Search results for: induced pluripotent stem cells

Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

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Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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Authors: Ling-Ling E, Lin Feng, Hong-Chen Liu, Dong-Sheng Wang, Zhanping Shi, Juncheng Wang, Wei Luo, Yan Lv

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The objective of this study was to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severe combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The nHAC/PLA had significantly higher absorption water rate and protein adsorption rate than ß-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto ß-TCP; and the proliferation rate of the cells was significantly higher than that of ß-TCP on 1, 3 and 7 days of cell culture. DPSCs+ß-TCP had significantly higher ALP activity, calcium/phosphorus content and mineral formation than DPSCs+nHAC/PLA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point，but the percentage of mature bone formation area of DPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs+β-TCP group. These findings have provided a further knowledge that scaffold architecture has a different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs+β-TCP construct.

Keywords: dental pulp stem cells, nano-hydroxyapatite/collagen/poly(L-lactide), beta-tricalcium phosphate, periodontal tissue engineering, bone regeneration

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Authors: Lay Poh Tan, Chor Yong Tay, Haiyang Yu

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Micro-contact printing is a form of soft lithography that uses the relief patterns on a master polydimethylsiloxane (PDMS) stamp to form patterns of self-assembled monolayers (SAMs) of ink on the surface of a substrate through conformal contact technique. Here, we adopt this method to print proteins of different dimensions on our biodegradable polymer substrates. We started off with printing 20-500 μm scale lanes of fibronectin to engineer the shape of bone marrow derived human mesenchymal stem cell (hMSCs). After 8 hours of culture, the hMSCs adopted elongated shapes, and upon analysis of the gene expressions, genes commonly associated with myogenesis (GATA-4, MyoD1, cTnT and β-MHC) and neurogenesis (NeuroD, Nestin, GFAP, and MAP2) were up-regulated but gene expression associated to osteogenesis (ALPL, RUNX2, and SPARC) were either down modulated or remained at the nominal level. This is the first evidence that cellular morphology control via micropatterning could be used to modulate stem cell fate without external biochemical stimuli. We further our studies to modulate the focal adhesion (FA) instead of the macro shape of cells. Micro-contact printed islands of different smaller dimensions were investigated. We successfully regulated the FAs into dense FAs and elongated FAs by micropatterning. Additionally, the combined effects of hard (40.4 kPa), and intermediate (10.6 kPa) PA gel and FAs patterning on hMSCs differentiation were studied. Results showed that FA and matrix compliance plays an important role in hMSCs differentiation, and there is a cross-talk between different physical stimulants and the significance of these stimuli can only be realized if they are combined at the optimum level.

Keywords: micro-contact printing, polymer substrate, cell-material interaction, stem cell differentiation

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Authors: Daria Grechishnikova, Maria Poptsova

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Transposable elements play an important role in the evolution of various species from bacteria to human. Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs) are two major classes of retrotransposons that occupy a considerable part of any genome and their copy numbers can range form several hundreds to a million. Both LINEs and SINEs multiply through a copy-and-paste mechanism. LINEs encode proteins, which make them capable of self-propagation while SINEs are parasitic and require the machinery of LINEs to multiply. The mechanisms how LINE and SINE RNA is recognized by the LINE-encoded reverse transcriptase (RT) remain unclear. For some SINE-LINE pairs, it was shown that they share a common 3’-end with a stem-loop structure. Majority of the SINE-LINE pairs do not have a common 3’-end. Recently we have shown that in the human genome Alu-L1 pairs have structurally similar stem-loop structure at the 3’-end. Here we extended our analysis to a wide range of species and analyzed LINEs from 161 different species from Repbase and 217 SINE sequences from SINEBase. It appeared that all of the analyzed sequences contained stem-loop structures at the 3’-end. Here we conclude that it is very likely that a common evolutionary mechanism of transposon RNA recognition requires the presence of stem-loop structures at their 3’-end.

