Search results for: anger expression
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2138

Search results for: anger expression

1178 'Value-Based Re-Framing' in Identity-Based Conflicts: A Skill for Mediators in Multi-Cultural Societies

Authors: Hami-Ziniman Revital, Ashwall Rachelly

Abstract:

The conflict resolution realm has developed tremendously during the last half-decade. Three main approaches should be mentioned: an Alternative Dispute Resolution (ADR) suggesting processes such as Arbitration or Interests-based Negotiation was developed as an answer to obligations and rights-based conflicts. The Pragmatic mediation approach focuses on the gap between interests and needs of disputants. The Transformative mediation approach focusses on relations and suits identity-based conflicts. In the current study, we examine the conflictual relations between religious and non-religious Jews in Israel and the impact of three transformative mechanisms: Inter-group recognition, In-group empowerment and Value-based reframing on the relations between the participants. The research was conducted during four facilitated joint mediation classes. A unique finding was found. Using both transformative mechanisms and the Contact Hypothesis criteria, we identify transformation in participants’ relations and a considerable change from anger, alienation, and suspiciousness to an increased understanding, affection and interpersonal concern towards the out-group members. Intergroup Recognition, In-group empowerment, and Values-based reframing were the skills discovered as the main enablers of the change in the relations and the research participants’ fostered mutual recognition of the out-group values and identity-based issues. We conclude this transformation was possible due to a constant intergroup contact, based on the Contact Hypothesis criteria. In addition, as Interests-based mediation uses “Reframing” as a skill to acknowledge both mutual and opposite needs of the disputants, we suggest the use of “Value-based Reframing” in intergroup identity-based conflicts, as a skill contributes to the empowerment and the recognition of both mutual and different out-group values. We offer to implement those insights and skills to assist conflict resolution facilitators in various intergroup identity-based conflicts resolution efforts and to establish further research and knowledge.

Keywords: empowerment, identity-based conflict, intergroup recognition, intergroup relations, mediation skills, multi-cultural society, reframing, value-based recognition

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1177 Statistical Pattern Recognition for Biotechnological Process Characterization Based on High Resolution Mass Spectrometry

Authors: S. Fröhlich, M. Herold, M. Allmer

Abstract:

Early stage quantitative analysis of host cell protein (HCP) variations is challenging yet necessary for comprehensive bioprocess development. High resolution mass spectrometry (HRMS) provides a high-end technology for accurate identification alongside with quantitative information. Hereby we describe a flexible HRMS assay platform to quantify HCPs relevant in microbial expression systems such as E. Coli in both up and downstream development by means of MVDA tools. Cell pellets were lysed and proteins extracted, purified samples not further treated before applying the SMART tryptic digest kit. Peptides separation was optimized using an RP-UHPLC separation platform. HRMS-MSMS analysis was conducted on an Orbitrap Velos Elite applying CID. Quantification was performed label-free taking into account ionization properties and physicochemical peptide similarities. Results were analyzed using SIEVE 2.0 (Thermo Fisher Scientific) and SIMCA (Umetrics AG). The developed HRMS platform was applied to an E. Coli expression set with varying productivity and the corresponding downstream process. Selected HCPs were successfully quantified within the fmol range. Analysing HCP networks based on pattern analysis facilitated low level quantification and enhanced validity. This approach is of high relevance for high-throughput screening experiments during upstream development, e.g. for titer determination, dynamic HCP network analysis or product characterization. Considering the downstream purification process, physicochemical clustering of identified HCPs is of relevance to adjust buffer conditions accordingly. However, the technology provides an innovative approach for label-free MS based quantification relying on statistical pattern analysis and comparison. Absolute quantification based on physicochemical properties and peptide similarity score provides a technological approach without the need of sophisticated sample preparation strategies and is therefore proven to be straightforward, sensitive and highly reproducible in terms of product characterization.

Keywords: process analytical technology, mass spectrometry, process characterization, MVDA, pattern recognition

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1176 Hamilton-Jacobi Treatment of Damped Motion

Authors: Khaled I. Nawafleh

Abstract:

In this work, we apply the method of Hamilton-Jacobi to obtain solutions of Hamiltonian systems in classical mechanics with two certain structures: the first structure plays a central role in the theory of time-dependent Hamiltonians, whilst the second is used to treat classical Hamiltonians, including dissipation terms. It is proved that the generalization of problems from the calculus of variation methods in the nonstationary case can be obtained naturally in Hamilton-Jacobi formalism. Then, another expression of geometry of the Hamilton Jacobi equation is retrieved for Hamiltonians with time-dependent and frictional terms. Both approaches shall be applied to many physical examples.

