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

Exosomes with miR-574 transfer anti-HBV activity mediated by the interferon from macrophage to HBV-infected hepatocyte.

-

Related Articles

Exosomes with miR-574 transfer anti-HBV activity mediated by the interferon from macrophage to HBV-infected hepatocyte.

J Infect Dis. 2020 Jul 15;:

Authors: Wu W, Wu D, Yan W, Wang Y, You J, Wan X, Xi D, Luo X, Han M, Ning Q

Abstract
BACKGROUND: Interferon alpha (IFN-α) has been proven effective in treating chronic hepatitis B (CHB) due to its capability to suppress hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). However, the underlying mechanisms are blurred.
METHODS: We investigated the antiviral activities of exosomes from responders and non-responders to pegylated IFN-α (PegIFN-α) as well as the supernatants of IFN-α-treated THP-1 (the human leukemia monocyte cell line) derived macrophages. Then the expression profiles of exosomal microRNAs (miRNAs) were analyzed using miRNA sequencing. The luciferase reporter assay was used to locate the binding position of HBV genomic sequence targeted by the identified miRNA.
RESULTS: Exosomes from PegIFN-α treated patients particularly responders as well as the supernatants of IFN-α-treated macrophages exhibited anti-HBV activities as manifested by the suppression of HBsAg, hepatitis B e antigen (HBeAg), HBV DNA and cccDNA levels in HBV related cell lines. PegIFN-α treatment upregulated exosomal hsa-miR-193a-5p, hsa-miR-25-5p, and hsa-miR-574-5p that could partially inhibit HBV replication and transcription. Hsa-miR-574-5p reduced pgRNA and polymerase mRNA levels by binding to the 2750-2757 position of HBV genomic sequence.
CONCLUSIONS: Exosomes can transfer IFN-α-related miRNAs from macrophages to HBV-infected hepatocytes, and exhibit antiviral activities against HBV replication and expression.

PMID: 32663850 [PubMed - as supplied by publisher]

Maternal diabetes alters microRNA expression in fetal exosomes, human umbilical vein endothelial cells and placenta.

-

Related Articles

Maternal diabetes alters microRNA expression in fetal exosomes, human umbilical vein endothelial cells and placenta.

Pediatr Res. 2020 Jul 14;:

Authors: Shah KB, Chernausek SD, Teague AM, Bard DE, Tryggestad JB

Abstract
BACKGROUND: Exposure to diabetes in utero influences future metabolic health of the offspring. MicroRNAs (miRNA) are small noncoding RNAs that may contribute mechanistically to the effects on offspring imparted by diabetes mellitus (DM) during pregnancy. We hypothesized that exposure to DM during pregnancy influences select miRNAs in fetal circulation, in human umbilical vein endothelial cells (HUVEC), and placenta.
METHODS: miRNA abundance was quantified using real-time PCR from RNA isolated from umbilical cord serum exosomes, HUVEC, and placenta exposed to diabetes or normoglycemia during pregnancy. The abundance of each of these miRNAs was determined by comparison to a known standard and the relative expression assessed using the 2-ΔΔCt method. Multivariable regression models examined the associations between exposure to diabetes during pregnancy and miRNA expression.
RESULTS: miR-126-3p was highly abundant in fetal circulation, HUVEC, and placenta. Diabetes exposure during pregnancy resulted in lower expression of miR-148a-3p and miR-29a-3p in the HUVEC. In the placenta, for miR-126-3p, there was a differential effect of DM by birth weight between DM versus control group, expression being lower at the lower birth weight, however not different at the higher birth weight.
CONCLUSION: Exposure to DM during pregnancy alters miRNA expression in the offspring in a tissue-specific manner.
IMPACT: miRNAs are differentially expressed in fetal tissues from offspring exposed to in utero diabetes mellitus compared to those who were not exposed.miRNA expression differs among tissue types (human umbilical vein endothelial cells, placenta and circulation exosomes) and response to diabetes exposure varies according to tissue of origin.miRNA expression is also affected by maternal and infant characteristics such as infant birth weight, infant sex, maternal age, and maternal BMI.miRNAs might be one of the potential mechanisms by which offspring's future metabolic status may be influenced by maternal diabetes mellitus.