Keywords: LINE, SINE, mechanisms of retrotransposition, retrotransposons, stem-loop, stem-loop structures, transposons

Procedia PDF Downloads 331

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

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Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50, oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals and stem bark

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Authors: Aysegul Alyamac, Sukru Gulec

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Ankaferd Blood Stopper (ABS) is a plant extract used to stop bleeding caused by injuries and surgical interventions. ABS also involved in wound healing of intestinal mucosal damage due to oxidative stress and inflammation. Inflammatory Bowel Disease (IBD) is a common chronic disorder of the gastrointestinal tract that causes abdominal pain, diarrhea, and gastrointestinal bleeding, and increases the risk of colon cancer. Inflammation is an essential factor in the development of IBD. The various studies have been performed about the physiological effects of ABS; however, ABS dependent mechanism on colonic inflammation has not been elucidated. Thus, the protective effect of ABS on colonic inflammation was investigated in this study. The Caco-2 and RAW 264.7 murine macrophage cells were used as a model of in vitro colonic inflammation. RAW 264.7 cells were treated with lipopolysaccharide (LPS) for 12 hours to induce the inflammation, and a conditional medium was obtained. Caco-2 cells were treated with 15 µl/ml ABS for 4 hours, then incubated with conditional medium and the cells also were incubated with 15 µl/ml ABS and conditional medium together for 4 hours. Tumor necrosis factor alpha (TNF-α) protein levels were targeted in testing inflammatory condition and its level was significantly increased (25 fold, p<0.001) compared to the control group by using Enzyme-Linked Immunosorbent Assay (ELISA) method. The COX-2 mRNA level was used as a marker gene to show the possible anti-inflammatory effect of ABS in Caco-2 cells. RAW cells-derived conditional medium significantly (3.3 fold, p<0.001) induced cyclooxygenase-2 (COX-2) mRNA levels in Caco-2 cells. The pretreatment of Caco-2 cells caused a significant decrease (3.3 fold, p<0.001) in COX-2 mRNA levels relative to conditional medium given group. Furthermore, COX-2 mRNA level was significantly reduced (4,7 fold, p<0.001) in ABS and conditional medium treated group. These results suggest that ABS might have an anti-inflammatory effect in vitro.

Keywords: Ankaferd blood stopper, CaCo-2, colonic inflammation, RAW 264.7

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Authors: Ali Taher Othman Ali

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The aim of this research is to provide a draft proposal for the professional development of mathematics teachers in accordance with the orientation of science, technology, engineering and mathematics which is known by the abbreviation STEM, as a modern and contemporary orientation in the teaching and learning of mathematics and in order to achieve the objective of the research, the researcher used the theoretical descriptive method through the induction of the literature of education and the previous studies and experiments related to the topic. The researcher concluded by providing the proposal according to five basic axes, the first axe: professional development as a system, and its requirements include: development of educational systems, and allocate sufficient budgets to support the requirements of teaching STEM, identifying mechanisms for incentives and rewards for teachers attending professional development programs based on STEM; the second: development of in-depth knowledge content and its requirements include: basic sciences content development for STEM, linking the scientific understanding of teachers with real-world issues and problems, to provide the necessary resources to expand teachers' knowledge in this area; the third: the necessary pedagogical skills of teachers in the field of STEM, and its requirements include: identification of the required training and development needs and the mechanism of determining these needs, the types of professional development programs and the mechanism of designing it, the mechanisms and places of execution, evaluation and follow-up; the fourth: professional development strategies and mechanisms in the field of STEM, and its requirements include: using a variety of strategies to enable teachers to design and transfer effective educational experiences which reflect their scientific mastery in the fields of STEM, provide learning opportunities, and developing the skills of procedural research to generate new knowledge about the STEM; the fifth: to support professional development in the area of STEM, and its requirements include: support leadership within the school, provide a clear and appropriate opportunities for professional development for teachers within the school through professional learning communities, building partnerships between the Ministry of education and the local and international community institutions. The proposal includes other factors that should be considered when implementing professional development programs for mathematics teachers in the field of STEM.

Keywords: professional development, mathematics teachers, the orientation of science, technology, engineering and mathematics (STEM)

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Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

Procedia PDF Downloads 342

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals, stem bark extract

Procedia PDF Downloads 404

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: H. Mazouz, A. Belghachi, F. Hadjaj

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Solar cells used in orbit are exposed to radiation environment mainly protons and high energy electrons. These particles degrade the output parameters of the solar cell. The aim of this work is to characterize the effects of electron irradiation fluence on the J (V) characteristic and output parameters of gaAs solar cell by numerical simulation. The results obtained demonstrate that the electron irradiation-induced degradation of performances of the cells concerns mainly the short circuit current.

