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  • 1
    In: Stem Cells International, Hindawi Limited, Vol. 2020 ( 2020-10-31), p. 1-16
    Abstract: The bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone marrow mesenchymal stromal cells (MSCs) from higher-risk MDS patients were investigated. In our study, IO decreased the quantity and weakened the abilities of proliferation and differentiation of MSCs, and it inhibited the gene expressions of VEGFA, CXCL12, and TGF-β1 in MSCs regulating hematopoiesis. The increased level of reactive oxygen species (ROS) in MSCs caused by IO might be inducing apoptosis by activating caspase3 signals and involving in MDS progression by activating β-catenin signals. The damages of MSCs caused by IO could be partially reversed by an antioxidant or an iron chelator. Furthermore, the MSCs in IO MDS/AML patients had increased levels of ROS and apoptosis, and the expressions of caspase3 and β-catenin were increased even further. In conclusion, IO affects gene stability in higher-risk MDS patients and impairs MSCs by inducing ROS-related apoptosis and activating the Wnt/β-catenin signaling pathway, which could be partially reversed by an antioxidant or an iron chelator.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2573856-2
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  • 2
    Online Resource
    Online Resource
    IOP Publishing ; 2022
    In:  Environmental Research Letters Vol. 17, No. 6 ( 2022-06-01), p. 064032-
    In: Environmental Research Letters, IOP Publishing, Vol. 17, No. 6 ( 2022-06-01), p. 064032-
    Abstract: Heat extremes including heatwaves have an adverse impact not only on ecosystems but also on human health. The impact can be seriously exacerbated when both spatial extension and compound factors (such as humidity) are included. However, a unified frame combining compound humidity-heat extremes with their regional extension has received little scientific attention. This study solves this problem by taking the evolution of daily mean 2 m air temperature (Tmean) and relative humidity (RH) over a large domain as two dynamical systems (DSs), then the instantaneous coupling index from the DS method combined with clustering analysis can sort out the regional compound humidity-heat extremes with distinct spatial organized structures. Among them, the compound humidity-heat extremes with dipole Tmean and RH patterns may be missed by the methods based on regional averaging or undiscerned by DS method. Moreover, the mechanisms behind these regional compound humidity-heat extremes with dipole pattern are distinctive on both dynamics and thermodynamics, with a dipole structure found in the atmospheric low-level circulation. These novel findings can contribute considerably to the in-depth understanding on the compound humidity-heat extremes and their mechanisms.
    Type of Medium: Online Resource
    ISSN: 1748-9326
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2022
    detail.hit.zdb_id: 2255379-4
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Climate Dynamics Vol. 60, No. 11-12 ( 2023-06), p. 4099-4109
    In: Climate Dynamics, Springer Science and Business Media LLC, Vol. 60, No. 11-12 ( 2023-06), p. 4099-4109
    Type of Medium: Online Resource
    ISSN: 0930-7575 , 1432-0894
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 382992-3
    detail.hit.zdb_id: 1471747-5
    SSG: 16,13
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  • 4
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Cancers Vol. 15, No. 1 ( 2022-12-22), p. 67-
    In: Cancers, MDPI AG, Vol. 15, No. 1 ( 2022-12-22), p. 67-
    Abstract: Pim-2 kinase is overexpressed in multiple myeloma (MM) and is associated with poor prognosis in patients with MM. Changes in quantitative metabolism, glycolysis, and oxidative phosphorylation pathways are reportedly markers of all tumor cells. However, the relationship between Pim-2 and glycolysis in MM cells remains unclear. In the present study, we explored the relationship between Pim-2 and glycolysis. We found that Pim-2 inhibitors inhibited glycolysis and energy production in MM cells. Inhibition of Pim-2 decreased the proliferation of MM tumor cells and increased their susceptibility to apoptosis. Our data suggest that reduced Pim-2 expression inhibits the energy metabolism process in MM, thereby inhibiting tumor progression. Hence, Pim-2 is a potential metabolic target for MM treatment.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 10, No. 7 ( 2022-07-01), p. 811-828
    Abstract: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly aggressive tumor type that responds poorly to chemotherapy and immunotherapy. Comprehensive molecular characterization of ICC is essential for the development of novel therapeutics. Here, we constructed two independent cohorts from two clinic centers. A comprehensive multiomics analysis of ICC via proteomic, whole-exome sequencing (WES), and single-cell RNA sequencing (scRNA-seq) was performed. Novel ICC tumor subtypes were derived in the training cohort (n = 110) using proteomic signatures and their associated activated pathways, which were further validated in a validation cohort (n = 41). Three molecular subtypes, chromatin remodeling, metabolism, and chronic inflammation, with distinct prognoses in ICC were identified. The chronic inflammation subtype was associated with a poor prognosis. Our random forest algorithm revealed that mutation of lysine methyltransferase 2D (KMT2D) frequently occurred in the metabolism subtype and was associated with lower inflammatory activity. scRNA-seq further identified an APOE+C1QB+ macrophage subtype, which showed the capacity to reshape the chronic inflammation subtype and contribute to a poor prognosis in ICC. Altogether, with single-cell transcriptome-assisted multiomics analysis, we identified novel molecular subtypes of ICC and validated APOE+C1QB+ tumor-associated macrophages as potential immunotherapy targets against ICC.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2732517-9
