Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study.

Purpose: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial.

Patients And Methods: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.

Notch Signaling Modulates Macrophage Polarization and Phagocytosis Through Direct Suppression of Signal Regulatory Protein α Expression.

The Notch pathway plays critical roles in the development and functional modulation of myeloid cells. Previous studies have demonstrated that Notch activation promotes M1 polarization and phagocytosis of macrophages; however, the downstream molecular mechanisms mediating Notch signal remain elusive. In an attempt to identify Notch downstream targets in bone marrow-derived macrophages (BMDMs) using mass spectrometry, the signal regulatory protein α (SIRPα) appeared to respond to knockout of recombination signal-binding protein Jk (RBP-J), the critical transcription factor of Notch pathway, in macrophages.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.

[Prokaryotic Expression and Purification of the Notch Ligand and Its Effect on Hematopoiesis after Carbon Tetrachloride Damage].

Objective: To express and purify the mouse endothelial cell-targeted recombinant Notch ligand protein mD1R, and to investigate its effect on hematopoiesis after carbon tetrachloride damage.

Methods: PCR was performed to clone and construct the expression vector pET22b(+)-mD1R. The mD1R successfully transformed into E.

Protective roles and mechanisms of polysaccharides from Dendrobium officinal on natural aging-induced premature ovarian failure.

This study was designed to investigate the pharmacological effects and mechanisms of polysaccharides from Dendrobium officinal (DOP) on premature ovarian failure (POF) in natural aging mice. Fifteen months old female mice (n  =  28) and young adult female mice (n  =  14, 6 weeks) were used. DOP (70 mg/kg) was administrated to mice by oral gavage for 10 weeks and the protection effects of DOP on ovaries were investigated in vivo.

Recent advance on genome editing for therapy of β-hemoglobinopathies.

β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies.

[Establishment and Identification of SCL-tTA/BCR-ABL Transgenic Mouse Model with Chronic Myeloid Leukemia].

Objective: To establish transgenic mouse model with chronic myeloid leukemia(CML) by tetracycline withdrawal, so as to provide the experimental tool for studying pathogenesis of CML and searching new therapeutic method for this disease.

Methods: The BCR-ABL expression in stem and progenitor cells in SCL-tTA/BCR-ABL transgenic mice was induced by tetracycline withdrawal in drinking water; and the peripheral hemogram and spleen index were examined after identifying genotypes in mice; the distribution of hematopoietic lineage in bone marrow, spleen and peripheral blood was detected by flow cytometry.

Results: As compared with the control mice, the peripheral hemogram showed the obvious increase of neutrophile granulocyte count and spleen index in BCR-ABL transgenic mice.

Effect of Dendrobium officinale on D-galactose-induced aging mice.

Objective: To examine the effect of Dendrobium officinale (DO) on D-galactose-induced aging mice.

Methods: Aging mice was induced by D-galactose at 0.125 g/kg for 10 weeks through subcutaneous injection except for the negative control group.

The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group.

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide.

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice.

[Correlation between Plasma microRNA Expression and Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].

Objective: To investigate the microRNA (miRNA) expression in plasma of patients with aGVHD and without aGVHD after allo-hematopoietic stem cell transplantation (allo-HSCT).

Methods: The miRNAs (miR-423, mirR199a-3p, miR93*, miR377) expression levels in peripheral blood plasma of 25 patients before and after allo-HSCT were detected by real-time PCR.

Results: miR-423, miR199a-3p and miR-93* in aGVHD group were significantly upregulated (P<0.

Hyperglycemia-induced PATZ1 negatively modulates endothelial vasculogenesis via repression of FABP4 signaling.

Vascular endothelial dysfunction, a central hallmark of diabetes, predisposes diabetic patients to numerous cardiovascular complications. The POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1), is an important transcriptional regulatory factor and regulates divergent pathways depending on the cellular context, but its role in endothelial cells remains poorly understood. Herein, we report for the first time that endothelial PATZ1 expression was abnormally upregulated in diabetic endothelial cells (ECs) regardless of diabetes classification.

Disruption of Notch signaling aggravates irradiation-induced bone marrow injury, which is ameliorated by a soluble Dll1 ligand through Csf2rb2 upregulation.

Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice.

Endothelium-targeted human Delta-like 1 enhances the regeneration and homing of human cord blood stem and progenitor cells.

