Search results for: inhibition of cancer cells

Authors: Sarah A. Alotaibi, Mohammed A. Almutairi, Abdullah A. Alsayari, Adibah M. Almutairi, Somaiah K. Almubayedh

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Concerns over the presence of acrylamide in food date back to 2002, when Swedish scientists stated that, in carbohydrate-rich foods, amounts of acrylamide were formed when cooked at high temperatures. Similar findings were reported by other researchers which, consequently, caused major international efforts to investigate dietary exposure and the subsequent health complications in order to properly manage this issue. Due to this issue, in this work, we aim to determine the acrylamide level in different foods (coffee, potato chips, biscuits, and baby food) commonly consumed by the Saudi population. In a total of forty-three samples, acrylamide was detected in twenty-three samples at levels of 12.3 to 2850 µg/kg. In reference to the food groups, the highest concentration of acrylamide was found in coffee samples (<12.3-2850 μg/kg), followed by potato chips (655-1310 μg/kg), then biscuits (23.5-449 μg/kg), whereas the lowest acrylamide level was observed in baby food (<14.75 – 126 μg/kg). Most coffee, biscuits and potato chips products contain high amount of acrylamide content and also the most commonly consumed product. Saudi adults had a mean exposure of acrylamide for coffee, potato, biscuit, and cereal (0.07439, 0.04794, 0.01125, 0.003371 µg/kg-b.w/day), respectively. On the other hand, exposure to acrylamide in Saudi infants and children to the same types of food was (0.1701, 0.1096, 0.02572, 0.00771 µg/kg-b.w/day), respectively. Most groups have a percentile that exceeds the tolerable daily intake (TDI) cancer value (2.6 µg/kg-b.w/day). Overall, the MOE results show that the Saudi population is at high risk of acrylamide-related disease in all food types, and there is a chance of cancer risk in all age groups (all values ˂10,000). Furthermore, it was found that in non-cancer risks, the acrylamide in all tested foods was within the safe limit (˃125), except for potato chips, in which there is a risk for diseases in the population. With potato and coffee as raw materials, additional studies were conducted to assess different factors, including temperature, cocking time, and additives affecting the acrylamide formation in fried potato and roasted coffee, by systematically varying processing temperatures and time values, a mitigation of acrylamide content was achieved when lowering the temperature and decreasing the cooking time. Furthermore, it was shown that the combination of the addition of chitosan and NaCl had a large impact on the formation.

Keywords: risk assessment, dietary exposure, MOA, acrylamide, hazard

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Authors: Samuele Ghignoli, Valentina de Lorenzi, Gianmarco Ferri, Stefano Luin, Francesco Cardarelli

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Insulin and glucagon are the two essential hormones for maintaining proper blood glucose homeostasis, which is disrupted in Diabetes. A constantly growing research interest has been focused on the study of the subcellular structures involved in hormone secretion, namely insulin- and glucagon-containing granules, and on the mechanisms regulating their behaviour. Yet, while several successful attempts were reported describing the dynamic properties of insulin granules, little is known about their counterparts in α cells, the glucagon-containing granules. To fill this gap, we used αTC1 clone 9 cells as a model of α cells and ZIGIR as a fluorescent Zinc chelator for granule labelling. We started by using spatiotemporal fluorescence correlation spectroscopy in the form of imaging-derived mean square displacement (iMSD) analysis. This afforded quantitative information on the average dynamical and structural properties of glucagon granules having insulin granules as a benchmark. Interestingly, the iMSD sensitivity to average granule size allowed us to confirm that glucagon granules are smaller than insulin ones (~1.4 folds, further validated by STORM imaging). To investigate possible heterogeneities in granule dynamic properties, we moved from correlation spectroscopy to single particle tracking (SPT). We developed a MATLAB script to localize and track single granules with high spatial resolution. This enabled us to classify the glucagon granules, based on their dynamic properties, as ‘blocked’ (i.e., trajectories corresponding to immobile granules), ‘confined/diffusive’ (i.e., trajectories corresponding to slowly moving granules in a defined region of the cell), or ‘drifted’ (i.e., trajectories corresponding to fast-moving granules). In cell-culturing control conditions, results show this average distribution: 32.9 ± 9.3% blocked, 59.6 ± 9.3% conf/diff, and 7.4 ± 3.2% drifted. This benchmarking provided us with a foundation for investigating selected experimental conditions of interest, such as the glucagon-granule relationship with the cytoskeleton. For instance, if Nocodazole (10 μM) is used for microtubule depolymerization, the percentage of drifted motion collapses to 3.5 ± 1.7% while immobile granules increase to 56.0 ± 10.7% (remaining 40.4 ± 10.2% of conf/diff). This result confirms the clear link between glucagon-granule motion and cytoskeleton structures, a first step towards understanding the intracellular behaviour of this subcellular compartment. The information collected might now serve to support future investigations on glucagon granules in physiology and disease. Acknowledgment: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 866127, project CAPTUR3D).

