Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gßγ-VEGFR2 complex formation.

Gastric cancer (GC) is a prevalent digestive tract malignant tumor characterized by an insidious onset, ease of metastasis, rapid growth, and poor prognosis. Here, we report that fibronectin type III domain containing 1 (FNDC1) has high expression in GC and indicates poor outcomes in patients with GC. FNDC1 over-expression or knockdown promotes or inhibits tumorigenesis and metastasis, respectively. The expression of FNDC1 is upregulated by TWIST1, strengthening its interaction with Gßγ and VEGFR2. The formation of the trimers, TWIST1 plus Gßγ and VEGFR2, increases VEGFR2 phosphorylation and Gßγ trafficking, which activates RAS-MAPK and PI3K-AKT signaling, benefiting GC progression. In this study, we demonstrated that arsenite can efficiently suppress FNDC1 expression, attenuating the formation of the trimers and downstream pathways. Altogether, our results indicate that FNDC1 might be a promising target for clinical treatment and prognostic judgment, while FNDC1 inhibition by arsenite provides a new opportunity for overcoming this fatal disease.

Displacement sensing in a multimode SNAP microcavity by an artificial neural network.

Benefiting from the coupling between the Surface Nanoscale Axial Photonics (SNAP) microcavity and the waveguide, i.e., influenced by their abrupt field overlap, multiple axial modes in the transmission spectrum form a functional relationship with the coupling position, thus enabling displacement sensing. However, this functional relationship is complex and nonlinear, which is difficult to be fitted using analytical methods. We introduce a back-propagation neural network (BPNN) to model this functional relationship. The numerical results show that the multimode sensing scheme has great potential for practical large-range, high-precision displacement sensing platforms compared with the single-mode sensing based on the whispering gallery mode (WGM) resonators.

Asiaticoside alleviates cardiomyocyte apoptosis and oxidative stress in myocardial ischemia/reperfusion injury via activating the PI3K-AKT-GSK3ß pathway in vivo and in vitro.

Background: Myocardial ischemia/reperfusion (MI/R) is one of the most important links in myocardial injury, causing damage to cardiac tissues including cell apoptosis, oxidative stress, and other serious consequences. Asiaticoside (AS), a new compound synthesized from genistein, is cardioprotective. This paper presents new evidence for the protective role of AS against MI/R injury in vitro and in vivo. Methods: First, BALB/c mice underwent surgical ligation of the left anterior descending (LAD) artery to establish an MI/R animal model, and HL-1 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to establish an in vitro model. Myocardial infarct size was examined by triphenyl tetrazolium chloride (TTC) staining, histopathological changes detected in heart tissues were observed using hematoxylin and eosin (H&E) and Masson staining, heart tissue apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze cardiac troponin I (CTnI), creatine kinase-muscle and brain (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH). Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and live/dead assay. Cell apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential, and mitochondrial superoxide were detected by flow cytometry and fluorescence microscopy. Both the protein expression in myocardial tissues and cardiomyocytes were examined by western blot. Results: In the in vivo MI/R experiments,pretreatment of AS reduced myocardial infarct size, decrease leakage of myocardial enzyme, suppressed myocardial apoptosis, myocardial collagen deposition, and oxidative stress. In the in vitro OGD/R experiments, HL-1 cells pretreated with AS had increased cell viability, decreased apoptosis rates and depolarization of mitochondrial membrane potential, and attenuated intracellular ROS and mitochondrial superoxide. Moreover, AS downregulated the expression of apoptotic protein, and promoted phosphorylation of PI3K, AKT, and GSK3ß, which was reversed by PI3K inhibitor LY294002. Conclusions: The AS compound protects against MI/R injury by attenuating oxidative stress and apoptosis via activating the PI3K/AKT/GSK3ß pathway in vivo and vitro.

Astragaloside IV protects cardiomyocytes against hypoxia injury via HIF-1α and the JAK2/STAT3 pathway.

BACKGROUND: Hypoxia is an important cause of myocardial injury due to the heart's high susceptibility to hypoxia. Astragaloside IV (AS-IV) is the main component of Astragalus membranaceus and could exert cardiac protective role. Here, the effect of AS-IV on hypoxia-injured H9c2 cardiomyocytes was elucidated. METHODS: First, H9c2 cells were exposed to hypoxia and/or AS-IV treatment. Cell apoptosis, death, and viability as well as hypoxia-inducible factor 1α (HIF-1α) expression and apoptotic proteins were analyzed. Next, transfection of si-HIF-1α into H9c2 cells was carried out to test whether upregulation and stabilization of HIF-1α influences the effect of AS-IV on hypoxia-treated H9c2 cells. Furthermore, the regulatory role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling on HIF-1α levels was examined. RESULTS: Hypoxia suppressed viability and promoted the apoptosis and death of H9c2 cells. AS-IV eliminated hypoxia-induced H9c2 injury. Moreover, HIF-1α signaling was further activated and stabilized by AS-IV in hypoxia-challenged H9c2 cells. Downregulation of HIF-1α suppressed the function of AS-IV in hypoxia-challenged H9c2 cells. AS-IV promoted JAK2/STAT3 signaling in hypoxia-induced injury. The beneficial functions of AS-IV in hypoxia-exposed H9c2 cells were linked to HIF-1α upregulation and JAK2/STAT3 signaling activation. CONCLUSIONS: AS-IV relieved H9c2 cardiomyocyte injury after hypoxia, possibly by activating JAK2/STAT3-mediated HIF-1α signaling.

