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991.
Neuroimmune networks in the thymic microenvironment are thought to be involved in the regulation of T cell development. Here, we report upon an examination of the expression of the TrkA neurotrophin receptor, the high affinity receptor for nerve growth factor, during regeneration following acute involution induced by cyclophosphamide in the rat thymus. Light and electron microscopic immunocytochemistry demonstrated enhanced expression of the TrkA receptor in the subcapsular, paraseptal, perivascular, and cortical epithelial cells during thymus regeneration. In addition, various morphological alterations, suggestive of a hyperfunctional and dynamic state, of the subcapsular, paraseptal, and perivascular epithelial cells were also observed. The presence of TrkA protein in extracts from the control and regenerating rat thymus was confirmed by western blot. Furthermore, RT-PCR analysis supported these results by demonstrating that thymic extracts contain TrkA mRNA at higher levels during thymus regeneration. Thus, our results suggest that the TrkA receptor located on the thymic subcapsular, paraseptal, perivascular, and cortical epithelial cells could play a role in the development of new T cells to replace T cells damaged during thymus regeneration. 相似文献
992.
Shin JY Lee SK Kang CD Chung JS Lee EY Seo SY Lee SY Baek SY Kim BS Kim JB Yoon S 《Histology and histopathology》2003,18(2):435-447
A new antitumor therapeutic strategy utilizing the combined effect of chemotherapy and DC (dendritic cell)-based immunotherapy was designed, and the effect of intratumoral injections of unpulsed, immature DCs was evaluated after in vivo pretreatment of vincristine on tumor growth in a murine fibrosarcoma tumor model. Vincristine exerted a much more potent apoptosis/necrosis-inducing effect on MCA-102 tumor cells than on DCs both in vitro and in vivo. Moreover, CD11c, CD40, CD80 and CD86 molecules on DCs were not downregulated after treatment with vincristine either in vitro or in vivo. The growth of tumor significantly regressed in the group which received the combined vincristine chemotherapy with intratumoral administration of DCs in contrast to the untreated group, the group treated with DCs alone, and the group treated with vincristine alone. In particular, an upregulated expression of CD40, CD80 and CD86 molecules on DCs was found in the combination treatment group. Furthermore, the number of CD4+ and CD8+ T cells and the staining intensity of their CD4 and CD8 surface molecules also increased after the combination treatment. Therefore, our results indicate the feasibility of this combination therapy with vincristine chemotherapy and DC-based immunotherapy as an efficient antitumor strategy for the treatment of fibrosarcoma. 相似文献
993.
Poly(ethylene glycol)-grafted poly(3-hydroxyundecenoate) networks for enhanced blood compatibility 总被引:3,自引:0,他引:3
Chung CW Kim HW Kim YB Rhee YH 《International journal of biological macromolecules》2003,32(1-2):17-22
Poly(ethylene glycol)-grafted poly(3-hydroxyundecenoate) (PEG-g-PHU) networks were prepared by irradiating homogeneous solutions of poly(3-hydroxyundecenoate) (PHU) and the monoacrylate of poly(ethylene glycol) (PEG) with UV light. The resulting polymer networks were characterized by measuring the water contact angle, water uptake, and mechanical properties and by performing attenuated total reflectance infrared spectroscopy and scanning electron microscopy. These measurements showed that the PEG chains were present in polymer networks. Adsorption of blood proteins and platelets on cross-linked PHU (CLPHU) and PEG-g-PHU were examined using poly(L-lactide) (PLLA) surfaces as control. Blood proteins and platelets had significantly lower tendency of adhesion to surfaces composed of CLPHU and PEG-g-PHU networks than to PLLA. Blood compatibility of polymer networks increased as the fraction of grafted PEG increased. The results of this study suggest that PEG-g-PHU networks might be useful for blood-compatible biomedical applications. 相似文献
994.
Baek HJ Kim SS da Silva FM Volpe EA Evans S Mishra B Mishra L Marshall MB 《Biochemical and biophysical research communications》2006,346(4):1150-1157
Escape from TGF-beta inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-beta adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf-/- mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-beta signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-beta adaptor protein in suppressing early lung cancer. 相似文献
995.
996.
997.
Feasibility of supercritical CO2 treatment for controlling biofouling in the reverse osmosis process
Physical cleaning and/or chemical cleaning have been generally used to control biofouling in the reverse osmosis (RO) process. However, conventional membrane cleaning methods to control biofouling are limited due to the generation of by-products and the potential for damage to the RO membranes. In this study, supercritical carbon dioxide (SC CO2) treatment, an environmentally friendly technique, was introduced to control biofouling in the RO process. SC CO2 (100 bar at 35°C) treatment was performed after biofouling was induced on a commercial RO membrane using Pseudomonas aeruginosa PA01 GFP as a model bacterial strain. P. aeruginosa PA01 GFP biofilm cells were reduced on the RO membrane by >8 log within 30 min, and the permeate flux was sufficiently recovered in a laboratory-scale RO membrane system without any significant damage to the RO membrane. These results suggest that SC CO2 treatment is a promising alternative membrane cleaning technique for biofouling in the RO process. 相似文献
998.
999.
Adrian Oo Keivan Zandi Caitlin Shepard Leda C. Bassit Katie Musall Shu Ling Goh Young-Jae Cho Dong-Hyun Kim Raymond F. Schinazi Baek Kim 《The Journal of biological chemistry》2022,298(3)
The lack of antiviral innate immune responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is characterized by limited production of interferons (IFNs). One protein associated with Aicardi–Goutières syndrome, SAMHD1, has been shown to negatively regulate the IFN-1 signaling pathway. However, it is unclear whether elevated IFN signaling associated with genetic loss of SAMHD1 would affect SARS-CoV-2 replication. In this study, we established in vitro tissue culture model systems for SARS-CoV-2 and human coronavirus OC43 infections in which SAMHD1 protein expression was absent as a result of CRISPR–Cas9 gene KO or lentiviral viral protein X–mediated proteosomal degradation. We show that both SARS-CoV-2 and human coronavirus OC43 replications were suppressed in SAMHD1 KO 293T and differentiated THP-1 macrophage cell lines. Similarly, when SAMHD1 was degraded by virus-like particles in primary monocyte-derived macrophages, we observed lower levels of SARS-CoV-2 RNA. The loss of SAMHD1 in 293T and differentiated THP-1 cells resulted in upregulated gene expression of IFNs and innate immunity signaling proteins from several pathways, with STAT1 mRNA being the most prominently elevated ones. Furthermore, SARS-CoV-2 replication was significantly increased in both SAMHD1 WT and KO cells when expression and phosphorylation of STAT1 were downregulated by JAK inhibitor baricitinib, which over-rode the activated antiviral innate immunity in the KO cells. This further validates baricitinib as a treatment of SARS-CoV-2–infected patients primarily at the postviral clearance stage. Overall, our tissue culture model systems demonstrated that the elevated innate immune response and IFN activation upon genetic loss of SAMHD1 effectively suppresses SARS-CoV-2 replication. 相似文献
1000.
Daseul Im Joonhong Jun Jihyun Baek Haejin Kim Dahyun Kang Hyunah Bae Hyunwook Cho Jung-Mi Hah 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):472
Fms-like tyrosine kinase 3 (FLT3) has been verified as a therapeutic target for acute myeloid leukaemia (AML). In this study, we report a series of 2-(1H-indazol-6-yl)-1H-benzo[d]imidazol-5-yl benzamide and phenyl urea derivatives as potent FLT3 inhibitors based on the structural optimisation of previous FLT3 inhibitors. Derivatives were synthesised as benzamide 8a–k, 8n–z, and phenyl urea 8l–m, with various substituents. The most potent inhibitor, 8r, demonstrated strong inhibitory activity against FLT3 and FLT3 mutants with a nanomolar IC50 and high selectivity profiles over 42 protein kinases. In addition, these type II FLT3 inhibitors were more potent against FLT3 mutants correlated with drug resistance. Overall, we provide a theoretical basis for the structural optimisation of novel benzimidazole analogues to develop strong inhibitors against FLT3 mutants for AML therapeutics. 相似文献