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

Organic pollutants, nano- and microparticles in street sweeping road dust and washwater.

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Organic pollutants, nano- and microparticles in street sweeping road dust and washwater.

Environ Int. 2019 Nov 30;135:105337

Authors: Polukarova M, Markiewicz A, Björklund K, Strömvall AM, Galfi H, Andersson Sköld Y, Gustafsson M, Järlskog I, Aronsson M

Abstract
Road areas are pollution hotspots where many metals, organic pollutants (OPs) and nano/microparticles accumulate before being transported to receiving waters. Particles on roads originate from e.g. road, tyre and vehicle wear, winter road maintenance, soil erosion, and deposition. Street sweeping has the potential to be an effective and affordable practice to reduce the occurrence of road dust, and thereby the subsequent spreading of pollutants, but there is currently little knowledge regarding its effectiveness. In this paper we investigate the potential of street sweeping to reduce the amounts of OPs and nano/microparticles reaching stormwater, in a case study sampling road dust and washwater from a street sweeping machine, road dust before and after sweeping, and stormwater. The compound groups generally found in the highest concentrations in all matrices were aliphatics C5-C35 > phthalates > aromatics C8-C35 > PAH-16. The concentrations of aliphatics C16-C35 and PAHs in washwater were extremely high at ≤ 53,000 µg/L and ≤ 120 µg/L, respectively, and the highest concentrations were found after a 3-month winter break in sweeping. In general, fewer aliphatic and aromatic petroleum hydrocarbons and PAHs were detected in road dust samples than in washwater. The relative composition of the specific PAH-16 suggests tyre wear, vehicle exhausts, brake linings, motor oils and road surface wear as possible sources. The study indicates that many of the hydrophobic compounds quantified in washwater are attached to small particles or truly dissolved. The washwater contains a wide range of small particles, including nanoparticles in sizes from just below 1 nm up to 300 nm, with nanoparticles in the size range 25-300 nm present in the highest concentrations. The results also indicated agglomeration of nanoparticles in the washwater. The street sweeping collected a large amount of fine particles and associated pollutants, leading to the conclusion that washwater from street sweeping needs to be treated before disposal.

PMID: 31794938 [PubMed - as supplied by publisher]

Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer.

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Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer.

Clin Chim Acta. 2019 Nov 30;:

Authors: Cui Z, Chen Y, Hu M, Lin Y, Zhang S, Kong L, Chen Y

Abstract
BACKGROUND: Lactate dehydrogenase C4 (LDH-C4) as a cancer/testis antigen (CTA) is abnormally expressed in some malignant tumors. However, the expression and clinical significance of LDH-C4 in breast cancer (BC) has not been characterized.
METHODS: We determined LDHC mRNA expression in serum and serum-derived exosomes of BC patients by quantitative RT-PCR. We also evaluated the protein expression of LDH-C4 in BC tissues using high-throughput tissue microarray analysis and immunohistochemistry.
RESULTS: Our results showed high mRNA expression level of LDHC in serum and serum-derived exosomes of BC patients. The LDHC level in serum and exosomes could distinguish BC cases from healthy individuals based on their AUCs of 0.9587 and 0.9464, respectively. Besides, the LDHC level in exosomes of BC patients associated with tumor size, and positively correlated with HER2 and Ki-67 expressions (all with P < 0.05). Serum and exosomal level of LDHC negatively correlated with medical treatment and positively with the recurrence of BC. Survival analysis showed that LDH-C4 expression negatively correlated with BC prognosis.
CONCLUSION: Serum and exosomal LDHC may be an effective indicator for the diagnosis, efficacy evaluation, and monitoring the recurrence of BC. LDH-C4 may act as a biomarker that predicts BC prognosis.

PMID: 31794764 [PubMed - as supplied by publisher]

Protein-Sugar-Glass Nanoparticle Platform for the Development of Sustained-Release Protein Depots by Overcoming Protein Delivery Challenges.

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Protein-Sugar-Glass Nanoparticle Platform for the Development of Sustained-Release Protein Depots by Overcoming Protein Delivery Challenges.