Keywords: gaAs solar cell, MeV electron irradiation, irradiation fluence, short circuit

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Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: diabetic nephropathy, hyperglycemia, reactive oxygen species, oxidative stress, mtDNA, mitochondrial dysfunction, manganese superoxide dismutase, catalase

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Authors: Zhipeng Dong, Jing Guo

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Graphene-semiconductor contacts have been extensively studied recently, both as a stand-alone diode device for potential applications in photodetectors and solar cells, and as a building block to vertical transistors. Graphene is a two-dimensional nanomaterial with vanishing density-of-states at the Dirac point, which differs from conventional metal. In this work, image-charge-induced barrier lowering (BL) in graphene-semiconductor contacts is studied and compared to that in metal Schottky contacts. The results show that despite of being a semimetal with vanishing density-of-states at the Dirac point, the image-charge-induced BL is significant. The BL value can be over 50% of that of metal contacts even in an intrinsic graphene contacted to an organic semiconductor, and it increases as the graphene doping increases. The dependences of the BL on the electric field and semiconductor dielectric constant are examined, and an empirical expression for estimating the image-charge-induced BL in graphene-semiconductor contacts is provided.

Keywords: graphene, semiconductor materials, schottky barrier, image charge, contacts

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Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

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Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Otilia Ruxandra Vasile, Ecaterina Andronescu, Cristina Daniela Ghitulica, Bogdan Stefan Vasile, Roxana Trusca, Eugeniu Vasile, Alina Maria Holban, Carmen Mariana Chifiriuc, Florin Iordache, Horia Maniu

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Engineered powders offer great promise in several applications, but little information is known about cytotoxicity effects. The aim of the current study was the synthesis and cytotoxicity examination of silver powders using pyrosol method at temperatures of 600°C, 650°C and 700°C, respectively sol-gel method and calcinations at 500°C, 600°C, 700°C and 800°C. We have chosen to synthesize and examine silver particles cytotoxicity due to its use in biological applications. The synthesized Ag powders were characterized from the structural, compositional and morphological point of view by using XRD, SEM, and TEM with SAED. In order to determine the influence of the synthesis route on Ag particles cytotoxicity, different sizes of micro and nanosilver synthesized powders were evaluated for their potential toxicity. For the study of their cytotoxicity, cell cycle and apoptosis have been done analysis through flow cytometry on human colon carcinoma cells and mesenchymal stem cells and through the MTT assay, while the viability and the morphological changes of the cells have been evaluated by using cloning studies. The results showed that the synthesized silver nanoparticles have displayed significant cytotoxicity effects on cell cultures. Our synthesized silver powders were found to present toxicity in a synthesis route and time-dependent manners for pyrosol synthesized nanoparticles; whereas a lower cytotoxicity has been measured after cells were treated with silver nanoparticles synthesized through sol-gel method.

Keywords: Ag, cytotoxicity, pyrosol method, sol-gel method

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Authors: Debabrata Auddya, Bradley J. Roth

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The mechanical bidomain model is used to describe a colony of cells growing on a substrate. Analytical expressions are derived for the intracellular and extracellular displacements. Mechanotransduction events are driven by the difference between the displacements in the two spaces, corresponding to the force acting on integrins. The equation for the displacement consists of two terms: one proportional to the radius that is the same in the intracellular and extracellular spaces (the monodomain term) and one that is proportional to a modified Bessel function that is responsible for mechanotransduction (the bidomain term). The model predicts that mechanotransduction occurs within a few length constants of the colony’s edge, and an expression for the length constant contains the intracellular and extracellular shear moduli and the spring constant of the integrins coupling the two spaces. The model predictions are qualitatively consistent with experiments on human embryonic stem cell colonies, in which differentiation is localized near the edge.

