Search results for: induced pluripotent stem cells

Authors: Danielle Schneider, Ying Xie

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Middle school science, technology, engineering, and math (STEM) teachers experience an exceptional challenge in the expectation to incorporate curricula that builds strong spatial reasoning skills on rudimentary geometry concepts. Because spatial ability is so closely tied to STEM students’ success, researchers are tasked to determine effective instructional practices that create an authentic learning environment within the immersive virtual reality learning environment (IVRLE). This study looked to investigate the effect of the IVRLE on middle school STEM students’ spatial reasoning skills as a methodology to benefit the STEM middle school students’ spatial reasoning skills. This experimental study was comprised of thirty 7th-grade STEM students divided into a treatment group that was engaged in an immersive VR platform where they engaged in building an object in the virtual realm by applying spatial processing and visualizing its dimensions and a control group that built the identical object using a desktop computer-based, computer-aided design (CAD) program. Before and after the students participated in the respective “3D modeling” environment, their spatial reasoning abilities were assessed using the Middle Grades Mathematics Project Spatial Visualization Test (MGMP-SVT). Additionally, both groups created a physical 3D model as a secondary measure to measure the effectiveness of the IVRLE. The results of a one-way ANOVA in this study identified a negative effect on those in the IVRLE. These findings suggest that with middle school students, virtual reality (VR) proved an inadequate tool to benefit spatial relation skills as compared to desktop-based CAD.

Keywords: virtual reality, spatial reasoning, CAD, middle school STEM

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

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At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Simone F. Medeiros, Isabela F. Santos, Rodolfo M. Moraes, Jaspreet K. Kular, Marcus A. Johns, Ram Sharma, Amilton M. Santos

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Tissue engineering aims to develop alternatives to treat damaged tissues by promoting their regeneration. Its basic principle is to place cells on a scaffold capable of promoting cell functions, and for this purpose, polymeric nanoparticles have been successfully used due to the ability of some macro chains to mimic the extracellular matrix and influence cell functions. In general, nanoparticles require surface chemical modification to achieve cell adhesion, and recent advances in their synthesis include methods for modifying the ligand density and distribution onto nanoparticles surface. However, this work reports the development of biodegradable polymeric nanoparticles capable of promoting cellular adhesion without any surface chemical modification by ligands. Biocompatible and biodegradable nanoparticles based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) were synthesized by solvent evaporation method. The produced nanoparticles were small in size (85 and 125 nm) and colloidally stable against time in aqueous solution. Morphology evaluation showed their spherical shape with small polydispersity. Human osteoblast-like cells (MG63) were cultured in the presence of PHBHV nanoparticles, and growth kinetics were compared to those grown on tissue culture polystyrene (TCPS). Cell attachment on non-tissue culture polystyrene (non-TCPS) pre-coated with nanoparticles was assessed and compared to attachment on TCPS. These findings reveal the potential of PHBHV nanoparticles for cell adhesion and growth, without requiring a matrix ligand to support cells, to be used as scaffolds, in tissue engineering applications.

Keywords: tissue engineering, PHBHV, stem cells, cellular attachment

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Authors: Teodora Mocan, Matea Cristian, Cornel Iancu, Flaviu A. Tabaran, Florin Zaharie, Bartos Dana, Lucian Mocan

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Colon cancer (CC) a lethal human malignancy, is one of the most commonly diagnosed cancer. With its high increased mortality rate, as well as low survival rate combined with high resistance to chemotherapy CC, represents one of the most important global health issues. In the presented research, we have developed a distinct nanostructured colon carcinoma vaccine model based on a nano-biosystem composed of 39 nm gold nanoparticles conjugated to colon cancer epitopes. We prove by means of proteomic analysis, immunocytochemistry, flow cytometry and hyperspectral microscopy that our developed nanobioconjugate was able to contribute to an optimal prophylactic effect against CC by promoting major histocompatibility complex mediated (MHC) antigen presentation by dendritic cells. We may conclude that the proposed immunoprophylactic approach could be more effective than the current treatments of CC because it promotes recognition of the tumoral antigens by the immune system.

Keywords: anticancer vaccine, colon cancer, gold nanoparticles, tumor antigen

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Authors: Hyunjung Lim, Jeonghun Nam, Hyuk Choi

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High-throughput separation is an essential technique for cancer research and diagnosis. Here, we propose a viscoelastic microfluidic device for sheathless, high-throughput isolation of circulating tumor cells (CTCs) from white blood cells. Here, we demonstrate a viscoelastic method for separation and concentration of CTCs using closed-loop microfluidics. Our device is a rectangular straight channel with a low aspect ratio. Also, to achieve high-efficiency, high-throughput processing, we used a polymer solution with low viscosity. At the inlet, CTCs and white blood cells (WBCs) were randomly injected into the microchannel. Due to the viscoelasticity-induced lateral migration to the equilibrium positions, large CTCs could be collected from the side outlet while small WBCs were removed at the center outlet. By recirculating the collected CTCs from the side outlet back to the sample reservoir, continuous separation and concentration of CTCs could be achieved with high separation efficiency (~ 99%). We believe that our device has the potential to be applied in resource-limited clinical settings.

Keywords: circulating tumor cell, closed-loop microfluidics, concentration, separation, viscoelastic fluid

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Authors: Saule Shazhanbayeva, Denise van der Merwe

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Study hypothesis: Nazarbayev Intellectual School of Kyzylorda’s Biology teachers can use STEM-integrated learning to improve students' problem-solving ability and responsibility as global citizens. The significance of this study is to indicate how the use of STEM integrative learning during Biology lessons could contribute to forming globally-minded students who are responsible community members. For the purposes of this study, worldview is defined as a view that is broader than the country of Kazakhstan, allowing students to see the significance of their scientific contributions to the world as global citizens. The context of worldview specifically indicates that most students have never traveled outside of their city or region within Kazakhstan. In order to broaden student understanding, it is imperative that students are exposed to different world views and contrasting ideas within the educational setting of Biology as the science being used for the research. This exposure promulgates students understanding of the significance they have as global citizens alongside the obligations which would rest on them as scientifically minded global citizens. Integrative learning should be Biological Science - with Technology and engineering in the form of problem-solving, and Mathematics to allow improved problem-solving skills to develop within the students of Nazarbayev Intellectual School (NIS) of Kyzylorda. The school's vision is to allow students to realise their role as global citizens and become responsible community members. STEM allows integrations by combining four subject skills to solve topical problems designed by educators. The methods used are based on qualitative analysis: for students’ performance during a problem-solution scenario; and Biology teacher interviews to ascertain their understanding of STEM implementation and willingness to integrate it into current lessons. The research indicated that NIS is ready for a shift into STEM lessons to promote globally responsible students. The only additional need is for proper STEM integrative lesson method training for teachers.

Keywords: global citizen, STEM, Biology, high-school

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Authors: Sakhon Woothipatanapan, Surasit Prakobkit

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This paper presents a model for analysis the induced voltage of transmission lines (energized) acting on neighboring distribution lines (de-energized). From environmental restrictions, 22 kV distribution lines need to be installed under 115 kV transmission lines. With the installation of the two parallel circuits like this, they make the induced voltage which can cause harm to operators. This work was performed with the ATP-EMTP modeling to analyze such phenomenon before field testing. Simulation results are used to find solutions to prevent danger to operators who are on the pole.

Keywords: transmission system, distribution system, induced voltage, off-line operation

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Authors: Monika Rezacova

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Radiation-induced breast changes are a consequence of radiotherapy toxicity over the breast tissues either related to targeted breast cancer treatment or other thoracic malignancies (eg. lung cancer). This study has created an overview of different changes and their pathophysiology. The main conditions included were skin thickening, interstitial oedema, fat necrosis, dystrophic calcifications, skin retractions, glandular atrophy, breast fibrosis and radiation induced breast cancer. This study has performed focused literature search through multiple databases including pubmed, medline and embase. The study has reviewed English as well as non English publications. As a result of the literature the study provides comprehensive overview of radiation-induced breast changes and their pathophysiology with small focus on new development and prevention.

