MicroRNA-30e-3p reduces coronary microembolism-induced cardiomyocyte pyroptosis and inflammation by sequestering HDAC2 from the SMAD7 promoter.

This study investigates the mechanism by which microRNA (miR)-30e-3p reduces coronary microembolism (CME)-induced cardiomyocyte pyroptosis and inflammation. Cardiac function tests, histological staining, and transmission electron microscopy were performed on CME-model rats injected with adeno-associated viral vectors. Cardiomyocytes were transfected 24 h before a cellular model of pyroptosis was established via treatment with 1 µg/mL lipopolysaccharide (LPS) for 4 h and 5 mM ATP for 30 min. Pyroptosis, inflammation, and Wnt/ß-catenin signaling in cardiomyocytes were detected. Dual-luciferase reporter assays and/or RNA pull-down assays were performed to verify the binding of miR-30e-3p to HDAC2 mRNA or HDAC2 to the SMAD7 promoter. Chromatin immunoprecipitation was used to assess the level of H3K27 acetylation at the SMAD7 promoter. miR-30e-3p and SMAD7 expression levels were downregulated and HDAC2 expression was upregulated with CME. The overexpression of miR-30e-3p restored cardiac functions in CME-model rats and reduced serum cTnI, IL-18, and IL-1ß levels, microinfarcts, inflammatory cell infiltration, apoptosis, collagen content, and GSDMD-N, cleaved caspase-1, and NLRP3 expression in the myocardium, but these effects were reversed by SMAD7 knockdown. The overexpression of miR-30e-3p or knockdown of HDAC2 reduced LDH, IL-18, and IL-1ß secretion, propidium iodide intake, and GSDMD-N, NLRP3, cleaved caspase-1, Wnt3a, Wnt5a, and ß-catenin expression in the cardiomyocyte model. miR-30e-3p inhibited the expression of HDAC2 by binding HDAC2 mRNA. HDAC2 repressed the expression of SMAD7 by catalyzing H3K27 deacetylation at the SMAD7 promoter. miR-30e-3p, by binding HDAC2 to promote SMAD7 expression, reduces CME-induced cardiomyocyte pyroptosis and inflammation.

Detection of trace chlorine pollutants in recycled pulp using gas chromatography-tandem mass spectrometry with response surface-optimized carbon structure online catalysis.

RATIONALE: Chlorinated aromatics and alkanes are widely used for their flame retardancy, but they need to be monitored when used in recycled pulp. This paper reports the use of palladium acetate/activated carbon (Pa/Ac) activated by nitric acid as an online catalyst to determine chlorinated aromatics and chlorinated alkanes in recycled paper products using gas chromatography-tandem mass spectrometry (GC-MS/MS), which significantly improves the sensitivity of the method and remarkably lowers the detection limits. METHODS: The Pa/Ac catalyst was prepared using a self-made catalytic device and used as key to the online catalytic conversion of target chlorinated aromatic hydrocarbons and chlorinated alkanes for GC-MS/MS analysis. The response surface model was used to optimize catalytic conditions. Then GC-MS/MS in the multireaction monitoring mode with online catalysis was applied for the analysis of polychlorinated biphenyls, polychlorinated terphenyls, polychlorinated naphthalene, and chlorinated paraffins (CP) in recycled paper products. RESULTS: Compared with traditional methods, the Pa/Ac catalyst can transform chlorinated aromatic hydrocarbons into aromatic hydrocarbons through dechlorination hydrogenation, thus lowering the detection limit of the GC-MS/MS method significantly. It can transform paraffin chloride into the corresponding alkane to better distinguish short-chain, medium-chain, or long-chain CPs. Online catalytic conversion significantly improved the sensitivity and reproducibility (88.7%-113.1%) of the method. Tissue samples with various concentration levels of chlorinated aromatics and chlorinated alkanes were tested. The linearity range of the reduced target compounds in the reduction product solution was 0.02-1.00 µg/ml (R2  > 0.995). The quantitative detection limit was 0.03-0.05 µg/kg, and relative standard deviation was less than 6.9%. CONCLUSION: This study was the first to introduce the Pa/Ac catalytic device as an online catalytic unit in the determination of chlorinated aromatics and chlorinated alkanes using the GC-MS/MS method. The target compounds were converted into alkanes and aromatic hydrocarbons with unchanged carbon structures, and the method could achieve a low detection limit with no need for high-end methods such as GC-chemical ionization ion source (CI)-MS or high-resolution mass spectrometry. These methods are suitable for the determination of chlorine pollutants in recycled paper and its raw materials.