PMID: 32663836 [PubMed - as supplied by publisher]

Particulate plutonium released from the Fukushima Daiichi meltdowns.

-

Related Articles

Particulate plutonium released from the Fukushima Daiichi meltdowns.

Sci Total Environ. 2020 Jul 08;743:140539

Authors: Kurihara E, Takehara M, Suetake M, Ikehara R, Komiya T, Morooka K, Takami R, Yamasaki S, Ohnuki T, Horie K, Takehara M, Law GTW, Bower W, W Mosselmans JF, Warnicke P, Grambow B, Ewing RC, Utsunomiya S

Abstract
Traces of Pu have been detected in material released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) in March of 2011; however, to date the physical and chemical form of the Pu have remained unknown. Here we report the discovery of particulate Pu associated with cesium-rich microparticles (CsMPs) that formed in and were released from the reactors during the FDNPP meltdowns. The Cs-pollucite-based CsMP contained discrete U(IV)O2 nanoparticles, <~10 nm, one of which is enriched in Pu adjacent to fragments of Zr-cladding. The isotope ratios, 235U/238U, 240Pu/239Pu, and 242Pu/239Pu, of the CsMPs were determined to be ~0.0193, ~0.347, and ~0.065, respectively, which are consistent with the calculated isotopic ratios of irradiated-fuel fragments. Thus, considering the regional distribution of CsMPs, the long-distance dispersion of Pu from FNDPP is attributed to the transport by CsMPs that have incorporated nanoscale fuel fragments prior to their dispersion up to 230 km away from the Fukushima Daiichi reactor site.

PMID: 32663681 [PubMed - as supplied by publisher]

PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression.

-

Related Articles

PSMD11, PTPRM and PTPRB as novel biomarkers of pancreatic cancer progression.

Biochim Biophys Acta Gen Subj. 2020 Jul 11;:129682

Authors: Sahni S, Krisp C, Molloy MP, Nahm C, Maloney S, Gillson J, Gill AJ, Samra J, Mittal A

Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Surgery is the only curative intent therapy, but the majority of patients experience disease relapse. Thus, patients who do not benefit from highly morbid surgical resection needs to be identified and offered palliative chemotherapy instead. In this pilot study, we aimed to identify differentially regulated proteins in plasma and plasma derived microparticles from PDAC patients with poor and good prognosis.
METHODS: Plasma and plasma derived microparticle samples were obtained before surgical resection from PDAC patients. Sequential Windowed Acquisition of all Theoretical fragment ion spectra - Mass Spectrometry (SWATH-MS) proteomic analysis was performed to identify and quantify proteins in these samples. Statistical analysis was performed to identify biomarkers for poor prognosis.
RESULTS: A total of 482 and 1024 proteins were identified from plasma and microparticle samples, respectively, by SWATH-MS analysis. Statistical analysis of the data further identified nine and six differentially (log2ratio > 1, p < .05) expressed proteins in plasma and microparticles, respectively. Protein tyrosine phosphatases, PTPRM and PTPRB, were decreased in plasma of patients with poor PDAC prognosis, while proteasomal subunit PSMD11 was increased in microparticles of patients with poor prognosis.
CONCLUSION AND GENERAL SIGNIFICANCE: A novel blood-based biomarker signature for PDAC prognosis was identified.

PMID: 32663515 [PubMed - as supplied by publisher]

Magnetically collectable nanocellulose-coated polymer microparticles by emulsion templating.

-

Related Articles

Magnetically collectable nanocellulose-coated polymer microparticles by emulsion templating.

