized. Such data, along with surface and textured information, can form the basis for the provision of network support services.

Keywords: carbon materials, catalysis, BET, capacitors, lithium ion cell

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1359 Design of Ultra-Light and Ultra-Stiff Lattice Structure for Performance Improvement of Robotic Knee Exoskeleton

Authors: Bing Chen, Xiang Ni, Eric Li

Abstract:

With the population ageing, the number of patients suffering from chronic diseases is increasing, among which stroke is a high incidence for the elderly. In addition, there is a gradual increase in the number of patients with orthopedic or neurological conditions such as spinal cord injuries, nerve injuries, and other knee injuries. These diseases are chronic, with high recurrence and complications, and normal walking is difficult for such patients. Nowadays, robotic knee exoskeletons have been developed for individuals with knee impairments. However, the currently available robotic knee exoskeletons are generally developed with heavyweight, which makes the patients uncomfortable to wear, prone to wearing fatigue, shortening the wearing time, and reducing the efficiency of exoskeletons. Some lightweight materials, such as carbon fiber and titanium alloy, have been used for the development of robotic knee exoskeletons. However, this increases the cost of the exoskeletons. This paper illustrates the design of a new ultra-light and ultra-stiff truss type of lattice structure. The lattice structures are arranged in a fan shape, which can fit well with circular arc surfaces such as circular holes, and it can be utilized in the design of rods, brackets, and other parts of a robotic knee exoskeleton to reduce the weight. The metamaterial is formed by continuous arrangement and combination of small truss structure unit cells, which changes the diameter of the pillar section, geometrical size, and relative density of each unit cell. It can be made quickly through additive manufacturing techniques such as metal 3D printing. The unit cell of the truss structure is small, and the machined parts of the robotic knee exoskeleton, such as connectors, rods, and bearing brackets, can be filled and replaced by gradient arrangement and non-uniform distribution. Under the condition of satisfying the mechanical properties of the robotic knee exoskeleton, the weight of the exoskeleton is reduced, and hence, the patient’s wearing fatigue is relaxed, and the wearing time of the exoskeleton is increased. Thus, the efficiency and wearing comfort, and safety of the exoskeleton can be improved. In this paper, a brief description of the hardware design of the prototype of the robotic knee exoskeleton is first presented. Next, the design of the ultra-light and ultra-stiff truss type of lattice structures is proposed, and the mechanical analysis of the single-cell unit is performed by establishing the theoretical model. Additionally, simulations are performed to evaluate the maximum stress-bearing capacity and compressive performance of the uniform arrangement and gradient arrangement of the cells. Finally, the static analysis is performed for the cell-filled rod and the unmodified rod, respectively, and the simulation results demonstrate the effectiveness and feasibility of the designed ultra-light and ultra-stiff truss type of lattice structures. In future studies, experiments will be conducted to further evaluate the performance of the designed lattice structures.

Keywords: additive manufacturing, lattice structures, metamaterial, robotic knee exoskeleton

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1358 Exploring Structure of Human Chromosomes Using Fluorescence Lifetime Imaging

Authors: A. Bhartiya, S. Botchway, M. Yusuf, I. Robinson

Abstract:

Chromatin condensation is maintained by DNA-based proteins and some divalent cations (Mg²⁺, Ca²⁺, etc.). Condensation process during cell division maintains structural and functional organizations of chromosomes by transferring genetic information correctly to daughter cells. Fluorescence Lifetime Imaging (FLIM) technique measures the fluorescence decay of fixed human chromosomes by calculating the lifetime of fluorophores at a pixel x of the arrival of each photon as a function of time delay t, following excitation with a laser pulse. Fixed metaphase human chromosomes were labelled with DNA-binding dye, DAPI and later DAPI fluorescence lifetime measured using multiphoton microscopy. 5 out of 23 pairs of human chromosomes shown shorter lifetime at the centromere region, differentiating proportion of compaction along the length of chromosomes. Different lifetime was observed in a condensed and de-condensed chromosome. It clearly indicates the involvement of divalent cations in the process of condensation.