Keywords: radiotherapy toxicity, breast tissue changes, breast cancer treatment, radiation-induced breast changes

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Authors: Yousuf Al Suleimani, Ahmed Al Mahruqi

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A typical cannabinoid O-1602 induces vasorelaxation and activates the orphan G protein-coupled receptor GPR55 in human endothelial cells. The aim of this study is to characterize the mechanisms of endothelium-independent relaxation of O-1602 in the rat small mesenteric artery using wire myograph. In endothelium-denuded vessels, O-1602 partially produced concentration-dependent vasorelaxation. In vessels depleted of intracellular Ca2+ (by EGTA and methoxamine), CaCl2 produced concentration-dependent contraction. Preincubation with O-1602 (at 10 µM and 30 µM) abolished the contractile responses (P<0.01). The putative antagonist at novel “endothelial anandamide receptor” O-1918 (10 µM) significantly reversed the inhibitory effect of O-1602 on CaCl2-induced vasoconstriction. It is likely that the mechanism of endothelium-independent vasorelaxation to O-1602 is mediated by interfering with Ca2+ entry via an O-1918-sensitive pathway.

Keywords: O-1602, endothelium, vasorelaxation, calcium

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Authors: Premkumar Vincent, Hyeok Kim, Jin-Hyuk Bae

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Organic solar cells have high potential which enables these to absorb much weaker light than 1-sun in indoor environment. They also have several practical advantages, such as flexibility, cost-advantage, and semi-transparency that can have superiority in indoor solar energy harvesting. We investigate organic solar cells based on poly(3-hexylthiophene) (P3HT) and indene-C60 bisadduct (ICBA) for indoor application while Finite Difference Time Domain (FDTD) simulations were run to find the optimized structure. This may provide the highest short-circuit current density to acquire high efficiency under indoor illumination.

Keywords: indoor solar cells, indoor light harvesting, organic solar cells, P3HT:ICBA, renewable energy

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Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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Authors: Chittapon Jantararussamee, Malai Taweechotipatr, Udomsri Showpittapornchai, Wisuit Pradidarcheep

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Hepatic fibrosis is characterized by collagen accumulation in hepatic lobules following wound healing process. If lefts untreated, it could progress into hepatic cirrhosis, portal hypertension, and liver failure. Probiotics comprise of lactic acid bacteria which are crucial components of the intestinal microflora and possess many beneficial properties. The objective of this study is to investigate the hepatoprotective effects of probiotic lactic acid bacteria (mixture of Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus confusus at a ratio of 1: 1: 1) on thioacetamide-induced liver fibrotic rats in term of histomorphology study. Twenty-four male Wistar rats were randomly divided into four groups with 6 rats each: (A) control, (B) fibrotic, (C) fibrotic+probiotic, and (D) probiotic. Group (A) received daily oral administration of distilled water. Group (B and C) were induced by intraperitoneal injection of thioacetamide (TAA) (200 mg/kg BW) 3 times per week for consecutive 8 weeks. In probiotic-treated group (C and D), the number of a mixture of the viable microbial cells at 10⁹ CFU/ml was administered orally daily. After sacrifice, liver tissues were collected and processed for routine histological technique and stained with Sirius red. It was found that the fibrotic rats showed hepatic injury marked by area of inflammation, hydropic degeneration of hepatocytes, and accumulation of myofibroblast-like cells. The collagen fibers were substantially accumulated in the hepatic lobules. Moreover, probiotic-treated group significantly reduced the accumulation of collagen in rats treated by TAA. The liver damage was found to be lesser in the probiotic-treated group. It was noted that the liver tissues of control and probiotics groups were shown to be normal. Administration with probiotic lactic acid bacteria could improve the histomorphology in fibrotic liver and be useful for prevention of hepatic disorders.

