The Role of Extracellular Vesicles in Disease Progression and Detection of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer-related death worldwide. Despite the improvements in surveillance and treatment, the prognosis of HCC remains poor. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles circulating in the bloodstream and mediating intercellular communication. Emerging studies have shown that EVs play a crucial role in regulating the proliferation, immune escape, and metastasis of HCC. In addition, because EVs are present in the circulation at relatively early stages of disease, they are getting attention as an attractive biomarker for HCC detection. Over the past decade, dedicated efforts have been made to isolate EVs more efficiently and make them useful tools in different clinical settings. In this review article, we provide an overview of the EVs isolation methods and highlight the role of EVs as mediators in the pathogenesis and progression of HCC. Lastly, we summarize the potential applications of EVs in early-stage HCC detection.

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The Role of Histones and Heparin in Sepsis: A Review

Journal of Intensive Care Medicine ◽

10.1177/0885066621992320 ◽

2021 ◽

pp. 088506662199232

Author(s):

Xiaojuan Zhang ◽

Xin Li

Keyword(s):

Septic Shock ◽

Multiple Organ ◽

Clinical Settings ◽

The Past ◽

Life Saving ◽

Extracellular Histones ◽

Sepsis And Septic Shock ◽

Development And Management ◽

Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

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The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060902 ◽

2021 ◽

Vol 12 (6) ◽

pp. 902

Author(s):

Eva Costanzi ◽

Carolina Simioni ◽

Gabriele Varano ◽

Cinzia Brenna ◽

Ilaria Conti ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Extracellular Vesicles ◽

Tumor Metastasis ◽

Biological Processes ◽

Rna Molecules ◽

Expression Of Genes ◽

Non Coding Rna ◽

Donor Cells ◽

Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

Veterinary Pathology ◽

10.1177/0300985821999328 ◽

2021 ◽

pp. 030098582199932

Author(s):

Laura Bongiovanni ◽

Anneloes Andriessen ◽

Marca H. M. Wauben ◽

Esther N. M. Nolte-’t Hoen ◽

Alain de Bruin

Keyword(s):

Extracellular Vesicles ◽

Biologically Active ◽

Liquid Biopsies ◽

Donor Cells ◽

Recent Developments ◽

Veterinary Pathology ◽

Cell Components ◽

Potential Applications ◽

Intercellular Communications

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies.

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The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Cells ◽

10.3390/cells10092316 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2316

Author(s):

Lucia Catani ◽

Michele Cavo ◽

Francesca Palandri

Keyword(s):

Extracellular Vesicles ◽

Immune Escape ◽

Myeloproliferative Neoplasms ◽

Cell Communication ◽

Bioactive Molecules ◽

Driver Genes ◽

Hematopoietic Stem ◽

Increased Risk ◽

Patients Experience

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

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Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin

International Journal of Molecular Sciences ◽

10.3390/ijms20061503 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1503 ◽

Cited By ~ 6

Author(s):

Serena De Matteis ◽

Emanuela Scarpi ◽

Anna Granato ◽

Umberto Vespasiani-Gentilucci ◽

Giuliano La Barba ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Early Stage ◽

Mammalian Target Of Rapamycin ◽

Hypoxia Inducible Factor ◽

Significant Benefit ◽

Diabetic Patients ◽

Advanced Stage ◽

Metabolic Dysfunctions ◽

Worse Prognosis

The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1α) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1α expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1α as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC.

