Search results for: Oral Squamous Cell Carcinoma (OSCC)

Authors: Yusser Olguín, Diego Benavente, Fernando Dorta, Nicole Orellana, Cristian Acevedo

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One of the greatest challenges of tissue engineering is the generation of materials in which the highest possible number of conditions can be incorporated to stimulate the proliferation and differentiation of cells, which will be transformed together with the material into new functional tissue. In this sense, considering the properties of microfluidics and its relationship with cellular micro-environments, the possibility of controlling flow patterns and the ability to design diverse patterns in the chips, a microfluidic cell culture system can be established as a means for the evaluation of the effect of different parameters in a controlled and precise manner. Specifically in relation to the study and development of alternatives in peripheral nervous tissue engineering, it is necessary to consider different physical and chemical neurotrophic stimuli that promote cell growth and differentiation. Chemical stimuli include certain vitamins, glucocorticoids, gangliosides, and growth factors, while physical stimuli include topological stimuli, mechanical forces of the cellular environment and electrical stimulation. In this context, the present investigation shows the results of cell stimulation in a microbioreactor using electrical and chemical stimuli, where the differentiation of PC12 cells as a neuronal model is evidenced by neurite expression, dependent on the stimuli and their combination. The results were analysed with a multi-factor statistical approach, showing several relationships and dependencies between different parameters. Chip design, operating parameters and concentrations of neurotrophic chemical factors were found to be preponderant, based on the characteristics of the electrical stimuli.

Keywords: microfluidics, nerve tissue engineering, microbioreactor, electrical stimuli

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancers (HNC) are often associated with the development of non-HNC primaries, as the risk factors that predispose patients to HNC are often risk factors for other cancers. Aim: We sought to evaluate whether there was an increased risk of smoking and alcohol-related cancers and also other cancers in HNC patients and to evaluate whether there is a difference between the rates of non-HNC primaries in Aboriginal compared with non-Aboriginal HNC patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single center in Western Australia, identifying 80 Aboriginal and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, treatments, outcomes, and past and subsequent HNCs and non-HNC primaries. Results: In the overall study population, there were 86 patients (26.9%) with a metachronous or synchronous non-HNC primary. Non-HNC primaries were actually significantly more common in the non-Aboriginal population compared with the Aboriginal population (30% vs. 17.5%, p=0.02); however, half of these were patients with cutaneous squamous or basal cell carcinomas (cSCC/BCC) only. When cSCC/BCCs were excluded, non-Aboriginal patients had a similar rate as Aboriginal patients (16.7% vs. 15%, p=0.73). There were clearly more cSCC/BCCs in non-Aboriginal patients compared with Aboriginal patients (16.7% vs. 2.5%, p=0.001) and more patients with melanoma (2.5% vs. 0%, p value not significant (p=NS). Rates of most cancers were similar between non-Aboriginal and Aboriginal patients, including prostate (2.9% vs. 3.8%), colorectal (2.9% vs. 2.5%), kidney (1.2% vs. 1.2%), and these rates appeared comparable to Australian Age Standardised Incidence Rates (ASIR) in the general community. Oesophageal cancer occurred at double the rate in Aboriginal patients (3.8%) compared with non-Aboriginal patients (1.7%), which was far in excess of ASIRs which estimated a lifetime risk of 0.59% in the general population. Interestingly lung cancer rates did not appear to be significantly increased in our cohort, with 2.5% of Aboriginal patients and 3.3% of non-Aboriginal patients having lung cancer, which is in line with ASIRs which estimates a lifetime risk of 5% (by age 85yo). Interestingly the rate of Glioma in the non-Aboriginal population was higher than the ASIR, with 0.8% of non-Aboriginal patients developing Glioma, with Australian averages predicting a 0.6% lifetime risk in the general population. As these are small numbers, this finding may well be due to chance. Unsurprisingly, second HNCs occurred at an increased incidence in our cohort, in 12.5% of Aboriginal patients and 11.2% of non-Aboriginal patients, compared to an ASIR of 17 cases per 100,000 persons, estimating a lifetime risk of 1.70%. Conclusions: Overall, 26.9% of patients had a non-HNC primary. When cSCC/BCCs were excluded, Aboriginal and non-Aboriginal patients had similar rates of non-HNC primaries, although non-Aboriginal patients had a significantly higher rate of cSCC/BCCs. Aboriginal patients had double the rate of oesophageal primaries; however, this was not statistically significant, possibly due to small case numbers.

