231 research outputs found

    Role of ZEB family members in proliferation, metastasis, and chemoresistance of prostate cancer cells: revealing signaling networks

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    Prostate cancer (PCa) is one of the leading causes of death worldwide. A variety of strategies, including surgery, chemotherapy, radiotherapy, and immunotherapy, are applied for PCa treatment. PCa cells are responsive towards therapy at early stages, but they can obtain resistance in the advanced stage. Furthermore, their migratory ability is high in advanced stages. It seems that genetic and epigenetic factors play an important role in this case. Zinc finger E-box-binding home-obox (ZEB) is a family of transcription with two key members, including ZEB1 and ZEB2. ZEB family members are known due to their involvement in promoting cancer metastasis via EMT induction. Recent studies have shown their role in cancer proliferation and inducing therapy resistance. In the current review, we focus on revealing the role of ZEB1 and ZEB2 in PCa. ZEB family members are able to significantly promote the proliferation and viability of cancer cells. ZEB1 and ZEB2 enhance migration and invasion of PCa cells via EMT induction. Overexpression of ZEB1 and ZEB2 is associated with a poor prognosis of PCa. ZEB1 and ZEB2 upregulation occurs during PCa progression and can provide therapy resistance to cancer cells. PRMT1, Smad2, and non-coding RNAs can function as upstream mediators of the ZEB family. Besides, Bax, Bcl-2, MRP1, N-cadherin, and E-cadherin can be considered as downstream targets of the ZEB family in PCa

    MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy

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    Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression

    Transformations of respiratory epitelium in fibrous stage of acute respiratory distress-syndrome = Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома

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    Novikov Nikolay, Tumansky Valery, Fedotov Vasiliy. transformations of respiratory epitelium in fibrous stage of acute respiratory distress-syndrome = Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома. Journal of Health Sciences. 2014;4(14):117-120. ISSN 1429-9623 / 2300-665X. http://ojs.ukw.edu.pl/index.php/johs/article/view/2014%3B4%2814%29%3A117-120 http://journal.rsw.edu.pl/index.php/JHS/article/view/2014%3B4%2814%29%3A117-120 https://pbn.nauka.gov.pl/works/512256 DOI: 10.5281/zenodo.13322 http://dx.doi.org/10.5281/zenodo.13322 The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1107. (17.12.2013). © The Author (s) 2014; This article is published with open access at Licensee Open Journal Systems of Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. Conflict of interest: None declared. Received: 15.11.2014. Revised 05.12.2014. Accepted: 10.12.2014. transformations of respirAtory epitelium in fibrous stage of acute respiraTory distress-syndrome Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома Nikolay Yu Novikov Crimean State Medical University, Simferopol, Russian Federation Valery Alexeevich Tumansky Zaporozhye State Medical University, Ukraine Vasiliy Vladimirovich Fedotov Crimean State Medical University, Simferopol, Russian Federation Corr. Author Новиков Николай Юльевич докт. мед. наук, доцент ГУ «КГМУ имени С.И.Георгиевского», РФ, г. Симферополь Е-mail: [email protected] Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома АННОТАЦИЯ Цель. Определение признаков эпителиально-мезенхимальной трансформации (ЭМТ) для установления ее роли в развитии фиброза легких у пациентов с острым респираторным дистресс-синдромом. Метод. Иммуногистохимическое окрашивание гистологических срезов. Результат. В большинстве альвеолоцитов обнаруживается экспрессия маркеров эпителиального иммунофенотипа. Признаки мезенхимальной дифференцировки определяются в единичных альвеолоцитах. Вывод. ЭМТ не играет существенной роли в формировании фиброза респираторного отдела при ОРДС. Ключевые слова: респираторный эпителий; легкие; дистресс-синдром. transformations of respirAtory epitelium in fibrous stage of acute respiraTory distress-syndrome ABSTRACT The epithelial-mesenchimal transition of respiratory epithelium in Acute Respiratory Distress Syndrome (ARDS) was goal of investigation. Postmortem immunohistochemical stain of respiratory part histological sections was methods. Result: epithelial immunofenotype of epithelial cells was determinate in more cases. Conclusion. The epitelial-mesenchimal transition does not play main role to lungs fibrosis in ARDS. Keywords: respiratory epitelium; lungs; distress-syndrome.Novikov Nikolay, Tumansky Valery, Fedotov Vasiliy. Transformations of respiratory epitelium in fibrous stage of acute respiratory distress-syndrome = Трансформация респираторного эпителия в фазу фиброза острого респираторного дистресс-синдрома. Journal of Health Sciences. 2014;4(14):117-120. ISSN 1429-9623 / 2300-665X. http://ojs.ukw.edu.pl/index.php/johs/article/view/2014%3B4%2814%29%3A117-120 http://journal.rsw.edu.pl/index.php/JHS/article/view/2014%3B4%2814%29%3A117-120 https://pbn.nauka.gov.pl/works/512256 DOI: 10.5281/zenodo.13322 http://dx.doi.org/10.5281/zenodo.1332

