Search results for: autophagic lysosome reformation

Authors: Foluke Dada

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Prisons all over the world are set up by law to provide restraint and custody for individuals accused or convicted of crimes by the state. The Nigerian prison dates back to the colonial era and is modelled after the British system. It is a system that lays emphasis on punishment and deterrence. It emphasises retribution rather than reformation. These, it can be argued, results in the inhuman conditions of Nigerian prisons and the conscienceless treatment of convicts and awaiting trial inmates in Nigerian prisons. This paper attempts an examination of the challenges currently beguiling Nigerian prisons, the need for reforms in the prison systems and the imperative of these reforms to an efficient criminal justice delivery system in the country. This paper further postulates that rehabilitation should be favoured as against retribution f the development of the Nigerian criminal justice system in line with the shift towards reform.

Keywords: criminal justice, human rights, prison reforms, rehabilitation and retribution

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Authors: Michael J. Kristiono

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This paper attempts to investigate the reasons behind the negative sentiments directed towards Chinese Indonesians from International Relations (IR) perspective. By tracing back the treatment of the New Order government towards ethnic Chinese, it was found that such demonization initially happened due to two politically motivated reasons. Firstly, as part of de-Soekarnoization done by the New Order, the Chinese were outcast because Chinese identity does not conform to the 'Indonesian identity', which was in essence, the Javanese identity. Secondly, the condition reflected the change in Indonesian foreign policy which drifted apart from People’s Republic of China (PRC) as the latter was suspected to be involved in September 30 Movement. Then, this paper argues that due to those reasons, coupled by blatant maltreatment from the New Order Government, Chinese Indonesians were constructed as the Others, that is, as non-Indonesians. Such construct has been deeply embedded such that reconciliation attempts done by the Reformation Era government were not sufficient enough to stop ethnic discrimination towards Chinese Indonesians from happening even until the present.

Keywords: Chinese Indonesians, ethnic discrimination, identity, New Order

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Authors: Haga Abdelrahman Elimam

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This paper investigates the connotation, and some of the realistic implications, of the economic reform of health sector in under developed countries. The paper investigates the issues that economic reforms have to address, and the policy targets they are considered to accomplish. The work argues that the development of economic reform is not connected only with understanding the priorities and refining them, furthermore with reformation and restructuring the organizations through which health policies are employed. Considering various organizational values, that are likely to be regular to all economic reform programs, a regulatory approach to institutional reform is unsuitable. The paper further investigates the selection of economic reform that may as well influence via technical suggestions and analysis, but the verdict to continue, and the consequent success of execution, eventually depends on the progressive political sustainability. The paper concludes by giving examples of institutional reforms from various underdeveloped countries and includes recommendation of the responsibility and control of donor organizations.

Keywords: economic reform, health sector, underdeveloped countries, technical suggestions

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Authors: Irina Rönnqvist

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The world is constantly changing; therefore previous views or cultural patterns and programs formed by the “old world” cannot be suitable for solving actual problems. Indeed, reformation of an education system is unlikely to be effective without understanding of the processes that emerge in the field of employment. There is a problem in overcoming of the negative trends that determine imbalance of needs of the qualified work force and preparation of professionals by an education system. At the contemporary stage of economics the processes occurring in the field of labor and employment reproduce the picture of economic development of the country that cannot be imagined without the factor of labor mobility (e.g. migration). On the one hand, adult education has a significant impact on multifaceted development of economy. On the other hand, Sweden has one of the world's most generous asylum reception systems and the most liberal labor migration policy among the OECD countries. This effect affects the increased productivity. The focus of this essay is on problems of education and employment concerning social inclusion of migrants in working life in Sweden.

Keywords: migration, adaptation, formal learning, informal learning, Sweden

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Xinrui Gao

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This research aims to explore the potential of shifting urban villages to public housing in China. In common practice, the central and local governments established two divided systems of urban redevelopment and public housing, including aims, design ideas, policy, headquarters, and branch offices. In most cases, the urban regeneration and public housing projects satisfy only the selected part of the society who can afford it (urban regeneration) or meet the requirements (public housing), which fail to cover the housing demand. However, there are many similarities between these two types of housing under the background of a shared economy, especially in target groups, affordable prices, and efficient use of spaces. Shenzhen always takes the lead in China’s urban regeneration and housing reformation. There are some top-down approaches to transforming housing in the urban village into public housing at present. These new approaches will provide a good chance to evaluate existing practices and explore the future development path of urban villages; while at the same time it could positively influence the housing problem in China.

