Extracellular Vesicles and Exosomes: Insights From Exercise Science

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or ‘exerkines’). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or ‘mediators’ of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.

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Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽

10.3390/cells10040767 ◽

2021 ◽

Vol 10 (4) ◽

pp. 767

Author(s):

Courtney Davis ◽

Sean I. Savitz ◽

Nikunj Satani

Keyword(s):

Ischemic Stroke ◽

Extracellular Vesicles ◽

Neurovascular Unit ◽

Culture Conditions ◽

Therapeutic Effects ◽

Stroke Treatment ◽

Inflammatory Molecules ◽

The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

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Expression, Purification, and Characterization of (R)-Sulfolactate Dehydrogenase (ComC) from the Rumen MethanogenMethanobrevibacter milleraeSM9

Archaea ◽

10.1155/2017/5793620 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6

Author(s):

Yanli Zhang ◽

Linley R. Schofield ◽

Carrie Sang ◽

Debjit Dey ◽

Ron S. Ronimus

Keyword(s):

Biosynthetic Pathway ◽

Critical Role ◽

Reduction Reaction ◽

Coenzyme M ◽

Purification And Characterization ◽

The Third ◽

Optimal Activity ◽

Methyl Coenzyme M Reductase

(R)-Sulfolactate dehydrogenase (EC 1.1.1.337), termed ComC, is a member of an NADH/NADPH-dependent oxidoreductase family of enzymes that catalyze the interconversion of 2-hydroxyacids into their corresponding 2-oxoacids. The ComC reaction is reversible and in the biosynthetic direction causes the conversion of (R)-sulfolactate to sulfopyruvate in the production of coenzyme M (2-mercaptoethanesulfonic acid). Coenzyme M is an essential cofactor required for the production of methane by the methyl-coenzyme M reductase complex. ComC catalyzes the third step in the first established biosynthetic pathway of coenzyme M and is also involved in methanopterin biosynthesis. In this study, ComC fromMethanobrevibacter milleraeSM9 was cloned and expressed inEscherichia coliand biochemically characterized. Sulfopyruvate was the preferred substrate using the reduction reaction, with 31% activity seen for oxaloacetate and 0.2% seen forα-ketoglutarate. Optimal activity was observed at pH 6.5. The apparentKMfor coenzyme (NADH) was 55.1 μM, and for sulfopyruvate, it was 196 μM (for sulfopyruvate theVmaxwas 93.9 μmol min−1 mg−1andkcatwas 62.8 s−1). The critical role of ComC in two separate cofactor pathways makes this enzyme a potential means of developing methanogen-specific inhibitors for controlling ruminant methane emissions which are increasingly being recognized as contributing to climate change.

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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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Emerging Role of Extracellular Vesicles in Bone Remodeling

Journal of Dental Research ◽

10.1177/0022034518764411 ◽

2018 ◽

Vol 97 (8) ◽

pp. 859-868 ◽

Cited By ~ 28

Author(s):

M. Liu ◽

Y. Sun ◽

Q. Zhang

Keyword(s):

Bone Remodeling ◽

Extracellular Vesicles ◽

Transforming Growth Factor ◽

Tooth Development ◽

Osteoclast Differentiation ◽

Nuclear Factor Κb ◽

Transforming Growth Factor Β1 ◽

Bone Diseases ◽

Bioactive Molecules

Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.

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Expression, Purification, and Characterization of Blasticidin S Deaminase (BSD) from Aspergillus terreus: The Role of Catalytic Zinc in Enzyme Structure

The Journal of Biochemistry ◽

10.1093/oxfordjournals.jbchem.a022711 ◽

2000 ◽

Vol 127 (6) ◽

pp. 955-963 ◽

Cited By ~ 13

Author(s):

M. Kimura ◽

S. Sekido ◽

Y. Isogai ◽

I. Yamaguchi

Keyword(s):

Aspergillus Terreus ◽

Enzyme Structure ◽

Purification And Characterization ◽

Blasticidin S ◽

Catalytic Zinc

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Use of Ultrasound Biomicroscopy to Predict Long-Term Outcome of Sub-Tenon Needle Revision of Failed Trabeculectomy Blebs: A Pilot Study

