Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic ...effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.
Adipose-derived stem cells (ASCs) are an important stem cell type separated from adipose tissue, with the properties of multilineage differentiation, easy availability, high proliferation potential, ...and self-renewal. Exosomes are novel frontiers of intercellular communication regulating the biological behaviors of cells, such as angiogenesis, immune modulation, proliferation, and migration. ASC-derived exosomes (ASC-exos) are important components released by ASCs paracrine, possessing multiple biological activities. Tissue regeneration requires coordinated “vital networks” of multiple growth factors, proteases, progenitors, and immune cells producing inflammatory cytokines. Recently, as cell-to-cell messengers, ASC-exos have received much attention for the fact that they are important paracrine mediators contributing to their suitability for tissue regeneration. ASC-exos, with distinct properties by encapsulating various types of bioactive cargoes, are endowed with great application potential in tissue regeneration, mechanically via the migration and proliferation of repair cells, facilitation of the neovascularization, and other specific functions in different tissues. Here, this article elucidated the research progress of ASC-exos about tissue regeneration in plastic and cosmetic surgery, including skin anti-aging therapy, dermatitis improvement, wound healing, scar removal, flap transplantation, bone tissue repair and regeneration, obesity prevention, fat grafting, breast cancer, and breast reconstruction. Deciphering the biological properties of ASC-exos will provide further insights for exploring novel therapeutic strategies of tissue regeneration in plastic and cosmetic surgery.
Background
This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the ...outcomes in patients with head and neck squamous cell carcinoma.
Methods
CTCs were detected using a negative selection strategy and flow cytometry protocol.
Results
We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2‐4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression‐free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses.
Conclusion
In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.
Recently, flexible multifunctional sensors have attracted widespread attention from around the world. Here, we propose a novel PS/MXene-based triboelectric nanogenerator (PM-TENG), which has a drum ...structure design. Through comparative experiments, the optimal ratio of polystyrene (PS) materials was explored. The PS film and nylon film form the triboelectric materials, and copper foil acts as the conducive electrode. From the results, the open-circuit voltage (Voc) and short-circuit current (Isc) of the PM-TENG based on 35 mg/ml content of PS can reach 141 V and 5.9 µA, respectively. In addition, when the resistance value of the external load is 50 MΩ, the PM-TENG exhibits a maximum output power of 123 µW. Due to its excellent flexibility, the PM-TENG can be installed on the shoulders, neck, wrist, elbow, knee, and ankle to achieve all-round motion monitoring of football players. This research can promote the application of TENG sensors in the football monitoring field.
Industrial Internet of Things (IIoT) plays an indispensable role for Industry 4.0, where people are committed to implement a general, scalable, and secure IIoT system to be adopted across various ...industries. However, existing IIoT systems are vulnerable to single point of failure and malicious attacks, which cannot provide stable services. Due to the resilience and security promise of blockchain, the idea of combining blockchain and Internet of Things (IoT) gains considerable interest. However, blockchains are power-intensive and low-throughput, which are not suitable for power-constrained IoT devices. To tackle these challenges, we present a blockchain system with credit-based consensus mechanism for IIoT. We propose a credit-based proof-of-work (PoW) mechanism for IoT devices, which can guarantee system security and transaction efficiency simultaneously. In order to protect sensitive data confidentiality, we design a data authority management method to regulate the access to sensor data. In addition, our system is built based on directed acyclic graph -structured blockchains, which is more efficient than the Satoshi-style blockchain in performance. We implement the system on Raspberry Pi, and conduct a case study for the smart factory. Extensive evaluation and analysis results demonstrate that credit-based PoW mechanism and data access control are secure and efficient in IIoT.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that links extracellular signals to the control of cell survival, growth, proliferation and differentiation. Due to its ...frequent overexpression and hyperactivation, EGFR has been a therapeutic target for human malignancies. Unfortunately, the specialized inhibitors of EGFR or EGFR-mediated pathways have not yet achieved the desired clinical effects. Therefore, it is necessary to elucidate the EGFR-mediated molecular basis of tumourigenesis, development and therapeutic resistance and to identify potential therapeutic targets. Interestingly, emerging research has indicated that autophagy is closely related to tumourigenesis, tumour progression and chemoresistance. Both autophagy upregulation and downregulation have been observed in cancers, suggesting its dual oncogenic and tumour suppressor properties during malignant transformation. Importantly, EGFR has been demonstrated to be a critical determinant of whether autophagy has a cytoprotective or cytotoxic effect. Therefore, here, we mainly focus on the function of EGFR in autophagy, especially the potential mechanism. The EGFR-mediated pathways or proteins involved in autophagy regulation include (1) the EGFR-mTOR pathway; (2) the EGFR-RAS pathway; (3) EGFR-Beclin1; (4) the EGFR-STAT3 pathway and (5) EGFR-LAPTM4B (oncoprotein lysosomal-associated transmembrane protein 4B). In addition, we also describe the role of EGFR-mediated autophagy in chemoresistance and tumour therapy. We attempt to summarized the mechanism by which EGFR-mediated signalling pathways participate in regulating autophagy and to investigate how to use the existing knowledge to identify potential cancer therapeutic targets.
•EGFR or EGFR mutation-mediated autophagy plays a critical role in tumorigenesis, tumor progress and therapy resistance.•The role of EGFR-mediated autophagy in tumorigenesis and therapy resistance is highly cell-dependent.•Regulating EGFR-mediated autophagy might be a new strategy for the treatment of EGFR deregulated tumors.
Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions.
Clinically, tauopathies can present with a range of phenotypes that include ...cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics.
Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.
Extracellular bacteria, such as Pseudomonas aeruginosa and Klebsiella pneumoniae, have been reported to induce autophagy; however, the role and machinery of infection-induced autophagy remain ...elusive. We show that the pleiotropic Src kinase Lyn mediates phagocytosis and autophagosome maturation in alveolar macrophages (AM), which facilitates eventual bacterial eradication. We report that Lyn is required for bacterial infection-induced recruitment of autophagic components to pathogen-containing phagosomes. When we blocked autophagy with 3-methyladenine (3-MA) or by depleting Lyn, we observed less phagocytosis and subsequent bacterial clearance by AM. Both morphological and biological evidence demonstrated that Lyn delivered bacteria to lysosomes through xenophagy. TLR2 initiated the phagocytic process and activated Lyn following infection. Cytoskeletal trafficking proteins, such as Rab5 and Rab7, critically facilitated early phagosome formation, autophagosome maturation, and eventual autophagy-mediated bacterial degradation. These findings reveal that Lyn, TLR2 and Rab modulate autophagy related phagocytosis and augment bactericidal activity, which may offer insight into novel therapeutic strategies to control lung infection.
This article focuses on the asymptotic and transient behavior of a food chain model with vigilance in the biparameter spaces. Firstly, the local asymptotic stability conditions of the positive ...equilibrium point are obtained. Then, the transient dynamical behavior of the positive equilibrium point is analyzed based on eight parameters. Using numerical simulation, the stable regions of the model with single and double parameters are plotted, as well as the value changes of resilience, reactivity, and amplification envelope within the stable regions. The results show that the coexistence equilibrium point is always reactive, and the corresponding parameter ranges for system stability are large, but the resilience values are small. The vigilance parameter of the middle- and lower-level organisms has the greatest impact on the system’s resilience and reactivity, and the lowest vigilance corresponds to the maximum resilience and reactivity. Our results provide important references for effective management and protection of wild animal populations by the potential for transient amplification, disturbance growth time, and amplitude.
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