MicroRNA-136-5p protects cardiomyocytes from coronary microembolization through the inhibition of pyroptosis.

This study investigated how miR-136-5p partially affected cardiomyocyte pyroptosis in rats with coronary microembolization (CME). The cardiac function and structure of rats with CME were evaluated using echocardiography, hematoxylin and eosin staining, Masson staining, and troponin I level. Pyroptosis was induced by lipopolysaccharide (LPS) in isolated rat cardiomyocytes and evaluated by the expression of caspase-1, NOD-like receptor family pyrin domain-containing 3, interleukin-1ß, and gasdermin D-N. After cell transfection, the expression of Ataxin-1 like (ATXN1L), pyrin domain-containing 1 (PYDC1), and pyroptosis-related proteins was assessed. Dual-luciferase reporter and immunoprecipitation assays were used to verify the relationships among miR-136-5p, ATXN1L, and capicua (CIC). MiR-136-5p was under-expressed, whereas ATXN1L was overexpressed in rats with CME and in LPS-treated primary cardiomyocytes. MiR-136-5p targeted ATXN1L, and ATXN1L bound to CIC to suppress PYDC1 expression. MiR-136-5p overexpression suppressed pyroptosis by inhibiting the binding of ATXN1L with CIC and promoting PYDC1 expression, which was reversed by simultaneous elevation of ATXN1L. In conclusion, miR-136-5p suppressed pyroptosis by upregulating PYDC1 via ATXN1L/CIC axis, thereby attenuating cardiac damage caused by CME.

Green synthesis of ceramsite from industrial wastes and its application in selective adsorption: Performance and mechanism.

The increasing requirement and consumption of coal has resulted in a large accumulation of coal gangue. The reuse and recycling of coal gangue have become a high priority for sustainable development. A sustainable and efficient ceramsite adsorbent was prepared for copper ions adsorption by using coal gangue, coal fly ash, and copper slag as the main materials. The appropriate performance of the ceramsite could be obtained at a mixture of coal gangue, coal fly ash, and copper slag at a weight ratio of 3:4:1. The optimal sintering temperature and time were 1050 °C and 20 min, respectively. The main crystalline phases of ceramsite were quartz, mullite, and anorthite. Many micropores are connecting the interior on the surface of ceramsite under scanning electron microscope. The maximum copper ions adsorption capacity reached up to 20.6 mg/g at 303 K when pH and time were 5 and 1440 min, respectively. The adsorption kinetics and isotherm could be described by the pseudo-second-order model and Freundlich model, respectively. The adsorption mechanisms of Cu2+ with ceramsite were attributed to Cu(OH)2 precipitation formed on the alkaline surface of ceramsite and complexation reactions occurred between the O-containing groups (including C-O, Fe-O, and Si-O) from ceramsite and Cu2+. The prepared ceramsite may be also applied to other heavy metal wastewater treatments.

Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats.

Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown.Methods: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days. The expression of miR-133a was determined by fluorescence in situ hybridization. The learning and memory were evaluated by step-down, step-through, and morris water maze (MWM) tests.Results: In streptozotocin-injected rats, hyperglycemia dramatically induced miR-133a ectopic expressions in vascular endothelium, reduced GTPCH1 gene expressions and BH4 levels, which were reversed by berberine administration (1.0 g/kg/day, 8 weeks). Hyperglycemia also inhibited acetylcholine-induced vasorelaxation in middle cerebral artery and reduced blood supply to the brain, which were bypassed by berberine. Ex vivo studies indicated that miR-133a agomirs abolished these beneficial effects of berberine on acetylcholine-induced vasorelaxation, while supplement of L-sepiapterin prevented endothelial dysfunction in middle cerebral artery isolated from rats. By performing step-down, step-through, and MWM tests, we observed that hyperglycemia significantly caused the impairments of learning and memory in streptozotocin-injected rats. Importantly, these aberrant phenotypes in diabetic rats were normalized by berberine therapy. Finally, berberine reduced miR-133a expression, and increased both BH4 levels and NO production in cultured endothelial cells treated with high glucose.Conclusion: Berberine improves vascular dementia in diabetes, which is possibly related to the suppression of miR-133a ectopic expression in endothelial cells.

