Fetal hepatocytes protect the HSPC genome via fetuin-A.

The maintenance of genomic integrity in rapidly proliferating cells is a substantial challenge during embryonic development. Although numerous cell-intrinsic mechanisms have been revealed, little is known about genome-protective effects and influences of developmental tissue microenvironments on tissue-forming cells. Here we show that fetal liver hepatocytes provide protection to haematopoietic stem and progenitor cell (HSPC) genomes.

[Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia].

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms.

Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample -tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group.

[Hippocampal Development Deviation and Its Relationship With Cognition in Major Psychiatric Disorders].

Objective: To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder.

Methods: The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3.

FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia.

Background: Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown.

Preoperative LMR and Serum CA125 Level as Risk Factors for Advanced Stage of Ovarian Cancer.

This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging.

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia.

Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25% to 30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, they cannot eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel effective treatment strategies.

Combined Preoperative LMR and CA125 for Prognostic Assessment of Ovarian Cancer.

: To investigate the role of inflammation-related factors, lymphocyte-to-monocyte ratio (LMR) alone and combined detection with cancer antigen 125 (CA125), in the prognostic assessment of ovarian cancer (OC). : A retrospective clinicopathologic review was performed. The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC predicting mortality in OC patients were constructed.

Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia.

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.

Chemotherapy-induced niche perturbs hematopoietic reconstitution in B-cell acute lymphoblastic leukemia.

Background: Considerable efforts have been devoted toward the uncovering of the molecular mechanisms underlying the maintenance of hematopoietic stem cells (HSCs) by the normal bone marrow (BM) niche. Previously, we demonstrated that a chemotherapy-induced niche, which is mainly composed of mesenchymal stem cells (MSCs), protects the residual B-cell acute lymphoblastic leukemia (B-ALL) cells from the insult of chemotherapeutic drugs. However, the roles of chemotherapy-induced niche on HSCs functions in B-ALL remain unclear.

Leukaemic alterations of IKZF1 prime stemness and malignancy programs in human lymphocytes.

Somatic cells acquire stem cell-like properties during cancerous transformation; however, mechanisms through which committed cells develop stemness and malignancy remain largely unknown. Here we uncovered upregulated stem cell program in leukaemic lymphoblasts of patients with IKZF1 alterations by analysing the archived gene-expression profiling datasets. We then used a frequent IKZF1 deletion, IK6, as a model via transduction into human primitive haematopoietic cells, followed by xenotransplantation in mice.

Recipient bone marrow assimilates the myeloid/lymphoid reconstitution of distinct fetal hematopoietic stem cells.

The fetal liver (FL) is a source of hematopoietic stem and progenitor cells (HSPCs) for transplantation. However, whether FL-HSPCs collected at distinct developmental stages reconstitute similarly or differently in the recipient bone marrow (BM) remains undetermined. We examined this problem in a congeneic mouse transplantation model.

APC/C is essential for hematopoiesis and impaired in aplastic anemia.

Anaphase promoting complex/cyclosome (APC/C) is essential for cell cycle progression. Recently, its non-mitotic functions were also reported but less studied in several tissues including hematopoietic cells. Here, we developed an inducible (a core subunit of APC/C) knockout mice.

Neoplasms in the bone marrow niches: disturbance of the microecosystem.

Increasing studies have revealed that the interaction between malignant cells and the microenvironment (so called niche) in the bone marrow can influence the development and progression of the hematopoietic malignancies. Here, we reviewed the current findings in the field, focusing the niche alterations in promoting the emergency of malignancies, in interfering with the blood reconstitution of normal hematopoietic stem and progenitor cells, and in protecting leukemic stem cells from therapy which causes disease relapse. We made efforts to discuss these aspects in view of a kind of disturbance of the microecosystem within BM and thus proposed some new concepts in therapeutics of blood malignancies.

Self-assembled targeted folate-conjugated eight-arm-polyethylene glycol-betulinic acid nanoparticles for co-delivery of anticancer drugs.

In this study, a targeted nanoparticle platform for co-delivery of anticancer drugs based on folate-conjugated eight-arm-polyethylene glycol-betulinic acid (F-8arm-PEG-BA) was first presented. F-8arm-PEG-BA was synthesized by introducing target molecules (folate) and drug molecules (betulinic acid, BA) to hydrophilic molecules (8arm-PEG). Then another anticancer drug, hydroxycamptothecin (HCPT), was encapsulated into the self-assembled nanoparticles from the conjugate by a simple nanoprecipitation method.

Detoxification of corncob acid hydrolysate with SAA pretreatment and xylitol production by immobilized Candida tropicalis.

Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate.

Leukemia propagating cells rebuild an evolving niche in response to therapy.

Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL).

A novel cleaning process for industrial production of xylose in pilot scale from corncob by using screw-steam-explosive extruder.

Steam explosion is the most promising technology to replace conventional acid hydrolysis of lignocellulose for biomass pretreatment. In this paper, a new screw-steam-explosive extruder was designed and explored for xylose production and lignocellulose biorefinery at the pilot scale. We investigated the effect of different chemicals on xylose yield in the screw-steam-explosive extrusion process, and the xylose production process was optimized as followings: After pre-impregnation with sulfuric acid at 80 °C for 3 h, corncob was treated at 1.

CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts.

Human NK cells are divided into CD56(bright)CD16(-) cells and CD56(dim)CD16(+) cells. We tested the hypothesis that CD56(bright) NK cells can differentiate into CD56(dim) cells by prospectively isolating and culturing each NK subset in vitro and in vivo. Our results show that CD56(bright) cells can differentiate into CD56(dim) both in vitro, in the presence of synovial fibroblasts, and in vivo, upon transfer into NOD-SCID mice.

Vascular Endothelial Growth Factor and Its Receptor KDR/flk-1 Play Important Roles in Hematopoiesis.

It is widely accepted that hematopoietic and endothelial cell lineages are initiated from the same precursor cells (named as hemangioblast), although hemangioblast has not been proved. Vascular endothelial growth factor (VEGF) and its receptor KDR/flk-1 is a prime regulator of endothelial cell proliferation, angiogenesis, vasculogenesis and vascular permeability. It is speculated that VEGF and its receptor KDR/flk-1 may also play an important role in embryonic and postnatal hematopoiesis.