Keywords: liver fibrosis, probiotics, lactic acid bacteria, thioacetamide

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Authors: Anita Conti, Riccardo Ossanna, Lindsey A. Quintero, Giamaica Conti, Andrea Sbarbati

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Ischemia/reperfusion (IR) injury induces muscle fiber atrophy and skeletal muscle fiber death with subsequently functionality loss. The heterogeneous pool of cells, especially mesenchymal stem cells, contained in the stromal vascular fraction (SVF) of adipose tissue could promote muscle fiber regeneration. To prevent SVF dispersion, it has been proposed the use of injectable biopolymers that work as cells carrier. A significant element of the extracellular matrix is hyaluronic acid (HA), which has been widely used in regenerative medicine as a cell scaffold given its biocompatibility, degradability, and the possibility of chemical functionalization. Connective tissue micro-fragments enriched with SVF obtained from mechanical disaggregation of adipose tissue were evaluated for IR muscle injury regeneration using low molecular weight HA as a scaffold. IR induction. Hindlimb ischemia was induced in 9 athymic nude mice through the clamping of the right quadriceps using a plastic band. Reperfusion was induced by cutting the plastic band after 3 hours of ischemic period. Contralateral (left) muscular tissue was used as healthy control. Treatment. Twenty-four hours after the IR induction, animals (n=3) were intramuscularly injected with 100 µl of SVF mixed with HA (SVF-HA). Animals treated with 100 µl of HA (n=3) and 100 µl saline solution (n=3) were used as control. Treatment monitoring. All animals were in vivo monitored by magnetic resonance imaging (MRI) at 5, 7, 14 and 18 days post-injury (dpi). High-resolution morphological T2 weighed, quantitative T2 map and Dynamic Contrast-Enhanced (DCE) images were acquired in order to assess the regenerative potential of SVF-HA treatment. Ex vivo evaluation. After 18 days from IR induction, animals were sacrificed, and the muscles were harvested for histological examination. At 5 dpi T2 high-resolution MR images clearly reveal the presence of an extensive edematous area due to IR damage for all groups identifiable as an increase of signal intensity (SI) of muscular and surrounding tissue. At 7 dpi, animals of the SVF-HA group showed a reduction of SI, and the T2relaxation time of muscle tissue of the HA-SVF group was 29±0.5ms, comparable with the T2relaxation time of contralateral muscular tissue (30±0.7ms). These suggest a reduction of edematous overflow and swelling. The T2relaxation time at 7dpi of HA and saline groups were 84±2ms and 90±5ms, respectively, which remained elevated during the rest of the study. The evaluation of vascular regeneration showed similar results. Indeed, DCE-MRI analysis revealed a complete recovery of muscular tissue perfusion after 14 dpi for the SVF-HA group, while for the saline and HA group, controls remained in a damaged state. Finally, the histological examination of SVF-HA treated animals exhibited well-defined and organized fibers morphology with a lateralized nucleus, similar to contralateral healthy muscular tissue. On the contrary, HA and saline-treated animals presented inflammatory infiltrates, with HA slightly improving the diameter of the fibers and less degenerated tissue. Our findings show that connective tissue micro-fragments enriched with SVF induce higher muscle homeostasis and perfusion restoration in contrast to control groups.

Keywords: ischemia/reperfusion injury, regenerative medicine, resonance imaging, stromal vascular fraction

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Authors: Lie-Sian Yap, Ming-Chien Yang