Keywords: glucagon granules, single particle tracking, correlation spectroscopy, ZIGIR

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Authors: Mohammaad Afzal Khan, Ghazi Abdulmalik Ashoor , Fatimah Alanazi, Talal Shamma, Abdullah Altuhami, Hala Abdalrahman Ahmed, Abdullah Mohammed Assiri, Dieter Clemens Broering

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Microvascular injuries during inflammation are key causes of transplant malfunctioning and permanent failure, which play a major role in the development of chronic rejection of the transplanted organ. Inflammation-induced microvascular loss is a promising area to investigate the decisive roles of regulatory and effector responses. The present study was designed to investigate the impact of IL-10 on immunotolerance, in particular, the microenvironment of the allograft during rejection. Here, we investigated the effects of IL-10 blockade/ reconstitution and serially monitored regulatory T cells (Tregs), graft microvasculature, and airway epithelium in rejecting airway transplants. We demonstrated that the blocking/reconstitution of IL-10 significantly modulates CD4+FOXP3+ Tregs, microvasculature, and airway epithelium during rejection. Our findings further highlighted that blockade of IL-10 upregulated proinflammatory cytokines, IL-2, IL-1β, IFN-γ, IL-15, and IL-23, but suppressed IL-5 secretion during rejection; however, reconstitution of IL-10 significantly upregulated CD4+FOXP3+ Tregs, tissue oxygenation/blood flow and airway repair. Collectively, these findings demonstrate a potential reparative modulation of IL-10 during microvascular and epithelial repair, which could provide a vital therapeutic window to rejecting transplants in clinical practice.

Keywords: interleukin -10, regulatory T cells, allograft rejection, immunotolerance

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Authors: Andrea Tundis, Carlos García Cordero, Rolf Egert, Alfredo Garro, Max Mühlhäuser

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Resilience is an important system property that relies on the ability of a system to automatically recover from a degraded state so as to continue providing its services. Resilient systems have the means of detecting faults and failures with the added capability of automatically restoring their normal operations. Mastering resilience in the domain of Cyber-Physical Systems is challenging due to the interdependence of hybrid hardware and software components, along with physical limitations, laws, regulations and standards, among others. In order to overcome these challenges, this paper presents a modeling approach, based on the concept of Dynamic Cells, tailored to the management of Smart Grids. Additionally, a heuristic algorithm that works on top of the proposed modeling approach, to find resilient configurations, has been defined and implemented. More specifically, the model supports a flexible representation of Smart Grids and the algorithm is able to manage, at different abstraction levels, the resource consumption of individual grid elements on the presence of failures and faults. Finally, the proposal is evaluated in a test scenario where the effectiveness of such approach, when dealing with complex scenarios where adequate solutions are difficult to find, is shown.

Keywords: cyber-physical systems, energy management, optimization, smart grids, self-healing, resilience, security

Procedia PDF Downloads 323

Authors: Bunindro Nameirakpam, Sonia Sougrapakam, Shannon B. Olsson, Rajashekar Yallappa

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Natural sources for new pesticidal compounds hold promise in view of their eco-friendly nature, selectivity and mammalian safety. Despite a large number of plants that show insecticidal activity and diversity of natural chemistry with inherent eco-friendly nature, newer classes of insecticides have eluded discovery. Artemisia vulgaris, known as Mugwort, is a universal herb used for folk medicine and religious purposes throughout the ancient world. In India, the essential oils of Artemisia vulgaris are used for its insecticidal, anti parasiticidal and antimicrobial properties. Traditionally, the dried leaves of Artemisia vulgaris are used to repel insects as well as rats in and around the granaries in the North-East India. Artemisia vulgaris collected during November from different ecological sites were studied for the bio-pesticidal utility against the stored grain pests. The insecticidal activities were found in the crude extracts of n-hexane and methanol from the samples collected in Sikkim and Manipur respectively. Using silica gel column chromatography protocol, we have isolated one novel bioactive molecule from the aerial parts of Artemisia vulgaris L based on various physical-chemical and spectroscopic techniques (IR, 1H NMR, 13C NMR and mass). The novel bioactive molecule is highly toxic and very low concentration (4.35 µg/l) is needed to control the stored product insects. In additional experiment results clearly showed the involvement of sodium pumps inhibition in the insecticidal action of purified compound in the Sitophilus oryzae. The knockdown activity of the purified compound is concomitant with the in vivo inhibition of Na+/ K+- ATPase. Further, our study showed insignificant differences in the seed germination of control and the treated grains. The lack of adverse effect of the novel bioactive molecule on the seed germination is highly desirable for seed/grain protectant and showing the potential to be developed as possible natural fumigants for the control of stored grain pests. The novel bioactive molecule is selective insecticide with a high margin of safety to mammals and showed promise as novel biopesticide candidate for grain protection. It is believed that Bio-pesticides can serve as the most important pest management tools as far as global safety is concerned.

Keywords: Indian traditional plant, Artemisia vulgaris, bio-pesticides, Na+/ K+- ATPase, seed germination

Procedia PDF Downloads 190

Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Wararut Buncharoen, Kanokporn Saenphet, Supap Saenphet

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Benign prostatic hyperplasia (BPH) is a reproductive problem, affecting elderly men worldwide. Several factors particularly free radical reaction and oxidative damage have been contributed to be key factors leading to the development of BPH. A number of medicinal plants with high antioxidant properties are extensively constituted in Thai herbal pharmacopoeia for treating BPH. These plants may prevent or delay the progression of BPH through an antioxidant mechanism. Thus, this study was to prove the antioxidant and anti-lipid peroxidation potential of medicinal plants traditionally used for the treatment of BPH such as Artabotrys harmandii Finet & Gagnep. Miq., Uvaria rufa Blume, Anomianthus dulcis (Dunal) J. Sinclair and Caesalpinia sappan Linn. Antioxidant parameters including free radical (2, 2-azino-bis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS•+), 2, 2-diphenyl-1-picrylhydrazyl (DPPH•) and superoxide) scavenging, ferric reducing power and anti-lipid peroxidation activity were determined in different crude extracts from the stem of these four plants. Total phenolic and ascorbic contents were also investigated. The highest total phenolic content was shown in ethyl acetate crude extract of A. dulcis (510 ± 26.927 µg GAE/g extract) while the highest ascorbic content was found in ethanolic extract of U. rufa (234.727 ± 30.356 µg AAE/g extract). The strongest scavenging activity of ABTS•+ and DPPH• was found in ethyl acetate extract of C. sappan with the IC50 values of 0.469 and 0.255 mg/ml, respectively. The petroleum ether extracts of C. sappan and U. rufa at concentration of 1 mg/ml exhibited high scavenging activity toward superoxide radicals with the inhibition of 37.264 ± 8.672 and 34.434 ± 6.377 %, respectively. Ethyl acetate crude extract of C. sappan displayed the greatest reducing power. The IC50 value of water extract of A. dulcis was 1.326 mg/ml which indicated the strongest activity in the inhibition of lipid-peroxidation among all plant extracts whereas the IC50 value of the standard, butyl hydroxyl toluene was 1.472 µg/ml. Regarding all the obtained results, it can be concluded that the stem of A. dulcis, U. rufa and C. sappan are the potential natural antioxidants and could have an importance as therapeutic agents in the preventing free radicals and oxidative damage related diseases including BPH.

Keywords: anti-lipid peroxidation, antioxidant, benign prostatic hyperplasia, Thai medicinal plants

Procedia PDF Downloads 469

Authors: N. P. D. Tran, H. Q. D. Nguyen, M. C. Yang

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In this study, contact lenses were prepared through the polymerization of tris-(trimethyl-silyl-propyl-methacrylate) (TRIS), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), and cross-linked with ethylene glycol dimethylacrylate (EGDMA). The equilibrium water content (EWC), oxygen permeability (Dk), light transmittance, and in vitro cytotoxicity of TRIS-DMA-NVP with various ratios were measured. The results showed that the EWC increased while the Dk decreased with the increase of NVP content. For the sample with 25 wt% NVP, the EWC attained 53% whereas the Dk decreased to 46 barrers. All these lenses exhibited light transmittance over than 95%. In addition, all these lenses exhibited no inhibition to the growth of L292 fibroblasts. Thus, this study showed that TRIS-DMA-NVP can be applicable for making contact lens.

Keywords: DMA, TRIS, NVP, silicone hydrogel, contact lens

Procedia PDF Downloads 317

Authors: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik

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Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).

Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts

Procedia PDF Downloads 321

Authors: Puneet Goyal, Aarti Agarwal

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Background and Objective: Nutritional support is an integral part of palliative care of advanced non-resectable abdominal malignancy patients, though is frequently neglected aspect. Non-Healing high output Entero-cutaneous fistulas sometimes require long term parenteral nutrition, to take care of catabolism and replacement of nutrients. We present a case of inoperable pancreatic malignancy with high output entero-cutaneous fistula, which was provided parenteral nutritional support with the use of Totally Implantable Venous Access Device (TIVAD). Method and Results: 55 year old man diagnosed with carcinoma pancreas had developed high entero-cutaneous fistula. His tumor was found to be inoperable and was on total parenteral nutrition through routine central line. This line was difficult to maintain as he required it for a long term TPN. He was planned to undergo Totally Implantable Venous Access Device (TIVAD) implantation. 8Fr single lumen catheter with Groshong non-return Valve (Bard Access Systems, Inc. USA) was inserted through right internal jugular vein, under fluoroscopic guidance. The catheter was tunneled subcutaneously and brought towards infraclavicular pocket, cut at appropriate length and connected to port and locked. Port was sutured in floor of pocket. Free flow of blood aspirated, flushed with heparinized saline. There was no kink observed in entire length of catheter under fluoroscopy. Skin over infraclavicular pocket was sutured. Long term catheter care and associated risks were explained to patient and relatives. Patient continued to receive total parenteral nutrition as well as other supportive therapy though TIVAD for next 6 weeks, till his demise. Conclusion: TIVADs are standard of care for long term venous access solutions in cancer patients requiring chemotherapy. In this case, we extended its use for providing parenteral nutrition and other supportive therapy. TIVADs can be implanted in advanced cancer patients for providing venous access solution required for various palliative treatments and medications. This will help in improving quality of life and satisfaction amongst terminally ill cancer patients.

Keywords: parenteral nutrition, totally implantable venous access device, long term venous access, interventions in anesthesiology

