Search results for: expression success
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4447

Search results for: expression success

3067 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

Abstract:

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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3066 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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3065 Corporate Digital Responsibility in Construction Engineering-Construction 4.0: Ethical Guidelines for Digitization and Artificial Intelligence

Authors: Weber-Lewerenz Bianca

Abstract:

Digitization is developing fast and has become a powerful tool for digital planning, construction, and operations. Its transformation bears high potentials for companies, is critical for success, and thus, requires responsible handling. This study provides an assessment of calls made in the sustainable development goals by the United Nations (SDGs), White Papers on AI by international institutions, EU-Commission and German Government requesting for the consideration and protection of values and fundamental rights, the careful demarcation between machine (artificial) and human intelligence and the careful use of such technologies. The study discusses digitization and the impacts of artificial intelligence (AI) in construction engineering from an ethical perspective by generating data via conducting case studies and interviewing experts as part of the qualitative method. This research evaluates critically opportunities and risks revolving around corporate digital responsibility (CDR) in the construction industry. To the author's knowledge, no study has set out to investigate how CDR in construction could be conceptualized, especially in relation to the digitization and AI, to mitigate digital transformation both in large, medium-sized, and small companies. No study addressed the key research question: Where can CDR be allocated, how shall its adequate ethical framework be designed to support digital innovations in order to make full use of the potentials of digitization and AI? Now is the right timing for constructive approaches and apply ethics-by-design in order to develop and implement a safe and efficient AI. This represents the first study in construction engineering applying a holistic, interdisciplinary, inclusive approach to provide guidelines for orientation, examine benefits of AI and define ethical principles as the key driver for success, resources-cost-time efficiency, and sustainability using digital technologies and AI in construction engineering to enhance digital transformation. Innovative corporate organizations starting new business models are more likely to succeed than those dominated by conservative, traditional attitudes.

Keywords: construction engineering, digitization, digital transformation, artificial intelligence, ethics, corporate digital responsibility, digital innovation

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3064 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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3063 Cultural and Group Understandings of Disability and Sexuality

Authors: Luke Galvani

Abstract:

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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3062 Boosting the Chance of Organizational Change Success: The Role of Individuals’ Goal Orientation, Affectivity and Psychological Capital

Authors: P. P. L. Kwan, D. K. S. Chan

Abstract:

Organizations are constantly changing in today’s business environment. Research findings have revealed that overcoming resistance and getting employees ready for change is a crucial driver for organizational change success. Thus, change adaptability has become a more prominent selection criterion used in many organizations. Although change readiness could be situation-specific, employees’ personality, emotion, and cognition should also be crucial factors in shaping their readiness. However, relatively little research has focused on the roles of individual characteristics in organizational changes. The present study examines the relations between individual characteristics and change readiness with the aim to validate a model, which proposes three types of individual attributes as antecedents to change readiness. The three attributes considered are trait cynicism, positive affectivity, and personal valence covering personality, emotional, and cognitive aspects respectively. The model also hypothesizes that relations between the three antecedents and change readiness will be moderated by a positive mental resource known as psychological capital (PsyCap), which consists of hope, optimism, efficacy and resilience; and a learning culture within the organization. We are currently collecting data from a targeted sample size of 300 Hong Kong employees. Specifically, participants complete a questionnaire which was designed to measure their perceived change efficacy in response to three scenarios commonly happened in the workplace (i.e., business acquisition, team restructuring, and information system change) as a measure of change readiness, as well as the aforementioned individual characteristics. Preliminary analysis provides some support to the hypotheses. That is, employees who are less cynical in personality and more positive in their cognition and affectivity particularly welcome the potential changes in their organizations. Further data collection and analyses are continuously carried out for a more definitive conclusion. Our findings will shed light on employee selection; and on how strengthening positive psychological resources and promoting the culture of learning organization among employees may enhance the chance to succeed for organizations undergoing change.

