scholarly journals The Emerging Impact of RNA Editing in Tumor Growth and Metastasis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mehrdad Nasrollahzadehsabet ◽  
Javad Behroozi
Keyword(s):  
Tumor Growth ◽  
Rna Editing ◽  
General Mechanism ◽  
Metastatic Progression ◽  
Target Mrna ◽  
Cancer Pathogenesis ◽  
Wide Range ◽  
Cancer Initiation ◽  
And Function

Context: RNA editing is an essential modification that needs to develop normal cells and is involved in a wide range of biological processes. It can arise in both coding and non-coding sequences with different functional effects. Although the expansion of transcriptome diversity is the primary goal of RNA editing, dysregulation and aberrant editing may act as an essential contributor to cancer pathogenesis. Evidence Acquisition: The current review aimed to investigate the role of RNA editing in cancer initiation and progression. Science Direct and PubMed databases were reviewed from 2000 to 2020 and 2003 to 2020, respectively, using various combinations of "RNA editing" and "cancer" keywords. Results: The location of editing sites has different functional impacts on tumorigenesis. Nonsynonymous editing in antizyme inhibitor 1 (AZIN1) leads to a metastatic progression of colorectal and gastric cancer. Recoding editing events in bladder cancer-associated protein (BLCAP) is correlated with the progression of cervical carcinogenesis. Editing events located at 3′UTRs are also a general mechanism to promote tumor growth in different types of cancers. A significant number of editing events in microRNAs with a functional role in cancer are also reported. These editing sites could change the fate and function of microRNAs, either by preventing target mRNA recognition or by dysregulating an off-target mRNA. Conclusions: There are increasing shreds of evidence on the key role of RNA editing events in cancer initiation and progression.

scholarly journals Stem–loop formation drives RNA folding in mechanical unzipping experiments

2022 ◽  
Vol 119 (3) ◽  
pp. e2025575119
Author(s):  
Paolo Rissone ◽  
Cristiano V. Bizarro ◽  
Felix Ritort
Keyword(s):  
Optical Tweezers ◽  
Rna Structure ◽  
Nearest Neighbor ◽  
Rna Folding ◽  
General Mechanism ◽  
Loop Formation ◽  
Stem Loop ◽  
Wide Range ◽  
Irreversible Effects ◽  
And Function

Accurate knowledge of RNA hybridization is essential for understanding RNA structure and function. Here we mechanically unzip and rezip a 2-kbp RNA hairpin and derive the 10 nearest-neighbor base pair (NNBP) RNA free energies in sodium and magnesium with 0.1 kcal/mol precision using optical tweezers. Notably, force–distance curves (FDCs) exhibit strong irreversible effects with hysteresis and several intermediates, precluding the extraction of the NNBP energies with currently available methods. The combination of a suitable RNA synthesis with a tailored pulling protocol allowed us to obtain the fully reversible FDCs necessary to derive the NNBP energies. We demonstrate the equivalence of sodium and magnesium free-energy salt corrections at the level of individual NNBP. To characterize the irreversibility of the unzipping–rezipping process, we introduce a barrier energy landscape of the stem–loop structures forming along the complementary strands, which compete against the formation of the native hairpin. This landscape correlates with the hysteresis observed along the FDCs. RNA sequence analysis shows that base stacking and base pairing stabilize the stem–loops that kinetically trap the long-lived intermediates observed in the FDC. Stem–loops formation appears as a general mechanism to explain a wide range of behaviors observed in RNA folding.

scholarly journals Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2167
Author(s):  
Brock Humphries ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Breast Cancer ◽  
Membrane Trafficking ◽  
Rho Gtpases ◽  
Migration And Invasion ◽  
Breast Cancer Patients ◽  
Cancer Initiation ◽  
Cell Type Specific ◽  
And Function ◽  
Therapeutic Responses

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, tumor suppressor functions of Rho GTPases have also been revealed, suggesting a context and cell-type specific function for Rho GTPases in cancer. This review aims to summarize recent progresses in our understanding of the regulation and functions of Rho GTPases, specifically in the context of breast cancer. The potential of Rho GTPases as therapeutic targets and prognostic tools for breast cancer patients are also discussed.

scholarly journals Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia: Characteristics of the Human ApoB-100 Transgenic Mice

