Exploring the Role of Lycium barbarum Polysaccharide in Corneal Injury Repair and Investigating the Relevant Mechanisms through In Vivo and In Vitro Experiments.

Lycium barbarum polysaccharide (LBP) is the main active component of Fructus Lycii, exhibiting various biological activities. This study aims to explore the protective effects of LBP on human corneal epithelial cells (HCEC) and a rat corneal injury model. Potential target points for LBP improving corneal injury repair were screened from public databases, and functional and pathway enrichment analyses of core targets were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rat corneal alkali burns and HCEC oxidative stress injury models were established, and the results were validated through slit lamp examination, HE staining, TUNEL assay, immunofluorescence, CCK-8 assay, flow cytometry, scratch assay, and qRT-PCR methods. In the context of database retrieval, identification of 10 LBP monosaccharide components and 50 corneal injury repair-related targets was achieved. KEGG pathway analysis suggested that LBP might regulate the IL-17 and TNF signaling pathways through targets such as JUN, CASP3, and MMP9, thereby improving corneal damage. In vivo and in vitro experimental results indicated that LBP could reduce the increase of inflammation index scores (p < 0.05), inflammatory cell density (p < 0.01), TUNEL-positive cells (p < 0.01), corneal opacity scores (p < 0.01), and expression of corneal stromal fibrosis-related proteins α-SMA, FN, and COL (p < 0.01) caused by chemical damage to rat corneas. LBP inhibited oxidative stress-induced decreases in cell viability (p < 0.001) and migration healing ability (p < 0.01) in HCECs, reducing apoptosis rates (p < 0.001), ROS levels (p < 0.001), and the expression of inflammatory factors TNF-α and IL-6 (p < 0.01). qRT-PCR results demonstrated that LBP intervention decreased the mRNA levels of JUN, CASP3, and MMP9 in H2O2-induced alkaline-burned corneas and HCECs (p < 0.01).The integrated results from network pharmacology and validation experiments suggest that the inhibitory effects of LBP on apoptosis, inflammation, and fibrosis after corneal injury may be achieved through the suppression of the TNF and IL-17 signaling pathways mediated by JUN, CASP3, and MMP9.

Improved performance of IT-SOFC by negative thermal expansion Sm0.85Zn0.15MnO3addition in Ba0.5Sr0.5Fe0.8Cu0.1Ti0.1O3-δcathode.

To improve performance of intermediate temperature solid oxide fuel cells (IT-SOFCs), the negative thermal expansion (NTE) material Sm0.85Zn0.15MnO3(SZM) is introduced in Ba0.5Sr0.5Fe0.8Cu0.1Ti0.1O3-δ(BSFCT) cathode. XRD results indicate that BSFCT, SZM and Ce0.8Sm0.2O2-δ(SDC) oxides have good chemical compatibility up to 1173 K. The average linear thermal expansion coefficient of BSFCT-xSZM (x= 0, 10, 20 and 30 wt.%) decreases markedly from 29.2 × 10-6 K-1forx= 0 wt.% to 15.6 × 10-6 K-1forx= 30 wt.%. The electrochemical performance of single cells with configuration of NiO-BZCY|SDC|BSFCT-xSZM is comparatively investigated in the 773-973 K. The best performance is observed forx= 20 wt.%, which should be caused by the balance between thermal matching of cathode/electrolyte layers and oxygen reduction reaction activity of composite cathodes. The corresponding peak power density in the 773-973 K is 136-918 mW cm-2, which is 249%-64% higher than that (39-559 mW cm-2) with single BSFCT cathode. Due to the existence of electron blocking layer at anode/electrolyte interface, the open circuit voltage of all cells is higher than 1.0 V. In short, the introduction of NTE oxide in conventional cathode materials may provide an effective strategy to enhance the performance of IT-SOFCs with electron blocking layer.

Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425.