Mol Pharm. 2019 Dec 03;:

Authors: Polley P, Gupta S, Singh R, Pradhan A, Basu SM, V R, Yadava SK, Giri J

Abstract
Therapeutic protein depots have limited clinical success because of the presence of critical preparation barriers such as low encapsulation, uncontrolled release, and activity loss during processing and storage. In the present study, we used our novel protein-nanoencapsulation (into sugar-glass nanoparticle; SGnP) platform to prepare a protein depot to overcome the abovementioned formidable challenges. The SGnP-mediated microparticle protein depot has been validated using four model proteins (bovine serum albumin, horseradish peroxidase, fibroblastic growth factor, and epidermal growth factor) and model biodegradable poly(lactic-co-glycolic acid) polymer system. The results show that our protein-nanoencapsulation-mediated platform provides a new generic platform to prepare a protein depot through the conventional emulsion method of any polymer and single/multiple protein systems. This protein depot has the required pharmaceutical properties such as high encapsulation efficiency, burst-free sustained release, and protein preservation during processing and storage, making it suitable for off-the-shelf use in therapeutic protein delivery and tissue engineering applications.

PMID: 31794223 [PubMed - as supplied by publisher]

Oscillatory Viscoelastic Microfluidics for Efficient Focusing and Separation of Nanoscale Species.

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Oscillatory Viscoelastic Microfluidics for Efficient Focusing and Separation of Nanoscale Species.

ACS Nano. 2019 Dec 03;:

Authors: Asghari M, Cao X, Mateescu B, Van Leeuwen D, Aslan MK, Stavrakis S, deMello AJ

Abstract
The ability to precisely control particle migration within microfluidic systems is essential for focusing, separating, counting and detecting a wide range of biological species. To date, viscoelastic microfluidic systems have primarily been applied to the focusing, separation and isolation of micron-sized species, with their use in nanoparticle manipulations being underdeveloped and underexplored, due to issues related to nanoparticle diffusivity and a need for extended channel lengths. To overcome such issues, we herein present sheathless oscillatory viscoelastic microfluidics as a method for focusing and separating both micron and sub-micron species. To highlight the efficacy of our approach, we segment our study into three size regimes, namely micron (where characteristic particle dimensions are above 1 µm), sub-micron (where characteristic dimensions are between 1 µm and 100 nm) and nano (where characteristic dimensions are below 100 nm) regimes. Based on the ability to successfully manipulate particles in all these regimes, we demonstrate the successful isolation of p-bodies from biofluids (in the micron regime), the focusing of λ-DNA (in the sub-micron regime) and the focusing of extracellular vesicles (in the nano-regime). Finally, we characterize the physics underlying viscoelastic microflows using a dimensionless number that relates the lateral velocity (due to elastic effects) to the diffusion constant of the species within the viscoelastic carrier fluid. Based on the ability to precisely manipulate species in all three regimes, we expect that sheathless oscillatory viscoelastic microfluidics may be used to good effect in a range of biological and life science applications.

PMID: 31794192 [PubMed - as supplied by publisher]

HMGB1-Positive Platelet Microparticles May Be a Biomarker of Inflammatory Bowel Disease.

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HMGB1-Positive Platelet Microparticles May Be a Biomarker of Inflammatory Bowel Disease.

Inflamm Bowel Dis. 2019 Dec 03;:

Authors: Yang B, Liu X, Mei Q

PMID: 31793627 [PubMed - as supplied by publisher]

Plant defensin PvD1 modulates the membrane composition of breast tumour-derived exosomes.

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Plant defensin PvD1 modulates the membrane composition of breast tumour-derived exosomes.

Nanoscale. 2019 Dec 03;:

Authors: Skalska J, Oliveira FD, Figueira TN, Mello ÉO, Gomes VM, McNaughton-Smith G, Castanho MARB, Gaspar D

Abstract
One of the most important causes of failure in tumour treatment is the development of resistance to therapy. Cancer cells can develop the ability to lose sensitivity to anti-neoplastic drugs during reciprocal crosstalk between cells and their interaction with the tumour microenvironment (TME). Cell-to-cell communication regulates a cascade of interdependent events essential for disease development and progression and can be mediated by several signalling pathways. Exosome-mediated communication is one of the pathways regulating these events. Tumour-derived exosomes (TDE) are believed to have the ability to modulate TMEs and participate in multidrug resistance mechanisms. In this work, we studied the effect of the natural defensin from common bean, PvD1, on the formation of exosomes by breast cancer MCF-7 cells, mainly the modulatory effect it has on the level of CD63 and CD9 tetraspanins. Moreover, we followed the interaction of PvD1 with biological and model membranes of selected composition, by biophysical and imaging techniques. Overall, the results show that PvD1 induces a dual effect on MCF-7 derived exosomes: the peptide attenuates the recruitment of CD63 and CD9 to exosomes intracellularly and binds to the mature exosomes in the extracellular environment. This work uncovers the exosome-mediated anticancer action of PvD1, a potential nutraceutical agent.

