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The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways.
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Anormalidades Linfáticas , Vasos Linfáticos , Humanos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Anormalidades Linfáticas/genética , Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/patologia , Vasos Linfáticos/anormalidades , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Biomarcadores/metabolismoRESUMO
In brief: Since available therapeutic approaches for chemotherapy-induced non-obstructive azoospermia (NOA) patients are not enough efficient, an urgent need for treatment alternatives is felt. This study shows that adipose tissue-derived mesenchymal stem cells-derived exosome (AD-Exo) treatment is more effective in ameliorating busulfan-induced NOA rat models compared to platelet-rich plasma (PRP). Abstract: Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models.
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Azoospermia , Bussulfano , Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Espermatogênese , Masculino , Animais , Exossomos/metabolismo , Exossomos/transplante , Azoospermia/terapia , Azoospermia/patologia , Azoospermia/induzido quimicamente , Espermatogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Ratos , Bussulfano/farmacologia , Plasma Rico em Plaquetas/metabolismo , Humanos , Testículo/metabolismo , Testículo/patologia , Ratos Sprague-DawleyRESUMO
Cancer immunotherapy has made improvements due to the advances in chimaeric antigen receptor (CAR) T cell development, offering a promising treatment option for patients who have failed to respond to traditional treatments. In light of the successful use of adoptive CAR T cell therapy for cancer, researchers have been inspired to develop CARs for the treatment of other diseases beyond cancers such as viral infectious diseases. Nonetheless, various obstacles limit the efficacy of CAR T cell therapies and prevent their widespread usage. Severe toxicities, poor in vivo persistence, antigen escape, and heterogeneity, as well as off-target effect, are key challenges that must all be addressed to broaden the application of CAR T cells to a wider spectrum of diseases. The key advances in CAR T cell treatment for cancer and viral infections are reviewed in this article. We will also discuss revolutionary CAR T cell products developed to improve and enhance the therapeutic advantages of these treatments.
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Doenças Transmissíveis , Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Doenças Transmissíveis/terapia , Humanos , Neoplasias/etiologia , Neoplasias/terapia , Receptores de Antígenos Quiméricos/genética , Linfócitos TRESUMO
Colorectal cancer (CRC) is a common type of cancer and the second leading cause of cancer-related deaths worldwide. Competing endogenous RNAs (ceRNAs) that contain microRNA response elements (MREs) are involved in CRC progression. They can compete with microRNAs (miRNAs) via their MREs, which can combine non-coding and coding RNAs via complex ceRNA networks. This molecular interaction has the potential to affect a wide variety of biological processes, and many cancers can occur as a result of an imbalanced ceRNA network. Recent research indicates that numerous dysregulated RNAs in CRC may function as ceRNAs, regulating multiple biological functions of the tumour, including proliferation, apoptosis, metastasis, invasion and migration. In this review, we discuss the role of protein-coding and non-coding RNAs, such as long non-coding RNAs, circular RNAs and pseudogenes, in the occurrence of ceRNA networks in CRC, and their function in cancer-related pathways, such as Wnt/ß-catenin, mitogen-activated protein kinase and transforming growth factor-ß signalling pathways. Additionally, we discuss validated ceRNAs associated with CRC biological functions and their potential role as novel prognostic and diagnostic biomarkers. Examining the role of ceRNAs in CRC sheds new light on cancer treatment and pathogenesis.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Long non-coding RNAs (lncRNAs) have important roles in regulating the expression of genes and act as biomarkers in the initial development of different cancers. Increasing research studies have verified that dysregulation of lncRNAs occurs in various pathological processes including tumorigenesis and cancer progression. Among the different lncRNAs, DLX6-AS1 has been reported to act as an oncogene in the development and prognoses of different cancers, by affecting many different signalling pathways. This review summarises and analyses the recent research studies describing the biological functions of DLX6-AS1, its overall effect on signalling pathways and the molecular mechanisms underlying its action on the expression of genes in multiple human cancers. Our critical analysis suggests that different signalling pathways associated to this lncRNA may be used as a biomarker for diagnosis, or targets of treatment in cancers.