2020 ◽  
Vol 26 (13) ◽  
pp. 1486-1494 ◽  
Author(s):  
Melinda E. Tóth ◽  
Brigitta Dukay ◽  
Zsófia Hoyk ◽  
Miklós Sántha
Keyword(s):  
Transgenic Mouse ◽  
Serum Lipid ◽  
Lipoprotein Metabolism ◽  
Transgenic Mouse Models ◽  
Wild Type ◽  
Lipid Levels ◽  
Cerebrovascular Lesions ◽  
Wide Range ◽  
And Function

Serum lipid levels are closely related to the structure and function of blood vessels. Chronic hyperlipidemia may lead to damage in both the cardio- and the cerebrovascular systems. Vascular dysfunctions, including impairments of the blood-brain barrier, are known to be associated with neurodegenerative diseases. A growing number of evidence suggests that cardiovascular risk factors, such as hyperlipidemia, may increase the likelihood of developing dementia. Due to differences in lipoprotein metabolism, wild-type mice are protected against dietinduced hypercholesterolemia, and their serum lipid profile is different from that observed in humans. Therefore, several transgenic mouse models have been established to study the role of different apolipoproteins and their receptors in lipid metabolism, as well as the complications related to pathological lipoprotein levels. This minireview focused on a transgenic mouse model overexpressing an apolipoprotein, the human ApoB-100. We discussed literature data and current advancements on the understanding of ApoB-100 induced cardio- and cerebrovascular lesions in order to demonstrate the involvement of this type of apolipoprotein in a wide range of pathologies, and a link between hyperlipidemia and neurodegeneration.

scholarly journals Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies

2012 ◽  
Vol 30 (9) ◽  
pp. 1005-1014 ◽  
Author(s):  
Pasquale Sansone ◽  
Jacqueline Bromberg
Keyword(s):  
Interleukin 6 ◽  
Potential Role ◽  
Tumor Formation ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Metastatic Progression ◽  
And Function ◽  
Principal Pathway ◽  
Stat Pathway

The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers.

scholarly journals A hybrid three-scale model of tumor growth

2017 ◽  
Vol 28 (01) ◽  
pp. 61-93 ◽  
Author(s):  
H. L. Rocha ◽  
R. C. Almeida ◽  
E. A. B. F. Lima ◽  
A. C. M. Resende ◽  
J. T. Oden ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Differential Equations ◽  
Tumor Growth ◽  
Nonlinear Differential Equations ◽  
Reaction Diffusion Equations ◽  
Scale Model ◽  
Wide Range ◽  
Induced Stresses ◽  
The Impact

Cancer results from a complex interplay of different biological, chemical, and physical phenomena that span a wide range of time and length scales. Computational modeling may help to unfold the role of multiple evolving factors that exist and interact in the tumor microenvironment. Understanding these complex multiscale interactions is a crucial step toward predicting cancer growth and in developing effective therapies. We integrate different modeling approaches in a multiscale, avascular, hybrid tumor growth model encompassing tissue, cell, and sub-cell scales. At the tissue level, we consider the dispersion of nutrients and growth factors in the tumor microenvironment, which are modeled through reaction–diffusion equations. At the cell level, we use an agent-based model (ABM) to describe normal and tumor cell dynamics, with normal cells kept in homeostasis and cancer cells differentiated into quiescent, proliferative, migratory, apoptotic, hypoxic, and necrotic states. Cell movement is driven by the balance of a variety of forces according to Newton’s second law, including those related to growth-induced stresses. Phenotypic transitions are defined by specific rule of behaviors that depend on microenvironment stimuli. We integrate in each cell/agent a branch of the epidermal growth factor receptor (EGFR) pathway. This pathway is modeled by a system of coupled nonlinear differential equations involving the mass laws of 20 molecules. The rates of change in the concentration of some key molecules trigger proliferation or migration advantage response. The bridge between cell and tissue scales is built through the reaction and source terms of the partial differential equations. Our hybrid model is built in a modular way, enabling the investigation of the role of different mechanisms at multiple scales on tumor progression. This strategy allows representing both the collective behavior due to cell assembly as well as microscopic intracellular phenomena described by signal transduction pathways. Here, we investigate the impact of some mechanisms associated with sustained proliferation on cancer progression. Speci- fically, we focus on the intracellular proliferation/migration-advantage-response driven by the EGFR pathway and on proliferation inhibition due to accumulation of growth-induced stresses. Simulations demonstrate that the model can adequately describe some complex mechanisms of tumor dynamics, including growth arrest in avascular tumors. Both the sub-cell model and growth-induced stresses give rise to heterogeneity in the tumor expansion and a rich variety of tumor behaviors.