PMID: 31793603 [PubMed - as supplied by publisher]

[Reduction of plasma procoagulant activity in patients with schizophrenia during pharmacotherapy: thrombodynamic parameters of coagulation before and after treatment].

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[Reduction of plasma procoagulant activity in patients with schizophrenia during pharmacotherapy: thrombodynamic parameters of coagulation before and after treatment].

Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(10):51-55

Authors: Brusov OS, Karpova NS, Faktor MI, Sizov SV, Oleichik IV

Abstract
AIM: To detect plasma procoagulant activity in patients with schizophrenia at admission to the hospital in a state of exacerbation before (point 1) and after (point 2) pharmacotherapy and evaluate plasma and platelet hemostasis abnormalities.
MATERIAL AND METHODS: The study included 80 women, aged from 16 to 57 years, median age 28 years, with schizophrenia with continuous, paroxysmal-progressive or paroxysmal course (F20.00, F20.01, F20.02 according to ICD-10). In 42 of 80 patients, depressive disorders in the structure of schizophrenia were observed. The thrombodynamic test (TD) was performed on T-2 Trombodynamis device according to the manufacturer's instructions (Hemacore LLC, Moscow, Russia). Blood for the TD test was taken in admission to the hospital (point 1) and on discharge (point 2). All patients received standard pharmacotherapy according to their condition.
RESULTS: For the first time, it was established that in the whole group of patients (n=46) thrombodynamic indicators of the rate of growth of the clot: initial velocity (Vin), stationary velocity (Vst) and adjusted for spontaneous clots velocity (V) and the amount of clot for 30 minutes test TD (ClotSize, CS) were significantly higher compared to normal values. The mean time of occurrence of spontaneous thrombosis (Tsp) was significantly less than 30 min (p<0.0001), indicating rapid, spontaneous thrombosis. Other parameters of TD did not differ significantly from the norm. As a result of treatment, the initial growth rate of the clot from the activator (Vi) decreased from 58,5 μm/min to 54,5 μm/min; V speed from 37,4 μm/min to 33,5 μm/min; CS clot size from 1249 μm to 1219 μm; clot density - from 24 874 units up to 23 658 units. All these changes are significant. Such dynamics of plasma hemostasis clearly indicates a significant decrease in the coagulation activity of the blood plasma of patients as a result of treatment. An increase in the time of appearance of spontaneous clots after treatment (from 23.5 minutes to 30.5 minutes) indicates a decrease in the procoagulant activity of platelet microparticles after treatment, i.e. the reduction of platelet activation as a result of treatment.
CONCLUSION: Our studies have shown for the first time that treatment of patients with antidepressants and antipsychotics reduces the generation of spontaneous clots. The treatment of patients with schizophrenia is accompanied by a decrease in the activity of plasma and platelet hemostasis. This is of great practical importance, since hypercoagulation of spontaneous clots in schizophrenic patients aggravates their chronic inflammatory disorders and affects their resistance to treatment.

PMID: 31793543 [PubMed - in process]

[Isolation and biological characteristics of exosomes derived from periodontal ligament stem cells].

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[Isolation and biological characteristics of exosomes derived from periodontal ligament stem cells].

Shanghai Kou Qiang Yi Xue. 2019 Aug;28(4):343-348

Authors: Zhao LR, Mao JQ, Zhao BJ, Chen J

Abstract
PURPOSE: To isolate and identify exosomes derived from periodontal ligament stem cells (PDLSCs) collected by ultracentrifugation.
METHODS: Using the limiting dilution technique, human PDLSCs were isolated and expanded. The cell culture supernatant of PDLSCs was collected. Exosomes were collected and purified with a ultracentrifugation method. Biological characteristics of exosomes derived from PDLSCs were measured by transmission electron microscopy (TEM), Western blot and nanosight tracing analysis (NTA).
RESULTS: Exosomes could be successfully isolated from the supernatant of PDLSCs by a ultracentrifugation method. Under TEM, the PDLSC-derived exosomes exhibited elliptic or saucer-like shape and the central area had lower electron density than the circum area. The PDLSC-derived exosomes could express the common surface adhesion molecules CD9, CD63, CD81 and TSG101. NTA results showed that the collected exosomes had a size around (119±12.1) nm and an approximate concentration of (3.80±0.39)×108 particles/mL.
CONCLUSIONS: Exosomes derived from PDLSCs can be collected by a ultracentrifugation method, which expresses common membrane proteins and morphological characteristics of exosomes.

PMID: 31792471 [PubMed - in process]

Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles.

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Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles.