Keywords: head and neck cancer, synchronous and metachronous primaries, other primaries, Aboriginal

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Ila Shukla, Lubna Azmi, Shyam Sunder Gupta, C. V. Rao

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Treatments against Hepatitis-C virus (HCV) are already available, but the current high cost of such treatments limit them to wealthy patients only. Hence our current study is aimed at the rectification of HCV infection by using Lichen rangiferinus (LRE) extract in in vitro cultures. Anti-HCV activity of the given extract was evaluated using the virus grown in cell culture (HCVcc). Two control inhibitors, erlotinib and telaprevir, were systematically included in each experiment. At the end of the incubation period, we evaluated cell viability and viral replication. The LRE inhibited the growth of HCV in a dose dependent manner.

Keywords: Erlotinib, Hepatitis C, Lichen rangiferinus, Telaprevir

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Dileep Kumar Verma, Sunil Kumar Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Athanasios A. Tountas, Geoffrey A. Ozin, Mohini M. Sain

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Renewable hydrogen (H₂) carriers such as methanol (MeOH), dimethyl ether (DME), oxymethylene dimethyl ethers (OMEs), and conceivably ammonia (NH₃) can be reformed back into H₂ and are fundamental chemical conversions for the long-term viability of the H₂ economy due to their higher densities and ease of transportability compared to H₂. MeOH is an especially important carrier as it is a simple C1 chemical that can be produced from green solar-PV-generated H₂ and direct-air-captured CO₂ with a current commercially practical solar-to-fuel efficiency of 10% from renewable solar energy. MeOH steam reforming (MSR) in stationary systems next to H₂ fuel-cell filling stations can eliminate the need for onboard mobile reformers, and the former systems can be more robust in terms of attaining strict H₂ product specifications, and MeOH is a safe, lossless, and compact medium for long-term H₂ storage. Both thermal- and photo-catalysts are viable options for achieving the stable, long-term performance of stationary MSR systems.

Keywords: fuel-cell vehicle filling stations, methanol steam reforming, hydrogen transport and storage, stationary reformer, liquid hydrogen carriers

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Authors: Cristian Soitu, Alexander Feuerborn, Cyril Deroy, Alfonso Castrejon-Pita, Peter R. Cook, Edmond J. Walsh

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Microfluidics now stands as an academically mature technology after a quarter of a century research activities have delivered a vast array of proof of concepts for many biological workflows. However, translation to industry remains poor, with only a handful of notable exceptions – e.g. digital PCR, DNA sequencing – mainly because of biocompatibility issues, limited range of readouts supported or complex operation required. This technology exploits the domination of interfacial forces over gravitational ones at the microscale, replacing solid walls with fluid ones as building blocks for cell micro-environments. By employing only materials used by biologists for decades, the system is shown to be biocompatible, and easy to manufacture and operate. The method consists in displacing a continuous fluid layer into a pattern of isolated chambers overlaid with an immiscible liquid to prevent evaporation. The resulting fluid arrangements can be arrays of micro-chambers with rectangular footprint, which use the maximum surface area available, or structures with irregular patterns. Pliant, self-healing fluid walls confine volumes as small as 1 nl. Such fluidic structures can be reconfigured during the assays, giving the platform an unprecedented level of flexibility. Common workflows in cell biology are demonstrated – e.g. cell growth and retrieval, cloning, cryopreservation, fixation and immunolabeling, CRISPR-Cas9 gene editing, and proof-of-concept drug tests. This fluid-shaping technology is shown to have potential for high-throughput cell- and organism-based assays. The ability to make and reconfigure on-demand microfluidic circuits on standard Petri dishes should find many applications in biology, and yield more relevant phenotypic and genotypic responses when compared to standard microfluidic assays.

