Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in ...cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.
The extracellular matrix of vascular tissue is formulated as a bioink to engineer a bioinspired blood vessel using the 3D coaxial cell printing technique. Carrying progenitor cells and proangiogenic drugs, the transplanted construct exhibits remarkable therapeutic efficacy for ischemic diseases.
Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some ...biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
As the field of biomedical engineering has become more precise and sophisticated, the demand for highly-functionalized biomaterials has risen. In particular, novel organic/inorganic hybrid ...biomaterials with two or more chemical, physical, and optical properties are currently being developed and applied in various biomedical fields. In this review, we classify recently created advanced organic/inorganic hybrid nanomaterials as nanoparticles and nanocomposites and describe their structures, characteristics, and advantages. In addition, we outline the most recent trends in smart organic/inorganic hybrid nanomaterials and nanocomposites (bulk materials) in the fields of medical applications. Finally, we discuss the future direction of the nanomaterials and nanocomposites from the standpoint of current technology and its limitations. Functional organic/inorganic hybrid nanomaterials and nanocomposites, which have both physicochemical properties of organic and inorganic materials, have the potential for use as advanced biomaterials in various biomedical fields, with the ultimate goal of efficiently diagnosing and treating various human diseases.
Graphene oxide (GO), which has many oxygen functional groups, is a promising candidate for use in moisture‐responsive sensors and actuators due to the strong water–GO interaction and the ultrafast ...transport of water molecules within the stacked GO sheets. In the last 5 years, moisture‐responsive actuators based on GO have shown distinct advantages over other stimuli‐responsive materials and devices. Particularly, inspired by nature organisms, various moisture‐enabled soft robots have been successfully developed via rational assembly of the GO‐based actuators. Herein, the milestones in the development of moisture‐responsive soft robots based on GO are summarized. In addition, the working mechanisms, design principles, current achievement, and prospects are also comprehensively reviewed. In particular, the GO‐based soft robots are at the forefront of the advancement of automatable smart devices.
In recent years, moisture‐responsive actuators based on graphene oxide (GO) have revealed a series of distinct advantages over other stimuli‐responsive materials and devices. In this research news, the milestones in moisture‐responsive soft robots based on the GO, including working mechanisms, design principles, current achievement, and prospects, are comprehensively reviewed.
ABSTRACT
Elucidating the physiological mechanisms that underlie thermal stress and discovering how species differ in capacities for phenotypic acclimatization and evolutionary adaptation to this ...stress is critical for understanding current latitudinal and vertical distribution patterns of species and for predicting their future state in a warming world. Such mechanistic analyses require careful choice of study systems (species and temperature‐sensitive traits) and design of laboratory experiments that reflect the complexities of in situ conditions. Here, we critically review a wide range of studies of intertidal molluscs that provide mechanistic accounts of thermal effects across all levels of biological organization – behavioural, organismal, organ level, cellular, molecular, and genomic – and show how temperature‐sensitive traits govern distribution patterns and capacities for coping with thermal stress. Comparisons of congeners from different thermal habitats are especially effective means for identifying adaptive variation. We employ these mechanistic analyses to illustrate how species differ in the severity of threats posed by rising temperature. Counterintuitively, we show that some of the most heat‐tolerant species may be most threatened by increases in temperatures because of their small thermal safety margins and minimal abilities to acclimatize to higher temperatures. We discuss recent molecular biological and genomic studies that provide critical foundations for understanding the types of evolutionary changes in protein structure, RNA secondary structure, genome content, and gene expression capacities that underlie adaptation to temperature. Duplication of stress‐related genes, as found in heat‐tolerant molluscs, may provide enhanced capacity for coping with higher temperatures. We propose that the anatomical, behavioural, physiological, and genomic diversity found among intertidal molluscs, which commonly are of critical importance and high abundance in these ecosystems, makes this group of animals a highly appropriate study system for addressing questions about the mechanistic determinants of current and future distribution patterns of intertidal organisms.
Traditional safety concept, which is called Safety-I, and its relevant methods and models have much contributed toward enhancing the safety of industrial systems. However, they have proved ...insufficient to be applied to complex socio-technical systems. As an alternative, Safety-II and resilience engineering have emerged and gained much attention for the last two decades. However, it seems that safety professionals have still difficulty understanding their fundamental concepts and methods. Accordingly, it is necessary to offer an introductory guide to them that helps safety professionals grasp them correctly in consideration of their current practices.
This article firstly explains the limitations of Safety-I and how Safety-II can resolve them from the four points of view. Next, the core concepts of resilience engineering and Functional Resonance Analysis Method are described.
Workers' performance adjustment and performance variability due to it should be the basis for understanding human-related accidents in socio-technical systems. It should be acknowledged that successful and failed work performance have the same causes. However, they are not well considered in the traditional safety concept; in contrast, Safety-II and resilience engineering have conceptual bases and practical approaches to reflect them systematically.
It is necessary to move from a find-and-fix and reactive approach to a proactive approach to safety management. Safety-II and resilience engineering give a set of useful concepts and methods for proactive safety management. However, if necessary, Safety-I methods need to be properly used for situations where they can still be useful as well.
A facile and cost‐effective preparation of moisture‐responsive graphene bilayer paper by focused sunlight irradiation is reported. The smart graphene paper shows moisture‐responsive properties due to ...selective adsorption of water molecules, leading to controllable actuation under humid conditions. In this way, graphene‐based moisture‐responsive actuators including a smart claw, an orientable transporter, and a crawler paper robot are successfully developed.
Covering: December 2005 to June 2016. Previous review: Nat. Prod. Rep., 2006, 23, 673-698Over the last decade, great efforts have been made to conduct phytochemistry research on the genus Isodon, ...which have led to the isolation and identification of a number of diterpenoids. At the same time, these newly reported diterpenoids with diverse structures have led to new findings on their biological functions and chemical synthesis research. In this update, we review more than 600 new diterpenoids, including their structures, classifications, biogenetic pathways, bioactivities, and chemical synthesis.
Macrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident ...macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) in rats.
We depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy.
These data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.
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