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Stem Cell Research & Therapy Aug 2020Myocardial infarction (MI) is a severe disease that often associated with dysfunction of angiogenesis. Cell-based therapies for MI using mesenchymal stem cell...
BACKGROUND
Myocardial infarction (MI) is a severe disease that often associated with dysfunction of angiogenesis. Cell-based therapies for MI using mesenchymal stem cell (MSC)-derived exosomes have been well studied due to their strong proangiogenic effect. Genetic modification is one of the most common methods to enhance exosome therapy. This study investigated the proangiogenic and cardioprotective effect of exosomes derived from hypoxia-inducible factor 1-alpha (HIF-1α)-modified MSCs.
METHODS
Lentivirus containing HIF-1α overexpressing vector was packaged and used to infect MSCs. Exosomes were isolated from MSC-conditioned medium by ultracentrifugation. Human umbilical vein endothelial cells (HUVECs) were treated under hypoxia condition for 48 h co-cultured with PBS, control exosomes, or HIF-1α-overexpressed exosomes, respectively. Then the preconditioned HUVECs were subjected to tube formation assay, Transwell assay, and EdU assay to evaluate the protective effect of exosomes. Meanwhile, mRNA and secretion levels of proangiogenic factors were measured by RT-qPCR and ELISA assays. In vivo assays were conducted using the rat myocardial infarction model. PBS, control exosomes, or HIF-1α-overexpressed exosomes were injected through tail vein after MI surgery. Heart function was assessed by echocardiography at days 3, 14, and 28. At day 7, mRNA and protein expression levels of proangiogenic factors in the peri-infarction area and circulation were evaluated, respectively. At day 28, hearts were collected and subjected to H&E staining, Masson's trichrome staining, and immunofluorescent staining.
RESULTS
HIF-1α-overexpressed exosomes rescued the impaired angiogenic ability, migratory function, and proliferation of hypoxia-injured HUVECs. Simultaneously, HIF-1α-overexpressed exosomes preserved heart function by promoting neovessel formation and inhibiting fibrosis in the rat MI model. In addition, both in vitro and in vivo proangiogenic factors mRNA and protein expression levels were elevated after HIF-1α-overexpressed exosome application.
CONCLUSION
HIF-1α-overexpressed exosomes could rescue the impaired angiogenic ability, migration, and proliferation of hypoxia-pretreated HUVECs in vitro and mediate cardioprotection by upregulating proangiogenic factors and enhancing neovessel formation.
Topics: Animals; Exosomes; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mesenchymal Stem Cells; Myocardial Infarction; Neovascularization, Pathologic; Neovascularization, Physiologic; Rats
PubMed: 32859268
DOI: 10.1186/s13287-020-01881-7 -
Frontiers in Immunology 2022Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair...
BACKGROUND
Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair response. Herein, we aimed to uncover cellular functional heterogeneity in dermis between fibrotic and regenerative wound healing fates.
METHODS
The expression matrix of single-cell RNA sequencing (scRNA-seq) data of fibrotic and regenerative wound dermal cells was filtered, normalized, and scaled; underwent principal components analysis; and further analyzed by Uniform Manifold Approximation and Projection (UMAP) for dimension reduction with the Seurat package. Cell types were annotated, and cell-cell communications were analyzed. The core cell population myofibroblast was identified and the biological functions of ligand and receptor genes between myofibroblast and macrophage were evaluated. Specific genes between fibrotic and regenerative myofibroblast and macrophage were identified. Temporal dynamics of myofibroblast and macrophage were reconstructed with the Monocle tool.
RESULTS
Across dermal cells, there were six cell types, namely, EN1-negative myofibroblasts, EN1-positive myofibroblasts, hematopoietic cells, macrophages, pericytes, and endothelial cells. Ligand and receptor genes between myofibroblasts and macrophages mainly modulated cell proliferation and migration, tube development, and the TGF-β pathway. Specific genes that were differentially expressed in fibrotic compared to regenerative myofibroblasts or macrophages were separately identified. Specific genes between fibrotic and regenerative myofibroblasts were involved in the mRNA metabolic process and organelle organization. Specific genes between fibrotic and regenerative macrophages participated in regulating immunity and phagocytosis. We then observed the underlying evolution of myofibroblasts or macrophages.
CONCLUSION
Collectively, our findings reveal that myofibroblasts and macrophages may alter the skin wound healing fate through modulating critical signaling pathways.
Topics: Animals; Dermis; Endothelial Cells; Fibrosis; Ligands; Mice; Sequence Analysis, RNA; Wound Healing
PubMed: 35664010
DOI: 10.3389/fimmu.2022.875407 -
Cell Communication and Signaling : CCS Oct 2023Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is...