Keywords: urban village, public housing, sharing economy, urban redevelopment

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Authors: Ali Aldakhil

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This paper explores the many faces of the barriers and exclusionary attitudes and practices that disabled teachers and students experience in a school where they teach or attend. Critical disability studies and inclusive education theory were used to conceptualise this inquiry and ground it in the literature. These theories were used because they magnify and expose the problems of disability/disablism as within-society instead of within-individual. Similarly, disability-first language was used in this study because it seeks to expose the social oppression and discrimination of disabled. Data were generated through conducting in-depth semi-structured interviews with six disabled teachers who teach disabled children in a Saudi mainstream school. Thematic analysis of data concludes that the school is fettered by disabling barriers, attitudes, and practices, which reflect the dominant culture of disablism that disabled people encounter in the Saudi society on a daily basis. This leads to the conclusion that overall deconstruction and reformation of Saudi mainstream schools are needed, including non-disabled people’s attitudes, policy, spaces, and overall arrangements of teaching and learning.

Keywords: disablism, disability studies, mainstream schools, Saudi Arabia

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Authors: Muhammad Ilham Agus Salim, Saufa Ata Taqiyya

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In many Muslim countries, secularization has successfully reduced the role of Islamic law as a formal legal source during this last century. The most obvious fact was the reform of Daulah Utsmaniyah to be Secular Republic of Turkey. Religion is strictly separated from the state authorities in many countries today. But these last decades in Indonesia, a remarkable fact is apparent. Islamic law has expanded its role in Indonesian legal system, especially in districts regulations. In Aceh province, as a case in point, shariah has been the basic source of law in all regulations. There are more provinces in Indonesia which adopted Islamic law as a formal legal source by the end of 2014. Different from some other countries which clearly stipulates the status of Islam in formal ways, Indonesian constitution formally does not render any recognition for Islam to be the formal religion of the state. But in this Muslim majority country, Islamic law takes a place in democratic way, namely on the basis of the voice of majority. This paper will analyze how this reality increases significantly since what so called by Indonesian reformation era (end of nineties). Some causes will be identified regarding this tendency of expansion of role. Some lessons learned also will be recommended as the concluding remarks by the end of the paper.

Keywords: Islamic law, Indonesia, legal reform, Syariah local regulation

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Authors: Abdul Salim Amin

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This paper focuses on how judiciaries in post-conflict society gain legitimacy through reformation. Legitimacy plays a pivotal role in shaping peoples’ behavior to submit to the law and verifies the rightfulness of an organ for taking binding decisions. Among various dynamics, judicial independence, access to justice and behavioral changes of the judicial officials broadly contribute in legitimation of judiciary in general, and the court in particular. Increasing the independence of judiciary through reform limits the interference of governmental branches in judicial issues and protects basic rights of the citizens. Judicial independence does not only matter in institutional terms, individual independence also influences the impartiality and integrity of judges, which can be increased through education and better administration of justice. Finally, access to justice as an intertwined concept both at the legal and moral spectrum of judicial reform avails justice to the citizen and increases the level of public trust and confidence. Efficient legal decisions on fostering such elements through holistic reform create a rule of law atmosphere. Citizens do not accept illegitimate judiciary and do not trust its decisions. Lack of such tolerance and confidence deters the rule of law and, thus, undermines the democratic development of a society.

Keywords: legitimacy, judicial reform, judicial independence, access to justice, legal training, informal justice, rule of law

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Authors: Gatut Priyowidodo, I. I. Indrayani

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The relations between Indonesia and Malaysia are always full of colors. Indonesia is always known as old brother of Malaysia since it has similar history, religion also socio culturally. Some decades show that the declination of relationship the both countries. Another time, as ASEAN members the two countries devotes their nationalities to purify their collective identities as Eastern. The objective of the research is to extricate the construction of Kompas online and Utusan online toward news coverage of the borders dispute between Indonesia-Malaysia in 2010. This research is proposed to examine central issues which reported by Kompas online and Utusan online consistently. As a media industry, Kompas coverage dominates circulation nationally. Kompas.com was the pioneer of online news in Indonesia and born in reformation era. Utusan is prominent media industry in Malaysia that conducted by UMNO as the ruling party in Malaysia for some periods. The method used in this research is framing method by Robert N. Entman’s which consists of four steps identification: defining problem, diagnosing causes, moral judgment and a treatment recommendation. This research found that Kompas news covered the border dispute must be negotiated as recognition of Indonesia dignity. In contrary, Utusan’s spectacle focused on the Indonesia demonstrans anarchism during the dispute.

