Background
Previous studies revealed that urine-derived stem cells (USCs) could promote myogenesis after the impairment of the sphincter muscles. However, the effects of exosomes secreted by USCs (USCs-Exo) were not elucidated. Exosomes are nanosized membrane vesicles secreted by the cells. They have been proved to be effective in protecting against tissue injury and therapeutic in tissue repair. USCs are ideal sources of exosomes because of the noninvasive obtaining method and self-renewal abilitiy. This study aimed to show the therapeutic effects of USCs-Exo on improving stress urinary incontinence (SUI).
Methods
Rat SUI models were established in this study using vaginal balloon inflation, and urodynamic and histological examination were carried out after exosome application. The proliferation and differentiation of muscle satellite cells (SCs) were evaluated using EdU, Cell Counting Kit 8, immunofluorescence staining, and Western blot analysis. mRNAs and proteins related to the activation of SCs were detected by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis.
Results
After exosome injection, the urodynamic parameters significantly improved and the injured muscle tissue recovered well. The activation, proliferation, and differentiation of SCs were promoted. The phosphorylation of extracellular-regulated protein kinases (ERK) was enhanced. When ERK was inhibited, the promoting effect of USCs-Exo treatment disappeared.
Conclusion
The findings of this study elucidated the functional roles of USCs-Exo in satellite cell ERK phosphorylation and identified a novel agent for skeletal muscle regeneration, providing a basis for further exploring a cell-free correction for SUI.
Electronic supplementary material
The online version of this article (10.1186/s13287-019-1182-4) contains supplementary material, which is available to authorized users.
Reliability testing is often carried out with small sample sizes and short duration because of increasing costs and the restriction of development time. Therefore, for highly reliable products, zero-failure data are often collected in such tests, which could not be used to evaluate reliability by traditional methods. To cope with this problem, the match distribution curve method was proposed by some researchers. The key step needed to exercise this method is to estimate the failure probability, which has yet to be solved in the case of the Weibull distribution. This paper presents a method to estimate the intervals of failure probability for the Weibull distribution by using the concavity or convexity and property of the distribution function. Furthermore, to use the method in practice, this paper proposes using the approximate value of the shape parameter determined by either engineering experience or by hypothesis testing through apvalue. The estimation of the failure probability is thus calculated using a Bayesian approach. A numerical example is presented to validate the effectiveness and robustness of the method.
The q-Weibull distribution is a generalization of the Weibull distribution and could describe complex systems. We firstly point out how to derive the maximum likelihood estimates (MLEs) and least-squares estimates (LSEs) of the q-Weibull parameters. Next, three confidence intervals (CIs) for the q-Weibull parameters are constructed based on bootstrap methods and asymptotic normality of the MLEs. Explicit expressions for the Fisher information matrix necessary for the asymptotic CIs are derived. A Monte Carlo simulation study is conducted to compare the performances of the MLEs and LSEs as well as the different CIs. The simulation results show that the MLEs are superior to the LSEs in terms of both bias and mean squared error. The bootstrap CIs based on the MLEs are shown to have good coverage probabilities and average interval widths. Finally, a real data example is provided to illustrate the proposed methods.
Antifreeze proteins (AFPs) or thermal hysteresis (TH) proteins are biomolecular gifts of nature to sustain life in extremely cold environments. This family of peptides, glycopeptides and proteins produced by diverse organisms including bacteria, yeast, insects and fish act by non-colligatively depressing the freezing temperature of the water below its melting point in a process termed thermal hysteresis which is then responsible for ice crystal equilibrium and inhibition of ice recrystallisation; the major cause of cell dehydration, membrane rupture and subsequent cryodamage. Scientists on the other hand have been exploring various substances as cryoprotectants. Some of the cryoprotectants in use include trehalose, dimethyl sulfoxide (DMSO), ethylene glycol (EG), sucrose, propylene glycol (PG) and glycerol but their extensive application is limited mostly by toxicity, thus fueling the quest for better cryoprotectants. Hence, extracting or synthesizing antifreeze protein and testing their cryoprotective activity has become a popular topic among researchers. Research concerning AFPs encompasses lots of effort ranging from understanding their sources and mechanism of action, extraction and purification/synthesis to structural elucidation with the aim of achieving better outcomes in cryopreservation. This review explores the potential clinical application of AFPs in the cryopreservation of different cells, tissues and organs. Here, we discuss novel approaches, identify research gaps and propose future research directions in the application of AFPs based on recent studies with the aim of achieving successful clinical and commercial use of AFPs in the future.
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