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This study demonstrated a novel injectable hydrogel scaffold composing of Pluronic F127, carboxymethyl hexanoyl chitosan (CA) and glutaraldehyde (GA) for encapsulating human fetal osteoblastic cells (hFOB) 1.19. The hydrogel was prepared by mixing F127 and GA in CA solution at 4°C. The mechanical properties and cytotoxicity of this hydrogel were determined through rheological measurements and MTT assay, respectively. After encapsulation process, the hFOB 1.19 cells morphology was examined using fluorescent and confocal imaging. The results indicated that the Tgel of this system was around 30°C, where sol-gel transformation occurred within 90s and F127/CA/GA gel was able to remain intact in the medium for more than 1 month. In vitro cell culture assay revealed that F127/CA/GA hydrogels were non-cytotoxic. Encapsulated hFOB 1.19 cells not only showed the spherical shape and formed colonies, but also reduced their size. Moreover, the hFOB 1.19 cells showed that cells remain alive after the encapsulation process. Based on these results, these F127/CA/GA hydrogels can be used to encapsulate cells for tissue engineering applications.

Keywords: carboxymethyl hexanoyl chitosan, cell encapsulation, hFOB 1.19, Pluronic F127

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Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

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Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Jerome G. Chandraseelan, Samuel M. D. Oliveira, Antti Häkkinen, Sofia Startceva, Andre S. Ribeiro

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We used live E. coli containing synthetic genetic oscillators to study how the degree of synchrony between the genetic circuits of sister cells changes with temperature. We found that both the mean and the variability of the degree of synchrony between the fluorescence signals from sister cells are affected by temperature. Also, while most pairs of sister cells were found to be highly synchronous in each condition, the number of asynchronous pairs increased with increasing temperature, which was found to be due to disruptions in the oscillations. Finally we provide evidence that these disruptions tend to affect multiple generations as opposed to individual cells. These findings provide insight in how to design more robust synthetic circuits and in how cell division can affect their dynamics.

Keywords: repressilator, robustness, synchrony, synthetic biology

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Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of hesperidin was investigated in rats exposed to liver injury induced by a single intraperitoneal injection of cyclophosphamide (CYP) at a dose of 150 mg kg-1. Hesperidin treatment (100 mg kg-1/day, orally) was applied for seven days, starting five days before CYP administration. Hesperidin significantly decreased the CYP-induced elevations of serum alanine aminotransferase, and hepatic malondialdehyde and myeloperoxidase activity, significantly prevented the depletion of hepatic glutathione peroxidase activity resulted from CYP administration. Also, hesperidin ameliorated the CYP-induced liver tissue injury observed by histopathological examination. In addition, hesperidin decreased the CYP-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, Fas ligand, and caspase-9 in liver tissue. It was concluded that hesperidin may represent a potential candidate to protect against CYP-induced hepatotoxicity.

Keywords: hesperidin, cyclophosphamide, liver, rats

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Authors: Neeraj Malhotra

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Background: Bioreactors in tissue engineering are used as devices that apply mechanical means to influence biological processes. They are commonly employed for stem cell culturing, growth and expansion as well as in 3D tissue culture. Contemporarily there use is well established and is tested extensively in the medical sciences, for tissue-regeneration and tissue engineering of organs like bone, cartilage, blood vessels, skin grafts, cardiac muscle etc. Methodology: Literature search, both electronic and hand search, was done using the following MeSH and keywords: bioreactors, bioreactors and dentistry, bioreactors & dental tissue engineering, bioreactors and regenerative dentistry. Articles published only in English language were included for review. Results: Bioreactors like, spinner flask-, rotating wall-, flow perfusion-, and micro-bioreactors and in-vivo bioreactor have been employed and tested for the regeneration of dental and like-tissues. These include gingival tissue, periodontal ligament, alveolar bone, mucosa, cementum and blood vessels. Based on their working dynamics they can be customized in future for regeneration of pulp tissue and whole tooth regeneration. Apart from this, they have been successfully used in testing the clinical efficacy and biological safety of dental biomaterials. Conclusion: Bioreactors have potential use in testing dental biomaterials and tissue engineering approaches aimed at regenerative dentistry.