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Potential applications of personality assessments to the management of non-human primates: a review of 10 years of study

PeerJ ◽

10.7717/peerj.12044 ◽

2021 ◽

Vol 9 ◽

pp. e12044 ◽

Cited By ~ 1

Author(s):

Max Norman ◽

Lewis J. Rowden ◽

Guy Cowlishaw

Keyword(s):

Management Practices ◽

Personality Assessments ◽

Group Management ◽

The Past ◽

Conservation Implications ◽

Animal Management ◽

Personality Research ◽

Scientific Disciplines ◽

Potential Applications

Studies of primate personality have become increasingly common over the past three decades. Recently, studies have begun to focus on the health, welfare and conservation implications of personality, and the potential applications of incorporating quantitative personality assessments into animal management programmes. However, this literature is dispersed across a multitude of settings and scientific disciplines. We conducted a review of nonhuman primate personality studies relevant to these issues published since 2010, following on from an earlier review. The databases ScienceDirect, PubMed and Web of Science were used to identify relevant articles. After eliminating irrelevant or duplicate papers, 69 studies were selected. Our review reveals that, while primate personality research is carried out on a range of species, there is strong taxonomic bias. While 28 species appeared within the reviewed literature, 52% of studies were carried out on just five species. Further, the most common research focus (43%) was validating new assessment methods or describing personality in different species, rather than exploring the links between personality and animal welfare using existing validated methods. However, among the remaining studies that did explore the role of animal personality in husbandry, health, and welfare, we identified progression towards integrating personality data into various aspects of animal management. Evidence suggests the assessment of personality may benefit social group management, enrichment practices, training protocols, health and welfare monitoring, and conservation planning for endangered species. We argue that further research which develops our understanding of primate personality and its influence in these areas will provide a valuable tool to inform animal management practices.

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Mesenchymal Stem Cells and Extracellular Vesicles in Osteosarcoma Pathogenesis and Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms222011035 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11035

Author(s):

Virinder Kaur Sarhadi ◽

Ravindra Daddali ◽

Riitta Seppänen-Kaijansinkko

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Poor Prognosis ◽

Paracrine Signaling ◽

Mediated Communication ◽

Multipotent Stem Cells ◽

Genetic Complexity ◽

Potential Applications

Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.

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Validation of mRNAs in Early Diagnosis and Treatment of Hepatocellular Carcinoma

BioScientific Review ◽

10.32350/bsr.0303.03 ◽

2021 ◽

Vol 3 (3) ◽

Author(s):

Iqra Khalid ◽

Azra Quraishi ◽

Freeha Fiaz

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Early Stage ◽

Therapeutic Targets ◽

Minimal Invasive ◽

Detection Methods ◽

Circulating Micrornas ◽

Novel Biomarkers ◽

Diseased State

Poor and late diagnosis of HCV is main the cause of liver cancer. MicroRNAs are non-coding molecules that are involved in regulation of a variety of functions happening in the cell, in healthy and diseased state. Dysregulation of microRNAs is observed in different diseases, especially in liver cancer like hepatocellular carcinoma. The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for diagnosis at an earlier stage to minimize chances of liver cancer. Circulating microRNAs are novel and minimal invasive markers for early detection of HCV based hepatocellular carcinoma. In this review, the current progress on the potential role of miRNA as biomarkers for detection of HCC and therapeutic targets are summarized. We concluded that the expression of microRNAis upregulated in the patients of hepatocellular carcinoma when compared with the healthy ones. In-depth studies of miRNA in patients of HCC as genetic biomarkers will improve the diagnosis. It will also improve the prognosis of early stage HCC patients. This will also help in identifying a suitable and effective therapeutic targets so as to reduce the chances of failure of chemotherapy.

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Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms21072286 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2286 ◽

Cited By ~ 8

Author(s):

Stefania Raimondo ◽

Marzia Pucci ◽

Riccardo Alessandro ◽

Simona Fontana

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Immune Cell ◽

Immune Escape ◽

Immune Checkpoints ◽

Cancer Therapies ◽

Biological Functions ◽

Hallmarks Of Cancer ◽

Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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Anti-inflammatory Effects of Mesenchymal Stem Cells and Their Secretomes in Pneumonia

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210907115126 ◽

2021 ◽

Vol 22 ◽

Author(s):

Kamal Hezam ◽

Rigen Mo ◽

Chen Wang ◽

Yue Liu ◽

Zongjin Li

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Clinical Settings ◽

Multipotent Progenitor Cells ◽

Novel Coronavirus ◽

The Cost ◽

And Storage ◽

Potential Therapeutics

: Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

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