Doxorubicin (DOX) is an eff ;ective chemotherapeutic drug to suppress the progression of various types of tumors. However, its clinical application has been largely limited due to its potential cardiotoxicity. MicroRNAs (miRNAs) are emerged as critical regulators of cardiac injury. This study was aimed to explore the effects of irigenin (IR), as an isoflavonoid isolated from the rhizome of Belamcanda chinensis, on DOX-induced cardiotoxicity using the in vivo and in vitrostudies. The results indicated that DOX-induced fibrosis, cardiac dysfunction and injury were markedly attenuated by IR through reducing apoptosis, oxidative stress and inflammation in heart tissue samples. Importantly, DOX resulted in a remarkable decrease of miR-425 in heart tissues and cells, which was significantly rescued by IR. Receptor-interacting protein kinase 1 (RIPK1) was discovered to be a direct target of miR-425. DOX induced over-expression of RIPK1 both in vivo and in vitro, which were greatly decreased by IR. Transfection with miR-425 mimic could inhibit RIPK1 expression, whereas reducing miR-425 increased RIPK1 expression levels. In parallel to miR-425 over-expression, RIPK1 knockdown could attenuate apoptosis, reactive oxygen species (ROS) production and inflammation in HL-1 cells. However, over-expression of RIPK1 markedly abolished miR-425 mimic-induced apoptosis, ROS accumulation and inflammatory response in DOX-exposed cells. Herein, miR-425 could ameliorate cardiomyocyte injury through directly targeting RIPK1. Furthermore, activation of miR-425 by IR markedly improved DOX-induced cardiotoxicity, and therefore IR could be considered as a promising therapeutic agent for the treatment of cardiac injury.

PAFR-deficiency alleviates myocardial ischemia/reperfusion injury in mice via suppressing inflammation, oxidative stress and apoptosis.

Myocardial ischemia/reperfusion (I/R) still have high morbidity and mortality worldwide. Platelet activating factor (PAF) is a potent phospholipid regulator of inflammation. PAF acts on a single receptor (PAFR), which is expressed on cellular and nuclear membranes of various cell types. The study is aimed to explore if PAFR could modulate myocardial I/R injury in mice. PAFR expressions began to up-regulate at 1 h, and reached peak at 24 h. PAFR deletion markedly attenuated myocardial I/R injury, evidenced by the reduced infarct size and the improved cardiac function. Furthermore, PAFR-knockout inhibited inflammatory response, as demonstrated by down-regulated pro-inflammatory cytokines and chemokine, as well as the inactivation of nuclear factor κB (NF-κB). Additionally, PAFR-absence ameliorated oxidative stress induced by myocardial I/R, associated with the up-regulation of superoxide dismutase (SOD) and nuclear respiratory factor 2 (Nrf-2) activity. Finally, PAFR-deficiency impeded apoptosis, which was proved by the decreasing in terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL)-positive myocytes, and Caspase-3 cleavage. And the activation of Janus kinase 1-signal transducer and activator of transcription 1 (JAK1/STAT1) pathway was also suppressed by PAFR-knockout. The findings above were confirmed in lipopolysaccharide (LPS)-incubated cardiomyocytes with or without PAFR expressions in vitro. In summary, we supposed that inhibiting PAFR reduced inflammation, oxidative stress and apoptosis, and thus might be a promising therapeutic strategy to alleviate myocardial I/R injury.

miR-487b mitigates chronic heart failure through inhibition of the IL-33/ST2 signaling pathway.

We investigated the effects of microRNA-587b (miR-487b) in a rat model of chronic heart failure (CHF). Wistar rats were assigned to 10 groups (n=8 per group). Expression of interleukin-33 (IL-33), somatostatin 2 (ST2), IL-6, and TNF-α was higher in the CHF group than the control group. In the CHF, negative control (NC) for si-IL-33, NC for miR-487b mimic, NC for miR-487b inhibitor, and miR-487b inhibitor + si IL-33 groups, as compared to the blank and sham groups: steroid binding protein (SBP), D binding protein (DBP), left ventricular systolic pressure (LVSP), ± dp/dtmax, and superoxide dismutase (SOD) were all lower; myocardial fibrosis, MDA, left ventricular end-diastolic pressure (LVEDP), myocardial apoptosis rate, IL-6, and TNF-α were all higher; levels of IL-33 and ST2 mRNA and protein were higher; and levels of miR-487b were lower. Levels of IL-33 and ST2 mRNA and protein were lower, and SBP, DBP, LVSP, ± dp/dtmax, and SOD were higher in the miR-487b mimic and si-IL-33 groups than the CHF group. Expression of miR-487b was increased in the miR-487b mimic group, and expression of IL-33 and ST2 were increased and expression of miR-487b was decreased in the miR-487b inhibitor group. MiR-487b reduces apoptosis, inflammatory responses, and fibrosis in CHF by suppressing IL-33 through inhibition the IL-33/ST2 signaling pathway.