Background: Umbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell transplantation (HSCT). However, umbilical cord blood transplantation (UCBT) has been severely limited by low and finite numbers of hematopoietic stem cells and their delayed engraftment. New strategies are needed to improve ex vivo expansion efficiency and in vivo haematopoietic recovery.

Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: a multicenter prospective study of 2302 patients in China.

In an attempt to establish the advantages of fluorescence in situ hybridization (FISH) studies over conventional cytogenetic (CC) analysis, a total of 2302 de novo MDS patients from 31 Chinese institutions were prospectively selected in the present study for both CC and standardized FISH analysis for +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities. CC analysis was successful in 94.0% of the patients; of these patients, 35.

[Construction and expression of fusion protein TRX-hJagged1 in E.coli BL21].

This study was purposed to construct prokaryotic expression vector and to investigate the expression of Notch ligand Jagged1 in E.coli. An expression vector pET-hJagged1 was constructed, which can be inserted in Jagged1 with different lengths, but the DSL domain of human Jagged1 should be contained.

FHL1C induces apoptosis in Notch1-dependent T-ALL cells through an interaction with RBP-J.

Background: Aberrantly activated Notch signaling has been found in more than 50% of patients with T-cell acute lymphoblastic leukemia (T-ALL). Current strategies that employ γ-secretase inhibitors (GSIs) to target Notch activation have not been successful. Many limitations, such as non-Notch specificity, dose-limiting gastrointestinal toxicity and GSI resistance, have prompted an urgent need for more effective Notch signaling inhibitors for T-ALL treatment.

Endothelium-targeted Delta-like 1 promotes hematopoietic stem cell expansion ex vivo and engraftment in hematopoietic tissues in vivo.

Background: Notch ligands enhance ex vivo expansion of hematopoietic stem cells (HSCs). But to use Notch ligands in HSC therapies of human diseases, efforts are required to improve ex vivo expansion efficiency and in vivo transplant engraftment.

Design And Methods: We designed and produced an endothelium-targeted soluble Notch ligand, the DSL domain of Delta-like 1 fused with a RGD motif (D1R), and examined the effects of this protein on HSCs ex vivo and in vivo.

Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization.

Dendritic cells (DCs) are professional antigen presenting cells that activate and modulate immune responses, but the mechanisms underlying DC activation have not been fully understood. In this study, we investigated the role of Notch signaling in DC activation by using murine bone marrow-derived DCs. Triggering of Toll-like receptors (TLRs) of DCs led to upregulated expression of Notch ligands.

Differential regulation of bone marrow-derived endothelial progenitor cells and endothelial outgrowth cells by the Notch signaling pathway.

Endothelial progenitor cells (EPCs) are heterogeneous populations of cells that participate in vasculogenesis and promote tissue regeneration. However the different roles of EPC populations in vasculogenesis and tissue regeneration, as well as their regulation and mechanisms remain elusive. In the present study, we cultured bone marrow (BM)-derived early EPCs (EEPCs) and endothelial outgrowth cells (EOCs), and investigated their roles in liver regeneration and their regulation by the Notch signaling pathway.

Soluble extracellular domains of human SIRPα and CD47 expressed in Escherichia coli enhances the phagocytosis of leukemia cells by macrophages in vitro.

Signal regulatory protein (SIRP) α, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages.

Notch signaling pathway and cancer metastasis.

Cancer metastasis is the leading cause of cancer-related deaths all over the world at present. Accumulated researches have demonstrated that cancer metastasis is composed of a series of successive incidents, mainly including epithelial-mesenchymal transition (EMT), malignant cell migration, resistance to anoikis, and angiogenesis and lymphangiogenesis processes. However, the complicated cellular and molecular mechanisms underlying and modulating these processes have not been well elucidated.

Monocyte to macrophage differentiation-associated (MMD) positively regulates ERK and Akt activation and TNF-α and NO production in macrophages.

Macrophage activation is modulated by both environmental cues and endogenous programs. In the present study, we investigated the role of a PAQR family protein, monocyte to macrophage differentiation-associated (MMD), in macrophage activation and unveiled its underlying molecular mechanism. Our results showed that while MMD expression could be detected in all tissues examined, its expression level is significantly up-regulated upon monocyte differentiation.