Nat Commun. 2019 Dec 02;10(1):5476

Authors: Xie X, Nie H, Zhou Y, Lian S, Mei H, Lu Y, Dong H, Li F, Li T, Li B, Wang J, Lin M, Wang C, Shao J, Gao Y, Chen J, Xie F, Jia L

Abstract
There are disease-causing biohazards in the blood that cannot be treated with modern medicines. Here we show that an intelligently designed safe biomaterial can precisely identify, tow and dump a targeted biohazard from the blood into the small intestine. Positively charged mesoporous silica nanoparticles (MSNs) functionalized with EGFR-targeting aptamers (MSN-AP) specifically recognize and bind blood-borne negatively charged oncogenic exosomes (A-Exo), and tow A-Exo across hepatobiliary layers and Oddi's sphincter into the small intestine. MSN-AP specifically distinguish and bind A-Exo from interfering exosomes in cell culture and rat and patient blood to form MSN-AP and A-Exo conjugates (MSN-Exo) that transverse hepatocytes, cholangiocytes, and endothelial monolayers via endocytosis and exocytosis mechanisms, although Kupffer cells have been shown to engulf some MSN-Exo. Blood MSN-AP significantly decreased circulating A-Exo levels, sequentially increased intestinal A-Exo and attenuated A-Exo-induced lung metastasis in mice. This study opens an innovative avenue to relocate blood-borne life-threatening biohazards to the intestine.

PMID: 31792209 [PubMed - in process]

Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation.

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Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation.

Proc Natl Acad Sci U S A. 2019 Dec 02;:

Authors: Fisher JD, Balmert SC, Zhang W, Schweizer R, Schnider JT, Komatsu C, Dong L, Erbas VE, Unadkat JV, Aral AM, Acharya AP, Kulahci Y, Turnquist HR, Thomson AW, Solari MG, Gorantla VS, Little SR

Abstract
For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-β1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in allograft tissue. TRI-MP also enriched Treg and reduced inflammatory Th1 populations in allograft draining lymph nodes. This local immunotherapy imparted systemic donor-specific tolerance in otherwise immunocompetent rats, as evidenced by acceptance of secondary skin grafts from the hindlimb donor strain and rejection of skin grafts from a third-party donor strain. Ultimately, this therapeutic approach may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.

PMID: 31792185 [PubMed - as supplied by publisher]

Endothelium-mediated contributions to fibrosis.

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Endothelium-mediated contributions to fibrosis.

Semin Cell Dev Biol. 2019 Nov 29;:

Authors: Sun X, Nkennor B, Mastikhina O, Soon K, Nunes SS

Abstract
Fibrosis, characterized by abnormal and excessive deposition of extracellular matrix, results in compromised tissue and organ structure. This can lead to reduced organ function and eventual failure. Although activated fibroblasts, called myofibroblasts, are considered the central players in fibrosis, the contribution of endothelial cells to the inception and progression of fibrosis has become increasingly recognized. Endothelial cells can contribute to fibrosis by acting as a source of myofibroblasts via endothelial-mesenchymal transition (EndoMT), or by becoming senescent, by secretion of profibrotic mediators and pro-inflammatory cytokines, chemokines and exosomes, promoting the recruitment of immune cells, and by participating in vascular rarefaction and decreased angiogenesis. In this review, we provide an overview of the different aspects of fibrosis in which endothelial cells have been implicated.

PMID: 31791693 [PubMed - as supplied by publisher]

Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection.

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Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection.

Eur J Pharm Biopharm. 2019 Nov 29;:

Authors: Grenha A, Alves A, Guerreiro F, Pinho J, Simões S, José Almeida A, Manuela Gaspar M

Abstract
Tuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96.

PMID: 31790800 [PubMed - as supplied by publisher]

Generation, Purification and Engineering of Extracellular Vesicles and Their Biomedical Applications.

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Generation, Purification and Engineering of Extracellular Vesicles and Their Biomedical Applications.

Methods. 2019 Nov 29;:

Authors: Gao J, Dong X, Wang Z

Abstract
Extracellular vesicles (EVs), derived from cell membranes, demonstrate the potential to be excellent therapeutics and drug carriers. Although EVs are promising, the process to develop high-quality and scalable EVs for their translation is demanding. Within this research, we analyzed the production of EVs, their purification and their post-bioengineering, and we also discussed the biomedical applications of EVs. We focus on the developments of methods in producing EVs including biological, physical, and chemical approaches. Furthermore, we discuss the challenges and the opportunities that arose when we translated EVs in clinic. With the advancements in nanotechnology and immunology, genetically engineering EVs is a new frontier in developing new therapeutics in order to tailor to individuals and different disease stages in treatments of cancer and inflammatory diseases.