Keywords: learning organization, psychological capital, readiness for change, employee selection

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3061 To Handle Data-Driven Software Development Projects Effectively

Authors: Shahnewaz Khan

Abstract:

Machine learning (ML) techniques are often used in projects for creating data-driven applications. These tasks typically demand additional research and analysis. The proper technique and strategy must be chosen to ensure the success of data-driven projects. Otherwise, even exerting a lot of effort, the necessary development might not always be possible. In this post, an effort to examine the workflow of data-driven software development projects and its implementation process in order to describe how to manage a project successfully. Which will assist in minimizing the added workload.

Keywords: data, data-driven projects, data science, NLP, software project

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3060 Thai Student Ability on Speexx Language Training Program

Authors: Toby Gibbs, Glen Craigie, Suwaree Yordchim

Abstract:

Using the Speexx Online Language Training Program with Thai students has allowed us to evaluate their learning comprehension and track their progression through the English language program. Speexx sets the standard for excellence and innovation in web-based language training and online coaching services. The program is designed to improve the business communication skills of language learners for Thai students. Speexx consists of English lessons, exercises, tests, web boards, and supplementary lessons to help students practice English. The sample groups are 191 Thai sophomores studying Business English with the department of Humanities and Social Science. The data was received by standard deviation (S.D.) value from questionnaires and samples provided from the Speexx training program. The results found that most Thai sophomores fail the Speexx training program due to their learning comprehension of the English language is below average. With persisted efforts on new training methods, the success of the Speexx Language Training Program can break through the cultural barriers and help future students adopt English as a second language. The Speexx results revealed four main factors affecting the success as follows: 1) Future English training should be pursued in applied Speexx development. 2) Thai students didn’t see the benefit of having an Online Language Training Program. 3) There is a great need to educate the next generation of learners on the benefits of Speexx within the community. 4) A great majority of Thai Sophomores didn't know what Speexx was. A guideline for self-reliance planning consisted of four aspects: 1) Development planning: by arranging groups to further improve English abilities with the Speexx Language Training program and encourage using Speexx every day. Local communities need to develop awareness of the usefulness of Speexx and share the value of using the program among family and friends. 2) Humanities and Social Science staff should develop skills using this Online Language Training Program to expand on the benefits of Speexx within their departments. 3) Further research should be pursued on the Thai Students progression with Speexx and how it helps them improve their language skills with Business English. 4) University’s and Language centers should focus on using Speexx to encourage learning for any language, not just English.

Keywords: ability, comprehension, sophomore, speexx

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3059 An Exploration of the Integration of Guided Play With Explicit Instruction in Early Childhood Mathematics

Authors: Anne Tan, Kok-Sing Tang, Audrey Cooke

Abstract:

Play has always been a prominent pedagogy in early childhood. However, there is growing evidence of success in students’ learning using explicit instruction, especially in literacy in the early years. There is also limited research using explicit instruction in early childhood mathematics, and play is usually prominently mentioned. This proposed research aims to investigate the possibilities and benefits of integrating guided play with explicit instruction in early childhood mathematics education. While play has traditionally been a prominent pedagogy in early childhood, there is growing evidence of success in student learning through explicit instruction, particularly in literacy. However, limited research exists on the integration of explicit instruction in early childhood mathematics, where play remains prominently mentioned. This study utilises a multiple case study methodology to gather data and provide immediate opportunities for curriculum improvement. The research will commence with semi-structured interviews to gain insights into educators' background knowledge. Highly structured observations will be conducted to record the frequency and manner in which guided play is integrated with specific elements of explicit instruction during mathematics teaching in early childhood. To enhance the observations, video recordings will be made using cameras with video settings and Microsoft Teams meeting recordings. In addition to interviews and observations, educators will maintain journals and use the Microsoft Teams platform for self-reflection on the integration of guided play and explicit instruction in their classroom practices and experiences. The study participants will include educators with early childhood degrees and students in years one and two. The primary goal of this research is to inform the benefits of integrating two high-impact pedagogies, guided play, and explicit instruction, for enhancing student learning outcomes in mathematics education. By exploring the integration of these pedagogical approaches, this study aims to contribute to the development of effective instructional strategies in early childhood mathematics education.

Keywords: early childhood, early childhood mathematics, early childhood numbers, guided play, play-based learning, explicit instruction

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3058 Effect of Drying on the Concrete Structures

Authors: A. Brahma

Abstract:

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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3057 Rethinking Africa's 'Great Runner': Authoritarianism and Development in Post-Cold War Ethiopia

Authors: Frew Yirgalem Mane

Abstract:

This study has examined Africa’s experiment with authoritarian model of development drawing from the experience of Ethiopia. With the tectonic crisis of neoliberal ideology, the dominant policy agenda in Africa pertains to bringing the state back to development. More concretely, countries epitomized by Ethiopia, Rwanda and Uganda have been constructing a highly interventionist state with authoritarian character. The central motive appears to facilitate development and salvage people out of appalling and grinding poverty. Each country warrants closer inspection. However, this study focuses on Ethiopia- a country often applauded as ‘Africa’s Great Run’ for delivering socio-economic success over the past two decades. In fact, inspired by East Asia’s including Chinese model of authoritarian development, Ethiopia orchestrated a vanguard party, centralized rent control system with politicized bureaucracy and militaristic mobilization resources for development. This arrangement may explain Ethiopia economic success story as one the fastest growing countries in the world. However, this paper detected, Ethiopia’s attempt to bring the state back in development has precipitated institutionalization of a new breed of authoritarianism and informalization of public institutions. Ethiopia’s model of state-led development may constitute a noticeable shift away from the vengeful adherence to neoliberal policies. However, the manner the model has been practiced proved to be neither smooth nor appears to address Ethiopia’s aspiration for political and economic transformation. Partly, this can be illustrated by recent widespread grievances that fed into the popular uprising and animated opposition against the state. Sources of the grievance are complex, but they are highly ingrained with the way the authoritarian model of development is functioning and also the model’s dis-functioning in terms of benefiting people. In light of these findings, the study has arrived at the following conclusion. Africa’s attempt to emulate development models from other countries is not such a ‘bad’ thing. However, emulation makes sense if it is contextualized and sensitive to complex local socio-economic interests.

Keywords: Africa, authoritarianism, development, Ethiopia, neoliberalism

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3056 Corporate Demography: An Unexplored Trend along the Latin American Context

Authors: Jesus Argueta

Abstract:

This study aims to explore the Business Demography Phenomena along the Central American context, through the examination of its theoretical background, and the revision of Central American corporations success stories, that will eventually guide this research towards the business Demography Key Performance Indicators, across the Central American Business Ambiance. Considering that this analysis will support the development of a Small and Medium Business Observatory over the Honduran commercial landscapes, as platform for the reinforcement of this global topic.

Keywords: business demography, economic dynamism, small, medium and large enterprises, corporate demography

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3055 Dominant Ideology among Filipino Women as Dictated by Cosmopolitan Magazine

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

Abstract:

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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3054 Sustainable Transition of Universal Design for Learning-Based Teachers’ Latent Profiles from Contact to Distance Education

Authors: Alvyra Galkienė, Ona Monkevičienė

Abstract:

The full participation of all pupils in the overall educational process is defined by the concept of inclusive education, which is gradually evolving in education policy and practice. It includes the full participation of all pupils in a shared learning experience and educational practices that address barriers to learning. Inclusive education applying the principles of Universal Design for Learning (UDL), which includes promoting students' involvement in learning processes, guaranteeing a deep understanding of the analysed phenomena, initiating self-directed learning, and using e-tools to create a barrier-free environment, is a prerequisite for the personal success of each pupil. However, the sustainability of quality education is affected by the transformation of education systems. This was particularly evident during the period of the forced transition from contact to distance education in the COVID-19 pandemic. Research Problem: The transformation of the educational environment from real to virtual one and the loss of traditional forms of educational support highlighted the need for new research, revealing the individual profiles of teachers using UDL-based learning and the pathways of sustainable transfer of successful practices to non-conventional learning environments. Research Methods: In order to identify individual latent teacher profiles that encompass the essential components of UDL-based inclusive teaching and direct leadership of students' learning, the quantitative analysis software Mplius was used for latent profile analysis (LPA). In order to reveal proven, i.e., sustainable, pathways for the transit of the components of UDL-based inclusive learning to distance learning, latent profile transit analysis (LPTA) via Mplius was used. An online self-reported questionnaire was used for data collection. It consisted of blocks of questions designed to reveal the experiences of subject teachers in contact and distance learning settings. 1432 Lithuanian, Latvian, and Estonian subject teachers took part in the survey. Research Results: The LPA analysis revealed eight latent teacher profiles with different characteristics of UDL-based inclusive education or traditional teaching in contact teaching conditions. Only 4.1% of the subject teachers had a profile characterised by a sustained UDL approach to teaching: promoting pupils' self-directed learning; empowering pupils' engagement, understanding, independent action, and expression; promoting pupils' e-inclusion; and reducing the teacher's direct supervision of the students. Other teacher profiles were characterised by limited UDL-based inclusive education either due to the lack of one or more of its components or to the predominance of direct teacher guidance. The LPTA analysis allowed us to highlight the following transit paths of teacher profiles in the extreme conditions of the transition from contact to distance education: teachers staying in the same profile of UDL-based inclusive education (sustainable transit) or jumping to other profiles (unsustainable transit in case of barriers), and teachers from other profiles moving to this profile (ongoing transit taking advantage of the changed new possibilities in the teaching process).

Keywords: distance education, latent teacher profiles, sustainable transit, UDL

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3053 Transvaginal Repair of Anterior Vaginal Wall Prolapse with Polyvinylidene Fluoride (PVDF) Mesh: An Alternative for Previously Restricted Materials

Authors: Mohammad-Javad Eslami, Mahtab Zargham, Farshad Gholipour, Mohammadreza Hajian, Katayoun Bakhtiari, Sakineh Hajebrahimi, Melina Eghbal, Ziba Farajzadegan

Abstract:

Introduction: To study the mid-term safety and functional outcomes of transvaginal anterior vaginal wall prolapse repair using polyvinylidene fluoride (PVDF) mesh (DynaMesh®-PR4) by the double trans-obturator technique (TOT). Methods: Between 2015 and 2020, we prospectively included women with symptomatic high-stage anterior vaginal wall prolapse with or without uterine prolapse or stress urinary incontinence (SUI) in the study. The patients underwent transvaginal repair of the prolapse using PVDF mesh in two medical centers. We followed all patients for at least 12 months. We recorded the characteristics of vaginal and sexual symptoms, urinary incontinence, and prolapse stage pre- and postoperatively using International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS), International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF), and Pelvic Organ Prolapse Quantification (POP-Q) system, respectively. Results: One hundred eight women were included in the final analysis with a mean follow-up time of 34.5 ± 18.6 months. The anatomical success was achieved in 103 (95.4%) patients. There was a significant improvement in patients’ vaginal symptoms, urinary incontinence, and quality of life scores postoperatively (p < 0.0001). Only six patients (5.5%) had mesh extrusion, five of whom were managed successfully. The total rates of complications and de novo urinary symptoms were 21.3% and 7.4%, respectively. Significant pain was reported in 17 cases (15.7%). Conclusion: Our findings show that using PVDF mesh in the double TOT technique for anterior vaginal wall prolapse repair is a safe procedure with high anatomic and functional success rates and acceptable complication rates in mid-term follow-up.

Keywords: stress urinary incontinence (SU, incontinence questionnaire-vaginal symptoms (ICIQ-VS), polyvinylidene fluoride (PVDF) mes, double trans-obturator technique (TOT)

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3052 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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3051 Education, Learning and Management: Empowering Individuals for the Future

Authors: Ngong Eugene Ekia

Abstract:

Education is the foundation for the success of any society as its impact transcends across all sectors, including economics, politics, and social welfare. It is through education that individuals acquire the necessary knowledge and skills to succeed in life and contribute meaningfully to society. However, the world is changing rapidly, and it is vital for education systems to adapt to these changes to remain relevant. In this paper, we will discuss the current trends and challenges in education and management and propose solutions that can enable individuals to thrive in an ever-evolving world.