scholarly journals Role of Exosomes in Islet Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jordan Mattke ◽  
Srividya Vasu ◽  
Carly M. Darden ◽  
Kenjiro Kumano ◽  
Michael C. Lawrence ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Graft Function ◽  
Pancreatic Islet Transplantation ◽  
Complex Molecules ◽  
Wide Range ◽  
And Function ◽  
Antigen Presenting

Exosomes are known for their ability to transport nucleic acid, lipid, and protein molecules, which allows for communication between cells and tissues. The cargo of the exosomes can have a variety of effects on a wide range of targets to mediate biological function. Pancreatic islet transplantation is a minimally invasive cell replacement therapy to prevent or reverse diabetes mellitus and is currently performed in patients with uncontrolled type 1 diabetes or chronic pancreatitis. Exosomes have become a focus in the field of islet transplantation for the study of diagnostic markers of islet cell viability and function. A growing list of miRNAs identified from exosomes collected during the process of isolating islets can be used as diagnostic biomarkers of islet stress and damage, leading to a better understanding of critical steps of the isolation procedure that can be improved to increase islet yield and quality. Exosomes have also been implicated as a possible contributor to islet graft rejection following transplantation, as they carry donor major histocompatibility complex molecules, which are then processed by recipient antigen-presenting cells and sensed by the recipient immune cells. Exosomes may find their way into the therapeutic realm of islet transplantation, as exosomes isolated from mesenchymal stem cells have shown promising results in early studies that have seen increased viability and functionality of isolated and grafted islets in vitro as well as in vivo. With the study of exosomes still in its infancy, continued research on the role of exosomes in islet transplantation will be paramount to understanding beta cell regeneration and improving long-term graft function.

scholarly journals Using technology to connect generations: Some considerations of form and function

Comunicar ◽  
2015 ◽  
Vol 23 (45) ◽  
pp. 95-104 ◽  
Author(s):  
Mariano Sánchez-Martínez ◽  
Matthew Kaplan ◽  
Leah Bradley
Keyword(s):  
Intergenerational Relationships ◽  
Relationship Formation ◽  
Positive Potential ◽  
Technology Learning ◽  
Form And Function ◽  
Wide Range ◽  
Generational Groups ◽  
And Function ◽  
Los Grupos

Nowadays, as ageing increases in Western societies it has become more evident that multiple generations are ageing concurrently at any given time in history. Therefore, ageing must be approached as a multi-generational phenomenon, not just as a question of elders. In this context, situations that engender increased interactions between generations are garnering more attention. There is a growing emphasis on expanding the role of technology in intergenerational programmes, within the field of intergenerational studies. Consequently, this paper is focused on education and learning processes within intergenerational programmes with a strong technology component. Information from a total of 46 intergenerational programmes from 11 countries has been gathered through a survey. Level of impact, status of generational groups, and centrality of technology have been appraised for all programmes in the sample. Technology learning-teaching constitute the main area of intended impact of these programmes. However, the surveyed programmes employ as well a wide range of strategies to facilitate intergenerational communication, cooperation and relationship formation between generations involved. Interest of programmes examined does not just consist of teaching the use technology but of experimenting with technology in different forms and functions and exploring the positive potential for enhancing intergenerational relationships Actualmente, conforme el envejecimiento en las sociedades occidentales aumenta, resulta más evidente que en cualquier momento histórico dado hay varias generaciones envejeciendo simultáneamente. Por tanto, el envejecimiento debe ser estudiado como fenómeno multi-generacional y no solo como un asunto de personas mayores. En este contexto, están suscitando más atención las situaciones que implican más interacciones intergeneracionales. Dentro del campo intergeneracional está aumentando el interés en torno a las posibilidades de expandir el papel de la tecnología en los programas intergeneracionales. En consecuencia, este artículo se centra en los procesos de educación y aprendizaje acaecidos dentro de programas intergeneracionales con un fuerte componente tecnológico. Mediante un sondeo se recogió información sobre un total de 46 de este tipo de programas de 11 países. Todos se han evaluado en la muestra según su nivel de impacto, el estatus de los grupos generacionales y la centralidad de la tecnología. La enseñanza-aprendizaje de la tecnología constituye la principal área de impacto buscada por estos programas, que, no obstante, también utilizan una amplia variedad de estrategias para facilitar la comunicación, la cooperación y la formación de relaciones intergeneracionales entre las generaciones implicadas. El interés de los programas analizados no solo consiste en enseñar a utilizar la tecnología sino en experimentar diferentes formas y funciones con ella, así como en explorar el potencial positivo de la tecnología para mejorar las relaciones intergeneracionales

scholarly journals Email Consultations Between Patients and Doctors in Primary Care: Content Analysis