Keywords: Hamilton-Jacobi, time dependent lagrangians, dissipative systems, variational principle

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1175 The Evolution and Driving Forces Analysis of Urban Spatial Pattern in Tibet Based on Archetype Theory

Authors: Qiuyu Chen, Bin Long, Junxi Yang

Abstract:

Located in the southwest of the "roof of the world", Tibet is the origin center of Tibetan Culture.Lhasa, Shigatse and Gyantse are three famous historical and cultural cities in Tibet. They have always been prominent political, economic and cultural cities, and have accumulated the unique aesthetic orientation and value consciousness of Tibet's urban construction. "Archetype" usually refers to the theoretical origin of things, which is the collective unconscious precipitation. The archetype theory fundamentally explores the dialectical relationship between image expression, original form and behavior mode. By abstracting and describing typical phenomena or imagery of the archetype object can observe the essence of objects, explore ways in which object phenomena arise. Applying archetype theory to the field of urban planning helps to gain insight, evaluation, and restructuring of the complex and ever-changing internal structural units of cities. According to existing field investigations, it has been found that Dzong, Temple, Linka and traditional residential systems are important structural units that constitute the urban space of Lhasa, Shigatse and Gyantse. This article applies the thinking method of archetype theory, starting from the imagery expression of urban spatial pattern, using technologies such as ArcGIS, Depthmap, and Computer Vision to descriptively identify the spatial representation and plane relationship of three cities through remote sensing images and historical maps. Based on historical records, the spatial characteristics of cities in different historical periods are interpreted in a hierarchical manner, attempting to clarify the origin of the formation and evolution of urban pattern imagery from the perspectives of geopolitical environment, social structure, religious theory, etc, and expose the growth laws and key driving forces of cities. The research results can provide technical and material support for important behaviors such as urban restoration, spatial intervention, and promoting transformation in the region.

Keywords: archetype theory, urban spatial imagery, original form and pattern, behavioral driving force, Tibet

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1174 Significance of Molecular Autophagic Pathway in Gaucher Disease Pathology

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

Abstract:

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

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

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1173 Psychosocial Experience of Parents of Children with Conduct Disorder in Thulamela, South Africa

Authors: Constance Singo, Choja Oduaran

Abstract:

Child mental disorders are strongly associated with different forms of challenges, including behavioural problems. The burden of care for children with a mental disorder is high and put primary caregivers, parents in particular, at risk of poor mental wellbeing. Understanding the experience of parents of children with mental disorders is crucial to developing a relevant intervention to assist them to attain optimal mental wellbeing. The aim of this study was to explore the experiences of parents of children with conduct disorder by focussing on the psychological and social stress experience of the parents in raising and caring for their children with conduct disorder. A qualitative research approach, using in-depth interview was utilized in this study. Purposive and snowballing sampling techniques were used to select 9 parents of children with conduct disorder in Thulamela Municipality, Limpopo Province of South Africa. Participants comprising of 2 males and 7 females aged between 30 years and 49 years were interviewed individually at scheduled appointment in-home setting. Interviews were conducted in both English and Setswana language. Data collected in Setswana language were translated to English by 'expert in language translation'. Ethical approval was obtained from appropriate authority before data collection. Thematic analysis was conducted to analyse the collected data. The findings identified anger, fear, depressive symptoms, denial, and suicidal ideation as predominant psychological experiences of the parents. Furthermore, deteriorated interpersonal relationships with family and community members, financial stress, and stigma emerged as social problems being the experience of the parents. It was concluded that parents of children with conduct disorder are highly traumatized by the challenges of caring for their children. We recommend professional engagement in terms of counselling service to support the parents. There is also a need for massive enlightenment programmes for members of the community in order to support the parents of children with child mental disorders.

Keywords: conduct disorder, parents, psychosocial experiences, South Africa

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1172 Time Dependent Biodistribution Modeling of 177Lu-DOTATOC Using Compartmental Analysis

Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

Abstract:

In this study, 177Lu-DOTATOC was prepared under optimized conditions (radiochemical purity: > 99%, radionuclidic purity: > 99%). The percentage of injected dose per gram (%ID/g) was calculated for organs up to 168 h post injection. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. The biodistribution data showed the significant excretion of the radioactivity from the kidneys. The adrenal and pancreas, as major expression sites for somatostatin receptor (SSTR), had significant uptake. A pharmacokinetic model of 177Lu-DOTATOC was presented by compartmental analysis which demonstrates the behavior of the complex.