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MicroRNAs , Neoplasias , RNA Longo não Codificante , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Neoplasias/genética , Oncogenes/genética , RNA Longo não Codificante/genéticaRESUMO
INTRODUCTION: In recent years, platelet-rich plasma (PRP) has emerged as a promising autologous biological treatment modality for the use in aesthetic and regenerative medicine. PRP is a high concentration of platelets derived from whole blood which is isolated by centrifugation to separate and concentrate platelet-containing plasma from red blood cells. PRP comprises hundreds of bioactive proteins, including growth factors, peptides, and cytokines that stimulate healing of skin and soft tissues. Attractive features of PRP are the extended release of various growth and differentiation factors from activated platelets, tissue regenerative, and healing capabilities, as well as the lack of problems associated with immunogenicity. Because of the unique biological features of this whole blood-derived biological agent, multiple clinical uses for PRP exist for aesthetic and regenerative medicine. EVIDENCE ACQUISITIONS: A comprehensive review of the literature regarding the use of platelet-rich plasma in aesthetic and regenerative medicine was performed. EVIDENCE SYNTHESIS: Therapeutic applications of PRP including several methods for its clinical deployment in conditions related to aesthetic and regenerative medicine including wound healing, skin and facial rejuvenation, hair restoration, hand rejuvenation, breast augmentation, and musculoskeletal regeneration were reviewed. CONCLUSION: PRP treatment has shown itself as a bright future for a safe and efficient cosmetic intervention. However, more studies are needed to better our understanding of limitations and benefits in clinical phases associated with the aesthetic use of PRP. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Técnicas Cosméticas , Plasma Rico em Plaquetas , Regeneração , Rejuvenescimento , HumanosRESUMO
All-trans retinoic acid (ATRA) has promising activity against breast cancer. However, the exact mechanisms of ATRA's anticancer effects remain complex and not fully understood. In this study, a network pharmacology and molecular docking approach was applied to identify key target genes related to ATRA's anti-breast cancer activity. Gene/disease enrichment analysis for predicted ATRA targets was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), the Comparative Toxicogenomics Database (CTD), and the Gene Set Cancer Analysis (GSCA) database. Protein-Protein Interaction Network (PPIN) generation and analysis was conducted via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and cytoscape, respectively. Cancer-associated genes were evaluated using MyGeneVenn from the CTD. Differential expression analysis was conducted using the Tumor, Normal, and Metastatic (TNM) Plot tool and the Human Protein Atlas (HPA). The Glide docking program was used to predict ligand-protein binding. Treatment response predication and clinical profile assessment were performed using Receiver Operating Characteristic (ROC) Plotter and OncoDB databases, respectively. Cytotoxicity and gene expression were measured using MTT/fluorescent assays and Real-Time PCR, respectively. Molecular functions of ATRA targets (n = 209) included eicosanoid receptor activity and transcription factor activity. Some enriched pathways included inclusion body myositis and nuclear receptors pathways. Network analysis revealed 35 hub genes contributing to 3 modules, with 16 of them were associated with breast cancer. These genes were involved in apoptosis, cell cycle, androgen receptor pathway, and ESR-mediated signaling, among others. CCND1, ESR1, MMP9, MDM2, NCOA3, and RARA were significantly overexpressed in tumor samples. ATRA showed a high affinity towards CCND1/CDK4 and MMP9. CCND1, ESR1, and MDM2 were associated with poor treatment response and were downregulated after treatment of the breast cancer cell line with ATRA. CCND1 and ESR1 exhibited differential expression across breast cancer stages. Therefore, some part of ATRA's anti-breast cancer activity may be exerted through the CCND1/CDK4 complex.
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Diabetes mellitus (DM) is a pervasive global health issue with substantial morbidity and mortality, often resulting in secondary complications, including diabetic wounds (DWs). These wounds, arising from hyperglycemia, diabetic neuropathy, anemia, and ischemia, afflict approximately 15% of diabetic patients, with a considerable 25% at risk of lower limb amputations. The conventional approaches for chronic and diabetic wounds management involves utilizing various therapeutic substances and techniques, encompassing growth factors, skin substitutes and wound dressings. In parallel, emerging cell therapy approaches, notably involving adipose tissue-derived mesenchymal stem cells (ADMSCs), have demonstrated significant promise in addressing diabetes mellitus and its complications. ADMSCs play a pivotal role in wound repair, and their derived exosomes have garnered attention for their therapeutic potential. This review aimed to unravel the potential mechanisms and provide an updated overview of the role of ADMSCs and their exosomes in diabetes mellitus and its associated complications, with a specific focus on wound healing.
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Tecido Adiposo , Diabetes Mellitus , Exossomos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Cicatrização , Humanos , Exossomos/transplante , Exossomos/metabolismo , Cicatrização/fisiologia , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Diabetes Mellitus/terapia , Diabetes Mellitus/metabolismo , Animais , Transplante de Células-Tronco Mesenquimais/métodos , Doença Crônica , Úlcera/terapiaRESUMO
Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or tumor-specific (mutated) derived peptides are presented within the clefts of main histocompatibility complex (MHC) class I or class II molecules, they either activate cytotoxic T-lymphocytes (CTLs), CD4+ T or CD8+ T lymphocytes, which release cytokines that can suppress tumor cells growth. In cancer immunotherapies, CD8+ T lymphocytes are a major mediator of tumor repression. The effect of peptide-based vaccinations on cytokines in the activating CD8+ T cell against targeted tumor antigens is the subject of this review. It is believed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12, secreting CTL line by interacting with dendritic cell (DC), supposed to stimulate immune system. Additionally, mechanisms of CTL activation and dysfunction were also studied. According to most of the data resulted from in vivo and in vitro research works, it is assumed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12.
