95 research outputs found

    A Crucial Role of IL-17 and IFN-γ during Acute Rejection of Peripheral Nerve Xenotransplantation in Mice

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    Nerve injuries causing segmental loss require nerve grafting. However, autografts and allografts have limitations for clinical use. Peripheral nerve xenotransplantation has become an area of great interest in clinical surgery research as an alternative graft strategy. However, xenotransplant rejection is severe with cellular immunity, and Th1 cells play an important role in the process. To better understand the process of rejection, we used peripheral nerve xenografts from rats to mice and found that mononuclear cells expressing IFN-γ and IL-17 infiltrated around the grafts, and IFN-γ and IL-17 producing CD4+ and CD8+ T cells increased during the process of acute rejection. The changes of IL-4 level had no significant difference between xenotransplanted group and sham control group. The rejection of xenograft was significantly prevented after the treatment of IL-17 and IFN-γ neutralizing antibodies. These data suggest that Th17 cells contribute to the acute rejection process of peripheral nerve xenotransplant in addition to Th1 cells

    Advances in Acute Myeloid Leukemia Stem Cells

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    As a common hematological malignant tumor, acute leukemia is believed to originate from a subpopulation of special cancer cells, named cancer stem cells. Cancer stem cells are recognized to be the main source of tumor origin, multidrug resistance, metastasis, and recurrence. Leukemic stem cells (LSCs) were first identified and confirmed to play an important role in the occurrence and development of leukemia. In this article, we summarize the following content: special markers and sorting methods for acute myeloid leukemia stem cells and the role of cancer stem cells in treatment resistance, metastasis and invasion, recurrence, and target treatment of acute leukemia

    Advance in Pancreatic Cancer Diagnosis and Therapy

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    Pancreatic carcinoma is the fourth leading cause of cancer death in the word wild. Although the advance in treatment this disease, the 5-years survival rate is still rather low. In the recent year, many new therapy and treatment avenues have been developed for pancreatic cancer. In this chapter, we mainly focus on the following aspect: 1) the treatment modality in pancreatic cancer, including chemotherapy, radiotherapy, and immunotherapy; 2) the mechanism of pancreatic cancer treatment resistance, especially in cancer stem cells and tumor microenvironment; 3) the diagnosis tools in pancreatic cancer, including serum markers, imaging methods and endoscopic ultrasonography. Novel molecular probes based on the nanotechnology in the diagnosis of pancreatic cancer are also discussed

    Toll-like receptor 2 and Toll-like receptor 4 exhibit distinct regulation of cancer cell stemness mediated by cell death-induced high-mobility group box 1

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    Background: High-mobility group box 1 (HMGB1), a common extracellular damage associated molecular pattern molecule, is overexpressed in several solid tumors including pancreatic carcinoma. We previously observed that radiotherapy induced dying cells secrete HMGB1 and accelerate pancreatic carcinoma progression through an unclear mechanism.Methods: Using the Millicell system as an in vitro co-culture model, we performed quantitative reverse transcriptase-polymerase chain reaction, western blot and sphere forming ability analyses to access the effect of dying-cell-derived HMGB1 on CD133(+) cancer cell stemness in vitro and in vivo. Interactions between HMGB1 and Toll-like receptor 2(TLR2)/TLR4 were studied by co-immunoprecipitation. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect HMGB1 and TLR2/TLR4 signaling activity.Findings: Radiation-associated, dying-cell-derived HMGB1 maintained stemness and contributed to CD133(+) cancer stemcell self-renewal in vitro and in vivo. In overexpressing and silencing experiments, we demonstrated that the process was activated by TLR2 receptor, whereas TLR4 antagonized HMGB1-TLR2 signaling. Wnt/beta-catenin signaling supported the HMGB1-TLR2 mediated stemness of CD133(+) cancer cells.Interpretation: Our results show how irradiation-induced cell death might enhance the stemness of resident cancer cells, and indicate HMGB1-TLR2 signaling as a potential therapeutic target for preventing pancreatic cancer recurrence. (c) 2018 Haitao Zhu. Published by Elsevier B.V

    Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness

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    Differentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.</p

    Evaluating the Evacuation and Rescue Capabilities of Urban Open Space from a Land Use Perspective: A Case Study in Wuhan, China

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    This study proposes an innovative integrated method for evaluating the evacuation and rescue capabilities of open spaces through a case study in Wuhan, China. A dual-scenario network analysis model was set up to calculate travel time among communities, open spaces, and rescue facilities during peak and non-peak hours. The distribution of traffic flow was derived on the basis of a gravity model and used to construct supply-demand indexes (SDIs). SDIs such as evacuation (ESDI), rescue (RSDI), and comprehensive SDIs (CSDI) were used to evaluate the suitability of open space locations. This study drew five major findings as follows: (1) ESDI, RSDI, and CSDI can effectively evaluate the spatial suitability of open spaces when these SDIs are integrated with the gravity model. (2) The quadrant distribution analysis of ESDI can be an effective method for determining the reasons for the change in values in the two traffic scenarios and for helping planners in adjusting their policies to enhance the capability of an area. (3) The impact of the different β values on SDIs can show positive, negative, and inconspicuous correlations with large, moderate, and minimal variations, respectively. (4) The analysis of the supply-demand relationship of open spaces in Wuhan indicates a spatial mismatch in comprehensive evacuation and rescue capacities. (5) Traffic congestion can be a significant impact factor on evacuation and rescue capabilities but not on comprehensive capability

    Three-Phase Inverter Fault Diagnosis Based on an Improved Deep Residual Network

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    This study addresses the challenges of limited fault samples, noise interference, and low accuracy in existing fault diagnosis methods for three-phase inverters under real acquisition conditions. To increase the number of samples, Wavelet Packet Decomposition (WPD) denoising and a Conditional Variational Auto-Encoder (CVAE) are used for sample enhancement based on the existing faulty samples. The resulting dataset is then normalized, pre-processed, and used to train an improved deep residual network (SE-ResNet18) fault diagnosis model with a channel attention mechanism. Results show that the augmented fault samples improve the diagnosis accuracy compared with the original samples. Furthermore, the SE-ResNet18 model achieves higher fault diagnosis accuracy with fewer iterations and faster convergence, indicating its effectiveness in accurately diagnosing inverter open-circuit faults across various sample situations

    Internal Differentiation within the Rural Migrant Population from the Sustainable Urban Development Perspective: Evidence from China

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    Population mobility and attendant issues, especially housing issues, have a major impact on sustainable urban development. In the urbanization process, a number of micro-communities with various social characteristics have come to compose the rural migrant population (RMP), resulting in internal differentiation. This study aims to reveal the demographic structure of this specific group, and to analyze the effects of the mechanism between population flow trends and sustainable urban development, taking housing demand as a starting point. To this end, a clustering model for mixed-type data based on partitioning around the medoid is proposed, and the linked characteristics and potential laws of the RMP are analyzed, based on the dynamic data of the migrant population in eastern China. To achieve sustainable urban development, the locational preferences and coping strategies of inflowing micro-communities based on city types are demonstrated. The results show that the RMP can be divided into four groups that have strong representativeness and that show significant differences in population structure and housing demand. Super-large and medium-sized cities are the main migration destinations. Several suggestions are proposed, based on these results. Housing security policies should be designed according to the housing demand characteristics and the spatial distribution of different groups. Housing security policies should play a full and positive role in reasonably guiding RMP movement
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