Simulation and Optimization of SNAP-Taper Coupling System in Displacement Sensing.

Sensing applications based on whispering gallery mode (WGM) microcavities have attracted extensive attention recently, especially in displacement sensing applications. However, the traditional displacement sensing scheme based on shift in a single resonance wavelength, has a lot of drawbacks. Herein, a novel displacement sensing scheme based on the surface nanoscale axial photonics (SNAP) is proposed to achieve a wide range and high-resolution displacement sensor through analyzing the transmittance of multiple axial modes. By analyzing the surface plot of the resonance spectrum with different coupling positions, the ideal coupling parameters and ERV for displacement sensing are obtained. In the following, displacement sensing with high sensitivity and a wide range is theoretically realized through adjusting the sensitivity threshold and the number of modes. Finally, we present our views on the current challenges and the future development of the displacement sensing based on an SNAP resonator. We believe that a comprehensive understanding on this sensing scheme would significantly contribute to the advancement of the SNAP resonator for a broad range of applications.

3'-daidzein sulfonate protects myocardial cells from hypoxic-ischemic injury via the NRF2/HO-1 signaling pathway.

BACKGROUND: Myocardial infarction (MI) has a high mortality and disability rate and greatly affects human health. This study sought to explore the therapeutic effect and molecular mechanism of 3'-daidzein sulfonate (DSS) on MI. METHODS: A rat MI model was established and low and high doses of DSS were administered to the rats. An in vitro oxygen glucose deprivation model was used to verify the treatment role and mechanism of DSS. The establishment of the rat MI model was confirmed by electrocardiogram. The tissue changes were detected by HE, Masson's trichrome, TUNEL and TTC staining. Cell viability was detected by CCK-8. The viable and dead cells were detected by Calcein-AM/PI. Apoptotic cells, ROS and JC-1 were detected by flow cytometry apoptosis. The level of proteins was detected by western blotting. MDA, SOD and GSH were detected by ELISA. RESULTS: The results of Hematoxylin and eosin, TUNEL, and Masson staining showed that the myocardial tissue of the MI group was repaired by DSS. The serum levels of cardiac troponin I (CTnI), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and malondialdehyde (MDA) were decreased by DSS, while the serum levels of superoxide dismutase and glutathione were promoted by DSS. The treatment of DSS activated the Nuclear Factor Erythroid 2-Related Factor 2 (NRF-2)/Heme Oxygenase 1 (HO-1) pathway and inhibited the caspase-3 apoptosis pathway. The in vitro experiment showed that DSS greatly restored cell viability and reduced cell apoptosis. DSS also greatly inhibited mitochondrial membrane potential depolarization, reactive oxygen species production, and oxidative stress. The application of the NRF-2 inhibitor, C29H25N3O4S (ML385), greatly inhibited the treatment role of DSS and the NRF-2/HO-1 pathway, and activated the caspase-3 apoptosis pathway. CONCLUSIONS: In conclusion, this study first identified the beneficial role of DSS in MI. DSS protected myocardial cells by activating the NRF-2/HO-1 pathway and inhibiting cell apoptosis. DSS could be used as a novel drug in the treatment of MI.

3'-Daidzein sulfonate sodium provides neuroprotection by promoting the expression of the α7 nicotinic acetylcholine receptor and suppressing inflammatory responses in a rat model of focal cerebral ischemia.

In a previous study using a rat model of focal cerebral ischemia/reperfusion (I/R) injury, we found that 3'-Daidzein sulfonate sodium (DSS), a derivative of daidzein, exerts neuroprotective effects by alleviating brain edema and reducing levels of interleukin (IL)-6. The present study was designed to further examine the potential mechanisms of the neuroprotective properties of DSS in a rat model of cerebral I/R injury. We found that treatment with DSS ameliorated neurological deficit, infarct size, and cerebral water content in rats with cerebral I/R injury. Moreover, treatment with DSS significantly reduced the levels of IL-1ß, IL-6, and tumor necrosis factor (TNF)-α in serum and in the ischemic penumbra. Additionally, DSS treatment increased the expression of nicotinic acetylcholine receptor alpha 7 (α7nAChR), and inhibited the expression of glial fibrillary acidic protein, phosphorylated p65 nuclear factor κB, and phosphorylated inhibitor of NF-κBα, suggesting that DSS provides neuroprotection by suppressing inflammatory responses after focal cerebral I/R injury. Notably, α-bungarotoxin, an antagonist of α7nAChR, reversed the neuroprotective effects of DSS after cerebral I/R injury, suggesting that inhibition of α7nAChR expression is sufficient for reversal of the neuroprotective effects of DSS. In conclusion, we found that DSS treatment provides neuroprotection by promoting α7nAChR expression in a rat model of focal cerebral ischemia, thus establishing α7nAChR as a potential therapeutic target in cerebral I/R injury.