Keywords: biodistribution, compartmental modeling, ¹⁷⁷Lu, Octreotide

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1171 Therapeutic Role of T Subpopulations Cells (CD4, CD8 and Treg (CD25 and FOXP3+ Cells) of UC MSC Isolated from Three Different Methods in Various Disease

Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

Abstract:

Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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1170 Inclusive Design for Regaining Lost Identity: Accessible, Aesthetic and Effortless Clothing

Authors: S. Tandon, A. Oussoren

Abstract:

Clothing is a need for all humans. Besides serving the commonly understood function of protection, it also is a means of self-expression and adornment. However, most clothing for people with disabilities is developed to respond to their functional needs merely. Such clothing aggravates feelings of inadequacy and lowers their self-esteem. Investigations into apparel-related barriers faced by women with disabilities and their expectations and desires about clothing pointed to a huge void in terms of well-designed inclusive clothing. The incredible stories and experiences shared by the participants in this research highlighted the fact that people with disabilities wanted to feel, dress, and look at how they wanted to look by wearing what they wanted to wear. Clothing should be about self-expression – reflecting their moods, taste, and style and not limited to fulfilling merely their functional needs. Inclusive Design for Regaining Lost Identity was undertaken to design and develop accessible clothing that is inclusive and fashionable to foster psycho-social well-being and to enhance the self-esteem of women with disabilities. The research explored inclusive design solutions for the saree – a traditional Indian garment for women. The saree is an elaborate garment that requires precise draping, which makes the saree complicated to wear and inconvenient to carry, particularly for women with physical disabilities. For many women in India, the saree remains the customary dress, especially for work and occasions, yet minimal advancement has been made to enhance its accessibility and ease of use. The project followed a qualitative research approach whilst incorporating a combination of methods, which consisted of a questionnaire, an interview, and co-creation workshops. The research adhered to the principles of applied research such that the designed products aim to solve a problem that is functional and purposeful. In order to reduce the complications and to simplify the wrapping of the garment fabric around the body, different combinations of pre-stitching of the layers of the saree were created to investigate the outcomes. The technology of 3D drawing and printing was employed to develop feasible fasteners keeping in mind the participants’ movement limitations and to enhance their agency with these newly designed fasteners. The underlying principle of the project is that every individual should be able to access life the way they wish to and should not have to compromise their desires due to their disability.

Keywords: accessibility, co-creation, design ethics, inclusive

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1169 BingleSeq: A User-Friendly R Package for Single-Cell RNA-Seq Data Analysis

Authors: Quan Gu, Daniel Dimitrov

Abstract:

BingleSeq was developed as a shiny-based, intuitive, and comprehensive application that enables the analysis of single-Cell RNA-Sequencing count data. This was achieved via incorporating three state-of-the-art software packages for each type of RNA sequencing analysis, alongside functional annotation analysis and a way to assess the overlap of differential expression method results. At its current state, the functionality implemented within BingleSeq is comparable to that of other applications, also developed with the purpose of lowering the entry requirements to RNA Sequencing analyses. BingleSeq is available on GitHub and will be submitted to R/Bioconductor.

Keywords: bioinformatics, functional annotation analysis, single-cell RNA-sequencing, transcriptomics

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1168 Informality, Trade Facilitation, and Trade: Evidence from Guinea-Bissau

Authors: Julio Vicente Cateia

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This paper aims to assess the role of informality and trade facilitation on the export probability of Guinea-Bissau. We include informality in the Féchet function, which gives the expression for the country's supply probability. We find that Guinea-Bissau is about 7.2% less likely to export due to the 1% increase in informality. The export's probability increases by about 1.7%, 4%, and 1.1% due to a 1% increase in trade facilitation, R&D stock, and year of education. These results are significant at the usual levels. We suggest a development agenda aimed at reducing the level of informality in this country.

Keywords: development, trade, informality, trade facilitation, economy of Guinea-Bissau

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1167 Laban Movement Analysis Using Kinect

Authors: Bernstein Ran, Shafir Tal, Tsachor Rachelle, Studd Karen, Schuster Assaf

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Laban Movement Analysis (LMA), developed in the dance community over the past seventy years, is an effective method for observing, describing, notating, and interpreting human movement to enhance communication and expression in everyday and professional life. Many applications that use motion capture data might be significantly leveraged if the Laban qualities will be recognized automatically. This paper presents an automated recognition method of Laban qualities from motion capture skeletal recordings and it is demonstrated on the output of Microsoft’s Kinect V2 sensor.