Keywords: online media, media construction, the border dispute, Indonesia-Malaysia’s bilateral relations

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Nur Amalina Dayana Abd Aziz

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Assessment is an integral part of teaching and learning in any syllabus in the world. Recently, a new assessment system, School-Based Assessment (SBA) was introduced and implemented in the Malaysian education system to promote a more holistic, integrated and balanced assessment system. This effort is part of the reformation made in the Government Transformation Plan (GTP) to produce a world-class human capital as we are reaching and achieving the Vision 2020 in the near future. However, this new change has raised awareness and concerns from teachers, students, parents and non-profit organizations on how the new assessment is to be implemented and how it is affecting the students and teachers particularly. Therefore, this paper aims to investigate the issues that teachers face in implementing SBA in primary schools, the measures taken to address the issues and to propose ways of managing school-based assessment. Five national primary schools focusing in the urban areas in the Selangor state are chosen for this study to carry out. Data for the study will be gathered from interviews with teachers from each school, surveys and classrooms observation will be conducted in each school, and relevant documents are collected from the selected schools. The findings of this study will present the current issues that teachers from various types of national primary schools are facing and what actions they took to overcome the problems in carrying out SBA. Suggestions on how to better manage school-based assessment for teachers are also provided in this paper.

Keywords: community of practice, curriculum, managing change, school-based assessment

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Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: To describe a novel technique of trabeculectomy targeting triple modulation on wound healing to increase the overall success rate. Method: Ten eyes of 10 patients underwent trabeculectomy with subconjunctival mitomycin C (0.4mg/ml for 4 minutes) application combined with Ologen implantation subconjunctivally and subsclerally. Five of these patients underwent additional phacoemulsification with intraocular lens implantation. The Ologen implant was wet with 0.1 ml Bevacizumab. Result: All the eyes achieved target intraocular pressure (IOP), which was maintained until one year of follow-up. Two patients needed anterior chamber reformation at day two post surgery. One patient needed cataract surgery after four months of surgery and achieved target intraocular pressure on two topical antiglaucoma medicines. Conclusion: Vascular endothelial growth factor (VEGF) concentration has been seen to increase in the aqueous humor after filtration surgery. Ologen implantation helps in collagen remodelling, antifibroblastic response, and acts as a spacer. Bevacizumab augmented Ologen, in addition, targets the increased VEGF and helps in decreasing scarring. Anti-VEGF augmented Ologen in trabeculectomy with mitomycin C (MMC) hence appears to have encouraging short-term intraocular pressure control.

Keywords: ologen, anti-VEGF, trabeculectomy, scarring

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Authors: Gina Aurora Necula

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From its transformation into a taboo and its hiding under the so-called “Moldovan language” or under the euphemistic expression “state language” to its regained status recognition as an official language, the Romanian language spoken in the Republic of Moldova has undergone impressive reforms in the last 60 years. Meant to erase the awareness of citizens’ ethnic identity and turn a majority language into a minority one, all the laws and regulations issued on the field succeeded into setting numerous barriers for speakers of Romanian. Either manifested as social constraints or materialized into assumed rejection of mother tongue usage, all these laws have demonstrated their usefulness and major impact on the Romanian-speaking population. This article is the result of our research carried out over 10 years with the support of students, and Moldovan citizens, from the master's degree program "Romanian language - identity and cultural awareness." We present here a retrospective insight of the reforms, laws, and regulations that contributed to the shifted status of the Romanian language from the official language, seen as the language of common use both in the public and private spheres, in the minority language that surrendered its privileged place to the Russian language, firstly in the public sphere, and then, slowly but surely, in the private sphere. Our main goal here is to identify and make speakers understand what the barriers to learning Romanian language are nowadays when the social pressure on using Russian no longer exists.

