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.

Emerging roles for lncRNA-NEAT1 in colorectal cancer.

Colorectal cancer (CRC) is the third cause of cancer death in the world that arises from the glandular and epithelial cells of the large intestine, during a series of genetic or epigenetic alternations. Recently, long non-coding RNAs (lncRNAs) has opened a separate window of research in molecular and translational medicine. Emerging evidence has supported that lncRNAs can regulate cell cycle of CRC cells. LncRNA NEAT1 has been verified to participate in colon cancer development and progression. NEAT1 as a competing endogenous RNA could suppress the expression of miRNAs, and then regulate molecules downstream of these miRNAs. In this review, we summarized emerging roles of NEAT1 in CRC cells.

The pathogenic roles of lncRNA-Taurine upregulated 1 (TUG1) in colorectal cancer.

Colorectal cancer (CRC) is a gastrointestinal tumor that develops from the colon, rectum, or appendix. The prognosis of CRC patients especially those with metastatic lesions remains unsatisfactory. Although various conventional methods have been used for the treatment of patients with CRC, the early detection and identification of molecular mechanisms associated with CRC is necessary. The scientific literature reports that altered expression of long non-coding RNAs (lncRNAs) contributed to the pathogenesis of CRC cells. LncRNA TUG1 was reported to target various miRNAs and signaling pathways to mediate CRC cell proliferation, migration, and metastasis. Therefore, TUG1 might be a potent predictive/prognostic biomarker for diagnosis of CRC.

Primary mitral valve angiosarcoma: A multifaced ultra-rare tumor.

Malignant primary cardiac valve tumors are extremely rare neoplasms usually remaining silent up to late advanced stages. Getting to know the various features of this latent tumor, which needs prompt intervention, can assist in the earlier diagnosis. Herein we report a 24-year-old woman with angiosarcoma that originated from the mitral valve and manifested itself through dyspnea and pulmonary edema. The case is noteworthy with respect to appealing echocardiographic images.

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.

Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000-2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options.

Signaling-chemokine axis network in brain as a sanctuary site for metastasis.

BACKGROUND: Brain metastasis remains a major cause of death in patients with solid cancers. The co-operation between several molecular factors such as chemokines, chemokine receptors, and signaling pathways is involved in the pathogenesis of brain metastasis mostly from solid tumors. In this review, we examine the possible role of chemokine/receptor axis, as well as signaling pathways as prognostic biomarkers in brain metastasis. METHODS: Relevant English language literature were searched and retrieved from Google Scholar search engine (1993-2017). The following keywords were used: "chemokine," "signaling pathway," "brain," "metastasis," and "niche." RESULTS: Increased expression of chemokines like CXCL12 and dysregulated signaling intermediates such as Notch in patients with solid tumors (e.g., breast cancer) is associated with brain metastasis. CONCLUSIONS: As biomarkers for brain metastasis, chemokine, and signaling intermediates are potential prognostic factors in a number of solid tumor, including breast cancer, melanoma, and lung cancer.

Hepatic metastatic niche: from normal to pre-metastatic and metastatic niche.

Liver is the organ responsible for hematopoiesis during fetal life, which is also a target organ of metastasis for several cancers. In order to recognize the hepatic metastatic changes, obtain a better grasp of cancer prevention, treatment, and inhibition mode of hepatic metastasis progression, we investigate the changes and transformation of normal hepatic niche cells to metastatic niche ones in this review. On the other hand, since metastatic diseases alter the liver function, the changes in a number of cancers that metastasize to the liver have also been reviewed. Relevant English-language literature was searched and retrieved from PubMed (1994-2014) using the following keywords: hepatic stem cell niche, hepatic metastatic niche, chemokine, and microRNAs (miRNAs). Also, over 86 published studies were investigated, and bioinformatics analysis of differentially expressed miRNAs in hepatic cancer and metastasis was performed. Metastasis is developed in several stages with specific changes and mechanisms in each stage. Recognition of these changes would lead to detection of new biomarkers and clinical targets involved in specific stages of liver metastasis. Investigation of the hepatic stem cell niche, development of metastasis in liver tissue, as well as changes in chemokines and miRNAs in metastatic hepatic niche can significantly contribute to faster detection of liver metastasis progression.

New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia.

Hematoproliferative neoplasias like chronic myelogenous leukemia (CML) progressively affect bone marrow niche; however, there are only few specific clinical markers for prediction of disease progression. Here, we review the myeloproliferative niche and molecular changes including signaling pathways as well as microRNA (miRNA) in CML in order to better understand the therapeutic approaches. CML is a three-stage myeloproliferative disorder caused by reciprocal translocation between chromosome 9 and 22. There has been a new interest on treatment of this disorder. Therefore, in order to develop the appropriate therapy, an analysis of the molecular changes involved in malignant cells can be effective. A review of the signaling pathways, miRNA, and related targets can be helpful for better understanding of molecular pathogenesis of CML. Characterizing malignant cells and molecular changes with a focus on their targets may help researchers use molecular targets as effective therapeutic means for CML. On the other hand, interactions between leukemic stem cells and CML niche will help researchers investigate the causes of drug resistance in this disease.

Carbon nanotubes induce cytotoxicity and apoptosis through increasing protein levels of Bax and ROS in mouse skin fibroblasts.

Background and purpose: Carbon nanotubes (CNTs) are a significant discovery in nanotechnology, with widespread applications in modern technology. However, there are concerns about their potential toxicity, particularly in skin cells. This study aimed to investigate the mechanisms by which CNTs induced cytotoxicity and apoptosis in mouse skin fibroblasts. Experimental approach: The mice skin fibroblasts were isolated and exposed to two types of CNTs at various concentrations and then analyzed for changes in viability, reactive oxygen species (ROS) production, the levels of Bcl-2-associated X protein (Bax), and lactate production. Findings/Results: The results demonstrated that CNTs reduced cell viability and increased ROS production in a dose-dependent manner. Additionally, the current study found that CNTs increased the protein levels of Bax, a pro-apoptotic protein, in mouse skin fibroblasts. Furthermore, it was observed a significant decrease in lactate production in cells exposed to CNTs. Conclusion and implications: The findings concluded that CNTs have the potential to be toxic substances for skin fibroblasts, which serve as the body's first line of defense. This is evidenced by their ability to increase the production of ROS and the protein levels of Bax, as well as reduce lactic acid levels. As lactic acid has been reported to have beneficial effects on skin collagen production, further studies are needed to fully understand the impact of carbon nanotube exposure on human skin health.

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.

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.

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

Prostate cancer (PCa) is the second prevalent cancer in men. Recent studies have highlighted the critical role of prostate cancer stem cells (PCSCs) in driving tumor initiation and metastasis of the prostate tissue. PCSCs are a rare population of cells in the prostate that possess self-renewal and differentiation capabilities, making them a potential therapeutic target for effective PCa treatment. Therefore, targeting PCSCs might be a novel strategy for the treatment of PCs. Research has shown that various signaling pathways, such as Notch, SHH, TGF-ß, Wnt, STAT3, AKT, and EGFR, are involved in regulating PCSC proliferation, migration, and invasion. Additionally, non-coding RNAs, such as long ncRNAs and miRNAs, have emerged as critical regulators of PCSC pathogenesis and drug resistance. Here, we highlight that targeting these pathways could offer new opportunities for the management of PCa. This review summarizes the current knowledge surrounding the essential signaling pathways implicated in PCSC tumorigenesis and invasiveness.

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.

Dental pulp stem cells - A basic research and future application in regenerative medicine.

Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.

MicroRNAs as a Novel Player for Differentiation of Mesenchymal Stem Cells into Cardiomyocytes.

Cardiovascular disease (CVD) is defined as a class of disorders affecting the heart and blood vessels. Cardiomyocytes and endothelial cells play important roles in cardiac regeneration and heart repair. However, the proliferating capacity of cardiomyocytes is limited. To overcome this issue, mesenchymal stem cells (MSCs) have emerged as an alternative strategy for CVD therapy. MSCs can proliferate and differentiate (or trans-differentiate) into cardiomyocytes. Several in vitro and in vivo differentiation protocols have been used to obtain MSCs-derived cardiomyocytes. It was recently investigated that microRNAs (miRNAs) by targeting several signaling pathways, including STAT3, Wnt/ß-catenin, Notch, and TBX5, play a crucial role in regulating cardiomyocytes' differentiation of MSCs. In this review, we focused on the role of miRNAs in the differentiation of MSCs into cardiomyocytes.

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.

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 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.

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.

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.