The chronic rejection responses and side effects of the systematic administration of immunosuppressants are the main obstacles to heart allograft and patient survival. The development of xenotransplantation also urgently requires more efficient immune regulation strategies. Herein, it is demonstrated that lymph‐node (LN)‐targeted drug delivery can realize LN‐specific immunomodulation with attenuated immune suppression on distant peripheral immune organs to effectively prolong long‐term survival after heart transplantation in a chronic murine heart transplantation model. A chemokine C‐C motif ligand 21 (CCL21) specific aptamer for LN targeting is decorated onto the surface of the hybrid nanoparticular delivery vector mainly composed of CaCO3/CaP/heparin. The targeting delivery system can dramatically enhance accumulation of the loaded immunosuppressant, fingolimod hydrochloride (FTY720), in draining lymph nodes (dLNs) for inducing powerful immune suppression. By promoting the generation of endogenous regulatory T cells (Tregs) and decreasing the proportion of effector T cells (Teffs) in dLNs after heart transplantation, the LN‐targeting strategy can effectively regulate local immune responses instead of systemic immunity, which reduces the incidence of long‐term complications. This study provides an efficient strategy to improve the survival rate after organ transplantation by precise and localized immunoregulation with minimized side effects of immunosuppression.
Background Tyrosine kinase inhibitors (TKIs) have achieved revolutionary results in the treatment of a wide range of tumors, and many studies on this topic continue to be published every year. Some of the published reviews provide great value for us to understand TKIs. However, there is a lack of studies on the knowledge structure, bibliometric analysis, and visualization results in TKIs research. Objective This paper aims to investigate the knowledge structure, hotspots, and trends of evolution of the TKIs research by co-word analysis and literature visualization and help researchers in this field to gain a comprehensive understanding of the current status and trends. Methods We retrieved all academic papers about TKIs published between 2016 and 2020 from the Web of Science. By counting keywords from those papers, we generated the co-word networks by extracting the co-occurrence relationships between keywords, and then segmented communities to identify the subdirections of TKIs research by calculating the network metrics of the overall and local networks. We also mapped the association network topology, including the network within and between TKIs subdirections, to reveal the association and structure among varied subdirections. Furthermore, we detected keyword bursts by combining their burst weights and durations to reveal changes in the focus of TKIs research. Finally, evolution venation and strategic diagram were generated to reveal the trends of TKIs research. Results We obtained 6782 unique words (total frequency 26,175) from 5584 paper titles. Finally, 296 high-frequency words were selected with a threshold of 10 after discussion, the total frequency of which accounted for 65.41% (17,120/26,175). The analysis of burst disciplines revealed a variable number of burst words of TKIs research every year, especially in 2019 and 2020, such as HER2, pyrotinib, next-generation sequencing, immunotherapy, ALK-TKI, ALK rearrangement. By network calculation, the TKIs co-word network was divided into 6 communities: C1 (non-small–cell lung cancer), C2 (targeted therapy), C3 (chronic myeloid leukemia), C4 (HER2), C5 (pharmacokinetics), and C6 (ALK). The venation diagram revealed several clear and continuous evolution trends, such as non-small–cell lung cancer venation, chronic myeloid leukemia venation, renal cell carcinoma venation, chronic lymphocytic leukemia venation. In the strategic diagram, C1 (non-small–cell lung cancer) was the core direction located in the first quadrant, C2 (targeted therapy) was exactly at the junction of the first and fourth quadrants, which meant that C2 was developing; and C3 (chronic myeloid leukemia), C4 (HER2), and C5 (pharmacokinetics) were all immature and located in the third quadrant. Conclusions Using co-word analysis and literature visualization, we revealed the hotspots, knowledge structure, and trends of evolution of TKIs research between 2016 and 2020. TKIs research mainly focused on targeted therapies against varied tumors, particularly against non-small–cell lung cancer. The attention on chronic myeloid leukemia and pharmacokinetics was gradually decreasing, but the focus on HER2 and ALK was rapidly increasing. TKIs research had shown a clear development path: TKIs research was disease focused and revolved around “gene targets/targeted drugs/resistance mechanisms.” Our outcomes will provide sound and effective support to researchers, funders, policymakers, and clinicians.
Iron deficiency (ID) is a global nutritional deficiency that was shown to be involved in the pathogenesis of aortic aneurysm and dissection (AAD) in our previous studies. Some studies suggested...
BACKGROUND Tyrosinase inhibitors (TKIs) have achieved revolutionary results in the treatment of a wide range of tumors, which have brought out a lot of literature in this field every year. And some reviews provide a great value for us to understand TKIs. However, there is a lack of studies on the knowledge structure and bibliometric analysis in TKIs research. OBJECTIVE This paper aims to investigate the knowledge structure, hotspots, and trends of evolution of the field of TKIs by co-word analysis and literature visualization. METHODS We obtained all academic papers about TKIs published in 2016-2020 from the Web of Science. Based on counting keywords from those papers, we generated the co-word networks by extracting the co-occurrence relationships between keywords, and segmented communities to identify the sub-directions of TKIs research by calculating the network metrics of the overall and local networks. We also mapped the association network topology, including the network within and between TKIs sub-directions, to reveal the association and structure among varied sub-directions. Finally, evolution venation and strategic diagram were generated to reveal the trends of TKIs research. RESULTS We obtained 6,782 unique words (total frequency 26,175) from 5,584 paper captions. Finally, 296 high-frequency words were selected with a threshold of 10 after discussion, the total frequency of which accounted for 65.41%. The analysis of burst disciplines revealed a variable number of burst words of TKIs research every year, especially in 2019 and 2020, such as HER2, Pyrotinib, Next-generation Sequencing, Immunotherapy, ALK-TKI, ALK Rearrangement, etc. By network calculation, the TKIs co-word network was divided into six communities: C1-Non-small Cell Lung Cancer, C2-Targeted Therapy, C3-Chronic Myeloid Leukemia, C4-HER2, C5-Pharmacokinetics, and C6-ALK. The venation diagram revealed several clear and continuous evolution trends, such as Non-small Cell Lung Cancer venation, Chronic Myeloid Leukemia venation, Renal Cell Carcinoma venation, Chronic Lymphocytic Leukemia venation, etc. In the strategic diagram, C1-Non-small Cell Lung Cancer was the core direction located in the first quadrant, C2-Targeted Therapy was exactly at the junction of the first and fourth quadrants that meant C2 was developing, and C3-Chronic Myeloid Leukemia, C4-HER2, and C5-Pharmacokinetics were all immature that all located in the third quadrant. CONCLUSIONS Using co-word analysis and literature visualization, we revealed the hotspots, knowledge structure, and trends of evolution of TKIs research during 2016-2020. TKIs research mainly focused on targeted therapies against varied tumors, particularly against NSCLC. The attention on CML and pharmacokinetics was gradually decreasing, but the heat of HER2 and ALK was rapidly increasing. TKIs research had shown a clear development path: TKIs research was disease-focused and revolved around "gene targets/targeted drugs/resistance mechanisms". Our outcomes will provide sound and effective support to researchers, funders, policymakers, and clinicians.
Despite being the gold-standard treatment for end-stage heart disease, heart transplantation is associated with acute cardiac rejection within 1 year of transplantation. The continuous application of immunosuppressants may cause side effects such as hepatic and renal toxicity, infection, and malignancy. Developing new pharmaceutical strategies to alleviate acute rejection after heart transplantation effectively and safely is of critical importance. In this study, we performed a murine model of MHC-full mismatch cardiac transplantation and showed that the combination of Rhodosin (Rho) and mycophenolate mofetil (MMF) could prevent acute rejection and oxidative stress injury and prolong the survival time of murine heart transplants. The use of Rho plus MMF in allografts improved the balance of Tregs/Teff cells, which had a protective effect on allotransplantation. We also isolated bone marrow-derived dendritic cells (BMDCs) and determined that Rho inhibited DC maturation by promoting mitochondrial fusion mainly through the mitochondrial fusion-related protein MFN1. Herein, we demonstrated that Rho, an active ingredient isolated from the plant Rhodiola rosea with antioxidant and anti-inflammatory activities, could efficiently alleviate acute rejection and significantly prolong murine heart allograft survival when used with a low dose of MMF. More importantly, we found that Rho restrained DC maturation by promoting mitochondrial fusion and decreasing reactive oxygen species (ROS) levels, which then alleviated acute rejection in murine cardiac transplantation. Interestingly, as a novel immunosuppressant, Rho has almost no side effects compared with other traditional immunosuppressants. Taken together, these results suggest that Rho has good clinical auxiliary applications as an effective immunosuppressant and antioxidant, and this study provides an efficient strategy to overcome the side effects of immunosuppressive agents that are currently used in organ transplantation.
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