Keywords: access to education, effective teaching and learning, strong management practices, and empowering and personal development

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3050 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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3049 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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3048 Creation and Management of Knowledge for Organization Sustainability and Learning

Authors: Deepa Kapoor, Rajshree Singh

Abstract:

This paper appreciates the emergence and growing importance as a new production factor makes the development of technologies, methodologies and strategies for measurement, creation, and diffusion into one of the main priorities of the organizations in the knowledge society. There are many models for creation and management of knowledge and diverse and varied perspectives for study, analysis, and understanding. In this article, we will conduct a theoretical approach to the type of models for the creation and management of knowledge; we will discuss some of them and see some of the difficulties and the key factors that determine the success of the processes for the creation and management of knowledge.

Keywords: knowledge creation, knowledge management, organizational development, organization learning

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3047 When Creativity Is the Solution: How to Transform Makkah into a Creative City

Authors: Saeed Al Amoudy

Abstract:

During the last decade, the rapidly growing prestige of so-called Creative Cities has inspired many other cities seeking to enhance their attractiveness, creativity, and success. However, the concept of a creative city seems to be an elusive one because it reflects a set of distinct ideologies which apply distinct ideas of creativity to physical and economic urban development. The main aim of this study is to investigate the ways in which the theoretical concept of the creative city can be usefully and practically employed to develop the urban services and global identity of Makkah, Saudi Arabia. This is a challenging prospect since no research on creative cities in the Middle East has previously been conducted. The city of Makkah and its holy sites is known as the focus of religious devotion for one and half billion Muslims around the globe, with millions travelling there on annual pilgrimage. The ideas of three of the key authors who have addressed relevant aspects of the concept of the creative city, Landry, Howkins and Florida, were explored in depth for the purpose of identifying the model which would be best suited to Makkah’s identity as a sacred city. Of these, it was the approach of Landry and others whose work was originally focused on finding creative solutions to the problems faced by cities which proved most suitable for the context of Makkah. The development strategies of five case studies of Creative Cities situated in different parts of the world, namely Vancouver, Yokohama, Glasgow, Barcelona, and Sydney, were also examined. Inspired by their diverse experiences, a model, referred to by the acronym CREATIVE, was developed by bringing together the key elements which seemed to ,account for the success of these five creative cities: Concept, Resources, Events, Attractiveness, Technology, Involvement, Vision and Enthusiasm. Expert opinion was sought on the model by presenting this for discussion at five international conferences. This model was used to guide both the process of data collection via interviews, documentation and field notes, and for analysing this, revealing that Makkah has great potential to become a Creative City. The results suggested that implementation of the CREATIVE model in Makkah would help produce creative solutions to address the problems that the city currently faces due to the growing number of pilgrims every year.

Keywords: creative city, city imaging, Makkah, sacred city

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3046 The Management of the Urban Project between Challenge and Need: The Case of the Modernization Project of Constantine

Authors: Mouhoubi Nedjima, Sassi Boudemagh Souad

Abstract:

In this article, and through the modernization project of metropolis of Constantine (PMMC) experience in Algeria, discussed to highlight the importance of management in an urban project at various levels: strategic and operational. The statement we attended to reach is to evaluate the modernization project of metropolis of Constantine in the light of management and prove the relation between a good urban management and the success of an urban project.