Keywords: divalent cations, FLIM (Fluorescence Lifetime Imaging), human chromosomes, multiphoton microscopy

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1357 Integration of an Augmented Reality System for the Visualization of the HRMAS NMR Analysis of Brain Biopsy Specimens Using the Brainlab Cranial Navigation System

Authors: Abdelkrim Belhaoua, Jean-Pierre Radoux, Mariana Kuras, Vincent Récamier, Martial Piotto, Karim Elbayed, François Proust, Izzie Namer

Abstract:

This paper proposes an augmented reality system dedicated to neurosurgery in order to assist the surgeon during an operation. This work is part of the ExtempoRMN project (Funded by Bpifrance) which aims at analyzing during a surgical operation the metabolic content of tumoral brain biopsy specimens by HRMAS NMR. Patients affected with a brain tumor (gliomas) frequently need to undergo an operation in order to remove the tumoral mass. During the operation, the neurosurgeon removes biopsy specimens using image-guided surgery. The biopsy specimens removed are then sent for HRMAS NMR analysis in order to obtain a better diagnosis and prognosis. Image-guided refers to the use of MRI images and a computer to precisely locate and target a lesion (abnormal tissue) within the brain. This is performed using preoperative MRI images and the BrainLab neuro-navigation system. With the patient MRI images loaded on the Brainlab Cranial neuro-navigation system in the operating theater, surgeons can better identify their approach before making an incision. The Brainlab neuro-navigation tool tracks in real time the position of the instruments and displays their position on the patient MRI data. The results of the biopsy analysis by 1H HRMAS NMR are then sent back to the operating theater and superimposed on the 3D localization system directly on the MRI images. The method we have developed to communicate between the HRMAS NMR analysis software and Brainlab makes use of a combination of C++, VTK and the Insight Toolkit using OpenIGTLink protocol.

Keywords: neuro-navigation, augmented reality, biopsy, BrainLab, HR-MAS NMR

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1356 Glucose Measurement in Response to Environmental and Physiological Challenges: Towards a Non-Invasive Approach to Study Stress in Fishes

Authors: Tomas Makaras, Julija Razumienė, Vidutė Gurevičienė, Gintarė Sauliutė, Milda Stankevičiūtė

Abstract:

Stress responses represent animal’s natural reactions to various challenging conditions and could be used as a welfare indicator. Regardless of the wide use of glucose measurements in stress evaluation, there are some inconsistencies in its acceptance as a stress marker, especially when it comes to comparison with non-invasive cortisol measurements in the fish challenging stress. To meet the challenge and to test the reliability and applicability of glucose measurement in practice, in this study, different environmental/anthropogenic exposure scenarios were simulated to provoke chemical-induced stress in fish (14-days exposure to landfill leachate) followed by a 14-days stress recovery period and under the cumulative effect of leachate fish subsequently exposed to pathogenic oomycetes (Saprolegnia parasitica) to represent a possible infection in fish. It is endemic to all freshwater habitats worldwide and is partly responsible for the decline of natural freshwater fish populations. Brown trout (Salmo trutta fario) and sea trout (Salmo trutta trutta) juveniles were chosen because of a large amount of literature on physiological stress responses in these species was known. Glucose content in fish by applying invasive and non-invasive glucose measurement procedures in different test mediums such as fish blood, gill tissues and fish-holding water were analysed. The results indicated that the quantity of glucose released in the holding water of stressed fish increased considerably (approx. 3.5- to 8-fold) and remained substantially higher (approx. 2- to 4-fold) throughout the stress recovery period than the control level suggesting that fish did not recover from chemical-induced stress. The circulating levels of glucose in blood and gills decreased over time in fish exposed to different stressors. However, the gill glucose level in fish showed a decrease similar to the control levels measured at the same time points, which was found to be insignificant. The data analysis showed that concentrations of β-D glucose measured in gills of fish treated with S. parasitica differed significantly from the control recovery, but did not differ from the leachate recovery group showing that S. parasitica presence in water had no additive effects. In contrast, a positive correlation between blood and gills glucose were determined. Parallel trends in blood and water glucose changes suggest that water glucose measurement has much potency in predicting stress. This study demonstrated that measuring β-D-glucose in fish-holding water is not stressful as it involves no handling and manipulation of an organism and has critical technical advantages concerning current (invasive) methods, mainly using blood samples or specific tissues. The quantification of glucose could be essential for studies examining the stress physiology/aquaculture studies interested in the assessment or long-term monitoring of fish health.