HDAC5 Inhibits Hepatic Lipogenic Genes Expression by Attenuating the Transcriptional Activity of Liver X Receptor.

BACKGROUND/AIMS: Liver X receptor (LXR), a member of the nuclear receptor superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown to play critical roles in glucose and lipids metabolism. However, the exact role of HDAC5 in lipogenesis remains elusive. METHODS: mRNA and protein levels of HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat-diet-induced and leptin receptor deficiency-induced obese mice. HDAC5 was overexpressed or depleted in HepG2 cells, followed by analysis of cellular triglycerides contents. Quantitative real-time PCR was used to detect the expression levels of lipogenic genes. Luciferase reporter assay was used to determine the regulation of HDAC on the transcriptional activity of LXR. Co-immunoprecipitation experiment was used to determine the interaction between HDAC5 and LXR. RESULTS: We found that mRNA and protein expression levels of hepatic HDAC5 were reduced in high-fat-diet-induced and leptin receptor deficiency-induced obese mice. In vitro studies further demonstrated that knockdown of HDAC5 promoted cellular triglycerides accumulation, accompanied with up-regulation of lipogenic genes. At the molecular level, HDAC5 was shown to interact with LXR, thereby attenuating its transcriptional activity. CONCLUSION: Overall, our data suggest that hepatic HDAC5 is an important regulator of lipogenesis.

An Efficient Data Compression Model Based on Spatial Clustering and Principal Component Analysis in Wireless Sensor Networks.

Wireless sensor networks (WSNs) have been widely used to monitor the environment, and sensors in WSNs are usually power constrained. Because inner-node communication consumes most of the power, efficient data compression schemes are needed to reduce the data transmission to prolong the lifetime of WSNs. In this paper, we propose an efficient data compression model to aggregate data, which is based on spatial clustering and principal component analysis (PCA). First, sensors with a strong temporal-spatial correlation are grouped into one cluster for further processing with a novel similarity measure metric. Next, sensor data in one cluster are aggregated in the cluster head sensor node, and an efficient adaptive strategy is proposed for the selection of the cluster head to conserve energy. Finally, the proposed model applies principal component analysis with an error bound guarantee to compress the data and retain the definite variance at the same time. Computer simulations show that the proposed model can greatly reduce communication and obtain a lower mean square error than other PCA-based algorithms.

[Anti-inflammatory effects of apoprotein AI are mediated via modulating macrophage polarity].

OBJECTIVE: To explore the anti-inflammatory mechanisms of high density lipoprotein (HDL) by observing the effects of apoprotein (apo)AI, a major protein component of HDL, on the inflammatory macrophage cell polarity. METHODS: Cultured mice marrow-derived macrophages were stimulated with lipopolysaccharide and interferon after 10 µg/ml of apoAI were added to the macrophages for 24 hours. The expression of membrane molecules CD16/32, CD206 were detected by fluorescence activated cell sorting (FACS). ELISA was used to detect the secretion of IL-10 and IL-12. Real-time quantitative PCR was used to detect the mRNA expression of TLR4, MyD88 and IRF5. RESULTS: Compared to macrophages stimulated by interferon and lipopolysaccharide but without pretreatment with apoAI, pre-incubation with apoAI significantly downregulated the expression of CD16/32 (91.17% ± 1.99% vs.50.47% ± 1.02%, P < 0.05), IL-12 [(747.27 ± 3.74)pg/ml vs. (73.80 ± 4.56)pg/ml, P < 0.05], upregulated the expression of CD206(0.33% ± 0.12% vs. 3.00% ± 0.36%, P < 0.05), IL -10 expression [(23.56 ± 4.30) pg/ml vs.(32.91 ± 2.47) pg/ml, P < 0.05], and reduced the mRNA expression of TLR4 (1.000 ± 0.025 vs.0.708 ± 0.003, P < 0.05) , MyD88 (1.591 ± 0.005 vs. 1.341 ± 0.005, P < 0.05) , IRF5 (0.954 ± 0.005 vs. 0.463 ± 0.003, P < 0.05) . CONCLUSION: ApoAI enhances the switch of inflammatory macrophages to anti-inflammatory macrophages possibly through inhibiting TLR4-MyD88-IRF5 pathway.