Keywords: cell colony, integrin, mechanical bidomain model, stem cell, stress-strain, traction force

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Authors: Jutharat Sunprasert, Ekapong Hirunsirisawat, Narongrit Waraporn, Somporn Peansukmanee

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Metal Ship and Robotic Car is one of the hands-on activities in the course, the Fundamental of Engineering that can be divided into three parts. The first part, the metal ships, was made by using engineering drawings, physics and mathematics knowledge. The second part is where the students learned how to construct a robotic car and control it using computer programming. In the last part, the students had to combine the workings of these two objects in the final testing. This aim of study was to investigate the effectiveness of hands-on activity by integrating Science, Technology, Engineering and Mathematics (STEM) concepts to develop scientific and engineering skills. The results showed that the majority of students felt this hands-on activity lead to an increased confidence level in the integration of STEM. Moreover, 48% of all students engaged well with the STEM concepts. Students could obtain the knowledge of STEM through hands-on activities with the topics science and mathematics, engineering drawing, engineering workshop and computer programming; most students agree and strongly agree with this learning process. This indicated that the hands-on activity: “Metal Ship and Robotic Car” is a useful tool to integrate each aspect of STEM. Furthermore, hands-on activities positively influence a student’s interest which leads to increased learning achievement and also in developing scientific and engineering skills.

Keywords: hands-on activity, STEM education, computer programming, metal work

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: Bharti Gupta, Alaukik Sharma

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The first aim is to determine the effect of the Earth's magnetic field on the motion of a conductor to evaluate the variations of the orbital elements of the conductor due to these effects. The effects of Earth's magnetic field on the motion of conductors have been studied at different heights, longitudes and latitudes. When the conductor cut the geomagnetic line of force, then an electro-motive force (EMF) is induced across to the conductor. Due to this induced EMF, an induced current will flow through the conductor. Resulting, a Lorentz force will be applied on the conductor who opposes the motion of the conductor. So our second aim is to determine the accurate value of Induced EMF and induced Lorentz Force at different heights, longitudes and latitudes.

Keywords: induced EMF, Lorentz force, geomagnetic lines of force, moving conductor

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Authors: Elfatih M. Abdel-Rahman, Tobias Landmann, Richard Kyalo, George Ong’amo, Bruno Le Ru

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Maize (Zea mays L.) is a major staple food crop in Africa, particularly in the eastern region of the continent. The maize growing area in Africa spans over 25 million ha and 84% of rural households in Africa cultivate maize mainly as a means to generate food and income. Average maize yields in Sub Saharan Africa are 1.4 t/ha as compared to global average of 2.5–3.9 t/ha due to biotic and abiotic constraints. Amongst the biotic production constraints in Africa, stem borers are the most injurious. In East Africa, yield losses due to stem borers are currently estimated between 12% to 40% of the total production. The objective of the present study was therefore to predict stem borer larvae density in maize fields using RapidEye reflectance data and generalized linear models (GLMs). RapidEye images were captured for a test site in Kenya (Machakos) in January and in February 2015. Stem borer larva numbers were modeled using GLMs assuming Poisson (Po) and negative binomial (NB) distributions with error with log arithmetic link. Root mean square error (RMSE) and ratio prediction to deviation (RPD) statistics were employed to assess the models performance using a leave one-out cross-validation approach. Results showed that NB models outperformed Po ones in all study sites. RMSE and RPD ranged between 0.95 and 2.70, and between 2.39 and 6.81, respectively. Overall, all models performed similar when used the January and the February image data. We conclude that reflectance data from RapidEye data can be used to estimate stem borer larvae density. The developed models could to improve decision making regarding controlling maize stem borers using various integrated pest management (IPM) protocols.

Keywords: maize, stem borers, density, RapidEye, GLM

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Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

Procedia PDF Downloads 130

Authors: M. Assaad, J. Mäkiö, T. Mäkelä, M. Kankaanranta, N. Fachantidis, V. Dagdilelis, A. Reid, C. R. del Rio, E. V. Pavlysh, S. V. Piashkun

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To bring science and society together in Europe, thus increasing the continent’s international competitiveness, STEM (science, technology, engineering and mathematics) education must be more relatable to European youths in their everyday life. STIMEY (Science, Technology, Innovation, Mathematics, Engineering for the Young) project researches and develops a hybrid educational environment with multi-level components that is being designed and developed based on a well-researched pedagogical framework, aiming to make STEM education more attractive to young people aged 10 to 18 years in this digital era. This environment combines social media components, robotic artefacts, and radio to educate, engage and increase students’ interest in STEM education and careers from a young age. Additionally, it offers educators the necessary modern tools to deliver STEM education in an attractive and engaging manner in or out of class. Moreover, it enables parents to keep track of their children’s education, and collaborate with their teachers on their development. Finally, the open platform allows businesses to invest in the growth of the youths’ talents and skills in line with the economic and labour market needs through entrepreneurial tools. Thus, universities, schools, teachers, students, parents, and businesses come together to complete a circle in which STEM becomes part of the daily life of youths through a hybrid educational environment that also prepares them for future careers.