Procedia PDF Downloads 238

Authors: F. Madani, M. Doudi, L. Rahimzadeh Torabi

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The irregular consumption of current antibiotics contributes to an escalation in antibiotic resistance among urinary pathogens on a global scale. The objective of this research was to investigate the process of biologically synthesized silver nanoparticles through the utilization of Zataria multiflora extract. Additionally, the study aimed to evaluate the efficacy of these synthesized nanoparticles in inhibiting the growth of multi-drug resistant negative bacillus bacteria, which commonly contribute to urinary tract infections. The botanical specimen utilized in the current research investigation was Z. multiflora, and its extract was produced employing the Soxhlet extraction technique. The study examined the green synthesis conditions of silver nanoparticles by considering three key parameters: the quantity of extract used, the concentration of silver nitrate salt, and the temperature. The particle dimensions were ascertained using the Zetasizer technique. In order to identify synthesized Silver nanoparticles TEM, XRD, and FTIR methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through a biological method, different concentrations of silver nanoparticles were studied on 140 cases of Multiple drug resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections, for identification of bacteria were used of PCR test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were subjected to analysis using the statistical software SPSS, specifically employing nonparametric Kruskal-Wallis and Mann-Whitney tests. This study yielded noteworthy findings regarding the impacts of varying concentrations of silver nitrate, different quantities of Z. multiflora extract, and levels of temperature on nanoparticles. Specifically, it was observed that an increase in the concentration of silver nitrate, extract amount, and temperature resulted in a reduction in the size of the nanoparticles synthesized. However, the impact of the aforementioned factors on the index of particle diffusion was found to be statistically non-significant. According to the transmission electron microscopy (TEM) findings, the particles exhibited predominantly spherical morphology, with a diameter spanning from 25 to 50 nanometers. Nanoparticles in the examined sample. Nanocrystals of silver. FTIR method illustrated that the spectrums of Z. multiflora and synthesized nanoparticles had clear peaks in the ranges of 1500-2000, and 3500 - 4000. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E. coli, A. bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125 mg/ml and for A. bumanii 250 mg/ml. Comparing the growth inhibitory effect of chemically synthesized the results obtained from the experiment indicated that both nanoparticles and biologically synthesized nanoparticles exhibit a notable growth inhibition effect. Specifically, the chemical method of synthesizing nanoparticles demonstrated the highest level of growth inhibition at a concentration of 62.5 mg/mL The present study demonstrated an inhibitory effect on bacterial growth, facilitating the causative factors of urine infection and multidrug resistance (MDR).

Keywords: multiple drug resistance, negative bacillus bacteria, urine infection, Zataria multiflora

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Authors: Sang Chul Lee, Gi-Young Park, Dong Rak Kwon

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Objective: The aim of this study was to investigate regenerative effects of ultrasound (US)-guided injection with human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and/or polydeoxyribonucleotide (PDRN) injection in a chronic traumatic full-thickness rotator cuff tendon tear (FTRCTT) in a rabbit model. Material and Methods: Rabbits (n = 32) were allocated into 4 groups. After a 5-mm sized FTRCTT just proximal to the insertion site on the subscapularis tendon was created by excision, the wound was immediately covered by silicone tube to prevent natural healing. After 6 weeks, 4 injections (0.2 mL normal saline, G1; 0.2 mL PDRN, G2; 0.2 mL UCB-MSCs, G3; and 0.2 mL UCB-MSCs with 0.2ml PDRN, G4) were injected into FTRCTT under US guidance. We evaluated gross morphologic changes on all rabbits after sacrifice. Masson’s trichrome, anti-type 1 collagen antibody, bromodeoxyuridine, proliferating cell nuclear antigen, vascular endothelial growth factor and platelet endothelial cell adhesion molecule stain were performed to evaluate histological changes. Motion analysis was also performed. Results: The gross morphologic mean tendon tear size in G3 and 4 was significantly smaller than that of G1 and 2 (p < .05). However, there were no significant differences in tendon tear size between G3 and 4. In G4, newly regenerated collagen type 1 fibers, proliferating cells activity, angiogenesis, walking distance, fast walking time, and mean walking speed were greater than in the other three groups on histological examination and motion analysis. Conclusion: Co-injection of UCB-MSCs and PDRN was more effective than UCB-MSCs injection alone in histological and motion analysis in a rabbit model of chronic traumatic FTRCTT. However, there was no significant difference in gross morphologic change of tendon tear between UCB-MSCs with/without PDRN injection. The results of this study regarding the combination of UCB-MSCs and PDRN are worth additional investigations.

Keywords: mesenchymal stem cell, umbilical cord, polydeoxyribonucleotides, shoulder, rotator cuff, ultrasonography, injections

Procedia PDF Downloads 183

Authors: Umadevi B., Dinesh P. A., Indira. R., Vinay C. V.

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A mathematical model is developed to study the simultaneous effects of particle drag and slip parameter on the velocity as well as rate of flow in an annular cross sectional region bounded by two eccentric cylinders. In physiological flows this phenomena can be observed in an eccentric catheterized artery with inner cylinder wall is impermeable and outer cylinder wall is permeable. Blood is a heterogeneous fluid having liquid phase consisting of plasma in which a solid phase of suspended cells and proteins. Arterial wall gets damaged due to aging and lipid molecules get deposited between damaged tissue cells. Blood flow increases towards the damaged tissues in the artery. In this investigation blood is modeled as two phase fluid as one is a fluid phase and the other is particulate phase. The velocity of the fluid phase and rate of flow are obtained by transforming eccentric annulus to concentric annulus with the conformal mapping. The formulated governing equations are analytically solved for the velocity and rate of flow. The numerical investigations are carried out by varying eccentricity parameter, slip parameter and drag parameter. Enhancement of slip parameter signifies loss of fluid then the velocity and rate of flow will be decreased. As particulate drag parameter increases then the velocity as well as rate flow decreases. Eccentricity facilitates transport of more fluid then the velocity and rate of flow increases.

Keywords: catheter, slip parameter, drag parameter, eccentricity

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Authors: Anushaa A.