Elements characteristics and potential environmental risk assessment of jarosite residue and arsenic sulfide residue based on geochemical and mineralogical analysis.

The waste slag known as jarosite residue (JR) and arsenic sulfide residue (ASR) were produced following the creation of zinc by hydrometallurgical procedures. The increasing annual zinc mining has led to growing pressure to dispose of the resulting JR and ASR from zinc smelting, making it crucial to assess their environmental impact and feasibility for utilization. The main components, distribution characteristics of elements, and potential environmental risks of zinc smelting wastes are studied through toxicity leaching tests, sequential extraction procedures, and various characterization technologies such as XRF, XRD, and SEM-EDS. The mineral compositions of JR are natrojarosite, franklinite, and gunningite, and zinc mainly adheres to the crevices of the natrojarosite mineral. Meanwhile, the ASR of flocculent structures is composed of orpiment, greenockite, arsenic oxide, and calvertite, and As appears in the form of the S-As-O phase. The Zn, Cu, and Cd in JR were dominated by exchangeable bound (81.53-96.6 %), and the main form of As, Cd, Se, and Tl in ASR was organic matter bound (87.0-99.21 %). The Risk Assessment Code (RAC) method confirmed the risk of Cd, Cu, Zn, and Mo in JR is high, while the risk of Cd, Pb, and Cr in ASR is moderate. Compared to the standard value of "Identification Standard for Toxicity of Hazardous Waste Leaching (GB5085.3-2007)", the leachate concentrations of Zn in JR as well as Cd and As in ASR were exceeded, suggesting that the JR and ASR were in the type of hazardous waste and posed an environmental risk. The study provides theoretical guidance for the future rational management and effective utilization of hazardous waste.

[Anti-inflammation of simvastatin by polarization of murine macrophages from M1 phenotype to M2 phenotype].

OBJECTIVE: To explore the effects of statin on pro-inflammatory macrophage phenotype in a murine M1 macrophage model. METHODS: Macrophages isolated from murine bone barrow were stimulated with interferon-gamma (IFN-γ) and lipopolysaccharide (LPS) to establish a M1 macrophage model. And 1.0, 2.5, 5.0 µmol/L of simvastatin were added to M1 macrophages for a 9-hour culture. Cell surface markers CD16/23 and CD206 were detected by fluorescence activated cell sorter (FACS) and interleukin-10 (IL-10) and IL-12 by ELISA. RESULTS: The CD16/32 expression was 86.39% ± 2.24% and IL-12 secretion (1562 ± 217) pg/ml in IFN-γ and LPS-stimulated macrophages. After a 9-hour incubation with 1.0, 2.5, 5.0 µmol/L simvastatin, the CD206 expression levels were 68.10% ± 2.48%, 75.28% ± 1.66%, 86.32% ± 2.19% and the secretion of IL-10 (500 ± 5), (675 ± 28) and (916 ± 15) pg/ml respectively. By analysis of variance and q test of mean, the difference was statistically significant (all P < 0.01) between the groups of M1 model (9.67% ± 5.48%, (298 ± 11) pg/ml) . And the phenotypic features were similar to those of the groups of M2 model. CONCLUSION: Simvastatin may inhibit inflammation by enhancing the switching of M1 macrophage to M2 macrophage phenotype.

[Reduced circulating endothelial progenitor cells is a risk factor of coronary slow flow].

