课程文献中心 更多>>

关键词： HLA-immunized platelet transfusion   refractoriness   HLA-matched PLT units   Non-immune factors  

摘要： Immunized platelet transfusion refractoriness (IPTR) has a high incidence of death and complications. HLA-matched platelet unit can effectively treat HLA-immunized PTR. A cohort study was undertaken on nine patients with IPTR hematological disorders who underwent HLA-matched PLT units due to HLA immunization at the First Affiliated Hospital of Soochow University between April 2022 and April 2023. We calculated the 14-hour corrected count increments (14 h-CCI) to evaluate the effect of PLT transfusions. A 14 h- CCI > 5000 was considered to be a successful transfusion. A total of 113 PLT units were transfused to the nine patients with HLA-immunized PTR. Of the 113 PLT units, 50 were random, 34 were cross-matched, and 29 were HLA-matched. The median 14 h-CCI values were 1683 for random PLT units, 5246 for cross-matched PLT units, and 5643 for HLA-matched PLT units (P = 0.02). Moreover, 10, 25, and 43.8% of transfusions were successful for random, cross-matched, and HLA-matched PLT units with non-immune factors (P = 0.013). Regarding non-immune factors, we confirmed that random PLT units, infection, splenomegaly, and bleeding affected platelet transfusion increments (P < 0.05). (c) 2024 Socit francophone de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Brazil   HLA   HLA-A   new allele   next-generation sequencing   Rio de Janeiro  

摘要： The novel HLA-A*02:1196 allele, first described in a potential bone marrow donor from Brazil.

关键词： virtual screening   DrugBank   ZINC15   TME   IL-20RA   ritonavir   TNBC  

摘要： Targeting the tumor microenvironment (TME) is an attractive strategy for developing new drugs with anticancer activity against triple-negative breast cancer (TNBC). Interleukins (ILs) are key players in the TME cytokine network promoting cancer progression. Recent studies have highlighted the involvement of IL-20 receptor subunit alpha (IL-20RA) signalling in several cancers, including BC, in which IL-20RA is highly expressed, correlating with poor prognosis and influencing tumoral characteristics such as proliferation, cell death, invasiveness, and TME activity. Therefore, elucidating the role of the IL-20RA signalling pathway could form the basis for developing new therapeutic strategies. This study aimed to identify selective bioactive ligands able to affect IL-20RA activity. Virtual screening of over 310,000 compounds from both the DrugBank and ZINC15 databases identified four potential hit compounds tested for their anticancer activity against TNBC in vitro cell lines. Notably, Ritonavir, a well-known Human Immunodeficiency Virus Type 1 (HIV-1) protease inhibitor, significantly inhibited cell proliferation (about 40% at 50 mu M, p < 0.001). IL-20 preincubation counteracted Ritonavir's cytostatic effect while IL-20RA knockdown restored proliferation in Ritonavir-treated TNBC cells. In conclusion, these findings demonstrated that Ritonavir reduced TNBC cell proliferation through IL-20RA activity modulation, suggesting its potential repurposing as a therapeutic agent for TNBC management.

关键词： HLA   HLA-A*68:325   novel allele   sequencing-based typing  

摘要： HLA-A*68:325 differs from HLA-A*68:01:01:01 by one nucleotide substitution in codon -20 in exon 1.

关键词： Cancer cells  

摘要： Invasiveness and epithelial–mesenchymal transition (EMT) are main patterns of metastatic disease, which is the major cause cancer-related mortality in human malignant melanoma cells. Tea and its consumption extract are associated with a lower risk of several types of cancer and have anti-inflammatory and antioxidative biological effects. However, the anti-EMT and anti-cancer stemness effect of black tea ethanol extracts (BTEE) in human melanoma remain poorly understood. In this study, the effects of BTEE-reduced invasiveness, EMT, and cancer stemness were evaluated in human A 375 and A2058 melanoma cells. BTEE inhibited the activity of u-PA, migration, and invasiveness by repressing p-FAK signaling pathway. BTEE affected the EMT by downregulating the expression of β-catenin, N-cadherin, fibronectin, vimentin, and Twist-1. BTEE also reduced tumor necrosis factor-alpha (TNF-α)-induced invasiveness and cancer stemness characteristics in vitro. The growth of melanoma in nude mice xenograft model showed that BTEE suppressed A 375 tumor growth in vivo. © 2024 Wiley Periodicals LLC.