Keywords: Laban movement analysis, multitask learning, Kinect sensor, machine learning

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1166 POP Music and Tai Chi – Movement and Stillness Intertwined in The Contemporary World

Authors: Patricia Portugal Marques de Carvalho Lourenço

Abstract:

Pop Music embodies both the music that is popular with the audiences and the one that is widespread amongst the general public associated with a state of mind and rhythm. Tai Chi epitomises Yin and Yang, two interconnected opposite states of being. Undivided, they are one, a neutral state of consciousness that does not swing to either pole. It remains constant and even minded. Sound flows and vibrations cause movement, a physical response to the tempo. When an excessive movement is reached leads to stillness therefore, extreme Yang leads to Yin. Pop Music and Tai Chi are comparable to state of inner being versus a state of outer being, emotional control versus emotional expression, stillness, and movement; opposites that are independent of one another yet interdependent concepts in motion.

Keywords: Pop music, C-Pop, Tai Chi, Ba Gua, communication, entertainment education

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1165 Characterization of a Mesenchymal Stem Cells Pool in Killian Nasal Polyp

Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

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1164 ESDN Expression in the Tumor Microenvironment Coordinates Melanoma Progression

Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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1163 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

Abstract:

Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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1162 Implementation of Cord- Blood Derived Stem Cells in the Regeneration of Two Experimental Models: Carbon Tetrachloride and S. Mansoni Induced Liver Fibrosis

Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

Abstract:

Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

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1161 Cultural and Group Understandings of Disability and Sexuality

Authors: Luke Galvani

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The cultural representations of people with disabilities are frequently biased which can lead to a general misunderstanding of disability. Representations of disabled deviance are especially problematic given that they typify or generally abstract disability as being abnormal, which then begin to take root in the cultural mind. This study utilizes critical discourse analysis to investigate how discourses of disabled sexual deviance are promoted within two major films that portray disabled sexual subjects. The findings indicate that perceptions of disabled sexual deviance are heightened by cinematic representations of sex and disability, which characterize disabled sexual expression as being undesirable due to the ephemeral and abnormal qualities ascribed to it.

Keywords: deviance, disability, discourse analysis, sexuality

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1160 Effect of Drying on the Concrete Structures

Authors: A. Brahma

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The drying of hydraulics materials is unavoidable and conducted to important spontaneous deformations. In this study, we show that it is possible to describe the drying shrinkage of the high-performance concrete by a simple expression. A multiple regression model was developed for the prediction of the drying shrinkage of the high-performance concrete. The assessment of the proposed model has been done by a set of statistical tests. The model developed takes in consideration the main parameters of confection and conservation. There was a very good agreement between drying shrinkage predicted by the multiple regression model and experimental results. The developed model adjusts easily to all hydraulic concrete types.

Keywords: hydraulic concretes, drying, shrinkage, prediction, modeling

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1159 Dominant Ideology among Filipino Women as Dictated by Cosmopolitan Magazine

Authors: Yvonne Christelle M. de Guzman, Charity Faye T. Cabie

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This study analyzed the contents of ten issues of Cosmopolitan Magazine from 2011 to 2015. The researcher found out the hegemony among Filipino women as dictated by Cosmopolitan magazine through the use of Semiotic Analysis, Laura Mulvey’s Male Gaze and Gramsci’s concept of hegemony. The researcher also looked at the themes of cover stories, words used to describe women, meanings behind the color of magazine’s front cover, clothing, physique and pose such as gesture and facial expression used by the cover girl. However, the entire content of the magazine was not taken into account.

Keywords: dominant ideology, male gaze, semiotics, women

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1158 The Role of Cholesterol Oxidase of Mycobacterium tuberculosis in the Down-Regulation of TLR2-Signaling Pathway in Human Macrophages during Infection Process

Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

Abstract:

The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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1157 Eating Constitutes Human Dignity: A Metaphysical Anthropology Perspective

Authors: Sri Poedjiastoeti

Abstract:

One of the traits of living beings is eating. As the living beings, people must provide their life by taking material. They must assimilate for themselves with substances. They grow and develop themselves by changing what they eat and digest into their own substance. This happened in the so-called eating. This article aims to analyze distinction between human beings and other infrahumans when facing and eating food. It uses the analytical description with metaphysical anthropology approach. As a result, to give the expression that eating is not simply to put food in mouth, chew and swallow it. Eating constitutes a sacred ceremonial if it is done in accordance with human dignity. They face food with distance and moderation as well as civilize or make their behaviour better for it. Accordingly, they are being to be human.