Keywords: fluid walls, micro-chambers, reconfigurable, freestyle

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Authors: Mengying Wang, Dongjing Liu, Holger Schwender, Ping Wang, Hongping Zhu, Tao Wu, Terri H Beaty

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Background: Maternal smoking is a recognized risk factor for nonsyndromic cleft lip with or without cleft palate (NSCL/P). It has been reported that the effect of maternal smoking on oral clefts is mediated through genes that influence nicotine dependence. The polymorphisms of cholinergic receptor nicotinic alpha (CHRNA) and beta (CHRNB) subunits genes have previously shown strong associations with nicotine dependence. Here, we attempted to investigate whether the above genes are associated with clefting risk through testing for potential gene-gene (G×G) and gene-environment (G×E) interaction. Methods: We selected 120 markers in 14 genes associated with nicotine dependence to conduct transmission disequilibrium tests among 806 Chinese NSCL/P case-parent trios ascertained in an international consortium which conducted a genome-wide association study (GWAS) of oral clefts. We applied Cordell’s method using “TRIO” package in R to explore G×G as well as G×E interaction involving environmental tobacco smoke (ETS) based on conditional logistic regression model. Results: while no SNP showed significant association with NSCL/P after Bonferroni correction, we found signals for G×G interaction between 10 pairs of SNPs in CHRNA3, CHRNA5, and CHRNB4 (p<10-8), among which the most significant interaction was found between RS3743077 (CHRNA3) and RS11636753 (CHRNB4, p<8.2×10-12). Linkage disequilibrium (LD) analysis revealed only low level of LD between these markers. However, there were no significant results for G×ETS interaction. Conclusion: This study fails to detect association between nicotine dependence genes and NSCL/P, but illustrates the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P. This study also suggests nicotine dependence genes should be considered as important candidate genes for NSCL/P in future studies.

Keywords: Gene-Gene Interaction, Maternal Smoking, Nicotine Dependence, Non-Syndromic Cleft Lip with or without Cleft Palate

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Qasim A. El Dwairi, Saleh M. Banihani, Ayat S. Banihani, Ziad M. Bataineh

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Neurons in the spinal trigeminal nucleus of the camel were studied by Golgi impregnation. Neurons were classified based on differences in size and shape of their cell bodies, density of their dendritic trees, morphology and distribution of their appendages. In the spinal trigeminal nucleus of the camel, at least twelve types of neurons were identified. These neurons include, stalked, islets, octubus-like, lobulated, boat-like, pyramidal, multipolar, round, oval and elongated neurons. They have large number of different forms of appendages not only for their dendrites but also for their cell bodies. Neurons with unique large dilatations especially at their dendritic branching points were found. The morphological features of these neurons were described and compared with their counterparts in other species. Finding of large number of neuronal types with different size and shapes and large number of different forms of appendages for cell bodies and dendrites together with the presence of cells with unique features such as large dilated parts for dendrites may indicate to a very complex information processing for pain and temperature at the level of the spinal trigeminal nucleus in the camel that traditionally live in a very hard environment (the desert).

Keywords: camel, golgi, neurons , spinal trigeminal nucleus

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Authors: Astari Indarsari, Bastian B. Purba, Muhammad Fadlilah

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In Indonesian climates that have the tropic climate, one of the potential energy sources is coming from solar energy. From the solar energy, we can convert it into the others energy, such as electrical energy. In this topic, we want to do the research about Dye Sensitized Solar Cell (DSSC). The materials that we use as sensitizer is anthocyanin that we extract from apple skin, because the anthocyanin is one of the most effective as a sensitizer for DSSC. The variable in this research is pH. The pH that we used are pH 0,5; pH 1; pH 1,5; pH 2; pH 2,5. The method is electrolysis, and we use TiO2 as sensitized material. The hypothesis from this research is the smaller pH can make higher the efficiency of the absorbent of the solar energy.

