There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to ...strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA‐126‐3p (miR‐126‐3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis. We tested a therapeutic strategy involving controlled‐release exosomes derived from miR‐126‐3p‐overexpressing SMSCs combined with chitosan. Our in vitro results showed that exosomes derived from miR‐126‐3p‐overexpressing SMSCs (SMSC‐126‐Exos) stimulated the proliferation of human dermal fibroblasts and human dermal microvascular endothelial cells (HMEC‐1) in a dose‐dependent manner. Furthermore, SMSC‐126‐Exos also promoted migration and tube formation of HMEC‐1. Testing this system in a diabetic rat model, we found that this approach resulted in accelerated re‐epithelialization, activated angiogenesis, and promotion of collagen maturity in vivo. These data provide the first evidence of the potential of SMSC‐126‐Exos in treating cutaneous wounds and indicate that modifying the cells—for example, by gene overexpression—and using the exosomes derived from these modified cells provides a potential drug delivery system and could have infinite possibilities for future therapy. Stem Cells Translational Medicine 2017;6:736–747
•The effect of the quality of parent concrete on the properties of RAC.•Parent concrete with strength grades ranging from 30 to 100MPa was used.•The strength of RAC with 80 and 100MPa PCs was ...slightly higher than that of NAC.•The durability of RAC can be improved with RA are derived from higher strength PCs.•The RA derived from 80 and 100MPa PCs can be used to produce HPC.
This paper presents the experimental results of a study on the effect of the quality of parent concrete (PC) on the properties of recycled aggregates (RAs) that are derived from them, and on the mechanical and durability properties of normal strength and high performance recycled aggregate concrete (NSRAC and HPRAC). PC with strength grades ranging from 30 to 100MPa was crushed to the size of coarse aggregates (<20mm), and then used to produce new NSRAC and HPRAC mixes. The results indicated that the compressive strength of the NSRAC and HPRAC prepared with RA derived from 80 and 100MPa PCs was similar or slightly higher than that of natural aggregate concrete. Moreover, the concrete mixtures made with RA are derived from parent concrete with higher strength had lower drying shrinkage and higher resistance to chloride ion penetration. The RA derived from 80 and 100MPa PCs can be used to replace 100% natural aggregates for the production of high performance concrete.
Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo ...to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time-consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger. In the past few years, microfluidics-based technologies have gradually emerged and have come to play an essential role in the isolation, detection and analysis of EVs. Such technologies have several advantages, including low cost, low sample volumes, high throughput and precision. This review summarizes recent advances in microfluidics-based technologies, compares conventional and microfluidics-based technologies, and includes a brief survey of recent progress towards integrated "on-a-chip" systems. In addition, this review also discusses the potential clinical applications of "on-a-chip" systems, including both "liquid biopsies" for personalized medicine and DDS devices for precision medicine, and then anticipates the possible future participation of cloud-based portable disease diagnosis and monitoring systems, possibly with the participation of artificial intelligence (AI).
In recent years, it has been demonstrated that extracellular vesicles (EVs) can be released by almost all cell types, and detected in most body fluids. In the tumour microenvironment (TME), EVs serve ...as a transport medium for lipids, proteins, and nucleic acids. EVs participate in various steps involved in the development and progression of malignant tumours by initiating or suppressing various signalling pathways in recipient cells. Although tumour-derived EVs (T-EVs) are known for orchestrating tumour progression via systemic pathways, EVs from non-malignant cells (nmEVs) also contribute substantially to malignant tumour development. Tumour cells and non-malignant cells typically communicate with each other, both determining the progress of the disease. In this review, we summarise the features of both T-EVs and nmEVs, tumour progression, metastasis, and EV-mediated chemoresistance in the TME. The physiological and pathological effects involved include but are not limited to angiogenesis, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodelling, and immune escape. We discuss potential future directions of the clinical application of EVs, including diagnosis (as non-invasive biomarkers via liquid biopsy) and therapeutic treatment. This may include disrupting EV biogenesis and function, thus utilising the features of EVs to repurpose them as a therapeutic tool in immunotherapy and drug delivery systems. We also discuss the overall findings of current studies, identify some outstanding issues requiring resolution, and propose some potential directions for future research. Video abstract.
Note: RA-recycled aggregate, BF-basalt fiber, CP-chloride penetration.
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•Basalt fiber (BF) raises the early compressive strength of recycled aggregate (RA) concrete.•BF in a dosage ...dependent way lifts the splitting tensile strength of RA concrete.•BF is with a declined marginal utility in the reinforcement effect.•Concrete with low dosage of BF and high content RA has a higher specific strength.•BF decreases the porosity and the chloride penetration.