OBJECTIVE: To explore if reduced number of circulating endothelial progenitor cells (EPCs) is a risk factor for patients with coronary slow flow (CSF). METHODS: Thirty patients with CSF and 30 age and gender matched control subjects with normal coronary angiography were included in the study. Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation and plated on fibronectin-coated culture dishes. EPCs were characterized as adherent cells double positive for DiI-AcLDL-uptake and lectin-binding by converted fluorescence microscope (×200). RESULTS: Smoking, diabetes mellitus, hypertension and the levels of plasma lipoprotein profile were similar between the two groups (all P > 0.05). The number of EPCs was significantly lower in patients with CSF compared with control subjects (35.7 ± 5.9 vs.53.2 ± 5.9, P < 0.01). TIMI frame counts was correlated with circulating EPCs number (OR = 0.424, 95%CI 0.358 - 0.621, P < 0.01) and not associated with gender, age, smoking, diabetes mellitus, hypertension and the levels of plasma lipoprotein profile. CONCLUSION: Decreased circulating EPCs is an independent risk factor for CSF.

Niacin promotes the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway.

The accumulation of free cholesterol in macrophage lysosomes significantly enhances atherogenesis. Our recent study demonstrated that the cluster of differentiation 38 (CD38)/nicotinic acid adenine dinucleotide phosphate (NAADP)/Ca2+ signaling pathway plays a critical role in the efflux of lysosomal free cholesterol from macrophages in atherosclerosis. Niacin, known as nicotinic acid, is one of the oldest lipid-lowering medications showing unique anti-atherosclerotic activity. However, it is unknown whether this anti-atherosclerosis activity is associated with the efflux of lysosomal compartmentalized cholesterol in macrophages. In this study, we investigated the anti-atherosclerotic effects of niacin on the reduction of lysosomal free cholesterol via CD38/NAADP signaling in macrophages derived from low-density lipoprotein receptor (LDLr-/-) mice. Fluorescent filipin and Nile red labeling coupled with confocal microscopy demonstrated that niacin reduced free cholesterol accumulation in lysosomes in a concentration-dependent manner. Transmission electron microscopy also showed that niacin markedly decreased cholesterol crystal formation in lysosomes in oxidized LDL-containing LDLr-/- bone marrow-derived macrophages. Enzyme-linked immunosorbent assays showed that niacin increased NAADP production in a concentration-dependent manner, which was inhibited by small interfering RNA interference of CD38. Therefore, niacin may promote the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway.

Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis.

This study aims to explore the mechanism underlying miR-142-3p regulating myocardial injury induced by coronary microembolization (CME) through ATXN1L. miR-142-3p overexpression or ATXN1L knockout adenovirus vectors were injected into rats before CME treatment. Cardiac functions were examined by echocardiography, and pathologies of myocardial tissues were assessed. Then, serum cTnI and IL-1ß contents and concentrations of IL-1ß and IL-18 in cell supernatant were measured. Immunofluorescence determined the localization of histone deacetylase 3 (HDAC3). The interaction between miR-142-3p and ATXN1L as well as the binding between HDAC3 and histone 3 (H3) was identified. The binding of ATXN1L and HDAC3 to NOL3 promoter was verified using ChIP. The levels of ATXN1L, NOL3, and miR-142-3p as well as apoptosis- and pyroptosis-related proteins and acetyl-histone 3 (ac-H3) were evaluated. CME treatment impaired the cardiac functions in rats and increased cTnI content. CME rats showed microinfarction foci in myocardial tissues. After CME treatment, miR-142-3p and NOL3 were modestly expressed while ATXN1L content was elevated, in addition to increases in apoptosis and pyroptosis. miR-142-3p overexpression or ATXN1L knockout alleviated CME-induced myocardial injury, cardiomyocyte apoptosis, and pyroptosis in myocardial tissues. miR-142-3p regulated ATXN1L expression in a targeted manner. In the cellular context, miR-142-3p overexpression attenuated apoptosis and pyroptosis in cardiomyocytes, which was partly counteracted by ATXN1L overexpression. ATXN1L functioned on cardiomyocytes by promoting deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression. Inhibition of HDAC3 or overexpression of NOL3 ameliorated the promotive effects of ATXN1L on cardiomyocyte apoptosis and pyroptosis. In vivo and in vitro evidence in this study supported that miR-142-3p could attenuate CME-induced myocardial injury via ATXN1L/HDAC3/NOL3. HIGHLIGHTS: CME model witnessed aberrant expression of miR-142-3p, ATXN1L, and NOL3; miR-142-3p negatively regulated ATXN1L; miR-142-3p mediated CME-induced myocardial injury through ATXN1L; ATXN1L promoted deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression; ATXN1L acted on cardiomyocyte apoptosis and pyroptosis through HDAC3/NOL3 axis.