Langmuir. 2020 Jul 14;:

Authors: Fujisawa S, Kaku Y, Kimura S, Saito T

Abstract
Magnetic nano/microparticles offer potential benefits for environmental applications such as water purification. However, achieving functional and stable surfaces remains a critical challenge of magnetic particle design. Nanocellulose, a naturally occurring nanofiber, is a promising surface material candidate owing to its ease of functionalization and chemical stability. Here, we developed a magnetically collectable nanocellulose-coated polymer microparticle synthesis, based on Pickering emulsion templating. The average diameter of the core/shell microparticles was 2.7 μm, and they were well dispersed in water owing to the coverage with surface-carboxylated nanocelluloses. Magnetic Fe3O4 nanoparticles with 30 nm diameter were enriched at CNF/polymer interfaces, and most of the nanoparticles were encapsulated in the polymer core. The nanocellulose shell showed high loading of cationic dye molecules. In addition, the nanocellulose-coated microparticles could be recovered even after the dye loading, by exposing the aqueous dispersion to a magnetic field.

PMID: 32663405 [PubMed - as supplied by publisher]

Exosomal LINC01005 derived from oxidized low-density lipoprotein-treated endothelial cells regulates vascular smooth muscle cell phenotypic switch.

-

Related Articles

Exosomal LINC01005 derived from oxidized low-density lipoprotein-treated endothelial cells regulates vascular smooth muscle cell phenotypic switch.

Biofactors. 2020 Jul 14;:

Authors: Zhang Z, Yi D, Zhou J, Zheng Y, Gao Z, Hu X, Ying G, Peng X, Wen T

Abstract
Phenotype switch of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis (AS). Endothelial cells can regulate VSMC phenotypic switch by secreting exosomes, crucial mediators of intracellular communication. This study aimed to determine whether exosomal LINC01005 from oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) plays a role in regulating VSMC phenotypic switch and to validate the underlying molecular mechanism. Exosomes were extracted from ox-LDL-treated HUVECs (ox-LDL-Exo) and then administered into VSMCs. VSMC phenotypic switch was assessed by determining VSMC phenotypic markers using western blot. VSMC cell proliferation and migration were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and wound healing assay, respectively. The interaction between miR-128-3p and LINC01005 or Krüppel-like factor 4 (KLF4) was analyzed by luciferase reporter assay. ox-LDL-Exo contained high expression of LINC01005. Inhibition of LINC01005 expression in ox-LDL-Exo abrogated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Furthermore, LINC01005 acted as a sponge of miR-128-3p to upregulate KLF4 expression. Moreover, miR-128-3p overexpression and KLF4 silencing in VSMCs attenuated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Collectively, exosomal LINC01005 from ox-LDL-treated HUVECs promotes VSMC phenotype switch, proliferation, and migration by regulating the miR-128-3p/KLF4 axis.

PMID: 32663367 [PubMed - as supplied by publisher]

Factors influencing the measurement of the secretion rate of extracellular vesicles.

-

Related Articles

Factors influencing the measurement of the secretion rate of extracellular vesicles.

Analyst. 2020 Jul 14;:

Authors: Wen Y, Chen Y, Wang G, Abhange K, Xue F, Quinn Z, Mao W, Wan Y

Abstract
Extracellular vesicles (EVs) are cell-derived vesicles which encapsulate a variety of molecules. Numerous studies have demonstrated EVs as signaling mediators of intercellular communication and are heavily involved under physiological and pathological conditions. In translational medicine, EVs have been used for disease diagnosis and treatment monitoring. EVs as natural nanocarriers for drug delivery and therapeutic EVs are also under intense investigation. While still in its infancy, relevant EV studies have been growing. For EV-centered research to thrive, a few fundamental unanswered questions, such as EV biogenesis, EV secretion rate (SR), EV content sorting mechanisms, etc. require further investigation. In this study, we measured the SR of EVs derived from 6 cancerous cell lines. Several factors that may interfere with EV secretion, isolation, and storage were also investigated. Our results show that the SR of EVs derived from various cancer cells was significantly different, indicating a heterogeneous EV secretion behavior among cell types. Moreover, 5 different drugs that interfere with cellular metabolism significantly influenced EV release. In addition, we found that (1) more EVs can be harvested at 24 h compared to 48 h of serum-free cell culture with a similar degree of FBS contamination; (2) filtration of the cell culture supernatant with a 0.22 μm filter causes ∼70% loss of EVs; (3) the isolation efficiency of EVs with the prevalent ultracentrifugation is only ∼14%; (4) storage at 4 °C for 3 days causes ∼21% loss of EVs. Overall, our findings provide a guideline for proper EV collection and storage in laboratory settings.