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Cell Communication and Signaling Vol. 20, No. 1 ( 2022-10-27)
    In: Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2022-10-27)
    Abstract: Myelodysplastic syndrome (MDS) is a clonal disease of hematopoietic cells, characterized by hematopoietic cell hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). Although the underlying mechanism is unclear, MDS is often associated with immune system disorders, especially cellular immune abnormalities. We analyzed the number of lymphocyte subsets by flow cytometry assay and explored the alteration of lymphocyte subsets in MDS. Methods Healthy controls, inpatients with primary MDS and patients with AML diagnosed from January 2017 to July 2021 were included. Flow cytometry assays were used to study lymphocyte subsets obtained from the bone marrow of the participants as well as changes in natural killer (NK) cell function. One-way analysis of variance and Student’s t-test were used to analyze the data. Results We found a reduction in the number and function of NK cells in patients with MDS. By further measuring the activating and inhibitory receptors on the surface of NK cells, we found that the T cell immunoglobulin and ITIM domain (TIGIT) was the highest expressed marker on NK cells. Additionally, the expression of CD155, which is the ligand of TIGIT, was significantly higher than expressions of CD112 and CD113 on bone marrow mesenchymal stem cells (BMSCs). Conclusions The co-culture results of BMSCs and NK cells demonstrated that BMSCs regulate NK cells through the TIGIT/CD155 interaction, indicating that NK cells play a vital role in MDS progression. BMSCs regulate the function of NK cells via TIGIT/CD155.
    Type of Medium: Online Resource
    ISSN: 1478-811X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2126315-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  HemaSphere Vol. 7, No. S3 ( 2023-08), p. e9941541-
    In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e9941541-
    Type of Medium: Online Resource
    ISSN: 2572-9241
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2922183-3
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Critical Reviews in Oncology/Hematology Vol. 169 ( 2022-01), p. 103547-
    In: Critical Reviews in Oncology/Hematology, Elsevier BV, Vol. 169 ( 2022-01), p. 103547-
    Type of Medium: Online Resource
    ISSN: 1040-8428
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2025731-4
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-7)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-7)
    Abstract: Myelodysplastic syndrome (MDS) is a common hematological malignant disease, characterized by malignant hematopoietic stem cell proliferation in the bone marrow (BM); clinically, it mainly manifests clinically mainly by as pathological hematopoiesis, hemocytopenia, and high-risk transformation to acute leukemia. Several studies have shown that the BM microenvironment plays a critical role in the progression of MDS. In this study, we specifically evaluated mesenchymal stromal cells (MSCs) that exert immunomodulatory effects in the BM microenvironment. This immunomodulatory effect occurs through direct cell-cell contact and the secretion of soluble cytokines or micro vesicles. Several researchers have compared MSCs derived from healthy donors to low-risk MDS-associated bone mesenchymal stem cells (BM-MSCs) and have found no significant abnormalities in the MDS-MSC phenotype; however, these cells have been observed to exhibit altered function, including a decline in osteoblastic function. This altered function may promote MDS progression. In patients with MDS, especially high-risk patients, MSCs in the BM microenvironment regulate immune cell function, such as that of T cells, B cells, natural killer cells, dendritic cells, neutrophils, myeloid-derived suppressor cells (MDSCs), macrophages, and Treg cells, thereby enabling MDS-associated malignant cells to evade immune cell surveillance. Alterations in MDS-MSC function include genomic instability, microRNA production, histone modification, DNA methylation, and abnormal signal transduction and cytokine secretion.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2023
    In:  Cancer Medicine Vol. 12, No. 10 ( 2023-05), p. 11746-11759
    In: Cancer Medicine, Wiley, Vol. 12, No. 10 ( 2023-05), p. 11746-11759
    Abstract: Multiple myeloma (MM) is the second common hematologic malignancy manifesting as a clonal proliferation of plasma cells in the bone marrow. In recent years, high expression and activity of pim kinase have been found to be associated with both the progression and prognosis of a significant proportion of malignant diseases. Therefore, pim kinase has become a potential therapeutic target in the treatment of MM and some pim kinase inhibitors have demonstrated good efficacy in clinical trials. Based on nearly the entire literature searched from PubMed in the field of pim kinase in MM, the paper concluded how pim kinase got involved in the proliferation of myeloma cells, the progression of bone disease infiltration, and even in the regulation of the immune microenvironment. Next as a very promising drug, the effectiveness of pim kinase inhibitors as single agents or in combination with other drugs in the treatment of MM was also summarized. Our analysis will guide the clinical use of pim kinase inhibitors for managing tumor load and bone disease in MM patients.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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