Keywords: linguistic barriers, lingua franca, private sphere, public sphere, reformation

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Authors: Lalit Tejwani, Reetika Sharma, Arun Singhvi, Himanshu Shekhar

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Purpose: To assess the efficacy of collagen matrix implant (Ologen) in phacotrabeculectomy augmented with mitomycin C (MMC). Methods: A biodegradable collagen matrix (Ologen) was placed in the subconjunctival and subscleral space in twenty-two eyes of 22 patients with glaucoma and cataract who underwent combined phacoemulsification and trabeculectomy augmented with MMC. All of them were examined preoperatively and on the first postoperative day. They were followed for twelve months after surgery. Any intervention needed in follow-up period was noted. Any complication was recorded. The primary outcome measure was postoperative intraocular pressure at one year follow-up. Any additional postoperative treatments needed and adverse events were noted. Results: The mean age of patients included in the study was 57.77 ± 9.68 years (range=36 to 70 years). All the patients were followed for at least one year. Three patients had history of failed trabeculectomy. Fifteen patients had chronic angle closure glaucoma with cataract, five had primary open angle glaucoma with cataract, one had uveitic glaucoma with cataract, and one had juvenile open angle glaucoma with cataract. Mean preoperative IOP was 32.63 ± 8.29 mm Hg, eighteen patients were on oral antiglaucoma medicines. The mean postoperative IOP was 10.09 ± 2.65 mm Hg at three months, 10.36 ± 2.19 mm Hg at six months and 11.36 ± 2.72 mm Hg at one year follow up. No adverse effect related to Ologen was seen. Anterior chamber reformation was done in five patients, and three needed needling of bleb. Four patients needed additional antiglaucoma medications in the follow-up period. Conclusions: Combined phacotrabeculectomy with MMC with Ologen implantation appears to be a safe and effective option in glaucoma patients needing trabeculectomy with significant cataract. Comparative studies with longer duration of follow-up in larger number of patients are needed.

Keywords: combined surgery, ologen, phacotrabeculectomy, success

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Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: Advanced Glaucoma with Failed trab is not an uncommon sight in glaucoma clinic, and such cases usually tend to present with high intraocular pressure (IOP) and advanced cupping, or even glaucomatous atrophy stage. Re-surgery is needed for such cases, and wound modulation poses a major challenge in these cases. We share our experience in this case series with the use of Ologen (collagen matrix implant) along with MMC 0.04% used in surgery. The purpose of the study was to evaluate the efficacy and outcome of collagen matrix implant in re-trabeculectomy in advanced glaucoma cases. Methodology: Eleven eyes of 11 patients (one eye of one patient) underwent re-trabeculectomy surgery with MMC and Ologen. Ologen implant was used in sub scleral and subconjunctival space, as a spacer and wound modulator. In five cases, triple modulation with implant soaked in anti-VEGF was used. Results: All patients had cupping more than 0.9, and one case was GOA. All cases were on maximal medication at presentation and majority were on systemic anti-glaucoma therapy also. Post-surgery, follow-up ranged from 13 – 34 months, and all cases had a follow longer than the gap between previous surgery (which was failed) and re-trab. One case needed AC reformation and one needling was done. Phaco was done at same sitting in four cases. All cases had their IOP lowered post surgery, and vision was maintained in all, however one case was considered as failed re-surgery case. Topical medication was needed in seven cases post-surgery also. Conclusion: Ologen as adjuvant should be considered in all re-trab cases and all high risk and advanced cases, and triple modulation can be next step in these cases. Aggressive IOP control and non- reluctance to continue topical medications post second surgery should be considered in such cases, to give them best possible vision.

Keywords: failed trabeculectomy, ologen, trabeculectomy, advanced glaucoma

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Authors: Yujun Liu, Maosheng Ran

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Background: Chinese rural-to-urban migrant workers’ mental health problems raise attentions from different social sectors. However, situation of present mental health services provided to this population has not been discovered. This study attempts to describe the current mental health service situation, identify the gaps and give the future directions based on the quantitative data. Methods: Questionnaire surveys were conducted among 2017 rural-to-urban migrant workers in 13 cities and 100 social work service organizations in 5 cities in 2014. Data was collected by face-to-face structured interview by trained interviewers. Findings: Migrant workers’ mental health status was not good. Compared to the severity of mental distress, mental health service for this population was lacking and insufficient, which accounted for only 14.4% of all services in our sample. And the group work and case work were the most frequently-used methods. By estimating a series of regression models, we revealed that life experiences and working conditions were significantly associated with migrant workers’ mental health status. Therefore, the macro social work practices aimed at this whole group were advocated to promote their mental wellbeing. That is, practitioners should not only focus on the improvement of migrant workers’ emotion management capacity, but also pay attention to raise awareness and improve their living and working condition; not only concentrate on the solving of individuals’ dilemma, but also promote gradual reformation of present labor regime and hukou system in China.

