Screening key genes and microRNAs in sepsis by RNA-sequencing.

BACKGROUND: Sepsis is a life-threatening organ dysfunction, initiated by a dysregulated host response to infection. This study aimed to determine key genes and microRNAs (miRNAs) correlated with sepsis. METHODS: Three patients with sepsis and three healthy individuals treated as controls were recruited in the current study. To identify differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) between patients with sepsis and controls, RNA-sequencing and bioinformatics analysis were conducted. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Dataset GSE46955, used to validate the expression of selected DEmRNAs, was downloaded from the Gene Expression Omnibus database. RESULTS: Compared with septic patients, a total of 1199 DEmRNAs and 23 DEmiRNAs were identified. Based on DEmiRNA-target DEmRNAs analysis, hsa-miR-106b-5p (degree = 155), hsa-miR-128-3p (degree = 128), and hsa-miR-144-3p (degree = 79) were the top 3 DEmiRNAs that covered most DEmRNAs. The T cell receptor signaling pathway, pathways in cancer, FoxO signaling pathway, and influenza A were the significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways of DEmiRNA-target DEmRNAs in sepsis. CONCLUSION: We identified key genes and miRNAs related to sepsis. Our findings will provide new insights into understanding sepsis pathogenesis.

MicroRNA-214 Inhibits Left Ventricular Remodeling in an Acute Myocardial Infarction Rat Model by Suppressing Cellular Apoptosis via the Phosphatase and Tensin Homolog (PTEN).

The aims of the present study were to determine the role of miR-214 on left ventricular remodeling of rat heart with acute myocardial infarction (AMI) and to further investigate the underlying mechanism of miR-214-mediated myocardial protection. AMI was induced in which adenovirus-expressing miR-214 (Ad-miR-214), anti-miR-214, or Ad-GFP had been delivered into rats hearts 4 days prior, while a phosphatase and tensin homolog (PTEN) inhibitor was administered via intra-peritoneal injection 30 minutes prior to AMI. Changes in hemodynamic parameters were detected and recorded. Left ventricular (LV) dimensions and LV/BW were measured. Quantitative RT-PCR was used to determine the miR-214 expression levels of the myocytes in the infarcted, border, and non-infarcted areas of the LV. Myocardial infarct size was also measured. Flow cytometry analysis was performed to examine cellular apoptosis. Western blot analysis was performed to examine PTEN expression. The results showed that miR-214 was upregulated in both border and infarcted areas. Myocardial cell apoptosis was decreased in the Ad-miR-214 group, but was increased in the anti-miR-214 group, while there were no differences among the Ad-GFP-group, PTEN-ad-miR-214 group, or PTEN-anti-miR-214 group. Myocardial infarct size, LV dimensions, heart rate (HR), and LV end-diastolic pressure (LVEDP) were decreased while the maximal rates of rise or decline in blood pressure in the ventricular chamber (± dp/dt) and LV systolic pressure (LVSP) were increased in the Ad-miR-214 group, all of which exhibited opposite changes in the anti-miR-214 group. PTEN was downregulated in the Ad-miR-214 group and upregulated in the anti-miR-214 group. PTEN was decreased in both the border and infarcted areas compared with non-infarcted areas. The study results suggest that Ad-miR-214 improves LV remodeling and decreases the apoptosis of myocardial cells through PTEN, suggesting a possible mechanism by which Ad-miR-214 functions in protecting against AMI injury.

[Fabrication and Performance Study of Polydimethylsiloxane Intraocular Lens].

To simplify the production process of intraocular lens(IOL)and to solve the problem of lacking adjustable ability,we proposed a novel soft IOL with large-scale adjustable ability and rigid haptics based on heat-assisted method,and gravity-assisted method.Polydimethylsiloxane(PDMS)and rigid material--polymethyl methacrylate(PMMA)were used as the materials for fabricating optical lens(PDMS)and haptics(PDMS and PMMA)through changing the weight ratio of the solution.A lens-smartphone microscopy system was established to replace the traditional digital microscopy to measure the tiny displacements and shape changes.The PDMS lens has excellent optical property through an experiment in which the maximum optical power was around 273.2D.Experimental results indicated that the maximum optical power of PMMA IOL was 129.3D,and that in PDMS IOL,however,was only 56.0D.Thus,the rigid PMMA-IOL has a larger adjustable range.The production process of PDMS was mold-free,rapid,real-time,and highly repeatable and there was no need for a rigorous experimental environment either.This creative processing technology reduced the manufacturing steps from which an optical lens with high transmittance and high resolution,as well as hatics with accurate dimensions,were obtained.The rigidity of haptics affected more intensely than other factors did for improving the pre-displacement and changing the appearance of PDMS lens.Even though the rigidity of PMMA haptics is large enough for accommodating,there are many drawbacks during manufacturing.It is unavailable to rapid fabricate IOL using PMMA.Thus,further work will be required to alter the weight ratio of PDMS material,increase the rigidity,and enhance the adjustable ability of PDMS IOL.

Cardioprotective effect of erythropoietin on sepsis-induced myocardial injury in rats.

BACKGROUND: Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis. The cytoprotective function of erythropoietin (EPO) has been discovered and extensively studied. However, the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported. METHODS: The rat models of sepsis were produced by cecal ligation and perforation (CLP) surgery. Rats were randomly (random number) assigned to one of three groups (n=8 for each group): sham group, CLP group and EPO group (1000 IU/kg erythropoietin). Arterial blood was withdrawn at 3, 6, 12, and 24 hours after CLP. cTnI, BNP, CK-MB, LDH, AST, TNF-α, IL-6, IL-10, and CRP were tested by the ELISA assay. Changes of hemodynamic parameters were recorded at 3, 6, 12, 24 hours after the surgery. Histological diagnosis was made by hematoxylin and eosin. Flow cytometry was performed to examine cell apoptosis, myocardium mitochondrial inner membrane potential, and NF-κB (p65). Survival rate at 7 days after CLP was recorded. RESULTS: In the CLP group, myocardial enzyme index and inflammatory index increased at 3, 6, 12 and 24 hours after CLP compared with the sham group, and EPO significantly blocked the increase. Compared with the CLP group, EPO significantly improved LVSP, LV +dp/dt max, LV -dp/dt min, and decreased LVEDP at different time. EPO blocked the reduction of mitochondrial transmembrane potential, suppressed the cardiomyocyte apoptosis, inhibited the activation of NF-κB, and reduced the production of proinflmmatory cytokines. No difference in the survival rate at 7 days was observed between the CLP group and the EPO group. CONCLUSION: Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.

MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis.

OBJECTIVE: To determine the role of microRNA 21(miR-21) on left ventricular remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate the underlying mechanism of miR-21 mediated myocardium protection. METHODS: Rats were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery group. Changes in hemodynamic parameters were recorded at 1 week after I/R. Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells were measured. Primary cultures of neonatal rat cardiac ventricular myocytes were performed and cell ischemic injury was induced by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R). MiR-21 inhibitor and pre-miR-21 were respectively added to the culture medium for the miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine the miR-21 levels in cultured cells. Flow cytometry was performed to examine the cell apoptosis. RESULTS: In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the Ad-miR-21 significantly improved LVSP, LV +dp/dt(max), LV - dp/dt(min), and decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21 group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR-21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis. CONCLUSIONS: Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.