Keywords: anthocyanin, TiO2, DSSC, apple skin

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Authors: Ihn Sook Jeong, Eun Joo Lee, Jae Hyung Kim, Gun Ho Kim, Young Jun Hwang

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This study investigated intravenous (IV) infiltration using bioelectrical impedance for 27 hospitalized patients in a long-term care hospital. Impedance parameters showed significant differences before and after infiltration as follows. First, the resistance (R) after infiltration significantly decreased compared to the initial resistance. This indicates that the IV solution flowing from the vein due to infiltration accumulates in the extracellular fluid (ECF). Second, the relative resistance at 50 kHz was 0.94 ± 0.07 in 9 subjects without infiltration and was 0.75 ± 0.12 in 18 subjects with infiltration. Third, the magnitude of the reactance (Xc) decreased after infiltration. This is because IV solution and blood components released from the vein tend to aggregate in the cell membrane (and acts analogously to the linear/parallel circuit), thereby increasing the capacitance (Cm) of the cell membrane and reducing the magnitude of reactance. Finally, the data points plotted in the R-Xc graph were distributed on the upper right before infiltration but on the lower left after infiltration. This indicates that the infiltration caused accumulation of fluid or blood components in the epidermal and subcutaneous tissues, resulting in reduced resistance and reactance, thereby lowering integrity of the cell membrane. Our findings suggest that bioelectrical impedance is an effective method for detection of infiltration in a noninvasive and quantitative manner.

Keywords: intravenous infiltration, impedance, parameters, resistance, reactance

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Authors: Nabil A. Ahmed

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DC-DC converters are necessary to interface low-voltage fuel cell power generation systems to a higher voltage DC bus system. A system and method for generating a regulated output power from fuel cell power generation systems is proposed in this paper, this includes a soft-switching isolated DC-DC converter to reduce the idling and circulating currents. The system incorporates a high-frequency center tap transformer link DC-DC converter using secondary-side soft switching control. Snubber capacitors including the parasitic capacitance of the switching devices and the transformer leakage inductance are utilized to achieve zero-voltage switching (ZVS) in the primary side of the high-frequency transformer. Therefore, no extra resonant components are required for ZVS. The inherent soft-switching capability allows high power density, efficient power conversion, and compact packaging. A prototype rated at 6.5 kW is proposed and simulated. Simulation results confirmed a wide range of soft-switching operation and consequently high conversion efficiency will be achieved.

Keywords: secondary-side, phase-shift, high-frequency transformer, zero voltage, zero current, soft switching operation, switching losses

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Authors: Juneseok You, Kuewhan Jang, Chanho Park, Jaeyeong Choi, Hyunjun Park, Sehyun Shin, Changsoo Han, Sungsoo Na

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Nanomaterials occur toxic effects to human being or ecological systems. Some sensors have been developed to detect toxic materials and the standard for toxic materials has been established. Zinc oxide nanowire (ZnO NW) is known for toxic material. By ionizing in cell body, ionized Zn ions are overexposed to cell components, which cause critical damage or death. In this paper, we detected ZnO NW in water using QCM (Quartz Crystal Microbalance) and ssDNA (single strand DNA). We achieved 30 minutes of response time for real time detection and 100 pg/mL of limit of detection (LOD).

Keywords: zinc oxide nanowire, QCM, ssDNA, toxic material, biosensor

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Authors: Adnan Gohar

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This research work aims the importance of internal employees in the making of a brand (cell phone) through customer satisfaction which basically explains the connection of internal employees with external customers. This research is designed to measure the satisfaction level of internal employees which further connects to the product evolution as a brand leaving a brand image in the eye of the external customer. The main focus is that internal employees are as important as external customers for the uplift of the product resulting in the brand. Internal employees are individual organization employees, vendors, departments, and distributors.

Keywords: brand building, customer satisfaction, internal employees, mobile franchise

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Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

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Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: Yujin Jeong, Youkyung Son, Myounghwan Choi, Sanghyub Lee, Sangyeol Lee, Changho Hwang, Kyo-in Koo

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Dysphasia is difficulty in swallowing food because of oral cavity impairments induced by stroke, muscle damage, tumor. Intermittent oro-esophageal (IOE) tube feeding is one of the well-known feeding methods for the dysphasia patients. However, it is hard to insert at the proper position in esophagus. In this study, we design and fabricate the IOE tube guide using 3-dimensional (3D) printer. The printed IOE tube is tested in a mannequin (Airway Management Trainer, Co., Ltd., Copenhagen, Denmark) mimicking human’s esophagus. The gag reflex point is measured as the design point in the mannequin. To avoid the gag reflex, we design various shapes of IOE tube guide. One structure is separated into three parts; biting part, part through oral cavity, connecting part to oro-esophageal. We designed 6 types of IOE tube guide adjusting length and angle of these three parts. To evaluate the IOE tube guide, it is inserted in the mannequin, and through the inserted guide, an endoscopic camera successfully arrived at the oro-esophageal. We had planned to apply this mannequin-based design experience to patients in near future.