European Journal of Ophthalmology ◽

10.5301/ejo.2011.6468 ◽

2011 ◽

Vol 21 (6) ◽

pp. 700-707 ◽

Cited By ~ 3

Author(s):

Sushmita Kaushik ◽

Anamika Tiwari ◽

Surinder Singh Pandav ◽

Parul Ichhpujani ◽

Amod Gupta

Keyword(s):

Ultrasound Biomicroscopy ◽

Successful Outcome ◽

Term Outcome ◽

Long Term Outcome ◽

Successful Group ◽

Aqueous Flow ◽

Needle Revision

Purpose. To evaluate the role of ultrasound biomicroscopy (UBM) in predicting the long-term outcome of sub-Tenon needling revision of failed trabeculectomy blebs. Methods. Adult patients with a failed trabeculectomy bleb and unsatisfactory intraocular pressure (IOP) control were recruited. The aqueous flow under the partial thickness scleral flap was looked for and the blebs classified on UBM as scleral route patent (SRP) or scleral route occluded (SRO). All blebs underwent needling revision with injection of 5 mg/0.1 mL 5-fluorouracil. Survival of the revision procedure at the end of 2 years follow-up with regards to the baseline UBM characterization of the bleb was noted. Successful outcome was defined as IOP <22.0 mmHg and/or 30% reduction of baseline IOP with or without medication. Results. A total of 13 eyes had SRP and 5 eyes had SRO blebs on UBM. Only SRP blebs survived the needling procedure by the end of 2 years. Of the 13 SRP blebs, 10 blebs survived (76.9%). Needling had failed in all 5 SRO blebs. The overall success rate was 55.6 % at 2 years. There was no difference in age, IOP, and time from initial trabeculectomy between the failed and successful group. The outcome correlated significantly to the patency of the scleral route assessed by UBM (p=0.07). Conclusions. Ultrasound biomicroscopy characterization of failed blebs appears to help in predicting the outcome of needle revision. In SRO blebs, it may be better to plan a full bleb revision rather than needling alone. Ultrasound biomicroscopy may help in avoiding an unnecessary needling procedure in SRO blebs where it is likely to fail.

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The Corinth Rift Laboratory or an in situ Investigation on Interactions between Fluids and Active Faults

Scientific Drilling ◽

10.5194/sd-specialissue-35-2007 ◽

2007 ◽

Vol SpecialIssue ◽

pp. 35-38 ◽

Cited By ~ 2

Author(s):

F. H. Cornet

Keyword(s):

Fluid Flow ◽

Deformation Process ◽

Active Faults ◽

Localization Of Deformation

Earthquakes result from the sudden acceleration of a preliminary long-term slow deformation process. The objective of the Corinth Rift Laboratory (CRL) is to investigate <i>in situ</i> this quasistatic deformation process and mechanisms leading to a sudden catastrophic acceleration. Of particular interest is the characterization of the structure of the deforming zones and of the progressive localization of deformation. Special attention is given to the role of fluids but also on the influence of faults on regional fluid flow <br><br> doi:<a href="http://dx.doi.org/10.2204/iodp.sd.s01.20.2007" target="_blank">10.2204/iodp.sd.s01.20.2007</a>

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Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

Technology in Cancer Research & Treatment ◽

10.1177/15330338211037821 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110378

Author(s):

Qian Zhang ◽

Xiangling Yang ◽

Huanliang Liu

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Cancer Diagnosis ◽

Cancer Metabolism ◽

Metabolic Reprogramming ◽

Bioactive Molecules ◽

Diagnosis And Treatment ◽

Existing Problems ◽

Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

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Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

International Journal of Molecular Sciences ◽

10.3390/ijms20246339 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6339 ◽

Cited By ~ 12

Author(s):

Julie Gatien ◽

Pascal Mermillod ◽

Guillaume Tsikis ◽

Ophélie Bernardi ◽

Sarah Janati Idrissi ◽

...

Keyword(s):

Estrous Cycle ◽

Extracellular Vesicles ◽

Luteal Phase ◽

Early Embryo ◽

Proton Nuclear Magnetic Resonance ◽

Resonance Spectroscopy ◽

Metabolomic Profiling ◽

Late Luteal Phase

Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs’ metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development.

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