Keywords: e-learning, entrepreneurship, pedagogy, robotics, serious gaming, social media, STEM education

Procedia PDF Downloads 349

Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

Procedia PDF Downloads 157

Authors: M. Osibemhe, I. O. Onoagbe

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Diabetes mellitus is a common disease that has no known cure. The available orthodox drugs used for its management have one or more disadvantages. This study investigated the potency of aqueous and ethanol extracts of Strophanthus hispidus (SH) stem bark in the management of diabetes mellitus. Glucose concentration and lipid profile parameters of normal and streptozotocin-induced diabetic rats were monitored for 12weeks. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (55 mg/kg). Male rats (wistar strain) numbering 30 were randomly selected into six groups of five rats each. Groups 1 and 6 served as normal and diabetic control respectively and received distilled water for 12weeks. Groups 2 and 3 were normal rats treated orally with the aid of a gavage, 250 mg/kg of aqueous and ethanol extracts respectively for 12weeks. Groups 4 and 5 were diabetic rats and were treated with the respective dose of aqueous and ethanol extracts for the same period. A significant (P˂0.05) progressive decrease in blood glucose concentrations of both normal and diabetic rats treated with the extracts were observed from the 2nd to 12th weeks when compared with the respective controls. No significant (P˃0.05) effects were observed in the basal values of both normal and diabetic rats. Administration of both extracts of SH to diabetic rats significantly (P˂0.05) lowered the concentrations of Total cholesterol, TG, and LDL, whereas it increases the concentration of HDL when compared with diabetic control. The concentrations of total cholesterol and LDL in normal rats treated with SH were also reduced when compared with normal control whereas SH had no significant (P˃0.05) effect on HDL. However, TG level of normal control was significantly (P˂0.05) lower than normal rats treated with both extracts. A progressive increase in weight of normal and diabetic rats treated with the extracts was observed on the 2nd – 12th weeks of administration, whereas diabetic control showed a progressive decrease in weight. The findings from this study indicated that SH has hypoglycemic and anti-lipidemic properties as well as anti-diabetic potentials. It also showed that ethanol extract had greater glucose lowering effect. Hence, SH may be considered as a potent anti-diabetic plant and could be used as alternative drug for the management of diabetes mellitus.

Keywords: concentration, ethanol extract, hypoglycemic, total cholesterol

Procedia PDF Downloads 194

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

Procedia PDF Downloads 44

Authors: Hamed Nafar, Sajad Rezaei, Hamid Behbahani

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Safety analysis of the roads through the accident rates which is one of the widely used tools has been resulted from the direct exposure method which is based on the ratio of the vehicle-kilometers traveled and vehicle-travel time. However, due to some fundamental flaws in its theories and difficulties in gaining access to the data required such as traffic volume, distance and duration of the trip, and various problems in determining the exposure in a specific time, place, and individual categories, there is a need for an algorithm for prioritizing the road safety so that with a new exposure method, the problems of the previous approaches would be resolved. In this way, an efficient application may lead to have more realistic comparisons and the new method would be applicable to a wider range of time, place, and individual categories. Therefore, an algorithm was introduced to prioritize the safety of roads using the quasi-induced exposure method and utilizing the analytical hierarchy process. For this research, 11 provinces of Iran were chosen as case study locations. A rural accidents database was created for these provinces, the validity of quasi-induced exposure method for Iran’s accidents database was explored, and the involvement ratio for different characteristics of the drivers and the vehicles was measured. Results showed that the quasi-induced exposure method was valid in determining the real exposure in the provinces under study. Results also showed a significant difference in the prioritization based on the new and traditional approaches. This difference mostly would stem from the perspective of the quasi-induced exposure method in determining the exposure, opinion of experts, and the quantity of accidents data. Overall, the results for this research showed that prioritization based on the new approach is more comprehensive and reliable compared to the prioritization in the traditional approach which is dependent on various parameters including the driver-vehicle characteristics.

Keywords: road safety, prioritizing, Quasi-induced exposure, Analytical Hierarchy Process

Procedia PDF Downloads 317

Authors: Bhawna Chandravanshi, Ramesh Bhonde

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In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

Procedia PDF Downloads 240