Herein, the study conducts an experimental research on the mechanical strength and durability of chopped basalt fiber (BF) reinforced recycled aggregate (RA) concrete. BF at six volumetric dosages of 0, 0.25, 0.5, 0.75, 1 and 1.5% and RA at five volumetric substitution levels of 0, 25, 50, 75 and 100% are used in determining the compressive strength, the splitting tensile strength, the specific strength ratio of splitting tensile strength and apparent density and the chloride penetration. Results show that BF reinforces both RA and nature aggregate (NA) concrete in a dosage dependent way. Relative to the late strength, BF has a better reinforcement effect on the early strength of RA concrete. BF content though is positively related to the splitting tensile strength is with a declined marginal utility. The opitmal dosage thereby exists and is identifed as 1%. Given the reinforcement of BF and the lower density of RA, the combined use of BF at low dosage and RA in high content results in a specific strength that is higher than that of RA concrete. Besides the strength enhancement effect, BF also descends the porosity and ascends the resistance to chloride penetration of RA concrete. The respond surface methodology interestingly is found to have a prominent role in establishing a mathematical model between the compressive and the splitting tensile strength because both strengths have respond surfaces that are shaped by BF and RA. Aforementioned results verify inferior properties of RA concrete can be offset by BF addition, signifying a complementary effect between BF and RA.
This paper presents the findings of a long-term study on the mechanical and durability properties of concrete prepared with 0%, 50% and 100% recycled concrete aggregate that were cured in water or ...outdoor exposure conditions for 10years. The recycled aggregate concrete (RAC) was prepared by using 25%, 35% and 55% class-F fly ash, as cement replacements. It was found that, after 10years, the compressive strength and modulus of elasticity of the concrete prepared with 100% recycled concrete aggregate was still lower than that of the control concrete. Over this period, the highest gain in compressive strength and modulus of elasticity was recorded for the concrete mixture prepared with 55% fly ash. Fly ash improved the resistance to chloride ion penetration but it also increased the carbonation depth of the concrete.
Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary ...causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19 delivery is feasible. In this study, we investigated the possibility of using high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective nano-drug delivery system for LncRNA, and studied the function of EMNVs with a high content of LncRNA-H19 (
H19
EMNVs). The results, which were exciting, showed that
H19
EMNVs had a strong ability to neutralize the regeneration-inhibiting effect of hyperglycemia, and could remarkably accelerate the healing processes of chronic wounds. Our results suggest that bioengineered EMNVs can serve as a powerful instrument to effectively deliver LncRNA and will be an extremely promising multifunctional drug delivery system in the immediate future.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Two types of nano-TiO2 particles were blended into cement pastes and mortars. Their effects on the hydration and properties of the hydrated cement pastes were investigated. The addition of nano-TiO2 ...powders significantly accelerated the hydration rate and promoted the hydration degree of the cementitious materials at early ages. It was demonstrated that TiO2 was inert and stable during the cement hydration process. The total porosity of the cement pastes decreased and the pore size distribution were also altered. The acceleration of hydration rate and the change of microstructure also affected the physical and mechanical properties of the cement-based materials. The initial and final setting time was shortened and more water was required to maintain a standard consistence due to the addition of the nano-TiO2. The compressive strength of the mortar was enhanced, practically at early ages. It is concluded that the nano-TiO2 acted as a catalyst in the cement hydration reactions.
Kinesin family member 4A (KIF4A) was found to be implicated in the regulation of chromosome condensation and segregation during mitotic cell division, which is essential for eukaryotic cell ...proliferation. However, little is known about the role of KIF4A in colorectal carcinoma (CRC). This study explored the biological function of KIF4A in CRC progression and investigated the potential molecular mechanisms involved. Here, we found that KIF4A was remarkably upregulated in primary CRC tissues and cell lines compared with paired non-cancerous tissues and normal colorectal epithelium. Elevated expression of KIF4A in CRC tissues was significantly correlated with clinicopathological characteristics in patients as well as with shorter overall and disease-free cumulative survival. Multivariate Cox regression analysis revealed that KIF4A was an independent prognostic factor for poor survival in human CRC patients. Functional assays, including a CCK-8 cell proliferation assay, colony formation analysis, cancer xenografts in nude mice, cell cycle and apoptosis analysis, indicated that KIF4A obviously enhanced cell proliferation by promoting cell cycle progression in vitro and in vivo. Furthermore, gene set enrichment analysis, Luciferase reporter assays, and ChIP assays revealed that KIF4A facilitates cell proliferation via regulating the p21 promoter, whereas KIF4A had no effect on cell apoptosis. In addition, Transwell analysis indicated that KIF4A promotes migration and invasion in CRC. Taken together, these findings not only demonstrate that KIF4A contributes to CRC proliferation via modulation of p21-mediated cell cycle progression but also suggest the potential value of KIF4A as a clinical prognostic marker and target for molecular treatments.