PMID: 31790730 [PubMed - as supplied by publisher]

Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH.

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Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH.

J Enzyme Inhib Med Chem. 2020 Dec;35(1):280-288

Authors: Logozzi M, Mizzoni D, Capasso C, Del Prete S, Di Raimo R, Falchi M, Angelini DF, Sciarra A, Maggi M, Supuran CT, Fais S

Abstract
Acidity, hypoxia and increased release of exosomes are severe phenotypes of tumours. The regulation of pH in tumours involves the interaction of several proteins, including the carbonic anhydrases which catalyze the formation of bicarbonate and protons from carbon dioxide and water. Among CA isoforms, CA IX is over-expressed in a large number of solid tumours, conferring to cancer cells a survival advantage in hypoxic and acidic microenvironment, but there isn't evidence that CA IX expression could have a real clinical impact. Therefore, in this study for the first time the expression and activity of CA IX have been investigated in the plasmatic exosomes obtained from patients with prostate carcinoma (PCa). For this purpose, the study was performed through different methodological approaches, such as NTA, western blot analysis, enzyme activity assay, Nanoscale flow cytometry, ELISA, confocal microscopy. The results showed that PCa exosomes significantly overexpressed CA IX levels and related activity as compared to healthy donors. Furthermore, CA IX expression and activity were correlated to the exosome intraluminal pH, demonstrating for the first time that PCa exosomes are acidic. Our data suggest the possible use of the exosomal CA IX expression and activity as a biomarker of cancer progression in PCa.

PMID: 31790614 [PubMed - in process]

Carbonic anhydrase IX as a novel candidate in liquid biopsy.

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Carbonic anhydrase IX as a novel candidate in liquid biopsy.

J Enzyme Inhib Med Chem. 2020 Dec;35(1):255-260

Authors: Ozensoy Guler O, Supuran CT, Capasso C

Abstract
Among the diagnostic techniques for the identification of tumour biomarkers, the liquid biopsy is considered one that offers future research on precision diagnosis and treatment of tumours in a non-invasive manner. The approach consists of isolating tumor-derived components, such as circulating tumour cells (CTC), tumour cell-free DNA (ctDNA), and extracellular vesicles (EVs), from the patient peripheral blood fluids. These elements constitute a source of genomic and proteomic information for cancer treatment. Within the tumour-derived components of the body fluids, the enzyme indicated with the acronym CA IX and belonging to the superfamily of carbonic anhydrases (CA, EC 4.2.1.1) is a promising aspirant for checking tumours. CA IX is a transmembrane-CA isoform that is strongly overexpressed in many cancers being not much diffused in healthy tissues except the gastrointestinal tract. Here, it is summarised the role of CA IX as tumour-associated protein and its putative relationship in liquid biopsyfor diagnosing and monitoring cancer progression.

PMID: 31790601 [PubMed - in process]

Presence of Tat and transactivation response element in spinal fluid despite antiretroviral therapy.

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Presence of Tat and transactivation response element in spinal fluid despite antiretroviral therapy.

AIDS. 2019 Dec 01;33 Suppl 2:S145-S157

Authors: Henderson LJ, Johnson TP, Smith BR, Reoma LB, Santamaria UA, Bachani M, Demarino C, Barclay RA, Snow J, Sacktor N, Mcarthur J, Letendre S, Steiner J, Kashanchi F, Nath A

Abstract
OBJECTIVE: The aim of this study was to measure the protein concentration and biological activity of HIV-1 Tat in cerebrospinal fluid (CSF) of individuals on suppressive antiretroviral therapy (ART).
DESIGN: CSF was collected from 68 HIV-positive individuals on ART with plasma viral load less than 40 copies/ml, and from 25 HIV-negative healthy controls. Duration of HIV infection ranged from 4 to more than 30 years.
METHODS: Tat levels in CSF were evaluated by an ELISA. Tat protein and viral RNA were quantified from exosomes isolated from CSF, followed by western blot or quantitative reverse transcription PCR, respectively. Functional activity of Tat was assessed using an LTR transactivation assay.
RESULTS: Tat protein was detected in 36.8% of CSF samples from HIV-positive patients. CSF Tat concentration increased in four out of five individuals after initiation of therapy, indicating that Tat was not inhibited by ART. Similarly, exosomes from 34.4% of CSF samples were strongly positive for Tat protein and/or TAR RNA. Exosomal Tat retained transactivation activity in a CEM-LTR reporter assay in 66.7% of samples assayed, which indicates that over half of the Tat present in CSF is functional. Presence of Tat in CSF was highly associated with previous abuse of psychostimulants (cocaine or amphetamines; P = 0.01) and worse performance in the psychomotor speed (P = 0.04) and information processing (P = 0.02) cognitive domains.
CONCLUSION: Tat and TAR are produced in the central nervous system despite adequate ART and are packaged into CSF exosomes. Tat remains biologically active within this compartment. These studies suggest that Tat may be a quantifiable marker of the viral reservoir and highlight a need for new therapies that directly inhibit Tat.

