A Novel Hypoxia-Featured Genes Prognostic Model for Identification of Hypoxia Subtypes in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL), known as the predominant type of aggressive B-cell lymphoma, is biologically and clinically heterogeneous. The prognosis of DLBCL is quite different among subtypes. Hypoxia is one of the key elements in tumor microenvironment, promoting tumor progression by means of various mechanisms, such as increased proliferation, altered metabolism, enhanced angiogenesis, and greater migratory capability, among others.

Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1.

Atherosclerosis results from the deposition and oxidation of LDL and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Studies have shown that transcytosis transports circulating LDL across endothelial cells lining blood vessels. LDL transcytosis is initiated by binding to either scavenger receptor B1 (SR-B1) or activin A receptor-like kinase 1 on the apical side of endothelial cells leading to its transit and release on the basolateral side.

ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs.

Interconnectedness enhances network resilience of multimodal public transportation systems for Safe-to-Fail urban mobility.

The growing interconnectedness of urban infrastructure networks presents challenges to their ability to handle unforeseen disruptions, particularly in the context of extreme weather events resulting from climate change. Understanding the resilience of interconnected infrastructure systems is imperative to effectively manage such disruptions. This study investigates the role of interconnectedness in enhancing the resilience of public transportation systems in Hong Kong, a city heavily reliant on public transit.

Lenalidomide overcomes the resistance to third-generation CD19-CAR-T cell therapy in preclinical models of diffuse large B-cell lymphoma.

Purpose: Chimeric antigen receptor (CAR)-T cells against CD19 have been proven to be effective in treating B-cell hematological malignancies. However, the efficacy of this promising therapy is limited by many factors.

Methods: In this study, the germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) cell line OCI-Ly1, and patient-derived xenografted (PDX) mice (CY-DLBCL) were used as the CAR-T cell-resistant model.

HIF-1α mediates CXCR4 transcription to activate the AKT/mTOR signaling pathway and augment the viability and migration of activated B cell-like diffuse large B-cell lymphoma cells.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy with a high relapse rate. We previously found that C-X-C motif chemokine receptor 4 (CXCR4) was highly expressed in DLBCL and associated with poor prognosis. This study focused on the effect of hypoxia-inducible factor-1α (HIF-1α) on CXCR4 expression and the DLBCL progression.

A Novel and Validated 8-Pyroptosis-Related Genes Based Risk Prediction Model for Diffuse Large B Cell Lymphoma.

Background: Diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin's Lymphoma (NHL), has a lethal nature. Thus, the establishment of a novel model to predict the prognosis of DLBCL and guide its therapy is an urgency. Meanwhile, pyroptosis is engaged in the progression of DLBCL with further investigations required to reveal the underlying mechanism.

Dysregulated MDR1 by PRDM1/Blimp1 Is Involved in the Doxorubicin Resistance of Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

Introduction: The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL.

Methods: Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations.

Palmitoylation of NOD1 and NOD2 is required for bacterial sensing.

The nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2) are intracellular pattern-recognition proteins that activate immune signaling pathways in response to peptidoglycans associated with microorganisms. Recruitment to bacteria-containing endosomes and other intracellular membranes is required for NOD1/2 signaling, and NOD1/2 mutations that disrupt membrane localization are associated with inflammatory bowel disease and other inflammatory conditions. However, little is known about this recruitment process.

Characterization and tentative identification of new flunitrazepam metabolites in authentic human urine specimens using liquid chromatography-Q exactive-HF hybrid quadrupole-Orbitrap-mass spectrometry (LC-QE-HF-MS).

Flunitrazepam (FNZ) is a potent hypnotic, sedative, and amnestic drug used to treat severe insomnia. In our recent study, FNZ metabolic profiles were investigated carefully. Six authentic human urine samples were purified using solid phase extraction (SPE) without enzymatic hydrolysis, and urine extracts were then analyzed by liquid chromatography-Q exactive-HF hybrid quadrupole-Orbitrap-mass spectrometry (LC-QE-HF-MS), using the full scan positive ion mode and targeted MS/MS (ddms2) technique to make accurate mass measurements.

The severe cytokine release syndrome in phase I trials of CD19-CAR-T cell therapy: a systematic review.

CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017.

Clinical significance of chemokine receptor CXCR4 and mammalian target of rapamycin (mTOR) expression in patients with diffuse large B-cell lymphoma.

To assess the relevance of C-X-C chemokine receptor type 4 (CXCR4) and mammalian target of rapamycin (mTOR) to large-B-cell lymphoma (DLBCL), levels of protein expression were measured in 56 DLBCL patients who had received rituximab-based therapy. Of these, 34 were positive for CXCR4 expression (60.7%) and 31 for mTOR (55.

HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal misfolded Blimp-1s in lymphoma cells.

B lymphocyte-induced maturation protein-1 (Blimp-1) ensures B-cell differentiation into the plasma cell stage, and its instability constitutes a crucial oncogenic element in certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). However, the underlying degradation mechanisms and their possible therapeutic relevance remain unexplored. Here, we show that N-terminal misfolding mutations in ABC-DLBCL render Blimp-1 protein susceptible to proteasome-mediated degradation but spare its transcription-regulating activity.

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma.

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.

Low dose of lenalidmide and PI3K/mTOR inhibitor trigger synergistic cytoxicity in activated B cell-like subtype of diffuse large B cell lymphoma.

Background: Activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL) presents aggressive clinical courses and poor prognosis. Targeting key pathways may raise the possibility of improving clinical outcomes.

Methods: The synergetic effects were assessed by CCK-8 assay and measured by isobologram analysis.

Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma.

This study investigated the cytotoxic effect of oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, in human diffuse large B cell lymphoma (DLBCL) in vitro and in vivo and the potential molecular mechanisms for ORI-induced cell apoptosis. ORI treatment caused reactive oxygen species (ROS)-mediated oxidative DNA damage response (DDR) and the c-Jun N-terminal kinase (JNK) pathway activation, leading to an induction of intrinsic apoptosis. ROS abolition blocked ORI-induced apoptosis and attenuated the expression of phospho-histone H2AX and phospho-JNK, indicating that ROS-mediated DNA damage and JNK pathway activation were involved in ORI-induced apoptosis.

Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA.

BAFF level increased in patients with autoimmune hemolytic anemia.

Introduction: BAFF (B-cell activating factor of the TNF family), an important regulator of B-cell, has been observed to be over-expressed in a variety of autoimmune diseases. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease occurred when antibodies directed against autologous red blood cells. We assessed serum levels of BAFF in AIHA patients with different serological characteristics.

Combination of rituximab and mammalian target of rapamycin inhibitor everolimus (RAD001) in diffuse large B-cell lymphoma.

Abstract We evaluated the efficacy of the anti-CD20 monoclonal antibody rituximab in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus for treating diffuse large B-cell lymphoma (DLBCL). The combination of rituximab and everolimus was more effective for inhibiting cell growth compared with single-agent therapy. An increase in G0/G1 cell cycle arrest and an increased population of cells in apoptosis were observed in the combination treatment group.

Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma: clinical significance and inhibitory effect of rituximab.

Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma and accounts for approximately 30% of newly diagnosed lymphoid neoplasms in Western countries, and 40-50% in China. A better understanding of the biology of DLBCL is needed for the development of potential therapeutic agents that target specific intracellular pathways. In this study, expression of the important components of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway and their clinical significance were investigated in 73 DLBCL cases.

Summary of 615 patients of chronic myeloid leukemia in Shanghai from 2001 to 2006.

Background: To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006.

Methods: All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time.

Results: A total of 615 cases entered the study.

The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognised variability in molecular aetiology and clinical outcome. Though the use of agents such as rituximab significantly improves outcome, intrinsic genetic and morphological factors greatly affect the response to treatment. The objective of this study was to evaluate the prognostic value of immunohistochemical subtyping and the International Prognostic Index (IPI) for predicting treatment outcome in Chinese DLBCL patients.