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In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Wen-Yu Lin, Yi-Ching Chung, Jhao-Ren Lin, Tzyy-Rong Jinn

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It is well known that enterovirus 71(EV71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. And, several enterovirus 71 (EV71) of hand foot and mouth disease (HFMD) with high mortalities occurred in Asia country, such as Hong Kung (1985), Malaysia (1997), Taiwan (1998) and China (2008) that EV71 results in severe neurological complications and sudden death in infants and young children. However, there are still no effective drugs and vaccines to reduce and inhibit EV71 infection. Therefore, the development of specific and effective antiviral strategies against EV71 has become an urgent issue for the protection of children from the hazards of the HFMD. As reported, amantadine is effective in prophylaxis and treatment of the EV71 infections. Thus, the aim of this study was to further evaluate the synergistic antiviral activity of amantadine coupled with magnesium lithospermate B (MLB) against enterovirus 71 infection. In a preliminary test, it is shown that the infected RD cells were treated with amantadine after virus absorption, at concentrations of 3 and 5µM of amantadine suppressed EV71-induced CPE to 13% and 23%, respectively at MOI of 3. Alternatively, at concentrations of 5µg/ml of MLB combined with 3 and 5 µM of amantadine apparently suppressed EV71-induced CPE to 45% and 63%, respectively at MOI of 3. Thus, amantadine coupled with MLB may have the potential for further study to development as the chemopreventive reagents against EV71 infection.

Keywords: amantadine, Enterovirus 71, magnesium lithospermate B, RD cells, synergistic effects

Procedia PDF Downloads 238

Authors: Magdalena Chrabąszcz, Teresa Wolniewicz, Cezary Maciejewski, Joanna Czuwara

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BACKGROUND: Dermoscopy is a clinical tool known to improve the early detection of melanoma and other malignancies of the skin. Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Early diagnosis remains the best method to reduce melanoma and non-melanoma skin cancer– related mortality and morbidity. Dermoscopy is a noninvasive technique that consists of viewing pigmented skin lesions through a hand-held lens. This simple procedure increases melanoma diagnostic accuracy by up to 35%. Dermoscopy is currently the standard for clinical differential diagnosis of cutaneous melanoma and for qualifying lesion for the excision biopsy. Like any clinical tool, training is required for effective use. The introduction of small and handy dermoscopes contributed significantly to the switch of dermatoscopy toward a first-level useful tool. Non-dermatologist physicians are well positioned for opportunistic melanoma detection; however, education in the skin cancer examination is limited during medical school and traditionally lecture-based. AIM: The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard fourth year medical curriculum improves the ability of medical students to distinguish between benign and malignant lesions and assess acceptability and satisfaction with the intervention. METHODS: We performed a prospective study in 2 cohorts of fourth-year medical students at Medical University of Warsaw. Groups having dermatology course, were randomly assigned to:  cohort A: with limited access to dermatoscopy from their teacher only – 1 dermatoscope for 15 people  Cohort B: with a full access to use dermatoscopy during their clinical classes:1 dermatoscope for 4 people available constantly plus 15-minute dermoscopy tutorial. Students in both study arms got an image-based test of 10 lesions to assess ability to differentiate benign from malignant lesions and postintervention survey collecting minimal background information, attitudes about the skin cancer examination and course satisfaction. RESULTS: The cohort B had higher scores than the cohort A in recognition of nonmelanocytic (P < 0.05) and melanocytic (P <0.05) lesions. Medical students who have a possibility to use dermatoscope by themselves have also a higher satisfaction rates after the dermatology course than the group with limited access to this diagnostic tool. Moreover according to our results they were more motivated to learn dermatoscopy and use it in their future everyday clinical practice. LIMITATIONS: There were limited participants. Further study of the application on clinical practice is still needed. CONCLUSION: Although the use of dermatoscope in dermatology as a specialty is widely accepted, sufficiently validated clinical tools for the examination of potentially malignant skin lesions are lacking in general practice. Introducing medical students to dermoscopy in their fourth year curricula of medical school may improve their ability to differentiate benign from malignant lesions. It can can also encourage students to use dermatoscopy in their future practice which can significantly improve early recognition of malignant lesions and thus decrease melanoma mortality.

Keywords: dermatoscopy, early detection of melanoma, medical education, skin cancer

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Authors: Abdul Qadir Qadis, Satoru Goya, Minoru Yatsu, Yu-uki Yoshida, Toshihiro Ichijo, Shigeru Sato

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Bacterial probiotics are known to modulate the gut-associated lymphoid and epithelial tissue response to enhance the activities of intestinal and systemic immune system in human and animals. In cattle, the immune-stimulatory effects of probiotics have been evaluated during intestinal disorders. To investigate the effects of probiotic on the function of peripheral blood mononuclear cells, eight healthy Holstein calves (10 ± 3 weeks) were assigned to a 4 × 2 experimental design. The probiotic, consisting of Lactobacillus plantarum, Enterococcus faecium and Clostridium butyricum, was administered orally at 3.0 g/100 kg body weight to calves once daily for 5 consecutive days. Calves given no probiotic served as the control. In the treatment group, increases in numbers of CD282+ monocytes, CD3+ T-cells and CD4+, CD8+ and WC1+ γδ T- cell subsets were noted on day 7 post-placement compared to pre-dose day and the control group. Expression of interleukin-6, interferon-gamma and tumor necrosis factor-alpha was elevated in peripheral leukocytes on days 7 and 14. These results suggest that peripheral blood leukocytes in healthy calves may be stimulated via the gastrointestinal microbiota, which was increased by the oral probiotic treatment. The 5-day repeated administration of a bacterial probiotic may enhance cellular immune function in weaned calves.

