News

 

Information

General information, events and/or links.

 

 

EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs).

-

Icon for Elsevier Science Related Articles

Dissecting the effects of preconditioning with inflammatory cytokines and hypoxia on the angiogenic potential of mesenchymal stromal cell (MSC)-derived soluble proteins and extracellular vesicles (EVs).

Biomaterials. 2020 Dec 28;269:120633

Authors: Gorgun C, Ceresa D, Lesage R, Villa F, Reverberi D, Balbi C, Santamaria S, Cortese K, Malatesta P, Geris L, Quarto R, Tasso R

Abstract
Mesenchymal stromal cells (MSCs) are characterized by a regulatory phenotype and respond promptly to the environmental signals modulating their secretory activity. An appropriate preconditioning may induce MSCs to release secretomes with an enhanced regenerative potential. However, it fails to take into account that secretomes are composed by both soluble factors and extracellular vesicles (EVs), whose functions could be altered differently by the preconditioning approach. Here we demonstrate that the MSC secretome is strongly modulated by the simultaneous stimulation with hypoxia and pro-inflammatory cytokines, used to mimic the harsh environment present at the site of injury. We observed that the environmental variations strongly influenced the angiogenic potential of the different secretome fractions. Upon inflammation, the pro-angiogenic capacity of the soluble component of the MSC secretome was strongly inhibited, regardless of the oxygen level, while the EV-encapsulated component was not significantly affected by the inflammatory stimuli. These effects were accompanied by the modulation of the secreted proteins. On one hand, inflammation-activated MSCs release proteins mainly involved in the interaction with innate immune cells and in tissue remodeling/repair; on the other hand, when MSCs are not exposed to an inflamed environment, they respond to the different oxygen levels modulating the expression of proteins involved in the angiogenic process. The cargo content (in terms of miRNAs) of the corresponding EV fractions was less sensitive to the influence of the external stimuli. Our findings suggest that the therapeutic efficacy of MSC-based therapies could be enhanced by selecting the appropriate preconditioning approach and carefully discriminating its effects on the different secretome components.

PMID: 33453634 [PubMed - as supplied by publisher]

Circulating Exosomes of Neuronal Origin as Potential Early Biomarkers for Development of Stroke.

-

Icon for Springer Related Articles

Circulating Exosomes of Neuronal Origin as Potential Early Biomarkers for Development of Stroke.

Mol Diagn Ther. 2021 Jan 16;:

Authors: Yousif G, Qadri S, Haik M, Haik Y, Parray AS, Shuaib A

Abstract
Stroke is one of the major causes of morbidity and mortality globally, with devastating effects. It is diagnosed mainly by clinical assessment and brain imaging; however, it is challenging to discriminate stroke from similar conditions with parallel presentations. While brain imaging provides detection of stroke infarcts, it does not provide useful information on the biology and prognosis of the underlying disease process. The complex pathophysiology of stroke infarcts is a barrier in developing sensitive diagnostic tools, which consequently has a detrimental effect on development of treatment regimens. Early diagnosis of stroke is vital for better management, but currently there is no diagnostic blood-based biomarker. The cargo of exosomes can give an insight into the physiological or pathophysiological status of the cell. Exosomes have gained great interest as a means of intercellular communication and recently have been explored as a potential biomarker tool. Circulating exosomes in the blood result from of a contribution from all tissues. The sub-population of exosomes released from brain cells circulating in body fluids are known as neuronal exosomes. This overview presents the vital diagnostic function that could be performed by circulating exosomes of neuronal origin in identifying the subtype of stroke, its severity, and the recovery stages. A number of potential biomarkers that are obtained from circulating exosomes have showed promising potential to function as stroke biomarkers; however, further work is needed to characterize the neuronal exosomes and its payload and to determine the pathways it uses in the complex pathophysiology of stroke. The identification is a subset of exosomal biomarkers that are specific to stroke will enhance the early detection and prognosis of the disease.

PMID: 33453051 [PubMed - as supplied by publisher]

Exosomes from donor-derived adipose mesenchymal stem cells prolong the survival of vascularized composite allografts.

-

Icon for Wiley Related Articles

Exosomes from donor-derived adipose mesenchymal stem cells prolong the survival of vascularized composite allografts.