10.2196/18218 ◽  
2020 ◽  
Vol 22 (11) ◽  
pp. e18218
Author(s):  
Helen Atherton ◽  
Anne-Marie Boylan ◽  
Abi Eccles ◽  
Joanna Fleming ◽  
Clare R Goyder ◽  
...  
Keyword(s):  
Primary Care ◽  
General Practice ◽  
Content Analysis ◽  
Communication Technologies ◽  
Face To Face ◽  
The United Kingdom ◽  
Wide Range ◽  
The Face ◽  
And Function

Background Increasingly, consultations in health care settings are conducted remotely using a range of communication technologies. Email allows for 2-way text-based communication, occurring asynchronously. Studies have explored the content and nature of email consultations to understand the use, structure, and function of email consultations. Most previous content analyses of email consultations in primary care settings have been conducted in North America, and these have shown that concerns and assumptions about how email consultations work have not been realized. There has not been a UK-based content analysis of email consultations. Objective This study aims to explore and delineate the content of consultations conducted via email in English general practice by conducting a content analysis of email consultations between general practitioners (GPs) and patients. Methods We conducted a content analysis of anonymized email consultations between GPs and patients in 2 general practices in the United Kingdom. We examined the descriptive elements of the correspondence to ascertain when the emails were sent, the number of emails in an email consultation, and the nature of the content. We used a normative approach to analyze the content of the email consultations to explore the use and function of email consultation. Results We obtained 100 email consultations from 85 patients, which totaled 262 individual emails. Most email users were older than 40 years, and over half of the users were male. The email consultations were mostly short and completed in a few days. Emails were mostly sent and received during the day. The emails were mostly clinical in content rather than administrative and covered a wide range of clinical presentations. There were 3 key themes to the use and function of the email consultations: the role of the GP and email consultation, the transactional nature of an email consultation, and the operationalization of an email consultation. Conclusions Most cases where emails are used to have a consultation with a patient in general practice have a shorter consultation, are clinical in nature, and are resolved quickly. GPs approach email consultations using key elements similar to that of the face-to-face consultation; however, using email consultations has the potential to alter the role of the GP, leading them to engage in more administrative tasks than usual. Email consultations were not a replacement for face-to-face consultations.

scholarly journals Sirtuins, Bioageing, and Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
D. McGuinness ◽  
D. H. McGuinness ◽  
J. A. McCaul ◽  
P. G. Shiels
Keyword(s):  
Cell Cycle ◽  
Genomic Stability ◽  
Degenerative Diseases ◽  
Critical Junctures ◽  
Age Related ◽  
Wide Range ◽  
Telomere Function ◽  
And Function ◽  
High Degree

The Sirtuins are a family of orthologues of yeast Sir2 found in a wide range of organisms from bacteria to man. They display a high degree of conservation between species, in both sequence and function, indicative of their key biochemical roles. Sirtuins are heavily implicated in cell cycle, cell division, transcription regulation, and metabolism, which places the various family members at critical junctures in cellular metabolism. Typically, Sirtuins have been implicated in the preservation of genomic stability and in the prolongation of lifespan though many of their target interactions remain unknown. Sirtuins play key roles in tumourigenesis, as some have tumour-suppressor functions and others influence tumours through their control of the metabolic state of the cell. Their links to ageing have also highlighted involvement in various age-related and degenerative diseases. Here, we discuss the current understanding of the role of Sirtuins in age-related diseases while taking a closer look at their roles and functions in maintaining genomic stability and their influence on telomerase and telomere function.

scholarly journals Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25480 ◽  
Author(s):  
Ana Ana Maria ◽  
Moreno-Ramos Oscar Andréas ◽  
Neena B. Haider
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nuclear Receptors ◽  
System Development ◽  
Nuclear Hormone Receptor ◽  
Nervous System Development ◽  
Wide Range ◽  
And Function ◽  
The Impact

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

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