The adsorptive behaviour of kaolinite to sodium dodecyl benzene sulphonate and the structural variation of kaolinite.

Analysis of the adsorptive behaviour of kaolinite to sodium dodecyl benzene sulphonate (SDBS) at different concentrations can provides a basis for selecting the best concentration. The adsorptive capacity and adsorptive behaviour of kaolinite to SDBS at different concentrations were studied using ultraviolet spectrophotometer, pseudo-first-order adsorption kinetics model, and pseudo-second-order adsorption kinetics model. Scanning electron microscopy with energy dispersive spectrometry (SEM-EDS), X-ray diffraction (XRD), and infrared spectroscopy (FTIR) were used to study the variation characteristics of surface structure, crystallinity indices, and main functional groups on kaolinite before, and after, adsorption. The results show that as the SDBS concentration increase, the adsorptive capacity of kaolinite to SDBS increase. The adsorption process can be accurately fitted by the pseudo-secondary adsorption kinetic model, which means the adsorptive behaviour was mainly chemical in origin. The adsorption of SDBS by kaolinite mainly occurs on the surface. The solidification, lamellar aggregation, and crystallinity index of kaolinite are more obvious after the adsorption of SDBS, but the interlayer spacing of kaolinite did not change to any significant. After the adsorption of SDBS, the intensity ratio of 1000-1008 cm-1 bands changed significantly, indicating the change of the chemical environment, and the adsorptive behaviour was chemical.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

Pravastatin polarizes the phenotype of macrophages toward M2 and elevates serum cholesterol levels in apolipoprotein E knockout mice.

Objective Statins are clinically used for protection against cardiovascular disease with lipid-lowering and anti-inflammatory properties. These properties tip the balance of macrophage polarization, which is an essential process in the development and progression of atherosclerosis. This study aimed to investigate the effect of pravastatin on atherosclerosis of the aorta in apolipoprotein E knockout (apoE-KO) mice without high lipid feeding. Methods Six 8-week-old apoE-KO male mice were randomly divided into two groups: a control group and a pravastatin (40 mg·kg-1·day-1)-treated group. At 35 weeks, the mice were sacrificed and the size of plaques on the aorta was assessed by Oil Red O staining. M1 and M2 macrophages were identified by inducible nitric oxide synthase and arginase-I, respectively, using immunohistochemistry. Results Pravastatin increased the size of atherosclerotic plaques in apoE-KO mice without high lipid feeding. The ratio of M1/M2 macrophages increased in atherosclerotic plaques, which might slow the process of atherosclerosis, while blood cholesterol levels were elevated. Conclusion Our study suggests that pravastatin polarizes the phenotype of macrophages toward M2 in atherosclerotic lesions, despite an increase in serum cholesterol levels in ApoE-KO mice.

Pri-microRNA-124 rs531564 polymorphism minor allele increases the risk of pulmonary artery hypertension by abnormally enhancing proliferation of pulmonary artery smooth muscle cells.

