miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer.

Tumor-associated macrophages (TAMs), the main part of immune cells in tumor microenvironment (TME), play a potent role in promoting tumorigenesis through mechanisms such as stimulating angiogenesis, enhancing tumor migration and suppressing antitumor immunity. MicroRNAs (miRNAs) are considered as crucial regulators in multiple biological processes. The relationship between miRNAs and macrophages function has been extensively reported, but the roles that miRNAs play in regulating TAMs phenotype remain unclear.

Predictors of clinical responses to hypomethylating agents in acute myeloid leukemia or myelodysplastic syndromes.

Azacitidine and decitabine, two hypomethylating agents, are known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who cannot endure intensive cytotoxic chemotherapy or are not eligible for transplantation. However, the treatment response rate is low. The molecular mechanisms underlying the resistance to demethylation therapy are unclear.

Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions.

Background: Duchenne muscular dystrophy (DMD), the most common inherited muscular disease in childhood, is caused by dystrophin deficiency because of mutations in the gene. Although DMD is characterized by fatal progressive muscle wasting, cardiomyopathy is the most important nonmuscle symptom threatening the life of patients with DMD. The relationship between cardiac involvement and dystrophin isoforms has not been analyzed.

In Vivo Ovarian Cancer Gene Therapy Using CRISPR-Cas9.

Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) genome editing technology holds great promise for the field of human gene therapy. However, a lack of safe and effective delivery systems restricts its biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1).

Detection of prognostic methylation markers by methylC-capture sequencing in acute myeloid leukemia.

Clinical and genetic features incompletely predict outcome in acute myeloid leukemia (AML). The value of clinical methylation assays for prognostic markers has not been extensively explored. We assess the prognostic implications of methylC-capture sequencing (MCC-Seq) in patients with de novo AML by integrating DNA methylation and genetic risk stratification.

Effect of Antigen Retrieval Methods on Nonspecific Binding of Antibody-Metal Nanoparticle Conjugates on Formalin-Fixed Paraffin-Embedded Tissue.

Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissues provides important diagnostic and prognostic information in pathology. Metal nanoparticles (NPs) and, in particular, surface-enhanced Raman scattering (SERS) nanotags as a new class of labeling reagents are promising to be used for multiplexed protein profiling on tissue sections. However, nonspecific binding of NPs onto the tissue specimens greatly hampers their clinical applications.

Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing.

Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients.

A novel high drug loading mussel-inspired polydopamine hybrid nanoparticle as a pH-sensitive vehicle for drug delivery.

A novel high drug loading pH-cleavable polymer hybrid nanoparticle was prepared via doxorubicin (DOX) grafted onto PEGylated, mussel-inspired polydopamine (PDA) and then coated onto hollow silica nanoparticles for drug delivery. A series of characterization shed light on the formation mechanisms of PDA coatings on hollow silica. We hypothesized that dopamine was first absorbed onto the surface of hollow silica and then began self-polymerization.

ZEB1 confers stem cell-like properties in breast cancer by targeting neurogenin-3.

Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression and . The neurogenin 3 gene () is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness.

Preferred M2 Polarization by ASC-Based Hydrogel Accelerated Angiogenesis and Myogenesis in Volumetric Muscle Loss Rats.

Volumetric muscle loss (VML) injury resulted from massive muscle defects and diseases for which there are still no effective therapeutic treatments. This study aimed to investigate the effects of rat adipose-derived mesenchymal stem cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel on macrophage (MP) transition, myogenesis, and vascularization in the rat VML model. Laser Doppler results demonstrated much higher blood flow in the rASC- and CM-based hydrogel groups.

Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway.

The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant.

Granulocyte-Colony Stimulating Factor (G-CSF) Accelerates Wound Healing in Hemorrhagic Shock Rats by Enhancing Angiogenesis and Attenuating Apoptosis.

BACKGROUND Following severe trauma, treatment of cutaneous injuries is often delayed by inadequate blood supply. The aim of the present study was to determine whether granulocyte-colony stimulating factor (G-CSF) protects endothelial cells (ECs) and enhances angiogenesis in a rat model of hemorrhagic shock (HS) combined with cutaneous injury after resuscitation. MATERIAL AND METHODS The HS rats with full-thickness defects were resuscitated and randomly divided into a G-CSF group (200 μg/kg body weight), a normal saline group, and a blank control group.

Multilevel 3D Printing Implant for Reconstructing Cervical Spine With Metastatic Papillary Thyroid Carcinoma.

