Up-regulation of MiR-205 under hypoxia promotes epithelial-mesenchymal transition by targeting ASPP2

The epithelial–mesenchymal transition (EMT) is one of the crucial procedures for cancer invasion and distal metastasis. Despite undergoing intensive studies, the mechanisms underlying EMT remain to be completely elucidated. Here, we identified that apoptosis-stimulating protein of p53-2 (ASPP2) is a novel target of MiR-205 in various cancers. Interestingly, the binding site of MiR-205 at the 3′-untranslated region of ASPP2 was highly conserved among different species. An inverse correlation between MiR-205 and ASPP2 was further observed in vivo in cervical cancers, suggesting MiR-205 may be an important physiological inhibitor of ASPP2. Hypoxia is a hallmark of solid tumor microenvironment and one of such conditions to induce EMT. Notably, MiR-205 was remarkably induced by hypoxia in cervical and lung cancer cells. A marked suppression of ASPP2 was observed simultaneously. Further studies confirmed that hypoxia-induced ASPP2 suppression was mainly attributed to the elevated MiR-205. Interestingly, the alteration of MiR-205/ASPP2 under hypoxia was accompanied with the decreased epithelial marker E-cadherin and increased mesenchymal marker Vimentin, as well as a morphological transition from the typical cobblestone-like appearance to the mesenchymal-like structure. More importantly, MiR-205 mimics or ASPP2 silencing similarly promoted EMT process. By contrast, ASPP2 recovery or MiR-205 inhibitor reversed MiR-205-dependent EMT. Further studies demonstrated that the newly revealed MiR-205/ASPP2 axis promoted cell migration and also increased cell proliferation both in vivo and in vitro. These data together implicated a critical impact of MiR-205/ASPP2 on promoting EMT. MiR-205/ASPP2 may be potential diagnostic and therapeutic biomarkers in cervical and lung cancers

Recent progress in atomically precise Ag/Cu-based hydride clusters

Owing to advantages in synthesis, separation, structure determination, and low cost (compared to noble metal nanoclusters), Ag/Cu hydride clusters (and their alloys) have received increasing research interest in recent decades and have shown great potential in mediating reduction reactions and H2 storage applications. The atomic precision of the Ag/Cu hydride clusters with the combination of single-crystal X-ray diffraction, 1/2H nuclear magnetic resonance, electrospray ionization mass spectrometry, density functional theory, and particularly, single-crystal neutron diffraction, has provided pivotal information regarding its structural characteristics, facilitating a deep understanding of the inherent bonding principles therein. This review summarizes the research progress of atomically precise Ag/Cu hydride clusters (and their alloys) over the past three years (2021–2023), mainly focusing on the synthesis, structure analysis, and catalytic applications of the hydride clusters. We believe that this review can benefit the future design of different types of metal hydride clusters and aid in their application in various redox reactions

Exosomes and Their Application as Drug Delivery System in Cancer Therapy

Exosomes are extracellular vesicles naturally released from cells. Exosomes from different sources play different roles in cellular component exchange, signal transduction, and pathological development. Exosomes have distinct biological characteristics such as low immunogenicity, easy uptake by cells, crossing the blood-brain barrier, natural targeting, and easy modification. Many studies show that exosomes as drug carriers have a great application prospect in cancer therapy. In this review, we review the biogenesis, origin, biological characteristics of exosomes, and the exosome drug delivery system and its application for cancer therapy are summarized to provide a reference for the study of exosomes

“Adjust Zang and arouse spirit” electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice

IntroductionDiabetic cognitive impairment (DCI) is a chronic complication of the central nervous system (CNS) caused by diabetes that affects learning and memory capacities over time. Recently, acupuncture has been shown to improve cognitive impairment in streptozotocin-induced diabetic rats. However, the effects of electroacupuncture on DCI and its underlying mechanism have not yet been elucidated in detail. MethodsIn this study, we used db/db mice as DCI animal models which showed low cognitive, learning and memory functions. Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. The db/db mice with cognitive impairment were randomly divided into a model group (Mod) and an electroacupuncture treatment group (Acup), while db/m mice were used as a normal control group (Con). First, the mice were subjected to behavioural tests using the Morris water maze (MWM), and body weight, blood glucose, insulin, triglycerides (TG) and total cholesterol (TC) were observed; HE, Nissl, and TUNEL staining were used to observe the morphological changes and neuronal apoptosis in the mice hippocampus; Finally, Western blot and rt-PCR were applied to detect the essential proteins and mRNA of ERS and insulin signalling pathway, as well as the expression levels of Tau and Aβ.ResultsElectroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. Moreover, electroacupuncture attenuated diabetes-induced morphological structure change, neuronal apoptosis in the hippocampus of db/db mice. Our results revealed that electroacupuncture could regulate the expression levels of Tau and Aβ by improving hippocampal ERS levels in db/db mice, inhibiting JNK activation, attenuating IRS1 serine phosphorylation, and restoring normal transduction of the insulin signaling pathway.DiscussionIn summary, ERS and insulin signaling pathway paly causal roles in DCI development. Electroacupuncture can significantly alleviate the pathogenesis of DCI, improve mice's learning and memory ability, and improve cognitive dysfunction. This study adds to our understanding of the effect of acupuncture on DCI and opens the door to further research on DCI