BACKGROUND
Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation.
METHODS
THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed.
RESULTS
M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages.
CONCLUSIONS
Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstract.
Topics: Humans; Carcinoma, Hepatocellular; MicroRNAs; Interleukin-4; Liver Neoplasms; Capillary Permeability; Exosomes; Endothelial Cells; Cell Line, Tumor; Macrophages
PubMed: 37904170
DOI: 10.1186/s12964-022-00872-w -
Molecular Plant Mar 2017Maize is the most important agricultural crop used for food, feed, and biofuel as well as a raw material for industrial products such as packaging material. To increase... (Review)
Review
Maize is the most important agricultural crop used for food, feed, and biofuel as well as a raw material for industrial products such as packaging material. To increase yield and to overcome hybridization barriers, studies of maize gamete development, the pollen tube journey, and fertilization mechanisms were initiated more than a century ago. In this review, we summarize and discuss our current understanding of the regulatory components for germline development including sporogenesis and gametogenesis, the progamic phase of pollen germination and pollen tube growth and guidance, as well as fertilization mechanisms consisting of pollen tube arrival and reception, sperm cell release, fusion with the female gametes, and egg cell activation. Mechanisms of asexual seed development are not considered here. While only a few molecular players involved in these processes have been described to date and the underlying mechanisms are far from being understood, maize now represents a spearhead of reproductive research for all grass species. Recent development of essentially improved transformation and gene-editing systems may boost research in this area in the near future.
Topics: Fertilization; Ovule; Plant Proteins; Pollen Tube; Zea mays
PubMed: 28267957
DOI: 10.1016/j.molp.2017.01.012 -
Biochimica Et Biophysica Acta. General... Mar 2017Genome packaging and delivery are fundamental steps in the replication cycle of all viruses. Icosahedral viruses with linear double-stranded DNA (dsDNA) usually package...
Genome packaging and delivery are fundamental steps in the replication cycle of all viruses. Icosahedral viruses with linear double-stranded DNA (dsDNA) usually package their genome into a preformed, rigid procapsid using the power generated by a virus-encoded packaging ATPase. The pressure and stored energy due to this confinement of DNA at a high density is assumed to drive the initial stages of genome ejection. Membrane-containing icosahedral viruses, such as bacteriophage PRD1, present an additional architectural complexity by enclosing their genome within an internal membrane vesicle. Upon adsorption to a host cell, the PRD1 membrane remodels into a proteo-lipidic tube that provides a conduit for passage of the ejected linear dsDNA through the cell envelope. Based on volume analyses of PRD1 membrane vesicles captured by cryo-electron tomography and modeling of the elastic properties of the vesicle, we propose that the internal membrane makes a crucial and active contribution during infection by maintaining the driving force for DNA ejection and countering the internal turgor pressure of the host. These novel functions extend the role of the PRD1 viral membrane beyond tube formation or the mere physical confinement of the genome. The presence and assistance of an internal membrane might constitute a biological advantage that extends also to other viruses that package their linear dsDNA to high density within an internal vesicle.
Topics: Adenosine Triphosphatases; Bacteriophage PRD1; Capsid; Cell Membrane; DNA; DNA, Viral; Genome, Viral; Viral Proteins; Virus Assembly
PubMed: 27993658
DOI: 10.1016/j.bbagen.2016.12.013 -
Frontiers in Chemistry 2022The polymeric properties are tailored and enhanced by high energy radiation processing, which is an effective technique to tune the physical, chemical, thermal, surface,... (Review)
Review
The polymeric properties are tailored and enhanced by high energy radiation processing, which is an effective technique to tune the physical, chemical, thermal, surface, and structural properties of the various thermoplastic and elastomeric polymeric components. The gamma and electron beam radiation are the most frequent radiation techniques used for crosslinking, compatibilizing, and grafting of various polymer blends and composites systems. The gamma radiation-induced grafting and crosslinking are the effective, rapid, clean, user-friendly, and well-controlled techniques for the polymeric materials for their properties improvement for high performance applications such as nuclear, automobile, electrical insulation, ink curing, surface modification, food packaging, medical, sterilization, and health-care in a different environment. Similarly, electron beam radiations crosslinking has been a well-known technique for properties development and has economic benefits over chemical crosslinking techniques. This review focuses on the development of polymeric multi component systems (functionalized polymer, blends, and nanohybrids), where partially nanoscale clay incorporation can achieve the desired properties, and partially by controlled high energy radiations crosslinking of blends and nanocomposites. In this review, various investigations have been studied on the development and modifications of polymeric systems, and controlled dose gamma radiation processed the polymer blends and clay-induced composites. Radiation induced grafting of the various monomers on the polymer backbone has been focused. Similarly, comparative studies of gamma and electron beam radiation and their effect on property devlopment have been focused. The high energy radiation modified polymers have been used in several high performance sectors, including automotive, wire and cable insulation, heat shrinkable tube, sterilization, biomedical, nuclear and space applications.