MicroRNA-124 (miR-124) has been reported to be downregulated in the cells exposed to hypoxia, which was confirmed in our study. We then used online microRNA target prediction tools to identify GRB2, SMAD5, and JAG1 as the candidate target genes of miR-124, and we next validated GRB2 as a direct gene by using luciferase reporter system. We also established the regulatory relationship between miR-124 and GRB2 by showing the negative linear relationship between GRB2 and miR-124 expression. Furthermore, we investigated the miR-124 and GRB2 expression levels of different genotypes including CC (n=30), GC (n=18), and GG (n=4), which supported the hypothesis that the presence of minor allele (C) of rs531564 polymorphism compromised the expression of miR-124. Meanwhile, we also conducted real-time polymerase chain reaction and Western blot analysis to study the expression of GRB2 among different genotypes or pulmonary artery smooth muscle cells (PASMCs) treated with miR-124 mimics, GRB2 small interfering RNA, and miR-124 inhibitors, respectively, and found that introduction of miR-124 or GRB2 small interfering RNA could reduce the expression of GRB2 and inhibit the proliferation of PASMCs, while miR-124 upregulated the expression of GRB2 and promoted the proliferation of PASMCs. A total of 412 COPD patients with PAH (n=182) or without PAH (n=230) were recruited in this study, and more individuals carrying at least one minor allele of rs531564 were found in the COPD patients with PAH than in those without PAH (odds ratio: 0.61, 95% confidence interval: 0.41-0.91; P=0.166). In conclusion, the presence of rs531564 minor allele may increase the risk of PAH in COPD by reducing miR-124 expression, increasing GRB2 expression, and promoting the proliferation of PASMCs.

A Novel Classification Indicator of Type 1 and Type 2 Diabetes in China.

Because of the differences of treatment, it is extremely important to classify the types of diabetes, especially for the diagnosis made by clinician. In this study, we proposed a novel scheme calculating an indicator of classifying diabetes, which contains two stages: the first is a model of feature extraction, 17 features are automatically extracted from the curve of glucose concentration acquired by continuous glucose monitoring system (CGM); the second is a model of diabetes parameter regression based on an ensemble learning algorithm named double-Class AdaBoost. 1050 curves of glucose concentration of type 1 and type 2 diabetics were acquired at the Department of Endocrinology in People's Hospital of Zhengzhou University China, and an upper threshold µ was set to 7 mmol/L, 8 mmol/L, 9 mmol/L, 10 mmo/L, and 11 mmol/L respectively according to the guideline of WHO. The experiments show that the coincidence rate of our scheme and clinical diagnosis is 90.3%. The novel indicator extends the criteria in diagnosing types of diabetes and provides doctors with a scalar to classify diabetes of type 1 and type 2.

Atorvastatin reduces plasminogen activator inhibitor-1 expression in adipose tissue of atherosclerotic rabbits.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) expression are increased in adipose tissues/adipocytes of obese mice, which is associated with a hypofibrinolytic state that contributes to thrombosis. We recently demonstrated that PAI-1 expression increases in adipose tissues/adipocytes of cholesterol-fed rabbits. In this study, we evaluated the ability of atorvastatin to modulate PAI-1 expression in cholesterol-fed rabbits and the regulatory mechanism. METHODS: Male rabbits were randomly fed with normal diet and high-cholesterol diet for 8 weeks, following 4 weeks, those fed high-cholesterol diet were randomly assigned to 2.5 mg/kg/day atorvastatin or starch. At the end of 12 weeks, subcutaneous adipose was collected, and culture adipocyte. PAI-1 mRNA was detected by RT-PCR. PAI-1 concentrations were determined with ELISA. The effect of atorvastatin and mevalonate (MVA) on PAI-1 production in adipocytes in vitro was observed. RESULTS: Atorvastatin significantly reduced serum TC and LDL-C concentrations (p<0.05), and decreased plasma PAI-1 concentration and PAI-1 expression in adipose tissues/adipocytes from cholesterol-fed rabbits. In vitro, atorvastatin dose-dependently suppressed PAI-1 expression and protein secretion in adipocytes. MVA reversed the inhibitory effect of atorvastatin on PAI-1 expression in concentration-dependent manner. CONCLUSIONS: Atorvastatin reduces plasma PAI-1 concentration and PAI-1 expression in adipose tissue and adipocyte of atherosclerotic rabbit, and inhibits PAI-1 expression and protein secretion in adipocytes in vitro, suggesting that it may have an antithrombtic effect. We also suggest that the mevalonate pathway may play an important role in PAI-1 expression in adipocyte.

The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes.

Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People's Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction.