Gm6377 suppressed SP 2/0 xenograft tumor by down-regulating Myc transcription.

Purpose: Disturbed process of B-cell differentiation into plasmablasts (PBs)/plasma cells (PCs) is involved in multiple myeloma (MM). New strategies will be required to eliminate the MM cell clone for a long-term disease control. Because of its PB-like characteristics, the mus musculus myeloma SP 2/0 cell line was used in this study to search novel targets for PBs/PCs.

[Newly Diagnosed Acute Myeloid Leukemia Patients-Derived Bone Marrow Mesenchymal Stem Cells Suppress Daunorubicin Induced HL-60 Cell Apoptosis via Modulating Caspase-3/Survivin].

Objective: To explore the role of bone marrow niche in the chemotherapy resistance of patient with acute myeloid leukemia (AML), and to investigate the effects of the MSCs on the apoptosis of HL-60 cell and its underlying mechanisms.

Methods: MSCs were derived from the bone marrow of newly diagnosed AML patients (AML-MSCs) and health donors(MSCs) were co-cultured with HL-60 cells respectively. The apoptosis of HL-60 cells in the presence/absence of MSCs and/or Daunorubicin were determined by flow cytometry with Annexin V/PI double staining.

Dammarane-Type Saponins from Prevent Hypoxia-Induced Neural Injury through Activation of ERK, Akt, and CREB Pathways.

possesses neuroprotective bioactivity. However, the effect of gypenosides on hypoxia-induced neural damage remains obscure. In this study, Gyp, the active fraction extracted from and its bioactive compounds as well as the underlying molecular mechanisms were investigated.

FG-4592 Improves Depressive-Like Behaviors through HIF-1-Mediated Neurogenesis and Synapse Plasticity in Rats.

Depression, plus the accompanying memory impairment, is one of the leading causes of disability worldwide. Thus, there is a critical need to develop new drugs based on distinct strategies. FG-4592, an inhibitor of prolyl hydroxylase, activates the hypoxia-inducible factor-1 (HIF-1) pathway, to produce multiple effects on cell properties.

miR-129-5p Regulates the Immunomodulatory Functions of Adipose-Derived Stem Cells via Targeting Stat1 Signaling.

Adipose-derived stem cells (ASCs) have become one of the most promising stem cell populations for cell-based therapies in regenerative medicine and for autoimmune disorders owing to their multilineage differentiation and immunomodulatory capacities, respectively. One advantage of ASC-based therapy lies in their immunosuppressive potential. However, how to get ASCs to provide consistent immunosuppression remains unclear.

Manifold Learning of Dynamic Functional Connectivity Reliably Identifies Functionally Consistent Coupling Patterns in Human Brains.

Most previous work on dynamic functional connectivity (dFC) has focused on analyzing temporal traits of functional connectivity (similar coupling patterns at different timepoints), dividing them into functional connectivity states and detecting their between-group differences. However, the coherent functional connectivity of brain activity among the temporal dynamics of functional connectivity remains unknown. In the study, we applied manifold learning of local linear embedding to explore the consistent coupling patterns (CCPs) that reflect functionally homogeneous regions underlying dFC throughout the entire scanning period.

Altered resting-state functional connectivity of the insula in individuals with clinical high-risk and patients with first-episode schizophrenia.

Objectives: Abnormalities in insular functional connectivity have been implicated in many clinical features of schizophrenia. The aim of this study was to determine to what degree such abnormalities occur in individuals with clinical high risk for psychosis (CHR), and whether which is associated with symptom severity.

Methods: Resting-state fMRI data were collected from 47 healthy controls, 24 CHR individuals and 19 patients with first-episode schizophrenia.

[Deubiquitinase MYSM1 Regulates Differentiation of Human B Cells to Plasma Cells].

Objective: To study the regulatory effect of deubiquitinase MYSM1 on differentiation of B cells to plasma cells.

Methods: The interfering and overexpression plasmids of MYSM1 were constructed and then the corresponding lentiviruses were packaged. Human CD19 B cells were isolated from human peripheral blood with Miltenyi B cell isolation kit.

Tim-3 Promotes Listeria monocytogenes Immune Evasion by Suppressing Major Histocompatibility Complex Class I.

Background: T-cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint inhibitor that has therapeutic implications for many tumors and infectious diseases. However, the mechanisms by which Tim-3 promotes immune evasion remain unclear.

Methods: In this study, we demonstrated that Tim-3 inhibits the expression of major histocompatibility complex class I (MHC-I) in macrophages at both the messenger ribonucleic acid and protein levels by inhibiting the STAT1-NLRC5 signaling pathway.

Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats.

Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear.

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive.

Methods: Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities.

Cardiomyocyte dedifferentiation and remodeling in 3D scaffolds to generate the cellular diversity of engineering cardiac tissues.

The use of engineered cardiac tissues (ECTs) is a new strategy for the repair and replacement of cardiac tissues in patients with myocardial infarction, particularly at late stages. However, the mechanisms underlying the development of ECTs, including cell-scaffold interactions, are not fully understood, although they are closely related to their therapeutic effect. In the present study, we aimed to determine the cellular fate of cardiomyocytes in a 3D scaffold microenvironment, as well as their role in generating the cellular diversity of ECTs by single-cell sequencing analysis.

[Bone Marrow Mesenchymal Stem Cells from Newly Diagnosed Acute Myeloid Leukemia Patients Exhibit Enhanced Osteogenic Differentiation Capacity].

