Investigating the Effect of Aspirin on apoAI-Induced ATP Binding Cassette Transporter 1 Protein Expression and Cholesterol Efflux in Human Astrocytes.

Background: Neurons need a high amount of cholesterol to maintain the stability of their membrane-rich structures. Astrocytes synthesize and distribute cholesterol to neurons, and ABCA1 is a key mediator of cholesterol efflux to generate HDL for cholesterol transport in the brain. Several studies imply the effect of aspirin on ABCA1 expression in peripheral cells such as macrophages. Here, we compared the effect of aspirin with apoA-I on ABCA1 protein expression and cholesterol efflux in human astrocytes. Materials and Methods: Human astrocytes were cultured, and the effects of aspirin on the expression and protein levels of ABCA1 were investigated through RT-PCR and Western blot analysis. Additionally, the effect of co-treatment with apoA-I and aspirin on ABCA1 protein level and cholesterol efflux was evaluated. Results: Dose and time-course experiments showed that the maximum effect of aspirin on ABCA1 expression occurred at a concentration of 0.5 mM after 12 h of incubation. RT-PCR and western blot data showed that aspirin upregulates ABCA1 expression by up to 4.7-fold and its protein level by 67%. Additionally, co-treatment with aspirin and apoA-I increased cholesterol release from astrocytes, indicating an additive effect of aspirin on apoAI-mediated cholesterol efflux. Conclusions: The results suggest a potential role of aspirin in increasing ABCA1 expression and cholesterol efflux in astrocytes, similar to the effect of apoA-I. This indicates that aspirin could potentially regulate brain cholesterol balance and can be considered in certain neurological diseases, in particular in some neurological disorders related to cholesterol accumulation such as Alzheimer's disease.

Phenotypic Transitions the Processes Involved in Regulation of Growth and Proangiogenic Properties of Stem Cells, Cancer Stem Cells and Circulating Tumor Cells.

Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.

WITHDRAWN: Insights into the Biological Properties of Prostate Cancer Stem Cells: Implications for Cancer Progression and Therapy

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the website of the journal Current Stem Cell Research & Therapy.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham editorial policy on article withdrawal can be found at https://benthamscience.com/pages/editorialpolicies-main BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Paradoxical effect of Aß on protein levels of ABCA1 in astrocytes, microglia, and neurons isolated from C57BL/6 mice: an in vitro and in silico study to elucidate the effect of Aß on ABCA1 in the brain cells.

Impaired cholesterol metabolism has been reported in Alzheimer's disease. Since ABCA1 is one of the main players in the brain's cholesterol homeostasis, here we used the in-vitro and in-silico experiments to investigate the effect of Aß on ABCA1 protein levels in microglia, astrocytes, and neurons in mice. Microglia, astrocytes, and neurons were cultured and exposed to beta amyloid. ABCA1 in cell lysates was determined by Western blotting, and cholesterol efflux was measured in the conditioned media. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were conducted to gain a better understanding of the effects of Aß on ABCA1. In response to Aß, the protein levels of ABCA1 increase significantly in microglia, astrocytes, and neurons; however, its ability to enhance cholesterol efflux is diminished. Aß inhibited the function of ABCA1 by obstructing the extracellular tunnel that transports lipids outside the cell, as determined by molecular docking. MD simulation analysis validated these findings. Our results demonstrated that Aß could increase ABCA1 protein levels in various brain cells, regardless of cell type. Molecular docking, molecular dynamics simulation, and MM-GBSA studies indicate that Aß has a significant effect on the structural conformation of ABCA1, possibly interfering with its function. We believe that the conformational changes of ABCA1 will inhibit its ability to subsequently release cellular cholesterol. Aß may obstruct the extracellular tunnel of ABCA1, rendering it less accessible to proteases such as the calpain family, which may explain the increase in ABCA1 levels but decrease in its function.Communicated by Ramaswamy H. Sarma.

Adipose Tissue-Derived Mesenchymal Stem Cells Alter Metabolites of Brain Cholesterol Homeostasis in An Alzheimer's Model.

OBJECTIVE: Disruption of cholesterol homeostasis in Alzheimer's disease (AD) plays a crucial role in disease pathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treating cognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs on specific metabolites associated with brain cholesterol homeostasis in an AD rat model. MATERIALS AND METHODS: In this experimental study, animals were divided into three groups: control, AD, and AD+MSCs. AD was induced using amyloid beta (Aß) and confirmed through the Morris water maze (MWM) behavioural test and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast and adipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gas chromatography-mass spectrometry (GC)-MS and compared among the groups. RESULTS: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to the AD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbances in the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol, 27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment with MSCs resulted in significant alterations in the levels of these metabolites. CONCLUSION: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterol homeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance of investigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlying mechanisms of the therapeutic efficacy of MSCs in AD.

Amyloid Beta Alters the Expression of microRNAs Regulating HMGCR and ABCA1 Genes in Astrocytes of C57BL/6J Mice.

Dysregulation of brain cholesterol homeostasis causes the accumulation of extracellular protein deposits called amyloid plaques in the hippocampus which eventually leads to neuronal death, memory and learning deficits. The aim of the present study was to investigate the effect of beta amyloid on miRNAs regulating HMGCR and ABCA1 as cholesterol synthesis and homeostasis genes. Primary astrocytes were isolated from C57BL/6J mice, and were treated with 0.5 µM amyloid beta (Aß). Expression levels of genes and miRNAs were measured by real-time PCR. In comparison to control, Aß treatment resulted in a significant decrease in miR-96-5p expression as a positive and negative regulator of HMGCR and ABCA1, respectively. There was no significant increase in miR-27a-3p expression as a negative regulator of HMGCR. miR- 106b- 5p and miR-143-3p expressions were also dramatically decreased as ABCA1 negative regulators. Amyloid beta can alter the expression of major genes in the cholesterol homeostasis pathway via their regulatory miRNAs.

The Mechanisms of Long Non-coding RNA-XIST in Ischemic Stroke: Insights into Functional Roles and Therapeutic Potential.

Ischemic stroke, which occurs due to the occlusion of cerebral arteries, is a common type of stroke. Recent research has highlighted the important role of long non-coding RNAs (lncRNAs) in the development of cerebrovascular diseases, specifically ischemic stroke. Understanding the functional roles of lncRNAs in ischemic stroke is crucial, given their potential contribution to the disease pathology. One noteworthy lncRNA is X-inactive specific transcript (XIST), which exhibits downregulation during the early stages of ischemic stroke and subsequent upregulation in later stages. XIST exert its influence on the development of ischemic stroke through interactions with multiple miRNAs and transcription factors. These interactions play a significant role in the pathogenesis of the condition. In this review, we have provided a comprehensive summary of the functional roles of XIST in ischemic stroke. By investigating the involvement of XIST in the disease process, we aim to enhance our understanding of the mechanisms underlying ischemic stroke and potentially identify novel therapeutic targets.

Circular RNAs-mediated angiogenesis in human cancers

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as “hallmarks of cancer”. In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers (AU)

Potential roles of lncRNA MALAT1-miRNA interactions in ocular diseases.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that are longer than 200 nucleotides in length. LncRNAs are implicated in gene expression at the transcriptional, translational, and epigenetic levels, and thereby impact different cellular processes including cell proliferation, migration, apoptosis, angiogenesis, and immune response. In recent years, numerous studies have demonstrated the significant contribution of lncRNAs to the pathogenesis and progression of various diseases, such as stroke, heart disease, and cancer. Further investigations have shown that lncRNAs have altered expression patterns in ocular tissues and cell lines during pathological conditions. The pathogenesis of various ocular diseases, including glaucoma, cataract, corneal diseases, proliferative vitreoretinopathy, diabetic retinopathy, and retinoblastoma, is influenced by the involvement of specific lncRNAs which play a critical role in the development and progression of these diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a well-researched lncRNA in the context of ocular diseases, which has been shown to exert its biological effects through several signaling pathways and downstream targets. The present review provides a comprehensive summary of the molecular mechanisms underlying the biological functions and roles of MALAT1 in ocular diseases.

Functional Roles of lncRNAs in Recurrent Pregnancy Loss: A Review Study.