Keywords: Chinese rural-to-urban migrant workers, macro social work practice, mental health service needs, mental health status

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Authors: Tan Dexian Arthur, James Wei Ming Kwek, Ian Loh, Lee Tee Sin

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Statement of the Problem: Mucoceles most commonly affect the frontal sinus, which results from chronic obstruction of the sinus ostium or cystic dilatation of mucous glands with ductal obstruction. They are known to cause bony erosion of the sinus walls, which can lead to large defects. These defects were typically managed by obliteration or cranialization of the frontal sinus. Although short term outcomes of conservative management of significant posterior table defects from fractures are promising, there have been no studies on the long-term outcomes of large dehiscences in the posterior wall of the frontal sinus. Methodology & Findings : Computed Tomography (CT) Paranasal Sinuses images were analyzed and found complete spontaneous osteogenesis of a large dehiscent frontal sinus posterior wall, secondary to a large mucocele, 9 years from functional endoscopic sinus surgery with the defect managed conservatively. Conclusion & Significance: The dura is well known for its osteogenic properties. Prior studies have showed that dura could induce osteogenesis in cutaneous tissue in the absence of other central nervous system structures. It was also demonstrated that osteogenesis and chondrogenesis were possible in zygomatic fractures by transplanting neonatal dura grafts to the bony defects in rats. Extrapolating from these studies, the authors postulate that the presence of dura beneath the bony deformity of the posterior frontal sinus wall had likely initiated the osteogenesis and restored the bony defect in the patient. In our literature review, we did not find any reports of spontaneous osteogenesis of large frontal sinus defects. While our experience is incidental, it reinforces the osteogenetic potential of an intact dura and further highlights that selected large defects of the posterior wall of the frontal sinus can be conservatively managed.

Keywords: paranasal sinus mucocele, mucocele, osteogenesis, dehiscence

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

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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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Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

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Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: autophagy, cell death, digestive system, ultrastructure

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Authors: A. Pietro Rimoldi, B. Anilkumar Gopinath, C. Minimol Korulla

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Coastal engineering structure is conventionally designed for a shorter planning horizon usually 20 years. These structures are subjected to different offshore climatic externalities like waves, tides, tsunamis etc. during the design life period. The probability of occurrence of these different offshore climatic externalities varies. The impact frequently caused by these externalities on the structures is of concern because it has a significant bearing on the capital /operating cost of the project. There can also be repeated short time occurrence of these externalities in the assumed planning horizon which can cause heavy damage to the conventional coastal structure which are mainly made of rock. A replacement of the damaged portion to prevent complete collapse is time consuming and expensive when dealing with hard rock structures. But if coastal structures are made of Geo-synthetic containment systems such replacement is quickly possible in the time period between two successive occurrences. In order to have a better knowledge and to enhance the predictive capacity of these occurrences, this study estimates risk of encounter within the design life period of various externalities based on the concept of exponential distribution. This gives an idea of the frequency of occurrences which in turn gives an indication of whether replacement is necessary and if so at what time interval such replacements have to be effected. To validate this theoretical finding, a pilot project has been taken up in the field so that the impact of the externalities can be studied both for a hard rock and a Geosynthetic tube structure. The paper brings out the salient feature of a case study which pertains to a project in which Geosynthetic tubes have been used for reformation of a seawall adjacent to a conventional rock structure in Alappuzha coast, Kerala, India. The effectiveness of the Geosystem in combatting the impact of the short-term externalities has been brought out.

Keywords: climatic externalities, exponential distribution, geosystems, planning horizon

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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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Authors: Virag Vass, Ilona Bereczki, Erzsebet Szabo, Nora Debreczeni, Aniko Borbas, Pal Herczegh, Arpad Tosaki