PMID: 31789815 [PubMed - in process]

Isolated tumour microparticles induce endothelial microparticle release in vitro.

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Isolated tumour microparticles induce endothelial microparticle release in vitro.

Blood Coagul Fibrinolysis. 2019 Nov 26;:

Authors: Faulkner LG, Alqarni S, Maraveyas A, Madden LA

Abstract
: Cancer induces a hypercoagulable state, resulting in an increased risk of venous thromboembolism. One of the mechanisms driving this is tissue factor (TF) production by the tumour, released in small lipid bound microparticles. We have previously demonstrated that tumour cell line media-induced procoagulant changes in HUVEC. The aim of this study was to investigate the effect of tumour microparticles and recombinant human TF (rhTF) on the endothelium. Procoagulant microparticles from the PANC-1 cell line were harvested by ultrafiltration. HUVEC were then incubated with these procoagulant microparticles or rhTF. Flow cytometry was used to investigate the effect of endothelial cell surface protein expression and microparticle release. Microparticles but not soluble TF was responsible for the procoagulant activity of cell-free tumour media. We also demonstrated an increase in endothelial microparticle release with exposure to tumour microparticles, with a positive linear relationship observed (R  = 0.6630 P ≤ 0.0001). rhTF did not induce any of the changes observed with microparticles. Here we demonstrate that procoagulant activity of tumour cell line media is dependent on microparticles, and that exposure of endothelial cells to these microparticles results in an increase in microparticle release from HUVEC. This suggests a mechanism of transfer of procoagulant potential from the cancer to the remote endothelium.

PMID: 31789658 [PubMed - as supplied by publisher]

Development of recyclable iron sulfides/selenides microparticles with high performance for elemental mercury capture from smelting flue gas over a wide temperature range.

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Development of recyclable iron sulfides/selenides microparticles with high performance for elemental mercury capture from smelting flue gas over a wide temperature range.

Environ Sci Technol. 2019 Dec 02;:

Authors: Liu Z, Li Z, Xie X, Yang S, Fei J, Li Y, Xu Z, Liu H

Abstract
Fast and effective removal of elemental mercury in a wide temperature range is critical for smelting industry. In this work, a recyclable magnetic iron sulfide/selenide sorbent is developed to capture and recover Hg0 from smelting flue gas. Benefiting from Se doping, the Hg0 capture performance of prepared FeSxSey is significantly enhanced compared with traditional iron sulfide, especially at high temperature. Considering the recyclability and working temperature, FeS1.32Se0.11 exhibits the best Hg0 capture performance. The average capture rate of FeS1.32Se0.11 is 3.661 μg/g/min at 80 °C and its saturation adsorption capacity is 20.216 mg/g. The flue gas compositions have almost no effect on Hg0 capture. XPS and Hg-TPD suggest the stable active Se-Sn2- adsorption site can combine with Hg0 to form HgSe, consequently improving Hg0 capture performance at high temperature. After Hg0 capture, the spent FeSxSey can be collected by magnetic separation and regenerated through selective extraction, which facilitates harmless treatment and resource reuse of mercury. With the advantages of excellent Hg0 capture performance, wide operating temperature range and remarkable recycling property, FeSxSey microparticles may be a promising sorbent for Hg0 capture in industrial application, while opening a new avenue to realize the resource utilization toward toxic elements.

PMID: 31789509 [PubMed - as supplied by publisher]

Tuning the Porosity of Supraparticles.

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Tuning the Porosity of Supraparticles.

ACS Nano. 2019 Dec 02;:

Authors: Liu W, Kappl M, Butt HJ

Abstract
Supraparticles consisting of nano- or microparticles have potential applications as e.g., photonic crystals, drug carriers, or heterogeneous catalysts. To avoid the use of solvent or processing liquid one can make supraparticles by evaporating droplets of aqueous suspensions from super-liquid-repellent surfaces. Herein, a method to adjust the porosity of supraparticles is described; a high porosity is desired, e.g., in catalysis. To prepare highly porous TiO2 supraparticles, polymer nanoparticles are co-dispersed in the suspension. Supraparticles are formed through evaporation of aqueous suspension droplets on superamphiphobic surfaces followed by calcination of the sacrificial polymer particles. The increase of porosity of up to 92%, resulted in enhanced photocatalytic activity while maintaining sufficient mechanical stability.