    Energy Performance Optimisation of a Single Dwelling Archetype Targeted To Zeb in the Earthquake Zone

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    A single dwelling archetype design subjected to be constructed in Gaziantep City to provide accommodation for the earthquake victims was researched in this paper. It is aimed to find out the optimum building orientation, window-to-wall ratio, and aspect ratio as design variables to achieve Zero Emission Building target. In this regard, the GenOpt Optimisation tool was coupled with the EnergyPlus simulation tool to run the simulations and optimise proposed design scenarios. A threshold value for primary energy use based on the EPBD recommendation document as a guide was improved to determine ZEB design scenarios. It is evident from the 56.43% primary energy use difference between the lowest and highest energy performance among design scenarios that optimum design variables are highly effective in terms of energy efficiency. Besides, 82 design scenarios achieving the ZEB threshold were elaborated from the design variables’ point of view that rectangular forms and low WWRs are optimal for the selected region. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024

    Latent heat storage for centralized heating system in a ZEB living laboratory: integration and design

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    The ZEB Lab project, coordinated by SINTEF and NTNU, aims at building a ZEB (Zero Emission Building) in Trondheim (Norway) in 2019, to be used both as office building and living laboratory. An innovative latent heat storage (LHS) unit using phase change material (PCM) will be integrated in the centralized heating system. The LHS unit will be able to store excess heat from various heat sources connected to the heating system, when they are not required for space heating. One challenge is to make use of the full potential of the PCM latent heat to have a compact and effective unit, while the unit itself should have a low associated CO2-footprint. The LHS system consists of two units designed for a total heat storage capacity of 0.6 MWh, corresponding to the heat needed on top of the heat pump to cover for up to 3 consecutive days in the coldest period of the year, with a maximum combined effect of 26 kW. A bio-based wax is used as PCM with melting temperature 37 °C and measured latent heat 198 kJ/kg. Dynamic system modelling is used to support the design of the LHS unit and ensure sufficiently high heat transfer rates.publishedVersionOpen Access. Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI

    Reanalysis of occupant experiment in ZEB Living Lab

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    In 2015-2016, a six-month long experiment was carried out in the ZEB Living Lab, one of the first houses in Norway planned to reach net zero emission throughout its lifetime. By means of qualitative experiments, social scientists evaluated how six groups of occupants impacted the zero emission building, and how the zero emission building impacted its occupants in different ways. Data were collected through direct observation, diaries and interviews before, during and after the stay. In this paper, we take a closer look at the sensor data from the detailed monitoring system, generated during each group's 25-day long residing's. We find that despite the experiment being a controlled environment with many shared household characteristics, occupancy is determined by diverse factors, and the users' preferences and attitudes influence energy consumption. All major household appliances were the same, but the time of use, frequency, duration and type of use differed. The study contributes to increasing understanding of user behaviour and energy use in low energy houses. Providing occupancy profiles is valuable, in light of the increasing amount of local renewable energy production. These datasets can be used as input in energy simulation and planning of zero-emission neighbourhoods.publishedVersionContent from this work may be used under the terms of theCreative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. Published under licence by IOP Publishing Lt

    Effects of Physical Activity and Exercise Interventions on Health Outcomes in Occupational Drivers: A Systematic Review

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    Background: Occupational drivers are exposed to a wide range of risk factors, including sedentary behavior and physical inactivity, which can contribute to various chronic diseases. However, exercise interventions are likely to alleviate the negative associations and reduce chronic disease risks. This systematic review aimed to inventorize research studies investigating the effects of physical activity and exercise interventions on health outcomes in occupational drivers, and to assess interventions that have demonstrated effectiveness on health outcomes in occupational drivers.Methods: The electronic databases "Web of Science," "Scopus," and "PubMed" were searched using keywords related to "occupational drivers," "exercise," and "health outcomes." Studies were included if they examined the effects of physical activity and exercise among occupational drivers on the following health outcomes: pain, disability, lifestyle factors (sleep, weight, physical activity, nutrition), fatigue, stress, and cardiometabolic risk factors. The methodological quality of the studies was assessed by the Cochrane Risk of Bias tools for randomized and non-randomized studies.Results: Fourteen articles were included (three randomized and 11 non-randomized controlled trials). All studies were judged to have an overall risk of bias as "some concerns, low, moderate or serious." Evidence suggests that stretching and isometric exercises have significantly improved pain, disability, and fatigue. In contrast, multicomponent lifestyle interventions have enhanced physical activity levels, cardiometabolic risk factors, anthropometrics (body mass index, weight, waist circumference), sleep, and dietary intake among occupational drivers.Conclusion: The available evidence indicates the potential benefits of exercise interventions and physical activity for health outcomes in occupational drivers. However, high-quality studies are needed in the future to establish stronger evidence supporting the effect of the exercise intervention.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by Higher Education Commission of Pakistan (HEC), Grant No. HEC/HRD/OSS-III/ Batch-3/Belgium/2022/19745

    SAT-512 Severe Hypocalcemia Presenting as Status Epilepticus after Denosumab Use in Metastatic Prostate Cancer