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Hydrogen sulfide (H₂S) is a toxic gas, but it is produced by certain tissues in a small quantity. According to earlier studies, ibuprofen and H₂S has a protective effect against damaging heart tissue caused by ischemia-reperfusion. Recently, we have been investigating the effect of a new water-soluble H₂S releasing ibuprofen molecule administered after artificially generated ischemia-reperfusion on isolated rat hearts. The H₂S releasing property of the new ibuprofen derivative was investigated in vitro in medium derived from heart endothelial cell isolation at two concentrations. The ex vivo examinations were carried out on rat hearts. Rats were anesthetized with an intraperitoneal injection of ketamine, xylazine, and heparin. After thoracotomy, hearts were excised and placed into ice-cold perfusion buffer. Perfusion of hearts was conducted in Langendorff mode via the cannulated aorta. In our experiments, we studied the dose-effect of the H₂S releasing molecule in Langendorff-perfused hearts with the application of gradually increasing concentration of the compound (0- 20 µM). The H₂S releasing ibuprofen derivative was applied before the ischemia for 10 minutes. H₂S concentration was measured with an H₂S detecting electrochemical sensor from the coronary effluent solution. The 10 µM concentration was chosen for further experiments when the treatment with this solution was occurred after the ischemia. The release of H₂S is occurred by the hydrolyzing enzymes that are present in the heart endothelial cells. The protective effect of the new H₂S releasing ibuprofen molecule can be confirmed by the infarct sizes of hearts using the Triphenyl-tetrazolium chloride (TTC) staining method. Furthermore, we aimed to define the effect of the H₂S releasing ibuprofen derivative on autophagic and apoptotic processes in damaged hearts after investigating the molecular markers of these events by western blotting and immunohistochemistry techniques. Our further studies will include the examination of LC3I/II, p62, Beclin1, caspase-3, and other apoptotic molecules. We hope that confirming the protective effect of new H₂S releasing ibuprofen molecule will open a new possibility for the development of more effective cardioprotective agents with exerting fewer side effects. Acknowledgment: This study was supported by the grants of NKFIH- K-124719 and the European Union and the State of Hungary co- financed by the European Social Fund in the framework of GINOP- 2.3.2-15-2016-00043.

Keywords: autophagy, hydrogen sulfide, ibuprofen, ischemia, reperfusion

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Authors: Dina Tawfic, Robert Hassan

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The current chapter addresses Al-Azhar's strategy to counter extremism in tandem with reflecting on the ideology of the Islamic establishment itself. The topic is motivated by the fact that some of the Western governments have been relying on Al-Azhar to counter the ideology of Islamist radicalism and violent extremism, in particular during the rise of the Islamic State in Syria and Iraq (known as ISIS/ ISIL/ Daesh) in 2014/2015. In his visit to Egypt in June 2016, Brett McGurk, the then U.S. envoy for the global coalition to counter ISIS, commended Al-Azhar’s “intellectual and reforming role” in refuting the ideology of extremism. On the other hand, Egyptian liberal intellectuals, such as Farag Fouda (1945- 1992) and Nasr Hamed Abu Zeid (1943-2010), had always questioned the ideological capability of Al-Azhar to counter extremism, citing the rigidity and resistance of the Islamic establishment to carry out genuine reformation. This chapter aims to discuss the following research questions: what is the strategy of Al-Azhar to counter extremism? Does Al-Azhar have a solid strategy to combat online propaganda produced by violent extremist groups? Is it applicable to identify Al-Azhar ideological identity? and is it capable of countering extremism? To answer these questions, I conducted intensive interviews with seven senior scholars and officials at Al-Azhar and the Endowments ministry from September to December 2020. Using a qualitative approach as a backdrop, this project uses semi-structured interviews to collect data. Participants were briefed on the purpose of the study and consented to be interviewed and to record their interviews. Some of the participants chose to conceal their names. All the interviews were conducted in Arabic via Zoom. The researcher then transcribed and translated the interviews into English. A purposive sample is used to select the seven interviewees, based on their prominence and experience in the field of counter-extremism and Al-Azhar affairs. The researcher uses a snowball sample to select the sample, in which a personal contact recommends other officials within the establishment.