J Cell Physiol. 2021 Jan 16;:

Authors: Chen Z, Xue S, Zhang S, Cheng K, Ye Q

Abstract
Donor-derived adipose-derived mesenchymal stem cells (ADMSCs) dampen the alloimmune response and exosomes are reported to have biological activity similar to their parent cells. Here, we investigated the roles of exosomes from donor-derived ADMSCs (ADMSC-exo) in vascularized composite allotransplantation (VCA). Brown Norway-to-Lewis rat hindlimb transplantations were intravenously treated with either exosome from donor-derived ADMSCs or phosphate-buffered saline, combined with a short course of immunosuppression. We established that the treatment with ADMSC-exo prolongs the survival time of VCA grafts. Skin and muscle samples from ADMSC-exo-treated animals showed no histological signs of rejection, but samples from controls showed rejection of degree III. Comparing to the control group, a significant increase of donor cell chimerism, Tr1 and Treg, while a decrease of CD4+ T and Th1 cells were observed in the ADMSC-exo-treated group. Our findings imply that ADMSC-exo may be a valuable and safe treatment for extending VCA graft survival.

PMID: 33452713 [PubMed - as supplied by publisher]

Targeting the TXNIP-NLRP3 interaction with PSSM1443 to suppress inflammation in sepsis-induced myocardial dysfunction.

-

Icon for Wiley Related Articles

Targeting the TXNIP-NLRP3 interaction with PSSM1443 to suppress inflammation in sepsis-induced myocardial dysfunction.

J Cell Physiol. 2021 Jan 16;:

Authors: Wang L, Zhao H, Xu H, Liu X, Chen X, Peng Q, Xiao M

Abstract
Sepsis-induced myocardial dysfunction (SIMD), a deadly symptom in sepsis patients, is mainly caused by cardiovascular inflammation. However, it remains unclear how systemic inflammation triggers and aggravates cardiovascular inflammation in the pathogenesis of SIMD. This study found that proinflammatory cytokines and H2 O2 concentrations were significantly induced in SIMD-mice. In particular, a microarray analysis of CD63+ exosomes isolated from sham- and SIMD-monocytes revealed a significant induction of thioredoxin-interacting protein (TXNIP) and NLR family pyrin domain-containing 3 (NLRP3). We proved that oxidative stress caused the disassociation of the TXNIP-TRX2 (thioredoxin 2) complex and the assembly of the TXNIP-NLRP3 complex. In addition, this finding showed that the latter complex could be embedded into CD63+ exosomes and traffic from monocytes to the resident heart macrophages, where it activated caspase-1 and cleaved inactive interleukin 1β (IL-1β) and IL-18. Furthermore, using an amplified luminescent proximity homogeneous assay (Alpha) with GST-TXNIP and His-NLRP3, we obtained a small molecule named PSSM1443 that could disrupt the TXNIP-NLRP3 interaction in vitro, impairing NLRP3 downstream events. Of note, after administering PSSM1443 to the SIMD-mice, we found the small molecule could significantly suppress the activation of caspase-1 and the cleavage of pro-IL-1β and pro-IL-18, reducing inflammation in the SIMD-mice. Collectively, our results reveal that monocyte-derived exosomes harbor the overexpressed TXNIP-NLRP3 complex, which traffics from circulating monocytes to local macrophages and promotes the cleavage of inactive IL-1β and IL-18 in the macrophages, aggravating cardiovascular inflammation. PSSM1443 functions as an inhibitor of the TXNIP-NLRP3 complex and its administration can decrease inflammation in SIMD-mice.

PMID: 33452697 [PubMed - as supplied by publisher]

Recombinant extracellular vesicles as biological reference material for method development, data normalization and assessment of (pre-)analytical variables.

-

Icon for Nature Publishing Group Related Articles

Recombinant extracellular vesicles as biological reference material for method development, data normalization and assessment of (pre-)analytical variables.

Nat Protoc. 2021 Jan 15;:

Authors: Geeurickx E, Lippens L, Rappu P, De Geest BG, De Wever O, Hendrix A

Abstract
The diagnostic and therapeutic use of extracellular vesicles (EV) is under intense investigation and may lead to societal benefits. Reference materials are an invaluable resource for developing, improving and assessing the performance of regulated EV applications and for quantitative and objective data interpretation. We have engineered recombinant EV (rEV) as a biological reference material. rEV have similar biochemical and biophysical characteristics to sample EV and function as an internal quantitative and qualitative control throughout analysis. Spiking rEV in bodily fluids prior to EV analysis maps technical variability of EV applications and promotes intra- and inter-laboratory studies. This protocol, which is an Extension to our previously published protocol (Tulkens et al., 2020), describes the production, separation and quality assurance of rEV, their dilution and addition to bodily fluids, and the detection steps based on complementary fluorescence, nucleic acid and protein measurements. We demonstrate the use of rEV for method development, data normalization and assessment of pre-analytical variables. The protocol can be adopted by researchers with standard laboratory and basic EV separation/characterization experience and requires ~4-5 d.