Keywords: human beings, behaviour, eating, dignity

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1156 Modelling Soil Inherent Wind Erodibility Using Artifical Intellligent and Hybrid Techniques

Authors: Abbas Ahmadi, Bijan Raie, Mohammad Reza Neyshabouri, Mohammad Ali Ghorbani, Farrokh Asadzadeh

Abstract:

In recent years, vast areas of Urmia Lake in Dasht-e-Tabriz has dried up leading to saline sediments exposure on the surface lake coastal areas being highly susceptible to wind erosion. This study was conducted to investigate wind erosion and its relevance to soil physicochemical properties and also modeling of wind erodibility (WE) using artificial intelligence techniques. For this purpose, 96 soil samples were collected from 0-5 cm depth in 414000 hectares using stratified random sampling method. To measure the WE, all samples (<8 mm) were exposed to 5 different wind velocities (9.5, 11, 12.5, 14.1 and 15 m s-1 at the height of 20 cm) in wind tunnel and its relationship with soil physicochemical properties was evaluated. According to the results, WE varied within the range of 76.69-9.98 (g m-2 min-1)/(m s-1) with a mean of 10.21 and coefficient of variation of 94.5% showing a relatively high variation in the studied area. WE was significantly (P<0.01) affected by soil physical properties, including mean weight diameter, erodible fraction (secondary particles smaller than 0.85 mm) and percentage of the secondary particle size classes 2-4.75, 1.7-2 and 0.1-0.25 mm. Results showed that the mean weight diameter, erodible fraction and percentage of size class 0.1-0.25 mm demonstrated stronger relationship with WE (coefficients of determination were 0.69, 0.67 and 0.68, respectively). This study also compared efficiency of multiple linear regression (MLR), gene expression programming (GEP), artificial neural network (MLP), artificial neural network based on genetic algorithm (MLP-GA) and artificial neural network based on whale optimization algorithm (MLP-WOA) in predicting of soil wind erodibility in Dasht-e-Tabriz. Among 32 measured soil variable, percentages of fine sand, size classes of 1.7-2.0 and 0.1-0.25 mm (secondary particles) and organic carbon were selected as the model inputs by step-wise regression. Findings showed MLP-WOA as the most powerful artificial intelligence techniques (R2=0.87, NSE=0.87, ME=0.11 and RMSE=2.9) to predict soil wind erodibility in the study area; followed by MLP-GA, MLP, GEP and MLR and the difference between these methods were significant according to the MGN test. Based on the above finding MLP-WOA may be used as a promising method to predict soil wind erodibility in the study area.

Keywords: wind erosion, erodible fraction, gene expression programming, artificial neural network

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1155 Cardiotoxicity Associated with Radiation Therapy: The Role of Bone Marrow Mesenchymal Cells in Improvement of Heart Function

Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

Abstract:

Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

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1154 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

Abstract:

The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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1153 Detonating Culture, Statistic and Developmenet in Imo State of Nigeria

Authors: Ejikeme Ugiri

Abstract:

In an executive summary, UNESCO describes Framework for Cultural Statistics as a tool for organizing cultural statistics both nationally and internationally. This is based on conceptual foundation and a common understanding of culture that will enable the measurement of a wide range of cultural expressions. This means therefore that cultural expression in whatever guise has the potentiality of contributing reasonably to the development of a given society. The paper looked into the various tangible and intangible cultures in Imo State of Nigeria. Due to government’s insensitivity, there is need to remind ourselves of the need to pay adequate attention to the cultural heritage bequeathed to us by our forefathers for the sake of posterity. Documenting this information in written form therefore becomes imperative. The study concludes that culture if developed, could reasonably contribute to economic and social growth of the society.

Keywords: culture, detonation, development, statistics

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1152 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

Abstract:

G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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1151 Effect of a Synthetic Platinum-Based Complex on Autophagy Induction in Leydig TM3 Cells

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

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1150 Targeting Basic Leucine Zipper Transcription Factor ATF-Like Mediated Immune Cells Regulation to Reduce Crohn’s Disease Fistula Incidence

Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

Abstract:

Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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1149 3D Interactions in Under Water Acoustic Simulationseffect of Green Synthesized Metal Nanoparticles on Gene Expression in an In-Vitro Model of Non-alcoholic Steatohepatitis

Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

Abstract:

Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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