Keywords: Al-Azhar, Egypt, Counter-Extremism, Political Islam, Ideology

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Authors: Montree Bunruanses, Preecha Yupapin

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In this work, the quantum material called Amrita (elixir) is made from top-down gold into nanometer particles by fusing 99% gold with a laser and mixing it with drinking water using the atmospheric water (AWG) production system, which is made of water with air. The high energy laser power destroyed the four natural force bindings from gravity-weak-electromagnetic and strong coupling forces, where finally it was the purified Bose-Einstein condensate (BEC) states. With this method, gold atoms in the form of spherical single crystals with a diameter of 30-50 nanometers are obtained and used. They were modulated (activated) with a frequency generator into various matrix structures mixed with AWG water to be used in the upstream conversion (quantum reversible) process, which can be applied on humans both internally or externally by drinking or applying on the treated surfaces. Doing both space (body) and time (mind) will go back to the origin and start again from the coupling of space-time on both sides of time at fusion (strong coupling force) and push out (Big Bang) at the equilibrium point (singularity) occurs as strings and DNA with neutrinos as coupling energy. There is no distortion (purification), which is the point where time and space have not yet been determined, and there is infinite energy. Therefore, the upstream conversion is performed. It is reforming DNA to make it be purified. The use of Amrita is a method used for people who cannot meditate (quantum meditation). Various cases were applied, where the results show that the Amrita can make the body and the mind return to their pure origins and begin the downstream process with the Big Bang movement, quantum communication in all dimensions, DNA reformation, frequency filtering, crystal body forming, broadband quantum communication networks, black hole forming, quantum consciousness, body and mind healing, etc.

Keywords: quantum materials, quantum meditation, quantum reversible, Bose-Einstein condensate

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Authors: K. Anas, M. Selvakumar, Samson David, R. R. Babu, S. Chattopadhyay

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The dynamic deformation of a visco elastic material can cause heat generation. This heat generation is aspect energy dissipation. The present work investigates the contribution of various factors like; elastomer structure, cross link type and density, filler networking, reinforcement potential and temperature at energy dissipation mechanism. The influences of these elements are investigated using very high frequency analyzer (VHF ) and dynamical mechanical analysis(DMA).VHF follows transmissibility and vibration isolation principle whereas DMA works on dynamical mechanical deformation principle. VHF analysis of different types of elastomers reveals that elastomer can act as a transmitter or damper of energy depending on the applied frequency ratio (ω/ωn). Dynamic modulus (G') of low damping rubbers like natural rubber does not varies rapidly with frequency but vice-versa for high damping rubber like butyl rubber (IIR). VHF analysis also depicts that polysulfidic linkages has high damping ratio (ζ) than mono sulfidic linkages due to its dissipative nature. At comparable cross link density, mono sulfidic linkages shows higher glass transition temperature (Tg) than poly sulfidic linkages. The intensity and location of loss modulus (G'') peak of different types of carbon black filled natural rubber compounds suggests that segmental relaxation at glass transition temperature (Tg) is seldom affected by filler particles, but the filler networks can influence the cross link density by absorbing the curatives. The filler network breaking and reformation during a dynamic strain is a thermally activated process. Thus, stronger aggregates are highly dissipative in nature. Measurements indicate that at lower temperature regimes polymeric chain friction is highly dissipative in nature.

Keywords: damping ratio, natural frequency, crosslinking density, segmental motion, surface activity, dissipative, polymeric chain friction

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Authors: Angana Chatterjee

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The feminist scholars point out the various problematic issues in the traditional mainstream western thought and theories. The thought practices behind the discriminatory and oppressive social practices are based on concepts that play a pivotal role in theorisation. Therefore, many feminist philosophers take up reformation or reconceptualisation projects. Such projects have bearings on various aspects of philosophical thought, namely, ontology, epistemology, logic, ethics, social, political thought, and so on. In tune with this spirit, the present paper suggests a well-established thought pattern which is not western but has got the potential to deal with the problems of mainstream western thought culture that are identified by the feminist critics. The Indian thought pattern is theorised in the domain of Indian logic, which is a study of inference patterns. As, in the Indian context, the inference is considered as a source of knowledge, certain epistemological questions are linked with the discussion of inference. One of the key epistemological issues is one regarding justification. The study about the nature of derivation of knowledge from available evidence, and the nature of the evidence itself, are integral parts of the discipline called Indian logic. But if we contrast the western tradition of thought with the Indian one, we can find that the Indian logic has got some peculiar features which may be shown to deal with the problems identified by the feminist scholars in western thought culture more plausibly. The tradition of western logic, starting from Aristotle, has been maintaining sharp differences between two forms of reasoning, namely, deductive and inductive. These two different forms of reasoning have been theorised and dealt with separately within the domain of the study called ‘logic.’ There are various philosophical problems that are raised around concepts and issues regarding both deductive and inductive reasoning. Indian logic does not distinguish between deduction and induction as thought patterns, but their distinction is very usual to make in the western tradition. Though there can be found various interpretations about this peculiarity of Indian thought pattern, these mixed patterns were actually very close to the cross-cultural pattern in which human beings would tend to argue or infer from the available data or evidence. The feminist theories can successfully operate in the domain of lived experience if they make use of such a mixed pattern of reasoning or inference. By offering sound inferential knowledge on contextual evidences, the Indian thought pattern is potent to serve the feminist purposes in a meaningful way.