PMID: 33452501 [PubMed - as supplied by publisher]

BATF2 prevents glioblastoma multiforme progression by inhibiting recruitment of myeloid-derived suppressor cells.

-

Icon for Nature Publishing Group Related Articles

BATF2 prevents glioblastoma multiforme progression by inhibiting recruitment of myeloid-derived suppressor cells.

Oncogene. 2021 Jan 15;:

Authors: Zhang X, Liu Y, Dai L, Shi G, Deng J, Luo Q, Xie Q, Cheng L, Li C, Lin Y, Wang Q, Fan P, Zhang H, Su X, Zhang S, Yang Y, Hu X, Gong Q, Yu D, Zheng L, Deng H

Abstract
The basic leucine zipper ATF-like transcription factor 2 (BATF2) has been implicated in inflammatory responses and anti-tumour effects. Little, however, is known regarding its extracellular role in maintaining a non-supportive cancer microenvironment. Here, we show that BATF2 inhibits glioma growth and myeloid-derived suppressor cells (MDSCs) recruitment. Interestingly, extracellular vesicles (EVs) from BATF2-overexpressing glioma cell lines (BATF2-EVs) inhibited MDSCs chemotaxis in vitro. Moreover, BATF2 inhibited intracellular SDF-1α and contributes to decreased SDF-1α in EVs. In addition, BATF2 downregulation-induced MDSCs recruitment were reversed by blocking SDF-1α/CXCR4 signalling upon AMD3100 treatment. Specifically, detection of EVs in 24 pairs of gliomas and healthy donors at different stages revealed that the abundance of BATF2-positive EVs in plasma (BATF2+ plEVs) can distinguish stage III-IV glioma from stage I-II glioma and healthy donors. Taken together, our study identified novel regulatory functions of BATF2 in regulating MDSCs recruitment, providing a prognostic value in terms of the number of BATF2+ plEVs in glioma stage.

PMID: 33452462 [PubMed - as supplied by publisher]

Red blood cell exosome hemoglobin content increases after cardiopulmonary bypass and mediates acute kidney injury in an animal model.

-

Icon for Elsevier Science Related Articles

Red blood cell exosome hemoglobin content increases after cardiopulmonary bypass and mediates acute kidney injury in an animal model.

J Thorac Cardiovasc Surg. 2020 Dec 03;:

Authors: Pat B, Oh JY, Masjoan Juncos JX, Powell PC, Collawn JF, Patel RP, Dell'Italia LJ, Clinical Working Group

Abstract
OBJECTIVE: Hemolysis, characterized by formation of free hemoglobin (Hb), occurs in patients undergoing cardiopulmonary bypass (CPB). However, there is no study of the dynamic changes in red blood cell (RBC)-derived exosomes (Exos) released during CPB, nor whether these particles mediate acute kidney injury (AKI).
METHODS: This study is a comprehensive time-course analysis, at baseline, 30 minutes, to 24 hours post-crossclamp release (XCR) to determine (1) Exos Hb content; (2) free Hb/heme, haptoglobin, hemopexin; and (3) urinary markers of AKI over the same time period. In addition, we developed a model system in Sprague-Dawley rats to test for AKI after intravenous injection of Exos Hb released during CPB.
RESULTS: In 30 patients undergoing CPB, there is a significant increase in plasma Hb-positive Exos but not microvesicles 30 minutes post-XCR versus other time points, with a simultaneous decrease in the haptoglobin/Hb ratio. These changes presage a significant increase in urine neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 at 24 hours. Intravenous injection of plasma Exos (109-10 particles obtained 30 minutes post-XCR) into rats causes AKI at 72 hours, manifested by multifocal degeneration of proximal tubular epithelium. At 21 days, there is persistent tubular injury and interstitial fibrosis. Intravenous injection of Exos from 35-day-old stored RBCs into rats results in glomerular-tubular injury, increased kidney ferritin and hemoxygenase-1 expression, and significant elevation of kidney injury molecule-1 and proteinuria at 72 hours.
CONCLUSIONS: These combined studies raise the potential for RBC-derived Exos, released during CPB, to target the kidney and mediate AKI.