Keywords: urban project, strategic management, operational management, the modernization project of constantine

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3045 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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3044 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

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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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3043 Higher Education Leadership and Creating Sites of Institutional Belonging: A Global Case Study

Authors: Lisa M. Coleman

Abstract:

The focus on disability, LGBTQ+, and internationalization has certainly been the subject of much research and programmatic across higher education. Many universities have entered into global partnerships with varying success and challenges across the various areas, including laws and policies. Attentiveness to the specific nuances of global inclusion, diversity, equity, belonging, and access (GIDBEA) and the leadership to support these efforts is crucial to the development of longstanding success across the programs. There have been a number of shifts related to diversification across student and alumni bodies. These shifts include but are not limited to how people identify gender, race, and sexuality (and the intersections across such identities), as well as trends across emerging and diverse disability communities. NYU is the most international campus in the United States, with the most campuses and sites outside of its county of origin and the most international students and exchange programs than any other university. As a result, the ongoing work related to GIDEBA is at the center of much of the leadership, administrative, and research efforts. Climate assessment work across NYU’s diverse global campus landscape will serve as the foundation to exemplify best practices related to data collection and dissemination, community and stakeholder engagement, and effective implementation of innovative strategies to close gap areas as identified. The data (quantitative and qualitative) and related research findings represent data collected from close to 22,000 stakeholders across the NYU campuses. The case study centers on specific methodological considerations, data integrity, stakeholder engagement from across student-faculty, staff, and alumni constituencies, and tactics to advance specific GIDBEA initiatives related to navigating shifting landscapes. Design thinking, incubation, and co-creation strategies have been employed to expand, leverage, actualize, and implement GIDBEA strategies that are – concrete, measurable, differentiated, and specific to global sites and regions and emerging trends.

Keywords: disability, LGBTQ+, DEI, research, case studies

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3042 Detonating Culture, Statistic and Developmenet in Imo State of Nigeria

Authors: Ejikeme Ugiri

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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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3041 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

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

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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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3040 Effect of a Synthetic Platinum-Based Complex on Autophagy Induction in Leydig TM3 Cells

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

Abstract:

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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3039 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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3038 Effectiveness of Adrenal Venous Sampling in the Management of Primary Aldosteronism: Single Centered Cohort Study at a Tertiary Care Hospital in Sri Lanka

Authors: Balasooriya B. M. C. M., Sujeeva N., Thowfeek Z., Siddiqa Omo, Liyanagunawardana J. E., Jayawardana Saiu, Manathunga S. S., Katulanda G. W.

Abstract:

Introduction and objectives: Adrenal venous sampling (AVS) is the gold standard to discriminate unilateral primary aldosteronism (UPA) from bilateral disease (BPA). AVS is technically demanding and only performed in a limited number of centers worldwide. To the best of our knowledge, Except for one study conducted in India, no other research studies on this area have been conducted in South Asia. This study aimed to evaluate the effectiveness of AVS in the management of primary aldosteronism. Methods: A total of 32 patients who underwent AVS at the National Hospital of Sri Lanka from April 2021 to April 2023 were enrolled. Demographic, clinical and laboratory data were obtained retrospectively. A procedure was considered successful when adequate cannulation of both adrenal veins was demonstrated. Cortisol gradient across the adrenal vein (AV) and the peripheral vein was used to establish the success of venous cannulation. Lateralization was determined by the aldosterone gradient between the two sides. Continuous and categorical variables were summarized with mean, SD, and proportions, respectively. The mean and standard deviation of the contralateral suppression index (CSI) were estimated with an intercept-only Bayesian inference model. Results: Of the 32 patients, the average age was 52.47 +26.14 and 19 (59.4%) were males. Both AVs were successfully cannulated in 12 (37.5%). Among them, lateralization was demonstrated in 11(91.7%), and one was diagnosed as a bilateral disease. There were no total failures. Right AV cannulation was unsuccessful in 18 (56.25%), of which lateralization was demonstrated in 9 (50%), and others were inconclusive. Left AV cannulation was unsuccessful only in 2 (6.25%); one was lateralized, and the other remained inconclusive. The estimated mean of the CSI was 0.33 (89% credible interval 0.11-0.86). Seven patients underwent unilateral adrenalectomy and demonstrated significant improvement in blood pressure during follow-up. Two patients await surgery. Others were treated medically. Conclusions: Despite failure due to procedural difficulties, AVS remained useful in the management of patients with PA. Moreover, the success of the procedure needs experienced hands and advanced equipment to achieve optimal outcomes in PA.

Keywords: adrenal venous sampling, lateralization, contralateral suppression index, primary aldosteronism

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