Keywords: bacterial-probiotic, calf, interleukin, leukocyte

Procedia PDF Downloads 654

Authors: Marta Kwiatkowska, Paweł Jarosiewicz, Bożena Bukowska

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Glyphosate (N-phosphonomethylglycine) is a non-selected broad spectrum ingredient in the herbicide (Roundup) used for over 35 years for the protection of agricultural and horticultural crops. Glyphosate was believed to be environmentally friendly but recently, a large body of evidence has revealed that glyphosate can negatively affect on environment and humans. It has been found that glyphosate is present in the soil and groundwater. It can also enter human body which results in its occurrence in blood in low concentrations of 73.6 ± 28.2 ng/ml. Research conducted for potential genotoxicity and cytotoxicity can be an important element in determining the toxic effect of glyphosate. Due to regulation of European Parliament 1107/2009 it is important to assess genotoxicity and cytotoxicity not only for the parent substance but also its impurities, which are formed at different stages of production of major substance – glyphosate. Moreover verifying, which of these compounds are more toxic is required. Understanding of the molecular pathways of action is extremely important in the context of the environmental risk assessment. In 2002, the European Union has decided that glyphosate is not genotoxic. Unfortunately, recently performed studies around the world achieved results which contest decision taken by the committee of the European Union. World Health Organization (WHO) in March 2015 has decided to change the classification of glyphosate to category 2A, which means that the compound is considered to "probably carcinogenic to humans". This category relates to compounds for which there is limited evidence of carcinogenicity to humans and sufficient evidence of carcinogenicity on experimental animals. That is why we have investigated genotoxicity and cytotoxicity effects of the most commonly used pesticide: glyphosate and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA) and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs), mostly lymphocytes. DNA damage (analysis of DNA strand-breaks) using the single cell gel electrophoresis (comet assay) and ATP level were assessed. Cells were incubated with glyphosate and its impurities: PMIDA and bis-(phosphonomethyl)amine at concentrations from 0.01 to 10 mM for 24 hours. Evaluating genotoxicity using the comet assay showed a concentration-dependent increase in DNA damage for all compounds studied. ATP level was decreased to zero as a result of using the highest concentration of two investigated impurities, like bis-(phosphonomethyl)amine and PMIDA. Changes were observed using the highest concentration at which a person can be exposed as a result of acute intoxication. Our survey leads to a conclusion that the investigated compounds exhibited genotoxic and cytotoxic potential but only in high concentrations, to which people are not exposed environmentally. Acknowledgments: This work was supported by the Polish National Science Centre (Contract-2013/11/N/NZ7/00371), MSc Marta Kwiatkowska, project manager.

Keywords: cell viability, DNA damage, glyphosate, impurities, peripheral blood mononuclear cells

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Authors: Devadrita Dey Sarkar

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Regardless of the many technologic advances in the past decade, increased training and experience, and the obvious benefits of uniform standards, the false-negative rate in screening mammography remains unacceptably high .A computer aided neural network classification of regions of suspicion (ROS) on digitized mammograms is presented in this abstract which employs features extracted by a new technique based on independent component analysis. CAD is a concept established by taking into account equally the roles of physicians and computers, whereas automated computer diagnosis is a concept based on computer algorithms only. With CAD, the performance by computers does not have to be comparable to or better than that by physicians, but needs to be complementary to that by physicians. In fact, a large number of CAD systems have been employed for assisting physicians in the early detection of breast cancers on mammograms. A CAD scheme that makes use of lateral breast images has the potential to improve the overall performance in the detection of breast lumps. Because breast lumps can be detected reliably by computer on lateral breast mammographs, radiologists’ accuracy in the detection of breast lumps would be improved by the use of CAD, and thus early diagnosis of breast cancer would become possible. In the future, many CAD schemes could be assembled as packages and implemented as a part of PACS. For example, the package for breast CAD may include the computerized detection of breast nodules, as well as the computerized classification of benign and malignant nodules. In order to assist in the differential diagnosis, it would be possible to search for and retrieve images (or lesions) with these CAD systems, which would be reliable and useful method for quantifying the similarity of a pair of images for visual comparison by radiologists.

Keywords: CAD(computer-aided design), lesions, neural network, ROS(region of suspicion)

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Authors: Chia-Jung Li, Kuan-Hao Tsui

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As women age, the quality of their oocytes deteriorates irreversibly, leading to reduced fertility. To better understand the role of Ferroptosis-related genes in ovarian aging, we employed a multi-omics analysis approach, including spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsies. Our study identified excess lipid peroxide accumulation in aging germ cells, metal ion accumulation via oxidative reduction, and the interaction between ferroptosis and cellular energy metabolism. We used multi-histological prediction of ferroptosis key genes to evaluate 75 patients with ovarian aging insufficiency and then analyzed changes in hub genes after supplementing with DHEA, Ubiquinol CoQ10, and Cleo-20 T3 for two months. Our results demonstrated a significant increase in TFRC, GPX4, NCOA4, and SLC3A2, which were consistent with our multi-component prediction. We theorized that these supplements increase the mitochondrial tricarboxylic acid cycle (TCA) or electron transport chain (ETC), thereby increasing antioxidant enzyme GPX4 levels and reducing lipid peroxide accumulation and ferroptosis. Overall, our findings suggest that supplementation intervention significantly improves IVF outcomes in senescent cells by enhancing metal ion and energy metabolism and enhancing oocyte quality in aging women.