Keywords: bioreactors, biological process, mechanical stimulation, regenerative dentistry, stem cells

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Authors: Sylvanus N. Wosu

Abstract:

Research shows that factors, such as low motivation, preparation, resources, emotional and social integration, and fears of risk-taking, are the most common barriers to access, matriculation, and retention into science, technology, engineering, and mathematics (STEM) disciplines for underrepresented (URM) students. These factors have been shown to impact students’ attraction and success in STEM fields. Standardized tests such as the SAT and ACT often used as predictor of success, are not always true predictors of success for African and Hispanic American students. Without an adequate academic support environment, even a high SAT score does not guarantee academic success in science and engineering. This paper proposes a model for Academic Coaching for building success and inclusive excellence in STEM education. Academic coaching is framed as a process of motivating students to be independent learners through relational mentorship, facilitating learning supports inside and outside of the classroom or school environment, and developing problem-solving skills and success attitudes that lead to higher performance in the specific subjects. The model is formulated based on best strategies and practices for enriching Academic Performance Impact skills and motivating students’ interests in STEM. A scaled model for measuring the Academic Performance Impact (API) index and STEM is discussed. The study correlates API with state standardized test and shows that the average impact of those skills can be predicted by the Academic Performance Impact (API) index or Academic Preparedness Index.

Keywords: diversity, equity, graduate education, inclusion, inclusive excellence, model

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Authors: H. Bouaziz-Ketata, G. Ben Salah, Z. Aidi, C. Kallel, H. Kammoun, F. Fakhfakh, N. Zeghal

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The present study was performed to evaluate the potential protective effect of Hyparrhenia hirta methanolic extract in NaNO3-induced genotoxic and hematotoxic effects. Male Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 days with NaNO3 administered at a dose of 400 mg kg-1 bw either alone in drinking water or co-administered with Hyparrhenia hirta at a dose of 200 mg kg-1 bw. NaNO3 treatment showed a significant increase in the frequencies of total chromosomal aberrations, aberrant metaphases and micronucleus in bone-marrow cells. In parallel, the NaNO3-treated group showed a significant decrease in red blood cell count, hemoglobin and hematocrit and a significant increase in total white blood cell, in neutrophil and eosinophil counts. Platelet count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration remained unchanged in treated groups compared to those of controls. Hyparrhenia hirta methanolic extract appeared to be effective against genotoxic and hematotoxic changes induced by nitrate, as evidenced by the improvement of the markers cited above.

Keywords: Hyparrhenia hirta, sodium nitrate, erythrocytes, genotoxicity

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Authors: Isabel Medina, Mario Duran

Abstract:

Although Problem-based learning provides students with multiple opportunities for rigorous instructional experiences in which students are challenged to address problems in the community; there are still gaps in connecting community leaders to the PBL process. At a south Texas high school, community participation serves as an integral component of the PBL process. Problem-based learning (PBL) has recently gained momentum due to the increase in global communities that value collaboration and critical thinking. As an instructional approach, PBL engages high school students in meaningful learning experiences. Furthermore, PBL focuses on providing students with a connection to real-world situations that require effective peer collaboration. For PBL leaders, providing students with a meaningful process is as important as the final PBL outcome. To achieve this goal, STEM high school strategically created a space for community involvement to be woven within the PBL fabric. This study examines the impact community members had on PBL students attending a STEM high school in South Texas. At STEM High School, community members represent a support system that works through the PBL process to ensure students receive real-life mentoring from business and industry leaders situated in the community. A phenomenological study using a semi-structured approach was used to collect data about students’ perception of community involvement within the PBL process for one South Texas high school. In our proposed presentation, we will discuss how community involvement in the PBL process academically impacted the educational experience of high school students at STEM high school. We address the instructional concerns PBL critics have with the lack of direct instruction, by providing a representation of how STEM high school utilizes community members to assist in impacting the academic experience of students.

Keywords: phenomenological, STEM education, student engagement, community involvement

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Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob

Abstract:

Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.

Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus

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Authors: Kevin Zhao, Norman J. Horing

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A methodology for cells sorting and circulating tumor cell detection and discrimination is presented in this paper. The technique is based on Dielectrophoresis and microfluidic device theory. Specifically, the sorting of the cells is realized by adjusting the relation among the sedimentation forces, the drag force provided by the fluid, and the Dielectrophortic force that is relevant to the bias voltage applied on the device. The relation leads to manipulation of the elevation of the cells of the same kind to a height by controlling the bias voltage. Once the cells have been lifted to a position next to the bottom of the cell collection channel, the buffer fluid flashes them into the cell collection channel. Repeated elevation of the cells leads to a complete sorting of the cells in the sample chamber. A proof-of-principle example is presented which verifies the feasibility of the methodology.

Keywords: cell sorter, CTC cell, detection and discrimination, dielectrophoresisords, simulation

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Authors: Akbar Esmaeili, Fateme Dadashi

Abstract:

Bismuth can increase radiation and reduce the dose of radiotherapy. On the other hand, hyaluronic acid plays a role in healing damaged cells, and melittin has been used to destroy cancer cells. This research aims to destroy eye cancer cells and accelerate the recovery of damaged healthy cells during treatment. In this research, we used this nanoparticle, the sol-gel method. According to the optimization process that was carried out, we obtained the optimal value of the desired variables for the manufacture of nanoparticles. The advantage of doing this is reducing the amount of medicine used, as a result of reducing the number of side effects during the treatment and using melittin as an anti-eye cancer drug and the presence of hyaluronic acid to accelerate the recovery of cells, as well as coating the bismuth nanoparticle with chitosan to increase the half-life of the nanoparticle and prevent its adhesion.

Keywords: synthesis, nanoparticles, coated, cancer

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Authors: Kairat Uteulin, Azhar Iskakova, Serik Mukhambetzhanov, Bayan Yesbolayeva, Gabit Bari, Aslan Zheksenbai, Kabyl Zhambakin, Chingis Dzhabykbayev, Vladimir Piven, Izbasar Rakhimbaiev

Abstract:

To explore the potential for in vitro rapid regeneration of Russian dandelion (Taraxacum kok-saghyz Rodin), different concentrations of 6-Benzylaminopurine (BAP), 2,4-Dichlorophenoxyacetic acid (2.4-D) and BAP combined with Indole-3-acetic acid (IAA) were evaluated for their effects on the induction of somatic embryos from leaf, seed stem and root explants. Different explants were cultured on MS medium supplemented with various concentrations (0, 0.5, 1, 1.5, 2, 2.5 and 3 mg/l) of each kind of hormone. Callus induction percentage, fresh weight, color and texture of the callus were assessed after 14 and 28 days of culture. The optimum medium for the proliferation of embryogenic calli from leaf and root explants was MS supplemented with 2.5 mg/L BAP and 0.5 mg/L 2.4-D. Concentrations of 2.5 mg/L BAP and 1.5 mg/L IAA also had a remarkable effect on root and stem explants. The best concentration to produce callus from stem explants was 0.5 mg/L BAP and 1 mg/L IAA. Results of mean comparison showed that BAP and 2.4-D were more effective on different explants than BAP and IAA. Results of the double staining method proved that somatic embryogenesis occurred in the most concentrations of BAP and 2.4-D. Under microscopic observations, the different developmental stages of the embryos (globular, heart, torpedo and cotyledonary) were revealed together in callus cells, indicating that the most tested hormone combinations were effective for somatic embryogenesis formation in this species. Seed explants formed torpedo and cotyledonary stages faster than leaf and root explants in the most combinations. Most calli from seed explants were cream colored and friable, while calli were compact and light green from leaf and root explants. Some combinations gave direct regeneration and (3 mg/L BAP and 2 mg/L IAA) in seed explants and (0.5 mg/L BAP and 2.5 mg/L IAA) in leaf explants had the highest number of shoots with average of 21 and 27 shoots per callus. The developed protocol established the production of different callus types from seed, leaf, and root explants and plant regeneration through somatic embryogenesis.

Keywords: taraxacum kok-saghyz Rodin, callus, somatic embryogenesis

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Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

Abstract:

In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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