Objective: To study the influence of acute myeloid leukemia (AML) microenvironment on mesenchymal stem cells (MSCs).

Methods: MSCs were isolated from the bone marrow of newly diagnosed AML patients (AML-MSCs) and were cultured. The morphology of MSC was observed by inverted microscopy, the immunophenotypes of MSC were detected by flow cytometry, the proliferation ability of MSC was detected by using MTT method, the multi-differentation ability of MSC was assayed by osteogenic, lipogenic and chrondrogenic induction.

[Effects of Bone Marrow Mesenchymal Stem Cells Derived from Patients with Newly Diagnosed Acute Myeloid Leukemia on the Cell Proliferation, Cell Cycle and Immunophenotypes of HL-60 Cells].

Objective: To explore the role of bone marrow microenvironment(niche) in the development of acute myeloid leukemia (AML) and the effect of AML patients-derived MSC on the proliferation, cell cycle and immuno-phenotypes of HL-60 cells.

Methods: The MSC derived from bone marrow of patients with newly diagnosed AML were isolated and co-cultured with HL-60 cells. The effect of MSC on proliferation of HL-60 cells was detected by using 3H-TdR incorporation method, the cell cycle and immunophenotypes of HL-60 cells were detected by flow cytometry.

The effect of acute glutamate treatment on the functional connectivity and network topology of cortical cultures.

Microelectrode arrays (MEAs) allow the investigation of the pharmacological and toxicological effects of chemicals on cultured neuronal networks. Understanding the functional connections between neurons and the resulting neuronal networks is important for evaluating drugs that affect synaptic transmission. Therefore, we acutely treated a mature cultured neuronal network on MEAs with accumulating amounts of glutamate and recorded their altered electrophysiology.

[Effects of simulated high-altitude hypobaric hypoxia on cardiac structure and function in rats].

Objective: To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats.

Methods: A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group (hypoxia group) and normobaric normoxia group (control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment.

CKIP-1 regulates the immunomodulatory function of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are self-renewing multipotent cells with immunoregulatory function, which makes them attractive candidates for regenerative medicine. However, the detailed mechanisms of their immunomodulatory capacity are not fully characterized. Here, we found that casein kinase 2 interacting protein-1 (CKIP-1) expression was induced in the murine MSC cell line C3H/10T1/2 by LPS.

Predicting the regrowth of clinically non-functioning pituitary adenoma with a statistical model.

Background: Compared with clinically functioning pituitary adenoma (FPA), clinically non-functioning pituitary adenoma (NFPA) lacks of detectable hypersecreting serum hormones and related symptoms which make it difficult to predict the prognosis and monitoring for postoperative tumour regrowth. We aim to investigate whether the expression of selected tumour-related proteins and clinical features could be used as tumour markers to effectively predict the regrowth of NFPA.

Method: Tumour samples were collected from 295 patients with NFPA from Beijing Tiantan Hospital.

Modulation of Beta Oscillations for Implicit Motor Timing in Primate Sensorimotor Cortex during Movement Preparation.

Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking.

Construction and evaluation of SAK-HV protein oral dosage form based on chitosan quaternary ammonium salt-PLGA microsphere.

The aim of this study was to realize the oral delivery of SAK-HV protein and improve its oral bioavailability based on chitosan quaternary ammonium salt-PLGA microsphere. The results showed that the SAK-HV-loaded microsphere can overcome the multiple obstacles for oral adsorption and adhere effectively to the jejunal segment of a rat. The pharmacokinetic analysis of the oral drug-loaded microspheres in rats showed that the blood drug concentration of SAK-HV reached the peak value at 4 h after oral administration, and the relative oral bioavailability of SAK-HV was 3.

FKBP12 mediates necroptosis by initiating RIPK1-RIPK3-MLKL signal transduction in response to TNF receptor 1 ligation.

Necroptosis is a regulated form of necrotic cell death that is mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed-lineage kinase domain-like protein (MLKL), which mediates necroptotic signal transduction induced by tumor necrosis factor (TNF). Although many target proteins for necroptosis have been identified, no report had indicated that FK506-binding protein 12 (FKBP12, also known as FKBP1A), an endogenous protein that regulates protein folding and conformation alteration, is involved in mediating necroptosis. In this study, we found that FKBP12 acts as a novel target protein in mediating necroptosis and the related systemic inflammatory response syndrome triggered by TNF.

Up-regulation of FAM64A promotes epithelial-to-mesenchymal transition and enhances stemness features in breast cancer cells.

FAM64A was found to be markedly up-regulated in tumor samples and associated with worse overall survival in multiple cancer types, including breast cancer. However, the functional significance of FAM64A in breast cancer remains largely unknown. In this study, we systematically investigated the expression of FAM64A in multiple public breast cancer datasets.

Loc108167440 suppressed myeloma cell growth by P53-mediated apoptosis.

Multiple myeloma (MM) results from biased proliferation of cancerous plasma cells (PC). Therapeutic strategies that target MM PC will provide immense value to the treatment of MM. For this, it is necessary to identify novel molecules that differ between MM PC and healthy PC.

Mysm1 epigenetically regulates the immunomodulatory function of adipose-derived stem cells in part by targeting miR-150.

Adipose-derived stem cells (ASCs) are highly attractive for cell-based therapies in tissue repair and regeneration because they have multilineage differentiation capacity and are immunosuppressive. However, the detailed epigenetic mechanisms of their immunoregulatory capacity are not fully defined. In this study, we found that Mysm1 was induced in ASCs treated with inflammatory cytokines.