Keywords: multi-omics, nutrients, ferroptosis, ovarian aging

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Authors: Roman Matejka, Vaclav Prochazka, Tibor Izak, Jana Stepanovska, Martina Travnickova, Alexander Kromka

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Cell-based impedance spectroscopy is suitable method for electrical monitoring of cell activity especially on substrates that cannot be easily inspected by optical microscope (without fluorescent markers) like decellularized tissues, nano-fibrous scaffold etc. Special sensor for this measurement was developed. This sensor consists of corning glass substrate with gold interdigitated electrodes covered with diamond layer. This diamond layer provides biocompatible non-conductive surface for cells. Also, a special PPFC flow cultivation chamber was developed. This chamber is able to fix sensor in place. The spring contacts are connecting sensor pads with external measuring device. Construction allows real-time live cell imaging. Combining with perfusion system allows medium circulation and generating shear stress stimulation. Experimental evaluation consist of several setups, including pure sensor without any coating and also collagen and fibrin coating was done. The Adipose derived stem cells (ASC) and Human umbilical vein endothelial cells (HUVEC) were seeded onto sensor in cultivation chamber. Then the chamber was installed into microscope system for live-cell imaging. The impedance measurement was utilized by vector impedance analyzer. The measured range was from 10 Hz to 40 kHz. These impedance measurements were correlated with live-cell microscopic imaging and immunofluorescent staining. Data analysis of measured signals showed response to cell adhesion of substrates, their proliferation and also change after shear stress stimulation which are important parameters during cultivation. Further experiments plan to use decellularized tissue as scaffold fixed on sensor. This kind of impedance sensor can provide feedback about cell culture conditions on opaque surfaces and scaffolds that can be used in tissue engineering in development artificial prostheses. This work was supported by the Ministry of Health, grants No. 15-29153A and 15-33018A.

Keywords: bio-impedance measuring, bioreactor, cell cultivation, diamond layer, gold interdigitated electrodes, tissue engineering

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Authors: Adriana C. Panayi, Riaz A. Agha, Brady A. Sieber, Dennis P. Orgill

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Background: Increased rates of both breast cancer and obesity have resulted in more women seeking breast reconstruction. These women may be at increased risk for perioperative complications. A systematic review was conducted to assess the outcomes in obese women who have undergone breast reconstruction following mastectomy. Methods: Cochrane, PUBMED and EMBASE electronic databases were screened and data was extracted from included studies. The clinical outcomes assessed were surgical complications, medical complications, length of postoperative hospital stay, reoperation rate and patient satisfaction. Results: 33 studies met the inclusion criteria for the review and 29 provided enough data to be included in the meta-analysis (71368 patients, 20061 of which were obese). Obese women were 2.3 times more likely to experience surgical complications (95 percent CI 2.19 to 2.39; P < 0.00001), 2.8 times more likely to have medical complications (95 percent CI 2.41 to 3.26; P < 0.00001) and had a 1.9 times higher risk of reoperation (95 percent CI 1.75 to 2.07; P < 0.00001). The most common complication, wound dehiscence, was 2.5 times more likely in obese women (95 percent CI 1.80 to 3.52; P < 0.00001). Sensitivity analysis confirmed that obese women were more likely to experience surgical complications (RR 2.36, 95% CI 2.22–2.52; P < 0.00001). Conclusions: This study provides evidence that obesity increases the risk of complications in both implant and autologous reconstruction. Additional prospective and observational studies are needed to determine if weight reduction prior to reconstruction reduces the perioperative risks associated with obesity.

Keywords: autologous reconstruction, breast cancer, breast reconstruction, literature review, obesity, oncology, prosthetic reconstruction

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Authors: Sujeet Poudyal

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Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

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Authors: B. Kodedova, E. Filova, M. Kralovic, E. Amler

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Vitiligo is the most common depigmentation disorder of the skin characterized by loss of melanocyte in the epidermis that leads to white lesions. One of the possible treatments is autologous transplantation of melanocytes. Biodegradable electrospun polymeric nanofibers provide good mechanical properties and could serve as suitable scaffold for epithelial cells cultivation and follow up transplantation. Moreover the microarchitecture of nanofibers mimics the structure of extracellular matrix and its porosity allows nutrients and waste exchange. The aim of this work was to develop biocompatible and biodegradable polymeric scaffolds suitable for autologous melanocytes transplantation. Electrospun polyvinyl alcohol (PVA) nanofibers were modified by cold methane plasma to lower their hydrofility and to achieve better adhesion, proliferation and viability of the murine melanocyte (Melan-a). Cells were seeded on the modified scaffolds and their adhesion, metabolic activity, proliferation and melanin synthesis was evaluated and compared to non-modified scaffolds. Results clearly indicate that cold methane plasma modified PVA nanofibers are suitable for melanocyte cultivation and may be future candidate for vitiligo treatment. Furthermore, the nanofibers can be functionalized with various bioactive substances, for enhancement of the melanocyte proliferation, melanogenesis or healing and regenerative processes. The project was supported by the Ministry of Education, Youth and Sports NPU I: LO1309 and by Grant Agency of Charles University (grant No. 1228214).

Keywords: melanocyte, nanofibers, polyvinyl alcohol, plasma modification

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Rupinder Kaur, Parmjit S. Panesar, Ram S. Singh

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Whey is the lactose rich by-product of the dairy industry, having good amount of nutrient reservoir. Most abundant nutrients are lactose, soluble proteins, lipids and mineral salts. Disposing of whey by most of milk plants which do not have proper pre-treatment system is the major issue. As a result of which, there can be significant loss of potential food and energy source. Thus, whey has been explored as the substrate for the synthesis of different value added products such as enzymes. β-galactosidase is one of the important enzymes and has become the major focus of research due to its ability to catalyze both hydrolytic as well as transgalactosylation reaction simultaneously. The enzyme is widely used in dairy industry as it catalyzes the transformation of lactose to glucose and galactose, making it suitable for the lactose intolerant people. The enzyme is intracellular in both bacteria and yeast, whereas for molds, it has an extracellular location. The present work was carried to utilize the whey for the production of β-galactosidase enzyme using both yeast and fungal cultures. The yeast isolate Kluyveromyces marxianus WIG2 and various fungal strains have been used in the present study. Different disruption techniques have also been investigated for the extraction of the enzyme produced intracellularly from yeast cells. Among the different methods tested for the disruption of yeast cells, SDS-chloroform showed the maximum β-galactosidase activity. In case of the tested fungal cultures, Aureobasidium pullulans NCIM 1050, was observed to be the maximum extracellular enzyme producer.

