Analysis of Immune and Prognostic-Related lncRNA PRKCQ-AS1 for Predicting Prognosis and Regulating Effect in Sepsis.

Background: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis. Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan-Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit. Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress. Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.

Protective effect of intermittent hypobaric hypoxia against radiation-induced liver damage in Sprague-Dawley rats.

BACKGROUND: Without timely and effective interventions or treatments, radiation-induced liver damage (RILD) can lead to serious consequences for the patients and their families. OBJECTIVE: To investigate the protective effect of intermittent hypobaric hypoxia preconditioning (IHHP) in RILD. METHODS: Male adult SD rats were randomly divided into 8 groups including one control group, one only irradiation group and other experimental groups. Blood routine tests and liver function tests were all assessed with abdominal venous blood. Moreover, hematoxylin eosin (HE) staining and immunohistochemistry assay were used to detect the histopathological changes and expressions of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in radiated liver sections. RESULTS: Blood routing tests showed that RBC, WBC and Hb were all significantly increased while the differences of these results between different groups with same simulated altitude were approximate. However, liver function in the IHHP plus irradiation at 4000 m group was significantly decreased (P< 0.05) compared to only irradiation groups, and the manifestation of HE and lower positive expression of TNF-α showed improved histopathological changes in the liver section. Furthermore, no significant difference of HIF-1α expression between any two groups treated with IHHP was observed. CONCLUSION: IHHP at the altitude of 4000 m group could alleviate the radioactive liver damage by downregulating TNF-α and less strong positive expression of TGF-ß1. Furthermore, patients exposed to radiation might benefit from this treatment to prevent or reduce the RILD.

Natural deep eutectic ready to use extract of astilbin: Super high in vitro bioaccessibility, α-amylase and α-glucosidase enzyme inhibition kinetics.

Astilbin, a natural flavonoid, possesses multiple functionalities, while the poor bioavailability seriously restricts its application in functional food and medicine. Therefore, in this study, a natural deep eutectic solvent (NaDES) with choline chloride: lactic acid (CHCL-LAC) is selected to deliver astilbin by evaluating the bioaccessibility and antioxidant capacity during in vitro gastrointestinal digestion, and the inhibitory effect with underlying mechanism of astilbin-CHCL-LAC against α-amylase/α-glucosidase were investigated. The CHCL-LAC showed significant high astilbin bioaccessibility (84.1% bioaccessible) and DPPH and ORAC antioxidant capacity with 75.7% and 57.7% respectively after 3 h in vitro digestion, which may be attributed by hydrogen bond based supramolecule formed between astilbin and CHCL-LAC. Moreover, significant inhibitions of astilbin-CHCL-LAC on α-amylase (IC50 of 0.67 g/L) and α-glucosidase (IC50 of 0.64 g/L) were observed in mixed competitive and non-competitive manners. The dominant binding force between enzymes and astilbin were the hydrogen and hydrophobic interaction. This is the first time that the underlying mechanisms for astilbin delivered by NaDESs were revealed, suggesting that CHCL-LAC-based NaDESs are promising ready-to-use vehicles of natural inhibitors for carbohydrate-hydrolyzing enzymes.

Combination of remote ischemic perconditioning and remote ischemic postconditioning fails to increase protection against myocardial ischemia/reperfusion injury, compared with either alone.

Remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPostC) have been previously demonstrated to protect the myocardium against ischemia/reperfusion (IR) injury. However, their combined effects remain to be fully elucidated. In order to investigate this, the present study used an in vivo rat model to assess whether synergistic effects are produced when RIPerC is combined with RIPostC. The rats were randomly assigned to the following groups: Sham, IR, RIPerC, RIPostC and RIPerC + RIPostC groups. The IR model was established by performing 40 min of left coronary artery occlusion, followed by 2 h of reperfusion. RIPerC and RIPostC were induced via four cycles of 5 min occlusion and 5 min reperfusion of the hindlimbs, either during or subsequent to myocardial ischemia. On measurement of infarct sizes, compared with the IR group (49.45±6.59%), the infarct sizes were significantly reduced in the RIPerC (34.36±5.87%) and RIPostC (36.04±6.16%) groups (P<0.05). However, no further reduction in infarct size was observed in the RIPerC + RIPostC group (31.43±5.43%; P>0.05), compared with the groups treated with either RIPerC or RIPostC alone. Activation of the reperfusion injury salvage kinase (RISK) Akt, extracellular signal­regulated kinase 1/2 and glycogen synthase kinase­3ß, and survivor activating factor enhancement (SAFE) signal transducer and activator of transcription­3 pathways were enhanced in the RIPerC, RIPostC and the RIPerC + RIPostC groups, compared with the IR group, with no difference among the three groups. Therefore, whereas RIPerC and RIPostC were equally effective in providing protection against myocardial IR injury, the combination of RIPerC and RIPostC failed to provide further protection than treatment with either alone. The cardioprotective effects were found to be associated with increased activation of the RISK and SAFE pathways.

GRIM­19­mediated Stat3 activation is a determinant for resveratrol­induced proliferation and cytotoxicity in cervical tumor­derived cell lines.

Resveratrol is a natural phenol, produced from red grapes, berries and peanuts. Previous studies have suggested that resveratrol exerts anticancer effects. Activation of the signal transducer and activator of transcription 3 (Stat3) is important in cancer. However, the mechanisms by which resveratrol suppresses the Stat3 signaling pathway remain to be elucidated. The aim of the present study was to investigate the effects of resveratrol on GRIM­19­Stat3 signaling in HeLa cells, derived from a cervical tumor. HeLa cells were divided into experimental groups and treated with resveratrol. Western blotting was used to analyze the expression levels of p­Stat3, Stat3, GRIM­19 and ß­actin. Cell viability was determined using an MTT assay. The results showed that 100 µM resveratrol suppressed the proliferation and Stat3 phosphorylation in HeLa cells, and induced the expression of the gene associated with retinoid­IFN­induced mortality 19 (GRIM­19) protein. Overexpression of GRIM­19 suppressed the Stat3 signaling pathway in HeLa cells. The Stat3 signaling pathway was activated following the downregulation of GRIM­19 expression using short interfering RNAs (siRNAs). Resveratrol suppressed cell proliferation, however, this effect was decreased through the use of siRNAs. The suppression of Stat3 phosphorylation by resveratrol decreased following treatment with siRNAs. To the best of our knowledge, the present study is among the first to identify GRIM­19­Stat3 signaling as a target of resveratrol, and further elucidates the mechanisms underlying the antitumor activity of resveratrol.