PMID: 31789496 [PubMed - as supplied by publisher]

Autologous tumor‑derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and cellular respiration in gastric cancer cells.

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Autologous tumor‑derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and cellular respiration in gastric cancer cells.

Int J Oncol. 2019 Nov 26;:

Authors: Szatanek R, Weglarczyk K, Stec M, Baran J, Parlinska-Wojtan M, Siedlar M, Baj-Krzyworzeka M

Abstract
Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, intercellular signaling and cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and cellular respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on cellular respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.

PMID: 31789386 [PubMed - as supplied by publisher]

Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair.

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Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair.

Nanomedicine (Lond). 2019 Dec 02;:

Authors: Liu C, Li Y, Yang Z, Zhou Z, Lou Z, Zhang Q

Abstract
The effectiveness of mesenchymal stem cells (MSC) in the treatment of cartilage diseases has been demonstrated to be attributed to the paracrine mechanisms, especially the mediation of exosomes. But the exosomes derived from unsynchronized MSCs may be nonhomogeneous and the therapeutic effect varies between samples. Aim: To produce homogeneous and more effective exosomes for the regeneration of cartilage. Materials & methods: In this study we produced specific exosomes from bone marrow MSCs (BMSC) through kartogenin (KGN) preconditioning and investigated their performance in either in vitro or in vivo experiments. Results & conclusion: The exosomes derived from KGN-preconditioned BMSCs (KGN-BMSC-Exos) performed more effectively than the exosomes derived from BMSCs (BMSC-Exos). KGN preconditioning endowed BMSC-Exos with stronger chondral matrix formation and less degradation.

PMID: 31789105 [PubMed - as supplied by publisher]

Three-Dimensional Culture of Oral Progenitor Cells: Effects on small extracellular vesicles production and proliferative function.

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Three-Dimensional Culture of Oral Progenitor Cells: Effects on small extracellular vesicles production and proliferative function.

J Oral Pathol Med. 2019 Dec 01;:

Authors: Yang Y, Knight R, Stephens P, Zhang Y

Abstract
BACKGROUND: Small extracellular vesicles (SEVs), have a diameter between 30-150nm and play a key role in cell-cell communication. As cells cultured in 3D versus 2D behave differently, this project aimed to assess whether there were differences in SEVs derived from human oral mucosa lamina propria-progenitor cells (OMLP-PCs) cultured in a 3D matrix compared to traditional 2D monolayer cultures.
METHODS: OMLP-PCs were cultured in 3D type I collagen matrices or on traditional 2D tissue culture plastic. Cell morphology and viability were assessed by light microscopy, actin staining and trypan blue staining. SEVs secreted by OMLP-PCs were purified and quantitatively analyzed by a BCA assay and nanoparticle tracking analysis (NTA; nanosight™). SEVs were further characterized by flow cytometry. SEV proliferative function was assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS: Cells cultured in 3D grew well as observed by light microscopy and phalloidin staining with cells branching in three-dimensions (as opposed to the cells grown as monolayers on tissue culture plastic). NTA demonstrated a significantly higher number of SEV-sized particles in the conditioned medium of cells grown in 3D type I collagen matrices versus a 2D monolayer (P<0.01). Like SEVs from 2D culture, SEVs from 3D culture demonstrated a particle size within the expected SEV range. Tetraspannin analysis confirmed that 3D-derived SEVs were positive for typical, expected tetraspannins. Cell proliferation analysis demonstrated that SEVs produced through 3D cell culture conditions, significantly reduced the proliferation of skin fibroblasts when compared to SEVs from 2D monolayers (P<0.05).
CONCLUSION: 3D culture of OMLP-PCs produced typical SEVs but in a greater amount than when the same cells were cultured in 2D. The downstream proliferative potential of the SEVs was influenced by the initial culture methodology. Future work should now assess the potential effects of 3D SEVs on key wound healing activities.

PMID: 31788854 [PubMed - as supplied by publisher]

Construction of hypervesiculation Escherichia coli strains and application for secretory protein production.

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Construction of hypervesiculation Escherichia coli strains and application for secretory protein production.

Biotechnol Bioeng. 2019 Dec 02;:

Authors: Ojima Y, Sawabe T, Konami K, Azuma M

Abstract
Outer membrane vesicles (OMVs) are extracellular vesicles released from the surface of Gram-negative bacteria, including Escherichia coli. Several gene-deficient mutants relating to envelope stress (nlpI and degP) and phospholipid accumulation in the outer leaflet of the outer membrane (mlaA and mlaE) increase OMV production. This study examined the combinatorial deletion of these genes in E. coli and its effect on OMV production. The nlpI and mlaE double-gene-knockout mutant (ΔmlaEΔnlpI) showed the highest OMV production. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis-based quantitative analysis showed that OMV production by strain ΔmlaEΔnlpI was ~30 times that by the wild-type. In addition, to evaluate the protein secretion capacity of OMVs, green fluorescent protein (GFP) fused with outer membrane protein W (OmpW) was expressed in OMVs. Western blot analysis showed that GFP secretion through OMVs reached 3.3 mg/L in the culture medium of strain ΔmlaEΔnlpI /gfp, 500 times that for the wild-type. Our approach using OMVs for extracellular protein secretion in E. coli is an entirely new concept compared with existing secretion systems. This article is protected by copyright. All rights reserved.

PMID: 31788781 [PubMed - as supplied by publisher]

Interplay between Exosomes and Autophagy in Cardiovascular Diseases: Novel Promising Target for Diagnostic and Therapeutic Application.

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Interplay between Exosomes and Autophagy in Cardiovascular Diseases: Novel Promising Target for Diagnostic and Therapeutic Application.

Aging Dis. 2019 Dec;10(6):1302-1310

Authors: Tian J, Popal MS, Zhao Y, Liu Y, Chen K, Liu Y

Abstract
Exosome, is identified as a nature nanocarrier and intercellular messenger that regulates cell to cell communication. Autophagy is critical in maintenance of protein homeostasis by degradation of damaged proteins and organelles. Autophagy and exosomes take pivotal roles in cellular homeostasis and cardiovascular disease. Currently, the coordinated mechanisms for exosomes and autophagy in the maintenance of cellular fitness are now garnering much attention. In the present review, we discussed the interplay of exosomes and autophagy in the context of physiology and pathology of the heart, which might provide novel insights for diagnostic and therapeutic application of cardiovascular diseases.

PMID: 31788341 [PubMed]

Gene expression and lifestyles.

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Gene expression and lifestyles.

Fertil Steril. 2019 08;112(2):245

Authors: Di Pietro C

PMID: 31200967 [PubMed - indexed for MEDLINE]

Exosomal miRNAs as Biomarkers of Cancer: a Meta-Analysis.

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Exosomal miRNAs as Biomarkers of Cancer: a Meta-Analysis.

Clin Lab. 2019 May 01;65(5):

Authors: Yang B, Xiong WY, Hou HJ, Xu Q, Cai XL, Zeng TX, Ha XQ

Abstract
BACKGROUND: Tumor-derived exosomal miRNAs secreted by cancer cells play significant roles in the pathological processes of cancer, but no systematic meta-analysis has focused on the diagnostic efficiency of exosomal miRNAs. This meta-analysis assessed the diagnostic value of circulating exosomal miRNA in cancer.
METHODS: Studies evaluating the diagnostic value of exosomal miRNA were identified in EMBASE, PubMed, Cochrane Library, and Web of Science up to August 1, 2018. The quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2, and STATA 14.0 was used for the analyses. The true positive (TP), false positive (FP), true negative (TN), and false negative (FN) rates were extracted from each study to obtain the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CIs).
RESULTS: The meta-analysis included 16 studies with 1,591 patients. Five studies reported sensitivity values, and the pooled sensitivity was 0.86 (95% CI = 0.80 - 0.90, while 29 studies reported specificity values, and the pooled specificity was 0.89 (95% CI = 0.83 - 0.93). The pooled PLR was 7.8 (95% CI = 4.9 - 12.4), the pooled NLR was 0.16 (95% CI = 0.11 - 0.24), the pooled DOR was 48 (95% CI = 23 - 101), and the AUC was 0.94 (0.91 - 0.96).
CONCLUSIONS: Our meta-analysis indicated that body fluid exosomal miRNAs are highly accurate for distinguishing patients from healthy individuals, and exosomal miRNAs have superior diagnostic value in plasma, prostate cancer patients, and non-Asian individuals.

PMID: 31115208 [PubMed - indexed for MEDLINE]

The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.

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The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.

Cell Rep. 2018 05 15;23(7):2199-2210

Authors: Silla T, Karadoulama E, Mąkosa D, Lubas M, Jensen TH

Abstract
Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear pA+ RNA retention factor, counteracting nuclear export activity.

PMID: 29768216 [PubMed - indexed for MEDLINE]

 

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