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In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy.
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Imunoterapia Adotiva , Mieloma Múltiplo , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologiaRESUMO
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and the third leading cause of cancer-related fatalities. Long non-coding RNAs (lncRNAs) are key regulators of diverse physiological processes and are dysregulated in a wide range of pathophysiological circumstances such as CRC. Studies revealed that aberrant expressions of lncRNAs clearly modulate the expression level of p53 gene in CRC, thereby transactivating multiple downstream pathways. P53 is regarded as a crucial tumor suppressor gene which promotes cell-cycle arrest, DNA repair, senescence or apoptosis in response to cellular stresses. P53 is also mutated in CRC as well as various types of human malignancies. Therefore, lncRNAs interact with the p53 signaling pathway in numerus ways and significantly influence CRC-related processes. The current findings in the investigation of the crosstalk between lncRNAs and the P53 pathway in controlling CRC carcinogenesis, tumor progression, and therapeutic resistance are summarized in the this review. A deeper knowledge of CRC carcinogenesis may also have implications in CRC prevention and treatment through more research.
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Neoplasias Colorretais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genética , Carcinogênese , Neoplasias Colorretais/genética , Transdução de SinaisRESUMO
Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.
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Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Masculino , Humanos , RNA Longo não Codificante/genética , Epigênese Genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Pulmão/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
HIV is a virus that targets and hijacks the immune cells of the host. It multiplies by attacking the helper T-lymphocytes. HIV has remained one of the most difficult and dangerous infections in the world due to the inability to find a successful treatment and a lack of access to medical care. When the virus reaches the body, dendritic cells are the first cells it encounters. DCs have been identified as one of the most effective mediators of immune responses, implying a promising strategy against viral infection. The current state of knowledge about the function of dendritic cells and their subsets is critical for using their full potential as a candidate for the development of an HIV vaccine. Despite extensive efforts, a reliable vaccine with the fewest side effects has yet to be found, and further research is needed to find a dependable and efficient vaccine. The extent to which dendritic cell-based therapy is used to treat HIV was investigated in this study. As the virus attacks the host immune system, the dendritic cells can trigger an immune response against HIV-1 infection.
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Infecções por HIV , Humanos , Infecções por HIV/terapia , Células DendríticasRESUMO
Colorectal cancer (CRC) is the second most common cause of cancer mortality, with approximately 1.9 million new cases and 0.9 million deaths globally in 2020. One of the potential ways to treat colorectal cancer may be through the use of molecular methods to induce cell apoptosis. Apoptosis is a natural cellular event that regulates the growth and proliferation of body cells and prevents cancer. In this pathway, several molecules are involved; one group promotes this process, and some molecules that are representative of inhibitors of apoptosis proteins (IAPs) inhibit apoptosis. The most important human IAPs include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2, and Livin. Several studies have shown that the inhibition of IAPs may be useful in cancer treatment. MicroRNAs (miRNAs) may be effective in regulating the expression of various proteins, including those of the IAPs family; they are a large subgroup of non-coding RNAs that are evolutionarily conserved. Therefore, in this review, the miRNAs that may be used to target IAPs in colorectal cancer were discussed.
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Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Apoptose/genética , Neoplasias Colorretais/genéticaRESUMO
In cancer patients, chemo/radio therapy may cause infertility by damaging the spermatogenesis affecting the self-renewal and differentiation of spermatogonial stem cells (SSCs). In vitro differentiation of stem cells especially mesenchymal stem cells (MSCs) into germ cells has recently been proposed as a new strategy for infertility treatment. The aim of this study was to evaluate the proliferation and differentiation of SSCs using their co-culture with Sertoli cells and conditioned medium (CM) from adipose tissue-derived MSCs (AD-MSCs). Testicular tissues were separated from 2-7 days old neonate Wistar Rats and after mechanical and enzymatic digestion, the SSCs and Sertoli cells were isolated and cultured in Dulbecco's modified eagle medium with 10% fetal bovine serum, 1X antibiotic, basic fibroblast growth factor, and glial cell line-derived neurotrophic factor. The cells were treated with the CM from AD-MSCs for 12 days and then the expression level of differentiation-related genes were measured. Also, the expression level of two major spermatogenic markers of DAZL and DDX4 was calculated. Scp3, Dazl, and Prm1 were significantly increased after treatment compared to the control group, whereas no significant difference was observed in Stra8 expression. The immunocytochemistry images showed that DAZL and DDX4 were positive in experimental group comparing with control. Also, western blotting revealed that both DAZL and DDX4 had higher expression in the treated group than the control group, however, no significant difference was observed. In this study, we concluded that the CM obtained from AD-MSCs can be considered as a suitable biological material to induce the differentiation in SSCs.