Keywords: dysphagia, feeding method, IOE tube guide, 3-D printer

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Gary J. Pickering, Sarah Lucas, Catherine E. Klodnicki, Nicole J. Gaudette

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Two taste pheno types that are of interest in the study of habitual diet-related risk factors and disease are 6-n-propylthiouracil (PROP) responsiveness and thermal tasting. Individuals differ considerable in how intensely they experience the bitterness of PROP, which is partially explained by three major single nucleotide polymorphisms associated with the TAS2R38 gene. Importantly, this variable responsiveness is a useful proxy for general taste responsiveness, and links to diet-related disease risk, including body mass index, in some studies. Thermal tasting - a newly discovered taste phenotype independent of PROP responsiveness - refers to the capacity of many individuals to perceive phantom tastes in response to lingual thermal stimulation, and is linked with TRPM5 channels. Thermal tasters (TTs) also experience oral sensations more intensely than thermal non-tasters (TnTs), and this was shown to associate with differences in self-reported food preferences in a previous survey from our lab. Here we report on two related studies, where we sought to determine whether PROP responsiveness and thermal tasting would associate with perceptual differences in the oral sensations elicited by sampled energy-dense foods, and whether in turn this would influence liking. We hypothesized that hyper-tasters (thermal tasters and individuals who experience PROP intensely) would (a) rate sweet and high-fat foods more intensely than hypo-tasters, and (b) would differ from hypo-tasters in liking scores. (Liking has been proposed recently as a more accurate measure of actual food consumption). In Study 1, a range of energy-dense foods and beverages, including table cream and chocolate, was assessed by 25 TTs and 19 TnTs. Ratings of oral sensation intensity and overall liking were obtained using gVAS and gDOL scales, respectively. TTs and TnTs did not differ significantly in intensity ratings for most stimuli (ANOVA). In a 2nd study, 44 female participants sampled 22 foods and beverages, assessing them for intensity of oral sensations (gVAS) and overall liking (9-point hedonic scale). TTs (n=23) rated their overall liking of creaminess and milk products lower than did TnTs (n=21), and liked milk chocolate less. PROP responsiveness was negatively correlated with liking of food and beverages belonging to the sweet or sensory food grouping. No other differences in intensity or liking scores between hyper- and hypo-tasters were found. Taken overall, our results are somewhat unexpected, lending only modest support to the hypothesis that these taste phenotypes associate with energy-dense food liking and consumption through differences in the oral sensations they elicit. Reasons for this lack of concordance with expectations and some prior literature are discussed, and suggestions for future research are advanced.

Keywords: taste phenotypes, sensory evaluation, PROP, thermal tasting, diet-related health risk

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Authors: Emanuel Teixeira, Anderson Ramos, Marisa Lourenço, Fernando J. Velez, Jon M. Peha

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This article discusses the benefit cost analysis aspects of millimetre wavebands (mmWaves) and Super High Frequency (SHF). The devaluation along the distance of the carrier-to-noise-plus-interference ratio with the coverage distance is assessed by considering two different path loss models, the two-slope urban micro Line-of-Sight (UMiLoS) for the SHF band and the modified Friis propagation model, for frequencies above 24 GHz. The equivalent supported throughput is estimated at the 5.62, 28, 38, 60 and 73 GHz frequency bands and the influence of carrier-to-noise-plus-interference ratio in the radio and network optimization process is explored. Mostly owing to the lessening caused by the behaviour of the two-slope propagation model for SHF band, the supported throughput at this band is higher than at the millimetre wavebands only for the longest cell lengths. The benefit cost analysis of these pico-cellular networks was analysed for regular cellular topologies, by considering the unlicensed spectrum. For shortest distances, we can distinguish an optimal of the revenue in percentage terms for values of the cell length, R ≈ 10 m for the millimeter wavebands and for longest distances an optimal of the revenue can be observed at R ≈ 550 m for the 5.62 GHz. It is possible to observe that, for the 5.62 GHz band, the profit is slightly inferior than for millimetre wavebands, for the shortest Rs, and starts to increase for cell lengths approximately equal to the ratio between the break-point distance and the co-channel reuse factor, achieving a maximum for values of R approximately equal to 550 m.