Unlabelled: MINI: A 3D printing technology is proposed for reconstructing multilevel cervical spine (C2-C4) after resection of metastatic papillary thyroid carcinoma. The personalized porous implant printed in Ti6AL4V provided excellent physicochemical properties and biological performance, including biocompatibility, osteogenic activity, and bone ingrowth effect.

Study Design: A unique case report.

Correlation Between Isocitrate Dehydrogenase Gene Aberrations and Prognosis of Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.

Whether isocitrate dehydrogenase () gene aberrations affected prognosis of patients with acute myeloid leukemia (AML) was controversial. Here, we conducted a meta-analysis to evaluate their prognostic value. PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies exploring how gene aberrations affected AML outcome.

Analysis and Management of Complications in a Cohort of 1,065 Minimally Invasive Cochlear Implantations.

Objectives: To analyze complications associated with minimally invasive cochlear implantation by comparing data from different centers, to discuss major reasons for complications, and to refine implantation techniques to decrease them.

Patients: Patients who underwent cochlear implantation at our center by the same surgeon (the corresponding author of this article) from March 2006 to March 2015 were enrolled.

Intervention: First, a retrospective analysis of the complications associated with minimally invasive cochlear implantation at our center was performed.

TNFSF15 inhibits VEGF-stimulated vascular hyperpermeability by inducing VEGFR2 dephosphorylation.

Vascular hyperpermeability is critical in ischemic diseases, including stroke and myocardial infarction, as well as in inflammation and cancer. It is well known that the VEGF-VEGFR2 signaling pathways are pivotal in promoting vascular permeability; however, counterbalancing mechanisms that restrict vascular permeability to maintain the integrity of blood vessels are not yet fully understood. We report that TNF superfamily member 15 (TNFSF15), a cytokine largely produced by vascular endothelial cells and a specific inhibitor of the proliferation of these same cells, can inhibit VEGF-induced vascular permeability and , and that death receptor 3 (DR3), a cell surface receptor of TNFSF15, mediates TNFSF15-induced dephosphorylation of VEGFR2.

Clinical implications of genome-wide DNA methylation studies in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. AML is a heterogeneous malignancy characterized by distinct genetic and epigenetic abnormalities. Recent genome-wide DNA methylation studies have highlighted an important role of dysregulated methylation signature in AML from biological and clinical standpoint.

Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence.

Macroautophagy/autophagy has profound implications for aging. However, the true features of autophagy in the progression of aging remain to be clarified. In the present study, we explored the status of autophagic flux during the development of cell senescence induced by oxidative stress.

Combined Tumor- and Neovascular-"Dual Targeting" Gene/Chemo-Therapy Suppresses Tumor Growth and Angiogenesis.

A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with antiangiogenesis/antitumor agents. The truncated bFGF peptide (tbFGF), which could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs) simultaneously loaded with PEDF gene and paclitaxel in this study.

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα.

Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method.

M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.

Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells.

JMJD3 promotes survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms.

JMJD3 (Jumonji domain containing-3), a histone H3 Lys27 (H3K27) demethylase, has been reported to be involved in the antigen-driven differentiation of germinal center B-cells. However, insight into the mechanism of JMJD3 in DLBCL (Diffuse large B-cell lymphoma) progression remains poorly understood. In this study, we investigated the subtype-specific JMJD3-dependent survival effects in DLBCL.

The influence of miR-34a expression on stemness and cytotoxic susceptibility of breast cancer stem cells.

In this study, we investigate the effect of miR-34a expression and biological characteristics of breast cancer stem cells (BCSCs). The mammospheres were formed from murine breast cancer cell line 4T1 and regarded as murine BCSCs. Identification of stemness molecules and cloning experiments validate the biological characteristics of BCSCs we have established.

Copper complexes based on chiral Schiff-base ligands: DNA/BSA binding ability, DNA cleavage activity, cytotoxicity and mechanism of apoptosis.

Four copper(II) complexes with chiral Schiff-base ligands, [Cu(R-L(1))2]·EtOAc (1) and [Cu(S-L(1))2]·EtOAc (2), [Cu(R-L(2))2]·EtOAc (3) and [Cu(S-L(2))2]·EtOAc (4), (R/S-HL(1) = (R/S)-(1-naththyl)-salicylaldimine, R/S-HL(2) = (R/S)-(1-naththyl)-3-methoxysalicylaldimine, EtOAc = ethyl acetate) were synthesized to serve as artificial nucleases and anticancer drugs. All complexes and R/S-HL(1) ligands were structurally characterized by X-ray crystallography. The interaction of these complexes with CT-DNA was researched via several spectroscopy methods, which indicates that complexes bind to CT-DNA by moderate intercalation binding mode.