关键词： miR-128-3p   IL-8   Hypoxia   HIF-1 alpha   Temozolomide (TMZ)   Glioblastoma multiforme (GBM)  

摘要： Glioblastoma multiforme (GBM) is an aggressive type of brain tumor known for its hypoxic microenvironment. Understanding the dysregulated mechanisms in hypoxic GBM is crucial for its effective treatment. Through data mining of The Cancer Genome Atlas (TCGA) with hypoxia enrichment scores and in vitro experiments, miR-1283p was negatively correlated with hypoxia signaling and the epithelial-mesenchymal transition (EMT). Additionally, lower miR-128-3p levels existed in hypoxic GBM, leading to desensitizing temozolomide (TMZ)'s efficacy, a first-line therapeutic drug for GBM. Overexpressing miR-128-3p enhanced both the in vitro and in vivo sensitivity of hypoxic gliomas to TMZ treatment. Mechanistically, HIF-1 alpha suppressed miR-128-3p expression in hypoxic GBM. Through establishing miR-128-3p-mediated transcriptomic profiles and data mining, interleukin (IL)-8 was selected. IL-8 respectively showed positive and negative correlations with hypoxia and miR-128-3p, and was associated with poor TMZ therapeutic results in GBM. Elevated miR-128-3p, which targets both the 3 '-untranslated region (UTR) and 5 ' UTR of IL-8, resulted in suppression of IL-8 expression. Moreover, IL-8 was validated to be involved in HIF-1 alpha/miR-128-3p-regulated TMZ sensitivity and the EMT in hypoxic GBM cells. Collectively, the HIF-1 alpha/miR-128-3p/IL-8 signaling pathway plays a critical role in promoting the progression of hypoxic GBM. Targeting this signaling pathway holds promise as a potential therapeutic strategy.

关键词： bone cancer pain   interleukin-18   microglia   nuclear factor of activated T cells 1   p38 MAPK  

摘要： AimsThis study aimed to test the hypothesis that nuclear factor of activated T cells 1 (NFAT1) signaling contributes to bone cancer pain by regulating interleukin (IL)-18 expression in spinal *** study was performed on male mice using a Lewis lung carcinoma-induced bone cancer pain model. Nociceptive behaviors were evaluated by measuring mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Expression levels were measured via real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence analysis. The effect of pharmacologic intervention of spinal NFAT1/IL-18 signaling on bone cancer pain was the primary ***1 expression was upregulated in the spinal microglia after tumor inoculation. Pharmacological inhibition of NFAT1 upregulation prevented and reversed bone cancer-related pain behaviors. In spinal microglia, NFAT1 inhibition decreased p38 MAPK phosphorylation and IL-18 production. Blocking NFAT1 signaling suppressed tumor-induced neuronal sensitization and microglial activation as well as activation of the N-methyl-D-aspartate receptor and the subsequent Ca2+-dependent *** NFAT1-p38 signaling contributes to bone cancer pain through IL-18-mediated central sensitization in spinal microglia. NFAT1 could be a potential target for therapeutic intervention to prevent bone cancer pain.

关键词： HLA-B   new alleles   next-generation sequencing  

摘要： Genomic sequence of HLA-B*14:01:01:12, -B*15:01:01:67, -B*35:01:01:90, -B*35:03:01:38, -B*35:31:01:02, -B*41:01:01:09, -B*44:02:01:85 alleles.

关键词： Exosomes   Juvenile idiopathic arthritis   Human umbilical cord mesenchymal stem cells   MiR-29-3p/AhR   Interleukin-22  

摘要： BackgroundJuvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children. Human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (HUCMSCs-Exos) are involved in autoimmune diseases. This study investigates the mechanism of HUCMSC-Exos in improving JIA by targeting AhR through delivery of miR-29-3p to inhibit IL-22 expression in CD4+ T *** induced arthritis (CIA) mouse model was established, and mice were treated with HUCMSCs-Exos and miR-29-3p antagomir, respectively. CD4+ T cells from JIA patients were used for cell experiments. The mechanism was elucidated by histopathological staining, transmission electron microscopy (TEM), immunohistochemistry, CCK-8 assay, flow cytometry, Western blotting, real-time PCR, and enzyme-linked immunosorbent assay (ELISA), laser confocal microscopy, and luciferase ***-CD4+ T cells showed higher expression of IL-22 and lower the levels of miR-29-3p, while HUCMSCs-Exos significantly inhibited the expression of IL-22 and increased the levels of miR-29a-3p, miR-29b-3p, and miR-29c-3p in CD4+ T cells from JIA patients. The expression of miR-29a-3p, miR-29b-3p, miR-29c-3p, AhR, and IL-22 in CD4+ T cells was significantly reversed when co-cultured with HUCMSCs transfected with miR-29-3p mimic or miR-29-3p inhibitor. In vivo experiment, HUCMSCs-Exos ameliorated CIA mice by delivering miR-29-3p to inhibit AhR, IL-22, IL-22R1, MMP3, and MMP13 expression. Furthermore, HUCMSCs-Exos also deliver miR-29-3p targeting AhR expression to inhibit IL-22 in JIA-CD4 + T cells through alleviating arthritic synovial fibroblast ***-Exos loaded miR-29-3p targets AhR to improve JIA via inhibiting the expression of IL-22 in CD4+ T cell, which provides a scientific basis for the treatment of JIA.