AIMS This study intends to investigate the mechanisms of ubiqutin-specific protease 22 (USP22)/B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) on the biological phenotypes of glioma stem cells (GSCs) under hypoxia. MAIN METHODS Western blot, Cell Counting Kit-8, colony formation and flow cytometry assays were preformed to evaluate cells biological behaviors. Luciferase assay was utilized to identify the associations among USP22, HIF-1α and BMI1. KEY FINDINGS Silencing USP22 reduced the stemness and proliferation of GSCs, and increased its apoptosis in response to hypoxia.  https://www.selleckchem.com/products/bmh-21.html  Whilst, overexpression of BMI1 reversed these phenomena. Whilst, a significant decrease in proliferation and stemness of GSCs caused by HIF-1α exhaustion were inversed by overexpression of USP22 or BMI1. SIGNIFICANCE Function of USP22-BMI1 on biological behaviors of GSCs was regulated by HIF-1α in response to hypoxia. BACKGROUND AND AIM Forkhead box protein O4 (FOXO4) is a transcription factor, and aberrant FOXO4 expression is associated with development of various human cancers. This study explored the role of FOXO4 in glioma in vitro and in vivo. METHODS FOXO4 expression was first assessed in normal brain tissues, low-grade glioma, glioblastoma multiforme (GBM), normal human astrocytes (HA), and GBM cell lines, while manipulation of FOXO4 expression in glioma cell lines was assessed using qRT-PCR, Western blot, and cell viability CCK-8, Transwell, and a nude mouse subcutaneous xenograft assays. KEY FINDINGS The data showed downregulated FOXO4 expression in GBM tissues and cell lines. FOXO4 overexpression induced by transfection with FOXO4 cDNA significantly inhibited GBM cell proliferation, migration, and invasion, but increased tumor cells to undergo apoptosis in vitro, while suppressed growth of GBM cell subcutaneous xenografts in nude mice. In conclusion, FOXO4 possesses an anti-cancer glioma activity, which could be a novel target for future control of GBM. AIMS Heart failure (HF) is characterized by compromised cardiac structure and function. Previous work has identified a link between upregulation of pro-inflammatory cytokines and HF. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory cytokine, which binds to fibroblast growth factor inducible 14 (Fn14), a ubiquitously expressed cell-surface receptor. The objective of this study was to investigate the role of TWEAK/Fn14 pathway in promoting cardiac inflammation under non ischemic stress conditions. MAIN METHODS Wild type (WT) and Fn14 knock out (Fn14-/-) mice were subjected to pressure overload [transaortic constriction (TAC)] for 1 or 6 weeks. A subset of WT TAC animals were treated with the Fn14 antagonist L524-0366. Cardiac function was measured by echocardiography. Cardiac fibrosis and macrophage infiltration were quantified using immunohistochemistry and flow cytometry, respectively. Cardiac fibroblasts were isolated for quantifying TWEAK-induced chemokine release. KEY FINDINGS Fn14-/- mice displayed improved cardiac function, reduced fibrosis and lower macrophage infiltration in heart compared to WT following TAC. L524-0366 mitigated maladaptive remodeling with TAC. TWEAK induced secretion of the pro-inflammatory chemokine, monocyte chemoattractant protein 1 from WT but not Fn14-/- fibroblasts in vitro, in part through activation of non-canonical NF-κB signaling. Finally, Fn14 expression was increased in mouse following TAC and in human failing hearts. SIGNIFICANCE Our findings support an important role for the TWEAK/Fn14 promoting macrophage infiltration and fibrosis in heart under non-ischemic stress, with potential for therapeutic intervention to improve cardiac function in the setting of HF. Long reconstitution times prior to patient administration remain an undesirable quality attribute for high concentration lyophilized protein formulations. In this study three approaches were developed to study reconstitution behavior of lyophilized, amorphous cakes of a highly concentrated monoclonal antibody (mAb) by exploring their wetting, disintegration and hydration behavior. As the mAb concentration increased from 0 to 83 mg/mL, reconstitution times were longer with poorer wetting, slower hydration and disintegration rates. Further, the effect of controlling ice nucleation temperature at -5 and -10 °C during freezing followed by either conservative or aggressive drying conditions on the reconstitution times was explored in formulations containing 40 and 83 mg/mL mAb. While no effect of either of the two processing conditions was noted at 40 mg/mL, aggressive drying led to faster reconstitution at both the nucleation temperatures with 83 mg/mL mAb. The current study combined with literature data suggests that below a protein to sugar ratio of 1, reconstitution was complete within 1 minute and when the ratio was greater than 1, the reconstitution times increased non-linearly. Disintegration and hydration were determined to be the key mechanisms contributing to the complete reconstitution of the lyophilized, amorphous cakes of the highly concentrated mAb in vials. Interest has developed in the bacillus Calmette-Guerin (BCG) cell wall skeleton (BCG-CWS) as a noninfectious adjuvant. Although BCG-CWS readily undergoes aggregation, in a previous study, we applied it to cancer immunotherapy via intravenous administration by encapsulating the BCG-CWS into nanoparticles (CWS-NPs). The CWS-NPs were taken up by major histocompatibility complex (MHC) class II+ (MHC-II+) cells and induced antigen-specific cytotoxic T lymphocyte (CTL) activity. However, the nature of the contribution of MHC-II+ cells to the CTL response continues to be unclear. In this study, we investigated the relationship between the distribution of CWS-NPs in the spleen and CTL activity. The main MHC-II+ cells that internalized the CWS-NPs were B cells. Decreasing the level of polyethylene glycol modification increased the uptake of CWS-NPs by B cells, leading to an increased CTL activity. A comparison of CWS-NPs with different uptake efficiencies into dendritic cells and B cells suggested that the DCs with internalized CWS-NPs may contribute to CTL activation compared with B cells.