PubMed: 35360545
DOI: 10.3389/fchem.2022.837111 -
Danish Medical Journal Mar 2022This study aimed to conduct a targeted needs assessment to identify and prioritise technical skills and procedures suited for simulation-based training (SBT) in private...
INTRODUCTION
This study aimed to conduct a targeted needs assessment to identify and prioritise technical skills and procedures suited for simulation-based training (SBT) in private otorhinolaryngology (ORL) practice in Denmark, including mapping the learning environment related to implementation of SBT.
METHODS
A panel of trainers and trainees in private ORL practice was recruited. Using the Delphi method, three rounds of surveys were conducted. Round one consisted of a survey of the learning environment and a brainstorming phase. Round two quantified the frequency of procedures, ranked the importance of procedural competency, impact on patient safety and feasibility for SBT. In round three, panelists eliminated and ranked procedures for final prioritisation.
RESULTS
A total of 26 of 57 invited trainers and trainees accepted participation. The educational environment was described and 136 skills were suggested in the brainstorming phase. "Non-technical" skills were removed, and the remaining 46 technical skills were grouped for appraisal in round two. In round three, panelists reduced these to eight technical skills and procedures which were maintained for final prioritisation for SBT with myringotomy with ventilation tube insertion ranking highest. Trainees and trainers indicated that close supervision and dedicated time for training were major strengths of the learning environment.
CONCLUSIONS
Our findings extend the results obtained in a previous general needs assessment and may inform curricular implementation of SBT in private ORL practice. A structured "package" with SBT and assessment for the identified procedures are desired by trainers. This work is already in progress and implementation is facilitated by a positive attitude towards SBT among trainers and trainees alike.
FUNDING
none.
TRIAL REGISTRATION
not relevant.
Topics: Curriculum; Delphi Technique; Humans; Needs Assessment; Otolaryngology; Simulation Training
PubMed: 35319453
DOI: No ID Found -
Journal of Diabetes Science and... Jul 2022The use of tube-free insulin pumps is increasing. To protect the environment, the use of resources and the amount of emissions into the environment should be kept as low...
BACKGROUND
The use of tube-free insulin pumps is increasing. To protect the environment, the use of resources and the amount of emissions into the environment should be kept as low as possible when designing these systems. In addition to basic waste avoidance, the composition of the waste produced must be considered.
METHODS
To compare current tube-free pumps from an ecological standpoint, a tube-free insulin pump with a modular design and two non-modular tube-free pumps were subjected to manual separation, manual sorting, characterization, and mass determination. The annual waste volume of a user was measured, and the recyclability was assessed. The global warming potential (GWP) resulting from extraction of raw materials, energetic utilization of waste, and landfill of the incineration residues was balanced.
RESULTS
For the modular tube-free pump, a total waste volume of 5.5 kg/a (recycling percentage 44.3%) was determined. The non-modular systems generated 4.9 kg/a (recycling percentage 14.6%) and 5.1 kg/a (recycling percentage 16.0%) waste. The product-specific GWP of the modular system was approximately 50% lower than that of the non-modular systems; the packaging-specific GWP was 2.5 times higher. In total, a GWP of 13.6 kg CO-equivalent per year could be determined for the modular system and a GWP of 15.5 kg CO-equivalent per year for the non-modular systems.
CONCLUSIONS
Although the modular micropump has a higher total waste volume, a greater ecological potential can be attributed to it. This is based on the recyclability of the system due to its modularity and the possible reduction of packaging waste.
Topics: Carbon Dioxide; Global Warming; Humans; Incineration; Insulins; Recycling
PubMed: 33576259
DOI: 10.1177/1932296821991523 -
Yakugaku Zasshi : Journal of the... 2021We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug... (Review)
Review
We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.
Topics: Abnormalities, Drug-Induced; Adult; Awareness; Breast Feeding; Cohort Studies; Databases, Factual; Dietary Supplements; Drug Information Services; Drug Labeling; Female; Folic Acid; Humans; Infant, Newborn; Japan; Neural Tube Defects; Pharmacists; Pregnancy; Prescription Drugs; Safety; Surveys and Questionnaires; Young Adult
PubMed: 33790112
DOI: 10.1248/yakushi.20-00184 -
American Journal of Translational... 2021ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been...
BACKGROUND
ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma.
METHODS
Differentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene .
RESULTS
ZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1.
CONCLUSION
ZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma.
PubMed: 34306331
DOI: No ID Found