PMID: 33451850 [PubMed - as supplied by publisher]

Proteomics and Metaproteomics Add Functional, Taxonomic and Biomass Dimensions to Modeling the Ecosystem at the Mucosal-luminal Interface.

-

Icon for HighWire Related Articles

Proteomics and Metaproteomics Add Functional, Taxonomic and Biomass Dimensions to Modeling the Ecosystem at the Mucosal-luminal Interface.

Mol Cell Proteomics. 2020 Sep;19(9):1409-1417

Authors: Li L, Figeys D

Abstract
Recent efforts in gut microbiome studies have highlighted the importance of explicitly describing the ecological processes beyond correlative analysis. However, we are still at the early stage of understanding the organizational principles of the gut ecosystem, partially because of the limited information provided by currently used analytical tools in ecological modeling practices. Proteomics and metaproteomics can provide a number of insights for ecological studies, including biomass, matter and energy flow, and functional diversity. In this Mini Review, we discuss proteomics and metaproteomics-based experimental strategies that can contribute to studying the ecology, in particular at the mucosal-luminal interface (MLI) where the direct host-microbiome interaction happens. These strategies include isolation protocols for different MLI components, enrichment methods to obtain designated array of proteins, probing for specific pathways, and isotopic labeling for tracking nutrient flow. Integration of these technologies can generate spatiotemporal and site-specific biological information that supports mathematical modeling of the ecosystem at the MLI.

PMID: 33451726 [PubMed - as supplied by publisher]

Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses.

-

Icon for HighWire Related Articles

Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses.

Mol Cell Proteomics. 2020 Jun;19(6):1017-1034

Authors: Podvin S, Jones A, Liu Q, Aulston B, Ransom L, Ames J, Shen G, Lietz CB, Jiang Z, O'Donoghue AJ, Winston C, Ikezu T, Rissman RA, Yuan S, Hook V

Abstract
Accumulation and propagation of hyperphosphorylated Tau (p-Tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating Tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-Tau pathology after injection into mouse brain. To gain an understanding of the mTau exosome cargo involved in Tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in 1) proteins uniquely present only in mTau, and not control exosomes, 2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and 3) shared proteins which were significantly upregulated or downregulated in mTau compared with control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-Tau. Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes. Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or downregulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-Tau neuropathology in mouse brain.

PMID: 33451707 [PubMed - as supplied by publisher]

Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals.

-

Icon for HighWire Related Articles

Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals.

Mol Cell Proteomics. 2020 Dec;19(12):2090-2104

Authors: Rowlison T, Cleland TP, Ottinger MA, Comizzoli P

Abstract
Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.

PMID: 33451639 [PubMed - as supplied by publisher]

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

-

Icon for HighWire Related Articles

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

Mol Cell Proteomics. 2020 Jan;19(1):78-100

Authors: Kaddour H, Lyu Y, Welch JL, Paromov V, Mandape SN, Sakhare SS, Pandhare J, Stapleton JT, Pratap S, Dash C, Okeoma CM

Abstract
Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein·Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.

PMID: 33451560 [PubMed - as supplied by publisher]

Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion.

-

Icon for HighWire Related Articles

Blistering1 Modulates Penicillium expansum Virulence Via Vesicle-mediated Protein Secretion.

Mol Cell Proteomics. 2020 Feb;19(2):344-361

Authors: Jurick WM, Peng H, Beard HS, Garrett WM, Lichtner FJ, Luciano-Rosario D, Macarisin O, Liu Y, Peter KA, Gaskins VL, Yang T, Mowery J, Bauchan G, Keller NP, Cooper B

Abstract
The blue mold fungus, Penicillium expansum, is a postharvest apple pathogen that contributes to food waste by rotting fruit and by producing harmful mycotoxins (e.g. patulin). To identify genes controlling pathogen virulence, a random T-DNA insertional library was created from wild-type P. expansum strain R19. One transformant, T625, had reduced virulence in apples, blistered mycelial hyphae, and a T-DNA insertion that abolished transcription of the single copy locus in which it was inserted. The gene, Blistering1, encodes a protein with a DnaJ domain, but otherwise has little homology outside the Aspergillaceae, a family of fungi known for producing antibiotics, mycotoxins, and cheese. Because protein secretion is critical for these processes and for host infection, mass spectrometry was used to monitor proteins secreted into liquid media during fungal growth. T625 failed to secrete a set of enzymes that degrade plant cell walls, along with ones that synthesize the three final biosynthetic steps of patulin. Consequently, the culture broth of T625 had significantly reduced capacity to degrade apple tissue and contained 30 times less patulin. Quantitative mass spectrometry of 3,282 mycelial proteins revealed that T625 had altered cellular networks controlling protein processing in the endoplasmic reticulum, protein export, vesicle-mediated transport, and endocytosis. T625 also had reduced proteins controlling mRNA surveillance and RNA processing. Transmission electron microscopy of hyphal cross sections confirmed that T625 formed abnormally enlarged endosomes or vacuoles. These data reveal that Blistering1 affects internal and external protein processing involving vesicle-mediated transport in a family of fungi with medical, commercial, and agricultural importance.