Keywords: millimetre wavebands, SHF band, SINR, cost benefit analysis, 5G

Procedia PDF Downloads 125

Authors: Roberta S. Ilinsky, Livia Eisler, Gustavo Mota, Kurt Faltin Jr., Cristina Lucia Feijó Ortolani

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The aim of the present study was to evaluate the presence of occlusal disorders associated with bottle feeding habits in children aged 4-6 years old. A cross-sectional study was performed in a sample of 466 preschool children aged 4-6 years, attending state preschools in the city of Sao Paulo, Brazil. Parents and caregivers answered a questionnaire about children’s oral habits, including bottle-feeding habit, and signed the Informed Consent form. The students underwent an oral examination to evaluate occlusal disorders. Data were analyzed by the SPSS 2.2 program (IBM, USA) and treated with non-parametric chi-square tests and multiple logistic regression with a significance level of p < 0.05. There was association between bottle-feeding and occlusal disorders (OR = 3.058, 95% CI = 1.561-5.991, PI < 0.001), with a higher significance for anterior open bite (OR = 2.855, 95% CI = 1.769-4.606, PI < 0.001) and canine class II (OR = 0.667, 95% CI = 0.449-0.990, PI < 0.045). There was no relationship between bottle-feeding habit and other occlusal disorders examined. It was possible to conclude that children who were bottle fed during childhood are more likely to develop occlusal disorders, especially anterior open bite and canine class II.

Keywords: anterior open-bite, bottle-feeding, habits, malocclusion

Procedia PDF Downloads 155

Authors: Mariam Dianat Sabet Gilani, Lars M. Blank, Birgitta E. Ebert

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Plant-derived lupane-type, pentacyclic triterpenoids are biologically active compounds that are highly interesting for applications in medical, pharmaceutical, and cosmetic industries. Due to the low abundance of these valuable compounds in their natural sources, and the environmentally harmful downstream process, alternative production methods, such as microbial cell factories, are investigated. Engineered Saccharomyces cerevisiae strains, harboring the heterologous genes for betulinic acid synthesis, can produce up to 2 g L-1 triterpenoids, showing high potential for large-scale production of triterpenoids. One limitation of the microbial synthesis is the intracellular product accumulation. It not only makes cell disruption a necessary step in the downstream processing but also limits productivity and product yield per cell. To overcome these restrictions, the aim of this study is to develop an in-situ extraction method, which extracts triterpenoids into a second organic phase. Such a continuous or sequential product removal from the biomass keeps the cells in an active state and enables extended production time or biomass recycling. After screening of twelve different solvents, selected based on product solubility, biocompatibility, as well as environmental and health impact, isopropyl myristate (IPM) was chosen as a suitable solvent for in-situ product removal from S. cerevisiae. Impedance-based single-cell analysis and off-gas measurement of carbon dioxide emission showed that cell viability and physiology were not affected by the presence of IPM. Initial experiments demonstrated that after the addition of 20 vol % IPM to cultures in the stationary phase, 40 % of the total produced triterpenoids were extracted from the cells into the organic phase. In future experiments, the application of IPM in a repeated batch process will be tested, where IPM is added at the end of each batch run to remove triterpenoids from the cells, allowing the same biocatalysts to be used in several sequential batch steps. Due to its high biocompatibility, the amount of IPM added to the culture can also be increased to more than 20 vol % to extract more than 40 % triterpenoids in the organic phase, allowing the cells to produce more triterpenoids. This highlights the potential for the development of a continuous large-scale process, which allows biocatalysts to produce intracellular products continuously without the necessity of cell disruption and without limitation of the cell capacity.