Keywords: β-galactosidase, fungus, yeast, whey

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Authors: Ravi Kiran Pothamsetty, Radha Rani Ghosh, Baby Paul Thaliath

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Radiation therapy has undergone many advancements and evloved from 2D to 3D. Recently, with rapid pace of drug discoveries, cutting edge technology, and clinical trials has made innovative advancements in computer technology and treatment planning and upgraded to intensity modulated radiotherapy (IMRT) which delivers in homogenous dose to tumor and normal tissues. The present study was a hospital-based experience comparing two different conformal radiotherapy techniques for brain tumors. This analytical study design has been conducted at Regional Cancer Centre, India from January 2014 to January 2015. Ten patients have been selected after inclusion and exclusion criteria. All the patients were treated on Artiste Siemens Linac Accelerator. The tolerance level for maximum dose was 6.0 Gyfor lenses and 54.0 Gy for brain stem, optic chiasm and optical nerves as per RTOG criteria. Mean and standard deviation values of PTV98%, PTV 95% and PTV 2% in IMRT were 93.16±2.9, 95.01±3.4 and 103.1±1.1 respectively; for 3DCRT were 91.4±4.7, 94.17±2.6 and 102.7±0.39 respectively. PTV max dose (%) in IMRT and 3D-CRT were 104.7±0.96 and 103.9±1.0 respectively. Maximum dose to the tumor can be delivered with IMRT with acceptable toxicity limits. Variables such as expertise, location of tumor, patient condition, and TPS influence the outcome of the treatment.

Keywords: brain tumors, intensity modulated radiotherapy (IMRT), three dimensional conformal radiotherapy (3D-CRT), radiation therapy oncology group (RTOG)

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Authors: M. I. Tyletc, O. I. Podgornya, T. G. Shaposhnikova, S. V. Shabelnikov, A. G. Mittenberg, M. A. Daugavet

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Ascidiacea is the most numerous class of the Tunicata subtype. These chordates' distinctive feature of the anatomical structure is a tunic consisting of cellulose fibrils, protein molecules, and single cells. The mechanisms of the tunic formation are not known in detail; tunic formation could be used as the model system for studying the interaction of cells with the extracellular matrix. Our model species is the ascidian Styela rustica, which is prevalent in benthic communities of the White Sea. As previously shown, the tunic formation involves morula blood cells, which contain the major 48 kDa protein p48. P48 participation in the tunic formation was proved using antibodies against the protein. The nature of the protein and its function remains unknown. The current research aims to determine the amino acid sequence of p48, as well as to clarify its role in the tunic formation. The peptides that make up the p48 amino acid sequence were determined by mass spectrometry. A search for peptides in protein sequence databases identified sequences homologous to p48 in Styela clava, Styela plicata, and Styela canopus. Based on sequence alignment, their level of similarity was determined as 81-87%. The correspondent sequence of ascidian Styela canopus was used for further analysis. The Styela rustica p48 sequence begins with a signal peptide, which could indicate that the protein is secretory. This is consistent with experimentally obtained data: the contents of morula cells secreted in the tunic matrix. The isoelectric point of p48 is 9.77, which is consistent with the experimental results of acid electrophoresis of morula cell proteins. However, the molecular weight of the amino acid sequence of ascidian Styela canopus is 103 kDa, so p48 of Styela rustica is a shorter homolog. The search for conservative functional domains revealed the presence of two Ca-binding EGF-like domains, thrombospondin (TSP1) and tyrosinase domains. The p48 peptides determined by mass spectrometry fall into the region of the sequence corresponding to the last two domains and have amino acid substitutions as compared to Styela canopus homolog. The tyrosinase domain (pfam00264) is known to be part of the phenoloxidase enzyme, which participates in melanization processes and the immune response. The thrombospondin domain (smart00209) interacts with a wide range of proteins, and is involved in several biological processes, including coagulation, cell adhesion, modulation of intercellular and cell-matrix interactions, angiogenesis, wound healing and tissue remodeling. It can be assumed that the tyrosinase domain in p48 plays the role of the phenoloxidase enzyme, and TSP1 provides a link between the extracellular matrix and cell surface receptors, and may also be responsible for the repair of the tunic. The results obtained are consistent with experimental data on p48. The domain organization of protein suggests that p48 is an enzyme involved in the tunic tunning and is an important regulator of the organization of the extracellular matrix.

Keywords: ascidian, p48, thrombospondin, tyrosinase, tunic, tunning

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Authors: Taha Kadir Yesin, Hanyu Liu, Zhangfan Ding, Amit Singh, Qi Tian, Yuheng Zhang, Biswajyoti Borah, Junyu Chen, Anjali P. Kusumbe

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The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent endogenous anabolic NCAM1-14.3.3. ζδ-derived- Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.ζδ-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.ζδ-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of bone. Moreover, the NCAM1-14.3.3.ζδ-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.ζδ-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.ζδ-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

Keywords: endothelial cell, NCAM1, Clec14a, 14.3.3.ζδ

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Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

Procedia PDF Downloads 76