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    Introduction: Denosumab decreases the incidence of skeletal-related events in patients with metastatic bone disease and is used routinely as part of the therapeutic strategy for various cancers. However, it is associated with a high risk of hypocalcemia with incidence of high-grade hypocalcemia (defined as total calcium < 7mg/dl) as high as 5.1% in patients with castrate-resistant prostate cancer. We present a case of severe hypocalcemia presenting with status epilepticus 32 days after administration of denosumab. Case: A 83 year old African American man presented to the emergency room with status epilepticus. Initial labs revealed a critically low calcium (Ca) of <5mg/dl (8.5-10.1) with albumin 2.2 g/dl (3.4-5.0), ionized calcium 1.09 mg/dl (4.6-5.1) and creatinine (Cr) 3.68 mg/dl (0.67-1.17). QTC was prolonged at 544ms (<400ms). He was intubated for airway protection and a continuous infusion of intravenous calcium gluconate was initiated. Three months prior, he had been diagnosed with prostate cancer with diffuse osteoblastic metastases to his ribs, cervical, thoracic, lumbar and sacral vertebrae, right humerus and bilateral iliac bones. He received a first dose of conventional chemotherapy and 120mg denosumab subcutaneously 32 days prior to hospital admission. Lab investigations then were pertinent for Ca of 9 mg/dl, Cr 1.46 mg/dl, and alkaline phosphatase 362 Units/L (25-125). A 25-hydroxy vitamin D (25-D) was not checked. Further evaluation demonstrated intact parathyroid hormone 677.2 pg/ml (18.4-80.1), alkaline phosphatase 397 Units/L, phosphorus 3.6 mg/dl (2.5-4.9) and 25-D 18 ng/ml (30-100). He was also found to have metastatic obstruction of both ureters which had resulted in acute kidney injury. He was slowly weaned off the intravenous calcium and started on calcitriol 2mcg twice daily, 4 gram elemental calcium daily via feeding tube and cholecalciferol 6000 units daily. Calcium levels remained stable at 8.0-8.5mg/dl on this regimen. Given the extensive metastatic disease, the patient’s family elected to pursue hospice care, and he passed away 9 days later. Conclusion: Patients with osteoblastic metastases and renal impairment are at particularly increased risk of hypocalcemia after denosumab, which can be potentially life-threatening. Physicians caring for patients with metastatic prostate cancer should ensure that vitamin D levels are replete and calcium levels are normal prior to administration of denosumab, monitor calcium levels closely, and counsel them about the signs and symptoms of hypocalcemia to allow prompt diagnosis and treatment

    Transcriptional and Translational control of the expression of the EMT transcription factor ZEB2 in cancer cells

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    Epithelial-mesenchymal transition (EMT) is a crucial process involved in the metastasis and invasion of cancer cells. EMT promotes migration, invasion and separation of individual cells from the primary cancer enabling them to access the vascular system and promoting tumour dissemination. In different types of human cancer, invading cells recapitulate elements of embryonic EMT pathways to extravasate into the blood stream and form metastases at distant sites. Several pleiotropically activated transcription factors, categorised as master regulators of EMT (EMT-TFs), acting downstream of EMT pathways have a central role in cancer. EMT-TFs include Zn finger transcription factors of SNAIL (SNAIL1 and SNAIL2) and ZEB (ZEB1 and ZEB2) families, basic helix-loop-helix (bHLH) proteins E47, TWIST1, TWIST2, a forkhead transcription factor FOXC2, and a few other relatively less studied proteins. Though ZEB family members, ZEB1 and ZEB2, are both efficient executers of EMT programs in human cancer and their roles in tumourigensis might be different. In particular, ZEB2, but not ZEB1 exhibited tumour-suppressive features in malignant melanoma and, possibly, hepatocellular carcinoma. Regulation of ZEB proteins expression occurs at different levels. The activity of three putative transcriptional enhancer controlling ZEB2 gene expression were analysed, and found that RE-4 regulatory element known to control ZEB2 expression in human embryonic stem cells (hESC) is also active in malignant melanoma cells. However, in contrast with hESC, in melanoma cells ZEB2 expression is not regulated by core pluripotency factors. Instead, in these cells, the activity of RE-4 element is affected by ZEB1- or ZEB2- induced EMT programs. By studying post-transcriptional level of ZEB regulation, a novel mechanism that limits ZEB2 protein synthesis was described in this study. A protein motif adjacent to the smad-binding domain within ZEB2 protein induces ribosome stalling and compromises translation. The activity of this motif is dependent on triplets of rare codons, Leu(UUA)-Gly(GGU)-Val(GUA). Introducing these stretches in the homologous region of ZEB1 has no effect on protein expression. By using retroviral expression of pBABE-ZEB2-mut, it was shown that these stretches might contribute to EMT. The data suggest that rare codons play a regulatory role in the context of appropriate protein structures and we speculate that pools of tRNA available for protein translation influence configuration of EMT programs in cancer cells
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