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Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.
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Doença de Crohn , Fístula , Doenças Inflamatórias Intestinais , Células-Tronco Mesenquimais , Adulto , Humanos , Doença de Crohn/terapia , Terapia Baseada em Transplante de Células e TecidosRESUMO
Long non-coding RNAs (lncRNAs) are transcribed RNA molecules longer than 200 nucleotides in length that have no protein-coding potential. They are able to react with DNA, RNA, and protein. Hence they involve in regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. LncRNAs have been proven to play an important role in human malignancies and prognostic outcomes. In this review, we will comprehensively and functionally discuss the role of a novel identified lncRNA, namely lncRNA WAPPH located on human chromosome 2q13, in various cancers. Increasing research studies have shown that lncRNA AWPPH is deregulated in different malignancies, including breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, leukemia, and others. LncRNA WAPPH serves as an oncogene in tumorigenesis and the development of cancer. Moreover, lncRNA AWPPH is involved in numerous biological processes of solid and blood cancers. Taken together, based on our scrutiny analysis, lncRNA AWPPH can be regarded as a putative biomarker for diagnosis or therapeutic target in human malignancies.
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INTRODUCTION: Extracellular vesicles (EVs) are one of the crucial means of intercellular communication, which takes many different forms. They are heterogeneous, secreted by a range of cell types, and can be generally classified into microvesicles and exosomes depending on their location and function. Exosomes are small EVs with diameters of about 30-150 nm and diverse cell sources. METHODS: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of recent years, using the search string "Exosome" and "Neurodegenerative diseases." RESULTS: The exosomes have attracted interest as a significant biomarker for a better understanding of disease development, gene silencing delivery, and alternatives to stem cell-based therapy because of their low-invasive therapeutic approach, repeatable distribution in the central nervous system (CNS), and high efficiency. Also, they are nanovesicles that carry various substances, which can have an impact on neural plasticity and cognitive functioning in both healthy and pathological circumstances. Therefore, exosomes are conceived as nanovesicles containing proteins, lipids, and nucleic acids. However, their composition varies considerably depending on the cells from which they are produced. CONCLUSION: In the present review, we discuss several techniques for the isolation of exosomes from different cell sources. Furthermore, reviewing research on exosomes' possible functions as carriers of bioactive substances implicated in the etiology of neurodegenerative illnesses, we further examine them. We also analyze the preclinical and clinical research that shows exosomes to have therapeutic potential.
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The occurrence of a novel coronavirus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), created a serious challenge worldwide. SARS-CoV-2 has high infectivity, the ability to be transmitted even during the asymptomatic phase, and relatively low virulence, which has resulted in rapid transmission. SARS-CoV-2 can invade epithelial cells, hence, many patients infected with SARS-CoV-2 have suffered from vascular diseases (VDs) in addition to pulmonary manifestations. Accordingly, SARS-CoV-2 may can worsen the clinical condition of the patients with pre-existing VDs. Endothelial cells express angiotensin-converting enzyme 2 (ACE2). ACE2 is a biological enzyme that converts angiotensin (Ang)- 2 to Ang-(1-7). SARS-CoV-2 uses ACE2 as a cell receptor for viral entry. Thus, the SARS-CoV-2 virus promotes downregulation of ACE2, Ang-(1-7), and anti-inflammatory cytokines, as well as, an increase in Ang-2, resulting in pro-inflammatory cytokines. SARS-CoV-2 infection can cause hypertension, and endothelial damage, which can lead to intravascular thrombosis. In this review, we have concentrated on the effect of SARS-CoV-2 in peripheral vascular diseases (PVDs) and ACE2 as an enzyme in Renin-angiotensin aldosterone system (RAAS). A comprehensive search was performed on PubMed, Google Scholar, Scopus, using related keywords. Articles focusing on ("SARS-CoV-2", OR "COVID-19"), AND ("Vascular disease", OR "Peripheral vascular disease", OR interested disease name) with regard to MeSH terms, were selected. According to the studies, it is supposed that vascular diseases may increase susceptibility to severe SARS-CoV-2 infection due to increased thrombotic burden and endothelial dysfunction. Understanding SARS-CoV-2 infection mechanism and vascular system pathogenesis is crucial for effective management and treatment in pre-existing vascular diseases.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Doenças Vasculares Periféricas , Humanos , Angiotensina II , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/patologia , Citocinas , Células Endoteliais , Hipertensão , SARS-CoV-2 , Doenças Vasculares Periféricas/metabolismo , Doenças Vasculares Periféricas/patologiaRESUMO
Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.