Beard Wichmann (squashhelium10)
Toxicity and drug resistance caused by chemotherapeutic drugs have become bottlenecks in treating tumors. The delivery of anticancer drugs based on nano-carriers is regarded as an ideal way to solve the aforementioned problems. In this study, a new anti-lymphoma nanodrug CD20 aptamer-RBCm@Ag-MOFs/PFK15 (A-RAMP) is designed and constructed, and it consists of two parts 1. metal-organic frameworks Ag-MOFs (AM) loaded with tumor aerobic glycolysis inhibitor PFK15 (P), forming a core part (AMP); 2. targeted molecule CD20 aptamer (A) is inserted into the red blood cell membrane (RBCm) to form the shell part (A-R). A-RAMP under the guidance of CD20 aptamer actively targets B-cell lymphoma both in vitro and in vivo. As a result, A-RAMP not only significantly inhibits the effect on tumor growth, but also shows no obvious side effects on the treated nude mice, indicating that A-RAMP can accurately target tumor cells, reprogram aerobic glycolysis and exert synergistic anti-tumor effect by Ag+ and PFK 15. Furthermore, the anti-tumor mechanism of A-RAMP in vivo by apoptotic pathway and targeting metabonomics are explored. These results suggest that A-RAMP has a promising application prospect as an smart, safe, effective and synergistic anti-lymphoma agent.The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) hold a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe3O4@polydopamine (PDA)@Bovine Serum Albumin (BSA)-Bi2S3 composite as a theranostic agent, by chemically-linking the Fe3O4@PDA with BSA-Bi2S3 via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe3O4 NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H2O2 in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA can prevent the oxidization of Fe3O4 and thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi2S3 component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi2S3 endow the Fe3O4@PDA@BSA-Bi2S3 composite with an excellent photo-thermal transforming ability which can lead to tumor hyperthermia. All these merits, play the synergism with the tumor microenvironment, qualify the Fe3O4@PDA@BSA-Bi2S3 NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.BACKGROUND/AIMS Oxidative stress and mitochondria dysfunction could be involved in the onset of non-alcoholic fatty liver disease (NAFLD) and in its progression to non-alcoholic steatohepatitis (NASH). Estrogens/phytoestrogens could counteract liver fat deposition with beneficial effects against NAFLD by unclear mechanisms. We aimed to analyze the protective effects elicited by genistein/estradiol in hepatocytes cultured in NAFLD-like medium on cell viability, triglycerides accumulation, mitochondrial function and oxidative stress and the role of NLRP3 inflammasome, toll like receptors 4 (TLR4), Akt and 5' AMP-activated protein kinase (AMPK)α1/2. METHODS Human primary hepatocytes/hepatoma cell line (Huh7.5 cells) were incubated with a 2 mM mixture of oleate/palmitate in presence/absence of genistein/17β-estradiol. In some experiments, Huh7.5 cells were exposed to various inhibitors of the above pathways and estrogenic receptors (ERs) and G protein-coupled estrogen receptor (GPER) blockers, before genistein/17r(s). Published by Cell Physiol Biochem Press.Tylenchidae is a widely distributed soil-inhabiting nematode family. Regardless their abundance, molecular phylogeny based on rRNA genes is pr