scholarly journals The Role of Exosomes and Their Applications in Cancer

2021 ◽  
Vol 22 (22) ◽  
pp. 12204
Author(s):  
Yuju Zhou ◽  
Ying Zhang ◽  
Huan Gong ◽  
Siqi Luo ◽  
Yan Cui
Keyword(s):  
High Efficiency ◽  
Biological Fluids ◽  
Cell Types ◽  
Therapeutic Delivery ◽  
Diagnosis And Prognosis ◽  
Multiple Cell ◽  
Diagnostic Applications ◽  
Different Sources ◽  
Target Cancer

Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers.

scholarly journals Exosomes: A Key Piece in Asthmatic Inflammation

2021 ◽  
Vol 22 (2) ◽  
pp. 963
Author(s):  
José A. Cañas ◽  
José M. Rodrigo-Muñoz ◽  
Marta Gil-Martínez ◽  
Beatriz Sastre ◽  
Victoria del Pozo
Keyword(s):  
Cell Types ◽  
Donor Cells ◽  
Wide Range ◽  
Spherical Structures ◽  
Multiple Cell ◽  
Extracellular Microenvironment ◽  
Almost All ◽  
Multiple Cells ◽  
Different Sources

Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.

scholarly journals Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

2016 ◽  
Vol 113 (34) ◽  
pp. E4995-E5004 ◽  
Author(s):  
Wen Lu ◽  
Michael Winding ◽  
Margot Lakonishok ◽  
Jill Wildonger ◽  
Vladimir I. Gelfand
Keyword(s):  
Cytoplasmic Streaming ◽  
Cell Types ◽  
Nurse Cells ◽  
Wild Type ◽  
Actin Cortex ◽  
Microtubule Motor ◽  
Multiple Cell ◽  
Cytoplasmic Microtubules ◽  
Two Populations

Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants.

scholarly journals Emerging role of extracellular vesicles in liver diseases

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Responses ◽  
Therapeutic Delivery ◽  
Disease States ◽  
Therapeutic Uses ◽  
Potential Biomarker ◽  
Secretion Pathways

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.

scholarly journals Chemokines—What Is Their Role in Colorectal Cancer?

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Early Stage ◽  
Distant Metastases ◽  
Cell Types ◽  
Diagnosis And Prognosis ◽  
Novel Biomarkers ◽  
Specific Receptors ◽  
Common Malignancy

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.

scholarly journals Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation

2020 ◽  
Vol 21 (4) ◽  
pp. 1274
Author(s):  
Hideka Saotome ◽  
Atsumi Ito ◽  
Atsushi Kubo ◽  
Masafumi Inui
Keyword(s):  
Cell Types ◽  
Live Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Post Translational Modifications ◽  
Extracellular Signal ◽  
Multiple Cell ◽  
Sox9 Activity ◽  
Reporter Signal

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

scholarly journals Nitric Oxide Transiently Converts Synaptic Inhibition to Excitation in Retinal Amacrine Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 2866-2877 ◽  
Author(s):  
Brian Hoffpauir ◽  
Emily McMains ◽  
Evanna Gleason
Keyword(s):  
Nitric Oxide ◽  
Hippocampal Neurons ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Cell Types ◽  
Synaptic Function ◽  
Positive Shift ◽  
Gabaergic Synapses ◽  
Multiple Cell

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl−. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl− in the absence of extracellular Cl− indicates that the increase in cytosolic Cl− is due to release of Cl− from an internal store. An NO-dependent release of Cl− from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl− store.

scholarly journals Tribbles in normal and malignant haematopoiesis

2015 ◽  
Vol 43 (5) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sarah J. Stein ◽  
Ethan A. Mack ◽  
Kelly S. Rome ◽  
Warren S. Pear
Keyword(s):  
E3 Ligase ◽  
Cell Types ◽  
Protein Family ◽  
Conserved Motifs ◽  
Tissue Specific ◽  
Cellular Events ◽  
Haematopoietic Cells ◽  
Evolutionarily Conserved ◽  
Multiple Cell

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types.

scholarly journals Extraction of Exosomes from Glioblastoma Multiforme Patients’ Blood Plasma

2019 ◽  
Vol 9 (3) ◽  
pp. 234-238
Author(s):  
I. F. Gareev ◽  
O. A. Beylerli ◽  
Sh. Zhao ◽  
G. Yang ◽  
J. Sun ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Blood Plasma ◽  
Biological Fluids ◽  
Morphological Characteristics ◽  
Spherical Shape ◽  
Experimental Protocol ◽  
Malignant Brain Tumour ◽  
Non Invasive ◽  
Diagnosis And Prognosis

Introduction. Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant brain tumour in adults associated with a poor prognosis. Exosomes have been shown to be useful non-invasive biomarkers for the diagnosis and prognosis of tumours, GBM included. Exosomes play a role of biological carriers which can perform various tasks through various signalling pathways of carcinogenesis, such as PI3K/AKT, SOX2, PTEN, ERK and STAT3.Materials and methods. Exosomes were isolated from blood plasma taken from patients diagnosed with GBM prior to surgical resection.Results and discussion. Plasma exosomes from patients with GBM had spherical shape and varied in size from 40 to 100 nm matching the exosomes’ morphological characteristics. The combination of ultrafiltration and double ultracentrifugation makes it possible to extract exosome examples from plasma without the presence of contaminating particles over 100 nm in size; the shape and size of these vesicles match the characteristics of exosomes isolated from other biological fluids.Conclusion. The experimental protocol for the extraction of exosomes from GBM patients’ plasma described here proves effective as a method used to ensure the purity of exosomes. Applying this method offers further opportunities for research into the role of exosomes in GBM pathogenesis. Equally this method can be used in research involving other human pathologies.

Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats

2000 ◽  
Vol 279 (5) ◽  
pp. R1753-R1762 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Patrice G. Guyenet
Keyword(s):  
Extracellular Recording ◽  
Splanchnic Nerve ◽  
Cell Types ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Catecholaminergic Neurons ◽  
Thoracic Spinal ◽  
Multiple Cell ◽  
Rvlm Neuron

The rostral ventrolateral medulla (RVLM) may play an important role in the sympatholytic and hypotensive effects of clonidine. The present study examined which type of presympathetic RVLM neuron is inhibited by clonidine, and whether the adrenergic presympathetic RVLM neurons are essential for clonidine-induced sympathoinhibition. In chloralose-anesthetized and ventilated rats, clonidine (10 μg/kg iv) decreased arterial pressure (116 ± 6 to 84 ± 2 mmHg) and splanchnic nerve activity (93 ± 3% from baseline). Extracellular recording and juxtacellular labeling of barosensitive bulbospinal RVLM neurons revealed that most cells were inhibited by clonidine (26/28) regardless of phenotype [tyrosine hydroxylase (TH)-immunoreactive cells: 48 ± 7%; non-TH-immunoreactive cells: 42 ± 5%], although the inhibition of most neurons was modest compared with the observed sympathoinhibition. Depletion of most bulbospinal catecholaminergic neurons, including 76 ± 5% of the rostral C1 cells, by microinjection of saporin anti-dopamine β-hydroxylase into the thoracic spinal cord (levels T2 and T4, 42 ng · 200 nl−1 · side−1) did not alter the sympatholytic or hypotensive effects of clonidine. These data show that although clonidine inhibits presympathetic C1 neurons, bulbospinal catecholaminergic neurons do not appear to be essential for the sympatholytic and hypotensive effects of systemically administered clonidine. Instead, the sympatholytic effect of clonidine is likely the result of a combination of effects on multiple cell types both within and outside the RVLM.

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