Keywords: brown trout, landfill leachate, sea trout, pathogenic oomycetes, β-D-glucose

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1355 Starch Incorporated Hydroxyapatite/Chitin Nanocomposite as a Novel Bone Construct

Authors: Reshma Jolly, Mohammad Shakir, Mohammad Shoeb Khan, Noor E. Iram

Abstract:

A nanocomposite system integrating hydroxyapatite, chitin and starch (n-HA/CT/ST) has been synthesized via co-precipitation approach at room temperature, addressing the issues of biocompatibility, mechanical strength and cytotoxicity required for Bone tissue engineering. The interactions, crystallite size and surface morphology against n-HA/CT (nano-hydroxyapatite/chitin) nanocomposite have been obtained by correlating and comparing the results of FTIR, SEM, TEM and XRD. The comparative study of the bioactivity of n-HA/CT and n-HA/CT/ST nanocomposites revealed that the incorporation of starch as templating agent improved these properties in n-HA/CT/ST nanocomposite. The rise in thermal stability in n-HA/CT/ST nanocomposite as compared to n-HA/CT has been observed by comparing the TGA results. The comparison of SEM images of both the scaffolds indicated that the addition of ST influenced the surface morphology of n-HA/CT scaffold which appeared to be rougher and porous. The MTT assay on murine fibroblast L929 cells and in-vitro bioactivity of n-HA/CT/ST matrix referred superior non-toxic property of n-HA/CT/ST nanocomposite and higher possibility of osteo-integration in-vivo, respectively.

Keywords: bioactive, chitin, hyroxyapatite, nanocomposite

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1354 Potential Applications and Future Prospects of Zinc Oxide Thin Films

Authors: Temesgen Geremew

Abstract:

ZnO is currently receiving a lot of attention in the semiconductor industry due to its unique characteristics. ZnO is widely used in solar cells, heat-reflecting glasses, optoelectronic bias, and detectors. In this composition, we provide an overview of the ZnO thin flicks' packages, methods of characterization, and implicit operations. They consist of Transmission spectroscopy, Raman spectroscopy, Field emigration surveying electron microscopy, and X-ray diffraction. This review content also demonstrates how ZnO thin flicks function in electrical components for piezoelectric bias, optoelectronics, detectors, and renewable energy sources. Zinc oxide (ZnO) thin films offer a captivating tapestry of possibilities due to their unique blend of electrical, optical, and mechanical properties. This review delves into the realm of their potential applications and future prospects, highlighting the pivotal contributions of research endeavors aimed at tailoring their functionalities.

Keywords: Zinc oxide, raman spectroscopy, thin films, piezoelectric devices

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1353 Somatic Hybridization of between Citrus and Murraya paniculata Cells Applied by Electro-Fusion

Authors: Hasan Basri Jumin

Abstract:

Protoplasts isolated from embryogenic callus of Citrus sinensis were electrically used with mesophyll protoplasts isolated from seedless Citrus relatives. Hybrid of somatic embryos plantlets was obtained after 7 months of culture. Somatic hybrid plants were regenerated into normal seedlings and successfully transferred to soil after strictly acclimatization in the glass pot. The somatic hybrid plants were obtained by screening on the basis of chromosomes count. The number of chromosome of root tip counting revealed plantlets tetraploids (2n = 4x = 36) and the other were diploids (2n = 2x = 18) morphologically resembling the mesophyll parent. This somatic hybrid will be utilized as a possible pollen parent for improving the Citrus sinensis. A complete protoplast-to-plant system of somatic hybrid was developed for Citrus sinensis and Citrus relatives which could facilitate the transfer of nuclear and cytoplasmic genes from this species into cultivated Citrus through protoplast fusion.

Keywords: chromosome, Murraya paniculata, protoplast fusion, somatic hybrid, tetrapoliod

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1352 Case Report: Ocular Helminth – In Unusual Site (Lens)

Authors: Chandra Shekhar Majumder, Shamsul Haque, Khondaker Anower Hossain, Rafiqul Islam

Abstract:

