Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo.

Targeting Senescent Alveolar Epithelial Cells Using Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles To Treat Pulmonary Fibrosis.

Type 2 alveolar epithelial cell (AEC2) senescence is crucial to the pathogenesis of pulmonary fibrosis (PF). The nicotinamide adenine dinucleotide (NAD)-consuming enzyme cluster of differentiation 38 (CD38) is a marker of senescent cells and is highly expressed in AEC2s of patients with PF, thus rendering it a potential treatment target. Umbilical cord mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) have emerged as a cell-free treatment with clinical application prospects in antiaging and antifibrosis treatments.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs.

COVID-19 in China and the US: Differences in Hospital Admission Co-Variates and Outcomes.

(1) Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites, there are few, if any, subject-level comparisons between sites in regions and countries. We investigated differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. (2) Methods: We retrospectively analyzed clinical data on 1859 hospitalized subjects with COVID-19 in Wuhan City, China, from 20 January to 4 April 2020.

Extracellular vesicles deposit to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration.

Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs).

Cancer increases risk of in-hospital death from COVID-19 in persons <65 years and those not in complete remission.

The impact of cancer on outcome of persons with coronavirus disease 2019 (COVID-19) after infection with acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is controversial. We studied 1859 subjects with COVID-19 from seven centers in Wuhan, China, 65 of whom had cancer. We found having cancer was an independent risk factor for in-hospital death from COVID-19 in persons <65 years (hazard ratio [HR] = 2.

Risk factors for death in 1859 subjects with COVID-19.

We studied 1859 subjects with confirmed COVID-19 from seven centers in Wuhan 1651 of whom recovered and 208 died. We interrogated diverse covariates for correlations with risk of death from COVID-19. In multi-variable Cox regression analyses increased hazards of in-hospital death were associated with several admission covariates: (1) older age (HR = 1.

Hematological features of persons with COVID-19.

We studied admission and dynamic demographic, hematological and biochemical co-variates in 1449 hospitalized subjects with coronavirus infectious disease-2019 (COVID-19) in five hospitals in Wuhan, Hubei province, China. We identified two admission co-variates: age (Odds Ratio [OR] = 1.18, 95% Confidence Interval [CI] [1.

Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3.

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents, such as vitamin D compounds, is a potential regimen to treat acute myeloid leukemia (AML) patients who are unfit for high-intensity chemotherapy. The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3 (1,25-D3). Here, firstly, cBioPortal database was used and we found out that vitamin D receptor (VDR) was highly expressed in acute monocytic leukemia (M5) and high VDR expression was associated with a poor survival of AML patients.

Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells.

Senescence in human mesenchymal stem cells (MSCs) not only contributes to organism aging and the development of a variety of diseases but also severely impairs their therapeutic properties as a promising cell therapy. Studies searching for efficient biomarkers that represent cellular senescence have attracted much attention; however, no single marker currently provides an accurate cell-free representation of cellular senescence. Here, we studied characteristics of MSC-derived microvesicles (MSC-MVs) that may reflect the senescence in their parental MSCs.

Interferon-γ alters the immune-related miRNA expression of microvesicles derived from mesenchymal stem cells.

Increasing studies have demonstrated that interferon gamma (IFN-γ), which serves as a critical inflammatory cytokine, is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs). However, the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood. MSC-derived microvesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs.

Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6.

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected.