The present study aimed to investigate the effects of lipoprotein-associated phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an
cell model of atherosclerosis, and to determine whether ...AMP-activated protein kinase (AMPK) mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392 patients with coronary artery disease (CAD), including various sub-conditions, were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In addition, an
model of atherosclerosis was established by exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to suppress AMPK expression. Lp-PLA2, AMPKα and phosphorylated-AMPKα (T172) expression in HUVECs were evaluated using western blot analysis. The concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) in cell culture supernatant were determined using commercially available ELISA kits. MTT assays were employed to indicate changes in cell viability. The current study found the plasma Lp-PLA2 levels were elevated in the CAD patients with stable angina pectoris, unstable angina pectoris, acute coronary syndromes and acute myocardial infarction, compared with a healthy control population. In addition, the
results showed that Lp-PLA2 expression levels were elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell viability, induce the production of NO and decrease the secretion of ET-1, in addition to suppressing the expression of cell adhesion molecules, including ICAM-1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPKα and phosphorylated-AMPKα (T172) was regulated by Lp-PLA2, and AMPK suppression was able to reverse the effects of Lp-PLA2 with regard to cell viability, endothelial vasorelaxation capacity and the secretion of adhesion molecules in oxLDL-exposed HUVECs. In conclusion, the present study provides initial evidence that Lp-PLA2 is able to cause endothelial dysfunction in an
model of atherosclerosis, and the effects of Lp-PLA2 on endothelial dysfunction was at least partially a result of the downregulation of AMPKα, thus contributing to the progression of atherosclerosis.
•A Li2FeSiO4/C nanocomposite is prepared via thermal vapor deposition technology.•The Li2FeSiO4/C nanocomposite is free from impurity and coated with carbon layer.•The Li2FeSiO4/C nanocomposite ...exhibits good rate capability and cycling stability.•Lithium benzoate serves as both lithium and carbon sources.
A Li2FeSiO4/C nanocomposite is prepared via solvothermal method in combination with carbon coating technology. The as-prepared Li2FeSiO4/C nanocomposite is a single phase Li2FeSiO4 with nano-tickness coated carbon layer and connected by the mutual cross-linked carbon conductive matrix. As cathode material for lithium ion battery, the composite delivers a discharge capacity of 154 mAh g−1 at 1C and exhibits good rate capability with a discharge capacity of 106 mAh g−1 at the rate of 10C, which is ascribed to the small particle size and enhanced electronic conductivity using carbon coating technology. The as-prepared Li2FeSiO4/C nanocomposite also behaves a good cycling stability with capacity retention of over 100 cycles.
This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney ...injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
We investigated the preventive effect of nicorandil on contrast-induced nephropathy (CIN) in patients with moderate renal insufficiency undergoing percutaneous coronary intervention (PCI). A total of ...250 patients with a creatinine clearance (crCl) ≤60 mL/min undergoing PCI were randomly assigned to either a nicorandil group (nicorandil 10 mg 3 times/d and hydration; n = 125) or a control group (hydration only; n = 125). The first end point was the incidence of CIN defined as an increase in serum creatinine (Scr) levels by ≥0.5 mg/dL or ≥25% within 72 hours after exposure to the contrast medium. The secondary end points were (1) changes in Scr, blood urea nitrogen, and crCl and (2) the incidence of major adverse events during hospitalization. The incidence of CIN was 1.6% (2/125) in the nicorandil group and 9.6% (12/125) in the control group (P = .011). There was no obvious difference in the incidence of major adverse events during hospitalization between the nicorandil and the control group (4.0% vs 4.8%, P = 1.000). Multivariate logistic regression analysis showed that nicorandil was a protective factor for CIN (odds ratios = 0.126, 95% confidence interval: −19.996 to −0.932, P = .012). Prophylactic administration of nicorandil may prevent against CIN in patients with moderate renal insufficiency undergoing PCI.
Modification of insoluble dietary fiber (IDF) for facilitating its applications has been encouraged in food industry. IDF from soybean residues was treated by dynamic high pressure microfluidization ...(DHPM), and effect of modified IDF (MIDF) addition on gelatinization and rheology of rice starch (RS) was investigated. It was found that DHPM could effectively reduce particle size of IDF, induce puffed morphology, and increase their water holding capacity. Addition of IDF/MIDF to RS increased peak and final viscosity of paste, and MIDF decreased breakdown and setback value, indicating MIDF may be a great candidate for increasing stability of paste and restraining short-term retrogradation of starch gels. Dynamic rheology indicated that supplementing MIDF changed rheological properties of RS less than IDF did. The results suggested that DHPM would provide an opportunity to change the physicochemical properties of IDF, and the resulting MIDF may be more suitable for designing fiber-enriched products.
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•Insoluble dietary fiber from soybean residue was microfluidized (DHPM).•DHPM changed particle size, morphology and water holding capacity of IDF.•Adding IDF or modified IDF changed pasting and rheology of rice starch.•Modified IDF may be suitable for designing fiber-enriched starchy foods.
“A Craftsman Must Sharpen His Tools to Do His Job,” said Confucius. Nuclear detection and readout techniques are the foundation of particle physics, nuclear physics, and particle astrophysics to ...reveal the nature of the universe. Also, they are being increasingly used in other disciplines like nuclear power generation, life sciences, environmental sciences, medical sciences, etc. The article reviews the short history, recent development, and trend of nuclear detection and readout techniques, covering Semiconductor Detector, Gaseous Detector, Scintillation Detector, Cherenkov Detector, Transition Radiation Detector, and Readout Techniques. By explaining the principle and using examples, we hope to help the interested reader underst and this research field and bring exciting information to the community.
Objective
To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD).
Methods
...This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay.
Results
Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD.
Conclusion
Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity.
As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus ...replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.
The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ
are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF ...biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks.
The CSF and genotyping data of 843 study subjects (199 CN, 85 SMC, 239 EMCI, 207 LMCI, 113 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed. PLINK was used to perform GWAS on the t-tau/Aβ
ratio using quality controlled genotype data, including 563,980 single nucleotide polymorphisms (SNPs), with age, sex and diagnosis as covariates. Gene-level p-values were obtained by VEGAS2. Genes with p-value ≤ 0.05 were mapped on to a protein-protein interaction (PPI) network (9,617 nodes, 39,240 edges, from the HPRD Database). We integrated a consensus model strategy into the iPINBPA network analysis framework, and named it as CM-iPINBPA. Four consensus modules (CMs) were discovered by CM-iPINBPA, and were functionally annotated using the pathway analysis tool Enrichr. The intersection of four CMs forms a common subnetwork of 29 genes, including those related to tau phosphorylation (GSK3B, SUMO1, AKAP5, CALM1 and DLG4), amyloid beta production (CASP8, PIK3R1, PPA1, PARP1, CSNK2A1, NGFR, and RHOA), and AD (BCL3, CFLAR, SMAD1, and HIF1A).
This study coupled a consensus module (CM) strategy with the iPINBPA network analysis framework, and applied it to the GWAS of CSF t-tau/Aβ1-42 ratio in an AD study. The genome-wide network analysis yielded 4 enriched CMs that share not only genes related to tau phosphorylation or amyloid beta production but also multiple genes enriching several KEGG pathways such as Alzheimer's disease, colorectal cancer, gliomas, renal cell carcinoma, Huntington's disease, and others. This study demonstrated that integration of gene-level associations with CMs could yield statistically significant findings to offer valuable biological insights (e.g., functional interaction among the protein products of these genes) and suggest high confidence candidates for subsequent analyses.
The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has ...not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD).
This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.
In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (
< 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group (
< 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97,
= 0.250).
In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.
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