Introduction: Ocular helminths are parasites that infect the eye or its adnexa. They can be either motile worms or sessile worms that form cysts. These parasites require two hosts for their life cycle, a definite host (usually a human) and an intermediate host (usually an insect). While there have been reports of ocular helminths infecting various structures of the eye, including the anterior chamber and subconjunctival space, there is no previous record of such a case involving the lens. Research Aim: The aim of this case report is to present a rare case of ocular helminth infection in the lens and to contribute to the understanding of this unusual site of infection. Methodology: This study is a case report, presenting the details and findings of an 80-year-old retired policeman who presented with severe pain, redness, and vision loss in the left eye. The examination revealed the presence of a thread-like helminth in the lens. The data for this case report were collected through clinical examination and medical records of the patient. The findings were described and presented in a descriptive manner. No statistical analysis was conducted. Case report: An 80-year-old retired policeman attended the OPD, Faridpur Medical College Hospital with the complaints of severe pain, redness and gross dimness of vision of the left eye for 5 days. He had a history of diabetes mellitus and hypertension for 3 years. On examination, L/E visual acuity was PL only, moderate ciliary congestion, KP 2+, cells 2+ and posterior synechia from 5 to 7 O’clock position was found. Lens was opaque. A thread like helminth was found under the anterior of the lens. The worm was moving and changing its position during examination. On examination of R/E, visual acuity was 6/36 unaided, 6/18 with pinhole. There was lental opacity. Slit-lamp and fundus examination were within normal limit. Patient was admitted in Faridpur Medical College Hospital. Diabetes mellitus was controlled with insulin. ICCE with PI was done on the same day of admission under depomedrol coverage. The helminth was recovered from the lens. It was thread like, about 5 to 6 mm in length, 1 mm in width and pinkish in colour. The patient followed up after 7 days, VA was HM, mild ciliary congestion, few KPs and cells were present. Media was hazy due to vitreous opacity. The worm was sent to the department of Parasitology, NIPSOM, Dhaka for identification. Theoretical Importance: This case report contributes to the existing literature on ocular helminth infections by reporting a unique case involving the lens. It highlights the need for further research to understand the mechanism of entry of helminths in the lens. Conclusion: To the best of our knowledge, this is the first reported case of ocular helminth infection in the lens. The presence of the helminth in the lens raises interesting questions regarding its pathogenesis and entry mechanism. Further study and research are needed to explore these aspects. Ophthalmologists and parasitologists should be aware of the possibility of ocular helminth infections in unusual sites like the lens.

Keywords: helminth, lens, ocular, unusual

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1351 Dependence of the Electro-Stimulation of Saccharomyces cerevisiae by Pulsed Electric Field at the Yeast Growth Phase

Authors: Jessy Mattar, Mohamad Turk, Maurice Nonus, Nikolai Lebovka, Henri El Zakhem, Eugene Vorobiev

Abstract:

The effects of electro-stimulation of S. cerevisiae cells in colloidal suspension by Pulsed Electric Fields ‎‎(PEF) with electric field strength E = 20 – 2000 V.cm-1 and effective PEF treatment time tPEF = 10^−5 – 1 s were ‎investigated. The applied experimental procedure includes variations in the preliminary fermentation time and ‎electro-stimulation by PEF-treatment. Plate counting was performed.‎ At relatively high electric fields (E ≥ 1000 V.cm-1) and moderate PEF treatment time (tPEF > 100 µs), the ‎extraction of ionic components from yeast was observed by conductivity measurements, which can be related to ‎electroporation of cell membranes. Cell counting revealed a dependency of the colonies’ size on the time of ‎preliminary fermentation tf and the power consumption W, however no dependencies were noticeable by varying the initial yeast concentration in the treated suspensions.‎

Keywords: intensification, yeast, fermentation, electroporation, biotechnology

Procedia PDF Downloads 453
1350 The Many Faces of Cancer and Knowing When to Say Stop

Authors: Diwei Lin, Amanda Jh. Tan

Abstract:

We present a very rare case of de novo large cell neuroendocrine carcinoma of the prostate (LCNEC) in an 84-year-old male on a background of high-grade, muscle-invasive transitional cell carcinoma of the bladder. While NE tumours account for 1% to 5% of all cases of prostate cancer and scattered NE cells can be found in 10% to 100% of prostate adenocarcinomas, pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate is thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing NE differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease, and a worse prognosis.

Keywords: large cell neuroendocrine cancer, prostate cancer, refractory cancer, medical and health sciences

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1349 Biological Evaluation and Molecular Modeling Study of Thiosemicarbazide Derivatives as Bacterial Type IIA Topoisomerases Inhibitors

Authors: Paweł Stączek, Tomasz Plech, Aleksandra Strzelczyk, Katarzyna Dzitko, Monika Wujec, Edyta Kuśmierz, Piotr Paneth, Agata Paneth

Abstract:

In this contribution, we will describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile, and molecular modeling evaluation. We have found that one of the tested compounds, 4-benzoyl-1-(2-methyl-furan-3-ylcarbonyl) thiosemicarbazide, remarkably inhibits the activity of S. aureus DNA gyrase with the IC50 below 5 μM. Besides, this compound displays antibacterial activity on Staphylococcus spp. and E. faecalis at non-cytotoxic concentrations in mammalian cells, with minimal inhibitory concentrations (MICs) values at 25 μg/mL. Based on the enzymatic and molecular modeling studies we propose two factors, i.e. geometry of molecule and hydrophobic/hydrophilic balance as important molecular properties for developing thiosemicarbazide derivatives as potent Staphylococcus aureus DNA gyrase inhibitors.

Keywords: bioactivity, drug design, topoisomerase, molecular modeling

Procedia PDF Downloads 547