Keywords: feminist thought, Indian logic, inference, justification, mixed thought pattern

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Authors: Mohanad Hammad

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Port institutions serve as a link connecting the land areas that receive the goods and the areas from where ships sail. These areas hold great significance for the conversion of goods into commodities of economic value, capable of meeting the needs of the society. Development of ports constitutes a fundamental component of the comprehensive economic development process. Recognizing this fact, developing countries have always resorted to this infrastructural element to resolve the numerous problems they face, taking into account its contribution to the reformation of their economic conditions. Iraqi ports have played a major role in boosting the commercial movement in Iraq, as they are the starting point of its oil exports and a key constituent in fulfilling the consumer and production needs of the various economic sectors of Iraq. With the Gulf wars and the economic blockade, Iraqi ports have continued to deteriorate and become unable to perform their functions as first-generation ports, prompting Iraq to use the ports of neighboring countries such as Jordan's Aqaba commercial port. Meanwhile, Iraqi ports face strong competition from the ports of neighboring countries, which have achieved progress and advancement as opposed to the declining performance and efficiency of Iraqi ports. The great developments in the economic conditions of Iraq lay a too great burden on the Iraqi maritime transport and ports, which require development in order to be able to meet the challenges arising from the fierce international and regional competition in the markets. Therefore, it is necessary to find appropriate solutions in support of the role that can be played by Iraqi ports in serving Iraq's foreign trade transported by sea and in keeping up with the development of foreign trade. Thus, this research aims at tackling the current situation of the Iraqi ports and their commercial activity and studying the problems and obstacles they face. The research also studies the future prospects of these ports, the potentials of maritime openness to Iraq under the fierce competition of neighboring ports, and the possibility of enhancing Iraqi ports’ competitiveness. Among the results produced by this research is the future scenario it proposes for Iraqi ports, mainly represented in the establishment of Al-Faw Port, which will contribute to a greater openness of maritime transport in Iraq, and the rehabilitation and expansion of existing ports. This research seeks to develop solutions to Iraq ports so that they can be repositioned as a vital means of promoting economic development.

Keywords: maritime transport, port, future prospects, regional integration

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Authors: Ioanna H. Lioliou, Despoina D. Zavraka

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The radical reformation that Greek urban space, has undergone over the last century, due to the socio-historical developments, technological development and political–geographic factors, has left its imprint on the urban landscape. While the big cities struggle to regain urban landscape balance, small towns are considered to offer high quality lifescapes, ensuring sustainable development potential. However, their unplanned urbanization process led to the loss of significant areas of nature, lack of essential infrastructure, chaotic built environment, incompatible land uses and urban cohesiveness. Natural environment reference points, such as springs, streams, rivers, forests, suburban greenbelts, and etc.; seems to be detached from urban space, while the public, open and green spaces, unequally distributed in the built environment, they are no longer able to offer a complete experience of nature in the city. This study focuses on Greek mainland, a small town Elassona, and aims to restore spatial coherence between the city’s homonymous river and its urban space surroundings. The existence of a linear aquatic ecosystem, is considered a precious greenway, also referred as blueway, able to initiate natural penetrations and ecosystems empowering. The integration of disconnected natural ecosystems forms the basis of a strategic intervention scheme, where the river becomes the urban integration tool / feature, constituting the main urban corridor and an indispensible part of a wider green network that connects open and green spaces, ensuring the function of all the established networks (transportation, commercial, social) of the town. The proposed intervention, introduces a green network highlighting the old stone bridge at the ‘entrance’ of the river in the town and expanding throughout the town with strategic uses and activities, providing accessibility for all the users. The methodology used, is based on the collection of design tools used in related urban river-design interventions around the world. The reinstallation/reactivation of the balance between natural and urban landscape, besides the environmental benefits, contributes decisively to the illustration/projection of urban green identity and re-enhancement of the quality of lifescape qualities and social interaction.

Keywords: green network, rehabilitation scheme, urban landscape, urban streams

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Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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