Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.

Quantum anomalous Hall effect and topological phase transition in two-dimensional antiferromagnetic Chern insulator NiOsCl6.

By doing calculations based on density functional theory, we predict that the two-dimensional anti-ferromagnetic (AFM) NiOsCl6 as a Chern insulator can realize the quantum anomalous Hall (QAH) effect. We investigate the magnetocrystalline anisotropy energies in different magnetic configurations and the Néel AFM configuration is proved to be ground state. When considering spin-orbit coupling (SOC), this layered material with spins perpendicular to the plane shows properties as a Chern insulator characterized by an inversion band structure and a nonzero Chern number. The nontrivial band gap is 37 meV and the Chern number C = -1, which are induced by a strong SOC and AFM order. With strong SOC, the NiOsCl6 system performs a continuous topological phase transition from the Chern insulator to the trivial insulator upon the increasing Coulomb repulsion U. The critical U c is indicated as 0.23 eV, at which the system is in a metallic phase with [Formula: see text]. Upon increasing U, the E g reduces linearly with C = -1 for 0 < U < U c and increases linearly with C = 0 for U > U c . At last we analysis the QAH properties and this continuous topological phase transition theoretically in a two-band [Formula: see text] model. This AFM Chern insulator NiOsCl6 proposes not only a promising way to realize the QAH effect, but also a new material to study the continuous topological phase transition.

Highly expressed long non-coding RNA CRNDE promotes cell proliferation through PI3K/AKT signalling in non-small cell lung carcinoma.

Recently, numerous studies have revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigate the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively. We also investigated the effect of abnormal CRNDE expression on cyclins and PI3K/AKT pathway. Furthermore, si-CRNDE NSCLC cell lines were injected subcutaneously into nude mice to explore tumour formation in vivo. The expression of CRNDE was significantly upregulated in NSCLC patients and cells. In addition, both loss and gain function assays revealed that CRNDE promoted NSCLC cell proliferation and growth both in vitro and in vivo. Moreover, CRNDE regulated the cell cycle transition from G0 /G1 stage to S stage and modulated the expression of CDK4, CDK6 and CCNE1. We further illustrated that CRNDE activated PI3K/AKT signalling in NSCLC cell lines. In conclusion, CRNDE was highly expressed in NSCLC malignant tissues and the heightened CRNDE strongly promoted NSCLC cell proliferation and growth through activating PI3K/AKT signalling; our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of NSCLC.