Keywords: betulinic acid, biocompatible solvent, in-situ extraction, isopropyl myristate, process development, secondary metabolites, triterpenoids, yeast

Procedia PDF Downloads 129

Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Eun-Soo Lim, Young-Min Kang

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M-type Sr-hexaferrite (SrFe₁₂O₁₉) have been studied during the past decades because it is the most utilized materials in permanent magnets due to their low price, outstanding chemical stability, and appropriate hard magnetic properties. Many attempts have been made to improve the intrinsic magnetic properties of M-type Sr-hexaferrites (SrM), such as by improving the saturation magnetization (MS) and crystalline anisotropy by cation substitution. It is well proved that the Ca-La-Co substitutions are one of the most successful approaches, which lead to a significant enhancement in the crystalline anisotropy without reducing MS, and thus the Ca-La-Co-doped SrM have been commercialized in high-grade magnet products. In this research, the effect of respective doping of Ca and La into the SrM lattices were studied with assumptions that these elements could substitute both of Fe and Sr sites. The hexaferrite samples of stoichiometric SrFe₁₂O₁₉ (SrM) and the Ca substituted SrM with formulae of Sr₁₋ₓCaₓFe₁₂Oₐ (x = 0.1, 0.2, 0.3, 0.4) and SrFe₁₂₋ₓCaₓOₐ (x = 0.1, 0.2, 0.3, 0.4), and also La substituted SrM of Sr₁₋ₓLaₓFe₁₂Oₐ (x = 0.1, 0.2, 0.3, 0.4) and SrFe₁₂₋ₓLaₓOₐ (x = 0.1, 0.2, 0.3, 0.4) were prepared by conventional solid state reaction processes. X-ray diffraction (XRD) with a Cu Kα radiation source (λ=0.154056 nm) was used for phase analysis. Microstructural observation was conducted with a field emission scanning electron microscopy (FE-SEM). M-H measurements were performed using a vibrating sample magnetometer (VSM) at 300 K. Almost pure M-type phase could be obtained in the all series of hexaferrites calcined at > 1250 ºC. Small amount of Fe₂O₃ phases were detected in the XRD patterns of Sr₁₋ₓCaₓFe₁₂Oₐ (x = 0.2, 0.3, 0.4) and Sr₁₋ₓLaₓFe₁₂Oₐ (x = 0.1, 0.2, 0.3, 0.4) samples. Also, small amount of unidentified secondary phases without the Fe₂O₃ phase were found in the samples of SrFe₁₂₋ₓCaₓOₐ (x = 0.4) and SrFe₁₂₋ₓLaₓOₐ (x = 0.3, 0.4). Although the Ca substitution (x) into SrM structure did not exhibit a clear tendency in the cell parameter change in both series of samples, Sr₁₋ₓCaₓFe₁₂Oₐ and SrFe₁₂₋ₓCaₓOₐ , the cell volume slightly decreased with doping of Ca in the Sr₁₋ₓCaₓFe₁₂Oₐ samples and increased in the SrFe₁₂₋ₓCaₓOₐ samples. Considering relative ion sizes between Sr²⁺ (0.113 nm), Ca²⁺ (0.099 nm), Fe³⁺ (0.064 nm), these results imply that the Ca substitutes both of Sr and Fe in the SrM. A clear tendency of cell parameter change was observed in case of La substitution into Sr site of SrM ( Sr₁₋ₓLaₓFe₁₂Oₐ); the cell volume decreased with increase of x. It is owing to the similar but smaller ion size of La³⁺ (0.106 nm) than that of Sr²⁺. In case of SrFe₁₂₋ₓLaₓOₐ, the cell volume first decreased at x = 0.1 and then remained almost constant with increase of x from 0.2 to 0.4. These results mean that La only substitutes Sr site in the SrM structure. Besides, the microstructure and magnetic properties of these samples, and correlation between them will be revealed.

Keywords: M-type hexaferrite, substitution, cell parameter, magnetic properties

Procedia PDF Downloads 193

Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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