The expression of MMP-3 protein are closely related to pathogenic mechanism of OA. It may be an important indicator of early diagnosis and the activity of the disease of osteoarthritis.
Differential evolution (DE) is a simple but powerful evolutionary algorithm, which has been widely and successfully used in various areas. In this paper, an event-triggered impulsive (ETI) control scheme is introduced to improve the performance of DE. Impulsive control (IPC), the concept of which derives from control theory, aims at regulating the states of a network by instantly adjusting the states of a fraction of nodes at certain instants, and these instants are determined by event-triggered mechanism (ETM). By introducing IPC and ETM into DE, we hope to change the search performance of the population in a positive way after revising the positions of some individuals at certain moments. At the end of each generation, the IPC operation is triggered when the update rate of the population declines or equals to zero. In detail, inspired by the concepts of IPC, two types of impulses are presented within the framework of DE in this paper: 1) stabilizing impulses and 2) destabilizing impulses. Stabilizing impulses help the individuals with lower rankings instantly move to a desired state determined by the individuals with better fitness values. Destabilizing impulses randomly alter the positions of inferior individuals within the range of the current population. By means of intelligently modifying the positions of a part of individuals with these two kinds of impulses, both exploitation and exploration abilities of the whole population can be meliorated. In addition, the proposed ETI is flexible to be incorporated into several state-of-the-art DE variants. Experimental results over the IEEE Congress on Evolutionary Computation (CEC) 2014 benchmark functions exhibit that the developed scheme is simple yet effective, which significantly improves the performance of the considered DE algorithms.
Poor viability of mesenchymal stem cells (MSCs) at the transplanted site often hinders the efficacy of MSCs-based therapy. Platelet lysate (PL) contains rich amounts of growth factors, which benefits cell growth. This study aimed to explore how human PL benefits umbilical cord-derived MSCs (huc-MSCs), and whether they have synergistic potential in osteoarthritis (OA) treatment. As quality control, flow cytometry and specific staining were performed to identify huc-MSCs, and ELISA was used to quantify growth factors in PL. CCK-8 and flow cytometry assays were performed to evaluate the effects of PL on the cell viability and cell cycle progression of huc-MSCs. Wound healing and transwell assays were conducted to assess the migration of huc-MSCs. RNA sequencing, real time PCR, and Western blot assays were conducted to explore the growth factors-based mechanism of PL. The in vitro results showed that PL significantly promoted the proliferation, cell cycle, and migration of huc-MSCs by upregulating relevant genes/proteins and activating beclin1-dependent autophagy via the AMPK/mTOR signaling pathway. The main growth factors (PDGF-AA, IGF-1, TGF-β, EGF, and FGF) contributed to the effects of PL in varying degrees. The in vivo data showed that combined PL and huc-MSCs exerted significant synergistic effect against OA. The overall study determined the beneficial effects and mechanism of PL on huc-MSCs and indicated PL as an adjuvant for huc-MSCs in treating OA. This is the first report on the growth factors-based mechanism of PL on huc-MSCs and their synergistic application. It provides novel knowledge of PLʹs roles and offers a promising strategy for stem cell-based OA therapy by combining PL and huc-MSCs.
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