PMID: 33451392 [PubMed - as supplied by publisher]

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.

-

Icon for BioMed Central Related Articles

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.

Cell Biosci. 2021 Jan 15;11(1):19

Authors: Rezaie J, Aslan C, Ahmadi M, Zolbanin NM, Kashanchi F, Jafari R

Abstract
Eukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.

PMID: 33451365 [PubMed - as supplied by publisher]

Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p.

-

Icon for BioMed Central Related Articles

Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p.

Cancer Cell Int. 2021 Jan 15;21(1):55

Authors: Liu J, Zhu S, Tang W, Huang Q, Mei Y, Yang H

Abstract
BACKGROUND: Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM.
METHODS: Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA.
RESULTS: Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM.
CONCLUSIONS: Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

PMID: 33451320 [PubMed - as supplied by publisher]

Cell-Based Tracers as Trojan Horses for Image-Guided Surgery.

-

Related Articles

Cell-Based Tracers as Trojan Horses for Image-Guided Surgery.

Int J Mol Sci. 2021 Jan 13;22(2):

Authors: Sier VQ, de Vries MR, van der Vorst JR, Vahrmeijer AL, van Kooten C, Cruz LJ, de Geus-Oei LF, Ferreira V, Sier CFM, Alves F, Muthana M

Abstract
Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these 'passive' tracers, there are other, more 'active' approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, 'humanized' nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS.

PMID: 33451116 [PubMed - as supplied by publisher]

pH-Dependent Molecular Gate Mesoporous Microparticles for Biological Control of Giardia intestinalis.

-

Related Articles

pH-Dependent Molecular Gate Mesoporous Microparticles for Biological Control of Giardia intestinalis.

Pharmaceutics. 2021 Jan 13;13(1):

Authors: González-Alvarez I, Vivancos V, Coll C, Sánchez-Dengra B, Aznar E, Ruiz-Picazo A, Bermejo M, Sancenón F, Dea-Ayuela MA, Gonzalez-Alvarez M, Martínez-Máñez R

Abstract
Giardiasis is a parasitism produced by the protozoa Giardia intestinalis that lives as trophozoite in the small intestine (mainly in the duodenum) attached to the intestinal villus by means of billed discs. The first line treatment is metronidazole, a drug with high bioavailability, which is why to obtain therapeutic concentrations in duodenum, it is necessary to administer high doses of drug to patients with the consequent occurrence of side effects. It is necessary to developed new therapeutical approaches to achieve a local delivery of the drug. In this sense, we have developed gated mesoporous silica microparticles loaded with metronidazole and with a molecular gate pH dependent. In vitro assays demonstrated that the metronidazole release is practically insignificant at acidic pHs, but in duodenum conditions, the metronidazole delivery from the microparticles is effective enough to produce an important parasite destruction. In vivo assays indicate that this microparticulate system allows to increase the concentration of the drug in duodenum and reduce the concentration in plasma avoiding systemic effects. This system could be useful for other intestinal local treatments in order to reduce doses and increase drug availability in target tissues.

PMID: 33451061 [PubMed - as supplied by publisher]

Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization.

-

Related Articles

Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization.