PMID: 32662497 [PubMed - as supplied by publisher]

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19.

-

Related Articles

Mesenchymal Stem Cell Derived Exosomes: a Nano Platform for Therapeutics and Drug Delivery in Combating COVID-19.

Stem Cell Rev Rep. 2020 Jul 13;:

Authors: Pinky, Gupta S, Krishnakumar V, Sharma Y, Dinda AK, Mohanty S

Abstract
The recent pandemic situation transpired due to coronavirus novel strain SARS-CoV-2 has become a global concern. This human coronavirus (HCov-19) has put the world on high alert as the numbers of confirmed cases are continuously increasing. The world is now fighting against this deadly virus and is leaving no stone unturned to find effective treatments through testing of various available drugs, including those effective against flu, malaria, etc. With an urgent need for the development of potential strategies, two recent studies from China using Mesenchymal Stem Cells (MSCs) to treat COVID-19 pneumonia have shed some light on a potential cure for the COVID-19 infected patients. However, MSCs, despite being used in various other clinical trials have always been questioned for their tendency to aggregate or form clumps in the injured or disease microenvironment. It has also been reported in various studies that exosomes secreted by these MSCs, contribute towards the cell's biological and therapeutic efficacy. There have been reports evaluating the safety and feasibility of these exosomes in various lung diseases, thereby proposing them as a cell-free therapeutic agent. Also, attractive features like cell targeting, low-immunogenicity, safety, and high biocompatibility distinguish these exosomes from other synthetic nano-vesicles and thus potentiate their role as a drug delivery nano-platform. Building upon these observations, herein, efforts are made to give an overview of stem cell-derived exosomes as an appealing therapeutic agent and drug delivery nano-carrier. In this review, we briefly recapitulate the recent evidence and developments in understanding exosomes as a promising candidate for novel nano-intervention in the current pandemic scenario. Furthermore, this review will highlight and discuss mechanistic role of exosomes to combat severe lung pathological conditions. We have also attempted to dwell into the nano-formulation of exosomes for its better applicability, storage, and stability thereby conferring them as off the shelf therapeutic.

PMID: 32661867 [PubMed - as supplied by publisher]

Ultrasonic microstreaming for complex-trajectory transport and rotation of single particles and cells.

-

Related Articles

Ultrasonic microstreaming for complex-trajectory transport and rotation of single particles and cells.

Lab Chip. 2020 Jul 14;:

Authors: Ma Z, Zhou Y, Cai F, Meng L, Zheng H, Ai Y

Abstract
Precisely controllable transport and rotation of microparticles and cells has great potential to enable new capabilities for single-cell level analysis. In this work, we present versatile ultrasonic microstreaming based manipulation that enables active and precise control of transport and rotation of individual microscale particles and biological cells in a microfluidic device. Two different types of ultrasonic microstreaming flow patterns can be produced by oscillating embedded microstructures in circular and rectilinear vibration modes, which have been validated by both numerical simulation and experimental observation. We have further showcased the ability to transport individual microparticles along the outlines of complex alphabet letters, demonstrating the versatility and simplicity of single-particle level manipulation with bulk vibration.

PMID: 32661536 [PubMed - as supplied by publisher]

Small extracellular vesicles combat senescence.

-

Related Articles

Small extracellular vesicles combat senescence.

