Breaking Tumor Chemoresistance via METTL3 Regulation Enhanced by Sequential Delivery of Dexamethasone.

The frequent occurrence of chemoresistance in breast tumors remains a challenge to achieving satisfactory therapeutic efficacy, and a smart drug delivery system with flexible properties is urgently needed to achieve an all-in-one combination anticancer therapy. In this study, an efficiency delivery system with a pH-triggered detachable PEG layer (sPEG) and a folic acid (FA)-modified cationic liposome core (FLip) is constructed for codelivering doxorubicin (DOX) and METTL3 siRNA (siMETTL3). The obtained codelivery nanoparticles (NPs), sPEG-FLip@DOX/siMETTL3, can maintain circulatory stability with minimized systemic toxicity, which is attributed to the negatively charged sPEG layer, and expose the positively charged FLip core in the weakly acidic extracellular environment to facilitate the internalization by MCF-7/ADR cells.

Kidney thrombotic microangiopathy with concurrent monoclonal gammopathy.

Background: The concurrence of monoclonal gammopathy and thrombotic microangiopathy (TMA) has been suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features.

Dexamethasone Pretreatment Potentiates a Folic Acid-Functionalized Delivery System for Enhanced Lung Cancer Therapy.

Folic acid (FA) has been widely engineered to promote the targeted delivery of FA-modified nanoparticles (NPs) by recognizing the folate receptor α (FRα). However, the efficacy of FA-targeted therapy significantly varied with the abundance of FRα and natural immunoglobulin levels in different tumors. Therefore, a sequential therapy of dexamethasone (Dex)-induced FRα amplification and immunosuppression combined with FA-functionalized doxorubicin (DOX) micelles to synergistically suppress tumor proliferation was proposed in this study.

Tumor immunosuppression relief via acidity modulation combined PD-L1 siRNA for enhanced immunotherapy.

The efficacy of immune checkpoint therapy is limited by the immunosuppressive tumor microenvironment (TME), and lactate, the most universal component of TME, has been rediscovered that plays important roles in the regulation of metabolic pathways, angiogenesis, and immunosuppression. Here, a therapeutic strategy of acidity modulation combined with programmed death ligand-1 (PD-L1) siRNA (siPD-L1) is proposed to synergistically enhance tumor immunotherapy. The lactate oxidase (LOx) is encapsulated into the hollow Prussian blue (HPB) nanoparticles (NPs) prepared by hydrochloric acid etching followed by the modification with polyethyleneimine (PEI) and polyethylene glycol (PEG) via sulfur bonds (HPB-S-PP@LOx), siPD-L1 is loaded via electrostatic adsorption to obtain HPB-S-PP@LOx/siPD-L1.

A multifunctional non-viral vector for the delivery of MTH1-targeted CRISPR/Cas9 system for non-small cell lung cancer therapy.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system adapted from bacteria is a programmable nuclease-based genome editing tool. The long-lasting effect of gene silencing or correction is beneficial in cancer treatment. Considering the need to broaden the practical application of this technology, highly efficient non-viral vectors are urgently required.

The complement system and autoimmune diseases.

The complement system plays a key role in the pathogenesis of autoimmune diseases, which usually injures the kidney. More and more studies have shown the pathogenic role and indicated that abnormal activation of the complement system was highly involved in the outbreak of autoimmune diseases. This review mainly introduced recent studies of complement system activation contributing to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, antiphospholipid syndrome, antineutrophil cytoplasmic antibody-associated vasculitides, and so on.

Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis.

We used radioresistant SU3-5R stem cells-inoculated subcutaneous glioma model to investigate the radiosensitization effect of apigenin. After treatment of glioma with apigenin 20 mg/kg for 12 days, irradiation 8 Gray twice or their combination, the tumor volume and weight were decreased, especially in the combination group. Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues.

Coadministration of iRGD peptide with ROS-sensitive nanoparticles co-delivering siFGL1 and siPD-L1 enhanced tumor immunotherapy.

The continuous activation and expansion of tumor-specific T cells by various means are the main goal of cancer immunotherapy. Tumor cells overexpress fibrinogen-like protein 1 (FGL1) and programmmed death-ligand 1 (PD-L1), which respectively bind to lymphocyte-activation gene 3 (LAG-3) and programmmed death-1(PD-1) on T cells, forming important signaling pathways (FGL1/LAG-3 and PD-1/PD-L1) that negatively regulate immune responses. In order to interfere with the inhibitory function of FGL1 and PD-L1 proteins, we designed a new type of reactive oxygen species (ROS)-sensitive nanoparticles to load FGL1 siRNA (siFGL1) and PD-L1 siRNA (siPD-L1), which was formed from a stimuli-responsive polymer with a poly-l-lysine-thioketal and modified cis-aconitate to facilitate endosomal escape.

Lactate Consumption via Cascaded Enzymes Combined VEGF siRNA for Synergistic Anti-Proliferation and Anti-Angiogenesis Therapy of Tumors.

Lactate, as the most abundant component with concentrations of 4-40 mm in tumors, contributes to the regulation of metabolic pathways, angiogenesis, and immunosuppression, exhibiting remarkable potential in cancer treatment. Therefore, a codelivery strategy that combined the cascaded enzymes Lactate oxidase/Catalase (LOx/CAT) and vascular endothelial growth factor (VEGF) siRNA (siVEGF) to suppress tumor proliferation and angiogenesis synergistically is creatively proposed. In brief, the cationic liposomes (LIP) encapsulated with LOx/CAT and siVEGF via hydrophilic interaction and electrostatic adsorption followed by coating with PEGylated phenylboronic acid (PP) is established (PPL@[LOX+CAT]).

Apigenin-induced HIF-1α inhibitory effect improves abnormal glucolipid metabolism in AngⅡ/hypoxia-stimulated or HIF-1α-overexpressed H9c2 cells.

Background: Apigenin, a natural flavonoid compound, can improve the myocardial abnormal glucolipid metabolism and down-regulate the myocardial hypoxia inducible factor-1α (HIF-1α) in hypertensive cardiac hypertrophic rats. However, whether or not the ameliorative effect of glucolipid metabolism is from the reduction of HIF-1α expression remains uncertain.

Purpose: This study aimed to investigate the exact relationship between them in angiotensin Ⅱ (Ang Ⅱ)/hypoxia-stimulated or HIF-1α overexpressed H9c2 cells.

Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway.

Stevioside, a natural glycoside compound, has many beneficial biological activities, but its protective effect on myocardial fibrosis has not been reported yet. This study aimed to investigate the effect of stevioside. The isoproterenol-induced model mice were orally given stevioside 75-300 mg kg-1 for 40 days.