Recurrent pregnancy loss (RPL) or recurrent miscarriage is the failure of pregnancy before 20-24 weeks that influences around 2-5% of couples. Several genetic, immunological, environmental and physical factors may influence RPL. Although various traditional methods have been used to treat post-implantation failures, identifying the mechanisms underlying RPL may improve an effective treatment. Recent evidence suggested that gene expression alterations presented essential roles in the occurrence of RPL. It has been found that long non-coding RNAs (lncRNAs) play functional roles in pregnancy pathologies, such as recurrent miscarriage. lncRNAs can function as dynamic scaffolds, modulate chromatin function, guide and bind to microRNAs (miRNAs) or transcription factors. lncRNAs, by targeting various miRNAs and mRNAs, play essential roles in the progression or suppression of RPL. Therefore, targeting lncRNAs and their downstream targets might be a suitable strategy for diagnosis and treatment of RPL. In this review, we summarized emerging roles of several lncRNAs in stimulation or suppression of RPL.

The Effect of Platelet-Rich Plasma on the Osteoblastic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are cell populations that have the potential to proliferate and differentiate. The process of stem cell differentiation from pluripotent cells to bone cells requires general changes in their pattern of gene expression, the most well-known of which are changes in miRNA-dependent settings. Platelet-enriched plasma (PRP) releases growth factors that are mitogenic to mesenchymal cells and can accelerate the process of osteogenic differentiation. The aim of this study was to investigate the effect of PRP on the expression changes of Let-7a, mir-27a, mir-31, mir-30c, mir-21, and mir-106a during osteogenic differentiation. METHODS: MSCs were isolated from adipose tissue after abdominoplasty and evaluated by flow cytometry. The ef-fect of PRP (10%) on the process of osteogenic differentiation was determined by measuring the expression of Let-7a, mir-27a, mir-31, mir-30c, mir-21, and mir-106a using the real-time polymerase chain reaction (PCR) technique. RESULTS: The increase in Let-7a expression was significant on the 14th day compared to the 3rd day. mir-27a expression rose significantly on the 3rd day. The expression of mir-30 exhibited a significant increase on the 14th day. mir-21 expression was significantly enhanced on the 3rd day and was downregulated on the 14th day. mir-106a expression showed a significant decreasing tendency between days 3 and 14 in a time-dependent pattern. CONCLUSIONS: These findings indicate that PRP probably accelerates the process of differentiation into bone. PRP, as a biological catalyst, showed a clear and distinct impact on the miRNAs regulating bone differentiation of human mesenchymal cells.

Potential roles of lncRNA-XIST/miRNAs/mRNAs in human cancer cells

Long non-coding RNAs (lncRNAs) are non-coding RNAs that contain more than 200 nucleotides but do not code for proteins. In tumorigenesis, lncRNAs can have both oncogenic and tumor-suppressive properties. X inactive-specific transcript (XIST) is a known lncRNA that has been implicated in X chromosome silencing in female cells. Dysregulation of XIST is associated with an increased risk of various cancers. Therefore, XIST can be a beneficial prognostic biomarker for human malignancies. In this review, we attempt to summarize the emerging roles of XIST in human cancers (AU)

Emerging roles of the long non-coding RNA NEAT1 in gynecologic cancers.

Gynecologic cancers are a worldwide problem among women. Recently, molecular targeted therapy opened up an avenue for cancer diagnosis and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules (> 200 nt) that are not translated into protein, and interact with DNA, RNA, and proteins. LncRNAs were found to play pivotal roles in cancer tumorigenesis and progression. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a lncRNA that mediates cell proliferation, migration, and EMT in gynecologic cancers by targeting several miRNAs/mRNA axes. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of breast, ovarian, cervical, and endometrial cancers. In this narrative review, we summarized various NEAT1-related signaling pathways that are critical in gynecologic cancers. Long non-coding RNA (lncRNA) by targeting various signaling pathways involved in its target genes can regulate the occurrence of gynecologic cancers.

Circular RNAs-mediated angiogenesis in human cancers.

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as "hallmarks of cancer". In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers.

An updated review of contribution of long noncoding RNA-NEAT1 to the progression of human cancers.

Long non-coding RNAs (lncRNAs) present pivotal roles in cancer tumorigenesis and progression. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1) as a lncRNA has been shown to mediate cell proliferation, migration, and EMT in tumor cells. NEAT1 by targeting several miRNAs/mRNA axes could regulate cancer cell behavior. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of some human cancers. In this review, we summarized various NEAT1-related signaling pathways that are critical in cancer initiation and progression.

Potential roles of lncRNA-XIST/miRNAs/mRNAs in human cancer cells.

Long non-coding RNAs (lncRNAs) are non-coding RNAs that contain more than 200 nucleotides but do not code for proteins. In tumorigenesis, lncRNAs can have both oncogenic and tumor-suppressive properties. X inactive-specific transcript (XIST) is a known lncRNA that has been implicated in X chromosome silencing in female cells. Dysregulation of XIST is associated with an increased risk of various cancers. Therefore, XIST can be a beneficial prognostic biomarker for human malignancies. In this review, we attempt to summarize the emerging roles of XIST in human cancers.

The stem cell-specific long non-coding RNAs in leukemia

Leukemia is defined as a heterogeneous group of hematological cancers whose prevalence is on the rise worldwide. Despite the large body of studies, the etiology of leukemia has not been fully elucidated. Leukemia stem cells (LSCs) are a subpopulation of cancer cells that sustain the growth of the leukemic clone and are the main culprit for the maintenance of the neoplasm. In contrast to most leukemia cells, LSCs are resistant to chemo- and radiotherapy. Several recent studies demonstrated the altered expression profile of long non-coding RNAs (lncRNAs) in LSCs and shed light on the role of lncRNAs in the survival, proliferation, and differentiation of LSCs. LncRNAs are transcripts longer than 200 nucleotides that are implicated in several cellular and molecular processes such as gene expression, apoptosis, and carcinogenesis. Likewise, lncRNAs have shown a prognostic marker in leukemia patients and represent novel treatment options. Herein, we review the current knowledge concerning lncRNAs’ implication in the pathogenesis of LSCs and discuss their prognostic, diagnostic, and therapeutic potential (AU)

Potential roles of endothelial cells-related non-coding RNAs in cardiovascular diseases.

Endothelial dysfunction is identified by a conversion of the endothelium toward decreased vasodilation and prothrombic features and is known as a primary pathogenic incident in cardiovascular diseases. An insight based on particular and promising biomarkers of endothelial dysfunction may possess vital clinical significances. Currently, non-coding RNAs due to their participation in critical cardiovascular processes like initiation and progression have gained much attention as possible diagnostic as well as prognostic biomarkers in cardiovascular diseases. Emerging line of proof has demonstrated that abnormal expression of non-coding RNAs is nearly correlated with the pathogenesis of cardiovascular diseases. In the present review, we focus on the expression and functional effects of various kinds of non-coding RNAs in cardiovascular diseases and negotiate their possible clinical implications as diagnostic or prognostic biomarkers and curative targets.

LncRNA MALAT1-related signaling pathways in osteosarcoma

Osteosarcoma (OS) is a common and malignant form of bone cancer, which affects children and young adults. OS is identified by osteogenic differentiation and metastasis. However, the exact molecular mechanism of OS development and progression is still unclear. Recently, long non-coding RNAs (lncRNA) have been proven to regulate OS proliferation and drug resistance. LncRNAs are longer than 200 nucleotides that represent the extensive applications in the processing of pre-mRNA and the pathogenesis of human diseases. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a well-known lncRNA known as a transcriptional and translational regulator. The aberrant expression of MALAT1 has been shown in several human cancers. The high level of MALAT1 is involved in OS cell growth and tumorigenicity by targeting several signaling pathways and miRNAs. Hence, MALAT1 might be a suitable approach for OS diagnosis and treatment. In this review, we will summarize the role of lncRNA MALAT1 in the pathophysiology of OS (AU)

The role of LncRNA MCM3AP-AS1 in human cancer

Long noncoding RNAs (lncRNA) play pivotal roles in every level of gene and genome regulation. MCM3AP-AS1 is a lncRNA that has an oncogenic role in several kinds of cancers. Aberrant expression of MCM3AP-AS1 has been reported to be involved in the progression of diverse malignancies, including colorectal, cervical, prostate, lymphoma, lung, ovary, liver, bone, and breast cancers. It is generally believed that MCM3AP-AS1 expression is associated with cancer cell growth, proliferation, angiogenesis, and metastasis. MCM3AP-AS1 by targeting various signaling pathways and microRNAs (miRNAs) presents an important role in cancer pathogenesis. MCM3AP-AS1 as a competitive endogenous RNA has the ability to sponge miRNA, inhibit their expressions, and bind to different target mRNAs related to cancer development. Therefore, MCM3AP-AS1 by targeting several signaling pathways, including the FOX family, Wnt, EGF, and VEGF can be a potent target for cancer prediction and diagnosis. In this review, we will summarize the role of MCM3AP-AS1 in various human cancers (AU)