Nat Rev Mol Cell Biol. 2020 Jul 13;:

Authors: Melidoni A

PMID: 32661343 [PubMed - as supplied by publisher]

Chemotherapeutic tumor microparticles elicit a neutrophil response targeting malignant pleural effusions.

-

Related Articles

Chemotherapeutic tumor microparticles elicit a neutrophil response targeting malignant pleural effusions.

Cancer Immunol Res. 2020 Jul 13;:

Authors: Xu P, Tang K, Ma J, Zhang H, Wang D, Zhu L, Chen J, Wei K, Liu J, Fang H, Tang L, Zhang Y, Xie J, Liu Y, Meng R, Liu L, Dong X, Yang K, Wu G, Ma F, Huang B

Abstract
Malignant pleural effusion (MPE) is a frequent complication of various cancers and often leads to a poor quality of life, prognosis, and life expectancy, and its management remains palliative. New approaches that can effectively treat MPE are highly desirable. Here, we show that methotrexate (MTX)-packaging, tumor cell-derived microparticles (MTX-MP) act as an effective immunotherapeutic agent to treat patients with MPE by mobilizing and activating neutrophils. We find that MTX-MPs perfusion via a pleural catheter elicits the recruitment of neutrophils in patients through macrophage-released CXCL1 and CXCL2. By performing ex vivo experiments, we find that the recruited neutrophils are activated and release reactive oxygen species (ROS) and neutrophil extracellular trap (NET) to kill tumor cells. Neutrophil-released NETs were also able to seal-off the damaged endothelium, facilitating MPE resolution in vitro and in tumor-bearing mice. These findings reveal the potential for use of cell-derived materials to package drugs as an immunotherapeutic agent against MPE.

PMID: 32661094 [PubMed - as supplied by publisher]

Circulating miRNAs as Biomarkers in Aggressive B Cell Lymphomas.

-

Related Articles

Circulating miRNAs as Biomarkers in Aggressive B Cell Lymphomas.

Trends Cancer. 2020 Jul 10;:

Authors: Drees EEE, Pegtel DM

Abstract
B cell lymphomas are heterogeneous malignancies of hematological origin with vastly different biology and clinical outcomes. Histopathology of tissue biopsies and image-based assessment guide clinical decisions. Given that tissue biopsies cannot be frequently repeated and will not inform on systemic responses to the treatment, more accessible biomarkers, such as circulating miRNAs, are considered. Aberrant miRNA expression in lymphoma tissues and ongoing immune reactions may lead to miRNA alterations in circulation. miRNAs bound to extracellular vesicles (EVs) are of interest because of their role in intercellular communication and organ crosstalk. Herein, we highlight the role of miRNAs and EVs in B cell lymphomagenesis and explain how circulating miRNAs may be turned into robust liquid biopsy tests for aggressive B cell lymphoma.

PMID: 32660885 [PubMed - as supplied by publisher]

Periprosthetic Osteolysis by Microparticles Mimicking a Tumour Process in the Right Hip in 18F-FDG PET/CT Study.

-

Related Articles

Periprosthetic Osteolysis by Microparticles Mimicking a Tumour Process in the Right Hip in 18F-FDG PET/CT Study.

Reumatol Clin. 2020 Jul 10;:

Authors: Espinosa Muñoz E, Gutiérrez Cardo AL, Puentes Zarzuela C

PMID: 32660836 [PubMed - as supplied by publisher]

TiO2 genotoxicity: An update of the results published over the last six years.

-

Related Articles

TiO2 genotoxicity: An update of the results published over the last six years.

Mutat Res. 2020 Jun - Jul;854-855:503198

Authors: Carriere M, Arnal ME, Douki T

Abstract
TiO2 particles are broadly used in daily products, including cosmetics for their UV-absorbing property, food for their white colouring property, water and air purification systems, self-cleaning surfaces and photoconversion electrical devices for their photocatalytic properties. The toxicity of TiO2 nano- and microparticles has been studied for decades, and part of this investigation has been dedicated to the identification of their potential impact on DNA, i.e., their genotoxicity. This review summarizes data retrieved from their genotoxicity testing during the past 6 years, encompassing both in vitro and in vivo studies, mostly performed on lung and intestinal models. It shows that TiO2 particles, both nano- and micro-sized, produce genotoxic damage to a variety of cell types, even at low, realistic doses.

PMID: 32660822 [PubMed - in process]

M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade.

-

Related Articles

M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade.

J Exp Clin Cancer Res. 2020 Jul 13;39(1):134

Authors: Zhang Y, Meng W, Yue P, Li X

Abstract
BACKGROUND: Transfer of noncoding microRNAs (miRNAs) by extracellular vesicles (EVs) promotes the development of chemoresistance in many tumor types. Additionally, restoration or depletion of several miRNAs has been observed in multiple cancer types including gastric cancer (GC). In this present study, we aimed to investigate the mechanism of miR-130b-3p in M2 macrophage-derived EVs in the development of GC through regulation of mixed lineage leukemia 3 (MLL3) and grainyhead-like 2 (GRHL2).
METHODS: Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. The predicted binding between miR-130b-3p and MLL3, together with the enrichment of MLL3, H3K4me1, and H3K27ac in gene enhancer region, was verified by luciferase activity assay and chromatin immunoprecipitation. Effects of miR-130b-3p on GC cell proliferation, apoptosis, migration and invasion, as well as tube formation of human umbilical endothelial vein cells (HUEVCs) were further determined by gain- and loss-of function assays in vitro.
RESULTS: miR-130b-3p was upregulated in GC tissues, and miR-130b-3p promoted survival, metastasis and angiogenesis of GC cells as well as enhanced tumor formation and angiogenesis in GC in vivo. Additionally, miR-130b-3p delivered in M2 macrophage-derived EVs promoted survival, migration, invasion, and angiogenesis of GC cells. Notably, MLL3 inhibited GC cell proliferation, migration, invasion, and vessel-like tube formation of HUEVCs by increasing GRHL2. Furthermore, downregulation of miR-130b-3p in M2 macrophage-derived EVs or upregulation of GRHL2 inhibited tumor formation and angiogenesis in GC.
CONCLUSION: This study highlights that EVs loaded with the specific miRNA cargo miR-130b-3p mediate communication between M2 macrophages and cancer cells in the tumor microenvironment through the modulation of MLL3 and GRHL2 in GC.

PMID: 32660626 [PubMed - in process]

Biodegradation of Crystalline Cellulose Nanofibers by Means of Enzyme Immobilized-Alginate Beads and Microparticles.

-

Related Articles

Biodegradation of Crystalline Cellulose Nanofibers by Means of Enzyme Immobilized-Alginate Beads and Microparticles.

Polymers (Basel). 2020 Jul 09;12(7):

Authors: Kamdem Tamo A, Doench I, Morales Helguera A, Hoenders D, Walther A, Madrazo AO

Abstract
Recent advances in nanocellulose technology have revealed the potential of crystalline cellulose nanofibers to reinforce materials which are useful for tissue engineering, among other functions. However, the low biodegradability of nanocellulose can possess some problems in biomedical applications. In this work, alginate particles with encapsulated enzyme cellulase extracted from Trichoderma reesei were prepared for the biodegradation of crystalline cellulose nanofibers, which carrier system could be incorporated in tissue engineering biomaterials to degrade the crystalline cellulose nanoreinforcement in situ and on-demand during tissue regeneration. Both alginate beads and microparticles were processed by extrusion-dropping and inkjet-based methods, respectively. Processing parameters like the alginate concentration, concentration of ionic crosslinker Ca2+, hardening time, and ionic strength of the medium were varied. The hydrolytic activity of the free and encapsulated enzyme was evaluated for unmodified (CNFs) and TEMPO-oxidized cellulose nanofibers (TOCNFs) in suspension (heterogeneous conditions); in comparison to solubilized cellulose derivatives (homogeneous conditions). The enzymatic activity was evaluated for temperatures between 25-75 °C, pH range from 3.5 to 8.0 and incubation times until 21 d. Encapsulated cellulase in general displayed higher activity compared to the free enzyme over wider temperature and pH ranges and for longer incubation times. A statistical design allowed optimizing the processing parameters for the preparation of enzyme-encapsulated alginate particles presenting the highest enzymatic activity and sphericity. The statistical analysis yielded the optimum particles characteristics and properties by using a formulation of 2% (w/v) alginate, a coagulation bath of 0.2 M CaCl2 and a hardening time of 1 h. In homogeneous conditions the highest catalytic activity was obtained at 55 °C and pH 4.8. These temperature and pH values were considered to study the biodegradation of the crystalline cellulose nanofibers in suspension. The encapsulated cellulase preserved its activity for several weeks over that of the free enzyme, which latter considerably decreased and practically showed deactivation after just 10 d. The alginate microparticles with their high surface area-to-volume ratio effectively allowed the controlled release of the encapsulated enzyme and thereby the sustained hydrolysis of the cellulose nanofibers. The relative activity of cellulase encapsulated in the microparticles leveled-off at around 60% after one day and practically remained at that value for three weeks.

PMID: 32660071 [PubMed]

A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies.

-

Related Articles

A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies.

Cancers (Basel). 2020 Jul 09;12(7):

Authors: Forterre A, Komuro H, Aminova S, Harada M

Abstract
In the field of molecular oncology, microRNAs (miRNAs) and their role in regulating physiological processes and cancer pathogenesis have been a revolutionary discovery over the last decade. It is now considered that miRNA dysregulation influences critical molecular pathways involved in tumor progression, invasion, angiogenesis and metastasis in a wide range of cancer types. Hence, altering miRNA levels in cancer cells has promising potential as a therapeutic intervention, which is discussed in many other articles in this Special Issue. Some of the most significant hurdles in therapeutic miRNA usage are the stability and the delivery system. In this review, we cover a comprehensive update on the challenges and strategies for the development of therapeutic miRNA delivery systems that includes virus-based delivery, non-viral delivery (artificial lipid-based vesicles, polymer-based or chemical structures), and recently emerged extracellular vesicle (EV)-based delivery systems.

PMID: 32660045 [PubMed]

Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity.

-

Related Articles

Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity.

Pharmaceutics. 2020 Jul 09;12(7):

Authors: Alhakamy NA, Ahmed OAA, Kurakula M, Caruso G, Caraci F, Asfour HZ, Alfarsi A, Eid BG, Mohamed AI, Alruwaili NK, Abdulaal WH, Fahmy UA, Alhadrami HA, Eldakhakhny BM, Abdel-Naim AB

Abstract
This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA.

PMID: 32660035 [PubMed]

Diagnostic Value of Circulating miR-202 in Early-Stage Breast Cancer in South Korea.

-

Related Articles

Diagnostic Value of Circulating miR-202 in Early-Stage Breast Cancer in South Korea.

Medicina (Kaunas). 2020 Jul 09;56(7):

Authors: Kim J, Park S, Hwang D, Kim SI, Lee H

Abstract
Background and objectives: Breast cancer is the most common cancer among women worldwide. Early stage diagnosis is important for predicting increases in treatment success rates and decreases in patient mortality. Recently, circulating biomarkers such as circulating tumor cells, circulating tumor DNA, exosomes, and circulating microRNAs have been examined as blood-based markers for the diagnosis of breast cancer. Although miR-202 has been studied for its function or expression in breast cancer, its potential diagnostic value in a clinical setting remains elusive and miR-202 has not been investigated in South Korea. In this study, we aimed to evaluate the diagnostic utility of miR-202 in plasma samples of breast cancer patients in South Korea. Materials and Methods: We investigated miR-202 expression in the plasma of 30 breast cancer patients during diagnosis along with 30 healthy controls in South Korea by quantitative reverse transcription PCR. Results: The results showed that circulating miR-202 levels were significantly elevated in the breast cancer patients compared with those in healthy controls (p < 0.001). The sensitivity and specificity of circulating miR-202 were 90.0% and 93.0%, respectively. Additionally, circulating miR-202 showed high positivity at early stage. The positive rate of miR-202 was as follows: 100% (10/10) for stage I, 90% (9/10) for stage II, and 80% (8/10) for stage III. miR-202 was also a predictor of a 9.6-fold high risk for breast cancer (p < 0.001). Conclusions: Additional alternative molecular biomarkers for diagnosis and management of pre-cancer patients are needed. Circulating miR-202 might be potential diagnostic tool for detecting early stage breast cancer.

PMID: 32659906 [PubMed - in process]

Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes.

-

Related Articles

Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes.

Cells. 2020 Jul 09;9(7):

Authors: Takeda Y, Kobayashi S, Kitakaze M, Yamada D, Akita H, Asai A, Konno M, Arai T, Kitagawa T, Ofusa K, Yabumoto M, Hirotsu T, Vecchione A, Taniguchi M, Doki Y, Eguchi H, Ishii H

Abstract
Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on their inside and express proteins and glycolipids on their outsides, every component of which plays a role in the transmission of genetic and/or epigenetic information in cell-to-cell communications. It is also known that miRNAs are involved in the signal transduction. Thus, EXs may be useful for monitoring the TME of tumor tissues and the invasion and metastasis, processes that are associated with patient survival. Because several solid tumors secrete immune checkpoint proteins, including programmed cell death-ligand 1, the EX-mediated mechanisms are suggested to be potent targets for monitoring patients. Therefore, a companion therapeutic approach against cancer metastasis to distant organs is proposed when surgical removal of the primary tumor is performed. However, EXs and immune checkpoint mechanisms in pancreatic cancer are not fully understood, we provide an update on the recent advances in this field and evidence that EXs will be useful for maximizing patient benefit in precision medicine.

PMID: 32659892 [PubMed - in process]

Extraction of mRNA from Stalled Ribosomes by the Ski Complex.

-

Icon for Elsevier Science Related Articles

Extraction of mRNA from Stalled Ribosomes by the Ski Complex.

Mol Cell. 2020 03 19;77(6):1340-1349.e6

Authors: Zinoviev A, Ayupov RK, Abaeva IS, Hellen CUT, Pestova TV

Abstract
The evolutionarily conserved Ski2-Ski3-Ski8 (Ski) complex containing the 3'→5' RNA helicase Ski2 binds to 80S ribosomes near the mRNA entrance and facilitates 3'→5' exosomal degradation of mRNA during ribosome-associated mRNA surveillance pathways. Here, we assayed Ski's activity using an in vitro reconstituted translation system and report that this complex efficiently extracts mRNA from 80S ribosomes in the 3'→5' direction in a nucleotide-by-nucleotide manner. The process is ATP dependent and can occur on pre- and post-translocation ribosomal complexes. The Ski complex can engage productively with mRNA and extract it from 80S complexes containing as few as 19 (but not 13) 3'-terminal mRNA nucleotides starting from the P site. The mRNA-extracting activity of the Ski complex suggests that its role in mRNA quality control pathways is not limited to acceleration of exosomal degradation and could include clearance of stalled ribosomes from mRNA, poising mRNA for degradation and rendering stalled ribosomes recyclable by Pelota/Hbs1/ABCE1.

PMID: 32006463 [PubMed - indexed for MEDLINE]

Toward standardization of assays measuring extracellular vesicle-associated tissue factor activity.

-

Icon for Wiley Icon for PubMed Central Related Articles

Toward standardization of assays measuring extracellular vesicle-associated tissue factor activity.

J Thromb Haemost. 2019 08;17(8):1261-1264

Authors: Nieuwland R, Gardiner C, Dignat-George F, Mullier F, Mackman N, Woodhams B, Thaler J

PMID: 31231949 [PubMed - indexed for MEDLINE]