Int J Mol Sci. 2021 Jan 13;22(2):

Authors: Pirlog R, Cismaru A, Nutu A, Berindan-Neagoe I

Abstract
Lung cancer is currently the first cause of cancer-related death. The major lung cancer subtype is non-small cell lung cancers (NSCLC), which accounts for approximatively 85% of cases. The major carcinogenic associated with lung cancer is tobacco smoke, which produces long-lasting and progressive damage to the respiratory tract. The progressive and diffuse alterations that occur in the respiratory tract of patients with cancer and premalignant lesions have been described as field cancerization. At the level of tumor cells, adjacent tumor microenvironment (TME) and cancerized field are taking place dynamic interactions through direct cell-to-cell communication or through extracellular vesicles. These molecular messages exchanged between tumor and nontumor cells are represented by proteins, noncoding RNAs (ncRNAs) and microRNAs (miRNAs). In this paper, we analyze the miRNA roles in the macrophage polarization at the level of TME and cancerized field in NSCLC. Identifying molecular players that can influence the phenotypic states at the level of malignant cells, tumor microenvironment and cancerized field can provide us new insights into tumor regulatory mechanisms that can be further modulated to restore the immunogenic capacity of the TME. This approach could revert alterations in the cancerized field and could enhance currently available therapy approaches.

PMID: 33451052 [PubMed - as supplied by publisher]

The Multiple Potential Biomarkers for Predicting Immunotherapy Response-Finding the Needle in the Haystack.

-

Related Articles

The Multiple Potential Biomarkers for Predicting Immunotherapy Response-Finding the Needle in the Haystack.

Cancers (Basel). 2021 Jan 13;13(2):

Authors: Adam T, Becker TM, Chua W, Bray V, Roberts TL

Abstract
Immune checkpoint inhibitors (ICIs) are being increasingly utilised in a variety of advanced malignancies. Despite promising outcomes in certain patients, the majority will not derive benefit and are at risk of potentially serious immune-related adverse events (irAEs). The development of predictive biomarkers is therefore critical to personalise treatments and improve outcomes. A number of biomarkers have shown promising results, including from tumour (programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB), stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a CARD (ASC)), from blood (peripheral blood mononuclear cells (PBMCs), circulating tumour DNA (ctDNA), exosomes, cytokines and metal chelators) and finally the microbiome.

PMID: 33451015 [PubMed - as supplied by publisher]

Formation of Rutin-β-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation.

-

Related Articles

Formation of Rutin-β-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation.

Polymers (Basel). 2021 Jan 13;13(2):

Authors: Franco P, De Marco I

Abstract
In this work, rutin (RUT)-β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± 2.12 µm. The formation of RUT-β-CD inclusion complexes has been proved by different analyses, including Fourier transform infrared spectroscopy, Differential Scanning Calorimetry, X-ray diffraction, and UV-vis spectroscopy. The dissolution tests reveal a significant improvement in the release rate of RUT from inclusion complexes. Indeed, compared to the unprocessed RUT, the dissolution rate is about 3.9 and 2.4 times faster in the case of the complexes RUT-β-CD 1:2 and 1:1 mol:mol, respectively. From a pharmaceutical/nutraceutical point of view, CD-based inclusion complexes allow the reduction of the polymer amount in the SAS composite formulations.

PMID: 33450873 [PubMed - as supplied by publisher]

Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation.

-

Related Articles

Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation.

Int J Mol Sci. 2021 Jan 13;22(2):

Authors: Zhang B, Lai RC, Sim WK, Choo ABH, Lane EB, Lim SK

Abstract
Severe psoriasis, a chronic inflammatory skin disease is increasingly being effectively managed by targeted immunotherapy but long-term immunotherapy poses health risk and loss of response. Therefore, there is a need for alternative therapy strategies. Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties. Here we investigated if topically applied MSC exosomes could alleviate psoriasis-associated inflammation. Topically applied fluorescent exosomes on human skin explants were confined primarily to the stratum corneum with <1% input fluorescence exiting the explant over a 24-h period. Nevertheless, topically applied MSC exosomes in a mouse model of imiquimod (IMQ) psoriasis significantly reduced IL-17 and terminal complement activation complex C5b-9 in the mouse skin. MSC exosomes were previously shown to inhibit complement activation, specifically C5b-9 complex formation through CD59. Infiltration of neutrophils into the stratum corneum is characteristic of psoriasis and neutrophils are a major cellular source of IL-17 in psoriasis through the release of neutrophil extracellular traps (NETs). We propose that topically applied MSC exosomes inhibit complement activation in the stratum corneum and this alleviates IL-17 release by NETS from neutrophils that accumulate in and beneath the stratum corneum.

PMID: 33450859 [PubMed - as supplied by publisher]

Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde.

-

Related Articles

Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde.

Life (Basel). 2021 Jan 13;11(1):

Authors: Purvinsh L, Gorshkov A, Brodskaia A, Vasin A

Abstract
Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.

PMID: 33450847 [PubMed - as supplied by publisher]

 

Previous page: Relevant links  Next page: EVents