Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Parkinson disease (PD) is an age-related neurodegenerative disease, which is associated with the loss of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc), and neuroinflammation may lead to the occurrence of PD. Wuzi Yanzong Pill (WYP) has demonstrated neuroprotective and anti-inflammatory properties, but its molecular mechanism of action is still unclear. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and LPS-mediated BV2 microglia to explore WYP intervention, anti-inflammatory effect and molecular mechanism in vivo and in vitro. The results showed that oral administration of WYP in MPTP-induced PD mice for 2 weeks ameliorated abnormal motor dysfunction, attenuated the loss of TH + neurons in SNpc, protected dopaminergic neurons, and inhibited the activation of microglia in MPTP-induced PD mice and LPS-stimulated BV2 cell. Meanwhile, WYP intervention inhibited the expression of IL-6, TNF-α, Pro-IL-1ß, IL-1ß, Pro-IL-18, IL-18 and enhanced the expression of IL-10 in the SNpc of PD mice. Simultaneously, WYP intervention inhibited the expression of NLRP3 inflammasome, accompanied by the decrease of the TLR4/MyD88/NF-κB pathway. However, the exact target and interaction of WYP on NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway still needs to be further investigated.

Quercetin inhibits testicular toxicity induced by the mixture of three commonly used phthalates in rats.

BACKGROUND: Phthalates (PEs), such as butyl benzyl phthalate, dibutyl phthalate and di(2-ethylhexyl) phthalate, are one of the most widely used plasticizers, and humans are increasingly exposed to them. Phytochemical quercetin (Que) is a typical flavonoid with several biological effects, such as antioxidative and anti-inflammatory. The present study was designed to explore the effect of Que on testicular toxicity caused by the mixture of three commonly used PEs (MPEs), and the underlying mechanism. Forty male Sprague-Dawley rats were randomly and equally divided into five groups (n = 8). Rats in control the group were orally treated with the excipient. Rats in the MPEs group were orally administered with 900 mg kg-1 day-1 MPEs, whereas rats in the MPEs+L-Que, MPEs+M-Que and MPEs+H-Que groups were simultaneously treated with 900 mg kg-1 day-1 MPEs and, respectively, 10, 30 and 90 mg kg-1 day-1 Que for 30 days. RESULTS: Compared with the control group, the testes weight, epididymides weight, serum testosterone, luteinizing hormone, follicle-stimulating hormone and estradiol levels, and anogenital distance in the MPEs group were significantly decreased (P < 0.05). The testicular tissues were injured with atrophy of seminiferous tubules, hyperplasia of Leydig cells and arrest of spermatogenesis in the MPEs group. Testicular steroidogenic proteins (StAR, P450scc, CYP17A1 and 17ß-HSD, P450arom) were up-regulated, whereas P-element-induced wimpy testis proteins (PIWIL1 and PIWIL2) were down-regulated in the MPEs group (P < 0.05). However, the alterations of these parameters were inhibited in the MPEs+M-Que and MPEs+H-Que groups. CONCLUSION: MPEs disturbed steroid hormone metabolism and caused testicular injuries. Que could inhibit testicular toxicity of MPEs, which might relate to the improved regulation of steroid hormone metabolism. © 2022 Society of Chemical Industry.

Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography.

BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited. METHODS: In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up. RESULTS: LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8-29.2] µm vs 13.2 [7.4-18.6] µm; P = 0.029), greater increases in minimum lumen area (0.20[0.10-0.33] mm2 vs 0.13 [0.12-0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8-24.5] vs. 8.4̊ [2.0-10.5]; P = 0.008). CONCLUSIONS: The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04851769 . Registered 2 Mar 2019.

MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin.

Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis.

Periprocedural heparin bridging in patients receiving oral anticoagulation: a systematic review and meta-analysis.

BACKGROUND: Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established. OBJECTIVES: To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants. METHODS: We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling. RESULTS: A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR = 3.23, 95%CI: 2.06-5.05), minor bleeding (OR = 1.52, 95%CI: 1.06-2.18) and overall bleeding (OR = 2.83, 95%CI: 1.86-4.30).While there was no significant difference in thromboembolic events (OR = 0.99,95%CI: 0.49-2.00), stroke or transient ischemic attack(OR = 1.45, 95%CI: 0.93-2.26,) or all-cause mortality (OR = 0.71, 95%CI: 0.31-1.65). CONCLUSIONS: Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.

Differential analysis of transcriptome of psychrophilic bacteria under different culture temperatures.

BACKGROUND: Psychrophilic bacteria can survive in a unique living environment. OBJECTIVE: To explore the mechanism of low temperature adaptation and the physiological function of thermophilic metabolic genes. METHOD: Serratia marcescens strain F13 stored in microbial laboratory was cultured at 5∘C, 10∘C and 25∘C respectively, and the obtained strains were sequenced by high-throughput transcriptome. Serratia marcescens strain CAV1761 was used as the reference strain. The data produced by transcriptome sequencing were statistically analyzed by biostatistics software such as soapnuke, soap and edger. The differentially expressed genes were found based on the gene expression, and analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: The results showed that there were 718 differential genes in F13-10 vs F13-5 comparison group, 1614 differential genes in F13-25 vs F13-5 comparison group and 1636 differential genes in F13-25 vs F13-10 comparison group. GO function enrichment analysis showed that the GO term mainly enriched by different genes in the three comparison groups was mostly related to the migration and transport of cellular or subcellular components, cell localization and transmembrane transporter activity, as well as cilia or flagella dependent cell movement. In the enrichment analysis of KEGG pathway, the three comparison groups all enriched the largest number of differential genes in the branch pathway of KEGG metabolism, followed by the branch pathway of environmental information processing. CONCLUSION: In F13-10 vs F13-5, the differential genes were mainly concentrated in 20 pathways such as ATP-binding cassette transport (ABC) transporters, thiamine metabolism and flagella assembly; In F13-25 vs F13-5, the differential genes are mainly concentrated in 20 pathways, such as (ABC) transporters, arginine and proline metabolism, two-component system and so on; In F13-25 vs F13-10, the differential genes are mainly concentrated in 20 pathways such as various types of glycan synthesis, two-component system and arginine metabolism.

miR-141-3p promotes paclitaxel resistance by attenuating ferroptosis via the Keap1-Nrf2 signaling pathway in breast cancer.

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo. Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

Integrated analysis of differentially expressed genes and miRNA expression profiles in dilated cardiomyopathy.

Background: Although dilated cardiomyopathy (DCM) is a prevalent form of cardiomyopathy, the molecular mechanisms underlying its pathogenesis and progression remain poorly understood. It is possible to identify and validate DCM-associated genes, pathways, and miRNAs using bioinformatics analysis coupled with clinical validation methods. Methods: Our analysis was performed using 3 mRNA datasets and 1 miRNA database. We employed several approaches, including gene ontology (GO) analysis, KEGG pathway enrichment analysis, protein-protein interaction networks analysis, and analysis of hub genes to identify critical genes and pathways linked to DCM. We constructed a regulatory network for DCM that involves interactions between miRNAs and mRNAs. We also validated the differently expressed miRNAs in clinical samples (87 DCM ，83 Normal) using qRT-PCR.The miRNAs' clinical value was evaluated by receiver operating characteristic curves (ROCs). Results: 78 differentially expressed genes (DEGs) and 170 differentially expressed miRNAs (DEMs) were associated with DCM. The top five GO annotations were collagen-containing extracellular matrix, cell substrate adhesion, negative regulation of cell differentiation, and inflammatory response. The most enriched KEGG pathways were the Neurotrophin signaling pathway, Thyroid hormone signaling pathway, Wnt signaling pathway, and Axon guidance. In the PPI network, we identified 10 hub genes, and in the miRNA-mRNA regulatory network, we identified 8 hub genes and 15 miRNAs. In the clinical validation, we found 13 miRNAs with an AUC value greater than 0.9. Conclusion: Our research offers novel insights into the underlying mechanisms of DCM and has implications for identifying potential targets for diagnosis and treatment of this condition.

Integrating genomic profiling to clinical data: assessing the impact of CD147 expression on plaque stability.

Background: Acute Coronary Syndrome (ACS) continues to be a leading cause of death and illness worldwide. Differentiating stable from unstable coronary plaques is essential for enhancing patient outcomes. This research investigates the role of CD147 as a biomarker for plaque stability among coronary artery disease patients. Methods: The study began with high-throughput sequencing of blood samples from six patients, divided equally between those with Stable Angina (SA) and Unstable Angina (UA), followed by bioinformatics analysis. Expanding upon these findings, the study included 31 SA patients and 30 patients with ACS, using flow cytometry to examine CD147 expression on platelets and monocytes. Additionally, logistic regression was utilized to integrate traditional risk factors and evaluate the predictive value of CD147 expression for plaque stability. Results: Initial sequencing displayed a notable difference in CD147 expression between SA and UA groups, with a significant increase in UA patients. Further analysis confirmed that elevated platelet CD147 expression was strongly associated with unstable plaques (OR = 277.81, P < .001), after adjusting for conventional risk factors, whereas monocyte CD147 levels did not show a significant difference. Conclusion: Elevated CD147 expression on platelets is a crucial biomarker for identifying unstable coronary artery plaques, offering insights into patient risk stratification and the development of targeted treatment strategies. This underscores the pivotal role of molecular research in understanding and managing coronary artery disease, paving the way for improved clinical outcomes.

Machine learning-based prediction model for myocardial ischemia under high altitude exposure: a cohort study.

High altitude exposure increases the risk of myocardial ischemia (MI) and subsequent cardiovascular death. Machine learning techniques have been used to develop cardiovascular disease prediction models, but no reports exist for high altitude induced myocardial ischemia. Our objective was to establish a machine learning-based MI prediction model and identify key risk factors. Using a prospective cohort study, a predictive model was developed and validated for high-altitude MI. We consolidated the health examination and self-reported electronic questionnaire data (collected between January and June 2022 in 920th Joint Logistic Support Force Hospital of china) of soldiers undergoing high-altitude training, along with the health examination and second self-reported electronic questionnaire data (collected between December 2022 and January 2023) subsequent to their completion on the plateau, into a unified dataset. Participants were subsequently allocated to either the training or test dataset in a 3:1 ratio using random assignment. A predictive model based on clinical features, physical examination, and laboratory results was designed using the training dataset, and the model's performance was evaluated using the area under the receiver operating characteristic curve score (AUC) in the test dataset. Using the training dataset (n = 2141), we developed a myocardial ischemia prediction model with high accuracy (AUC = 0.86) when validated on the test dataset (n = 714). The model was based on five laboratory results: Eosinophils percentage (Eos.Per), Globulin (G), Ca, Glucose (GLU), and Aspartate aminotransferase (AST). Our concise and accurate high-altitude myocardial ischemia incidence prediction model, based on five laboratory results, may be used to identify risks in advance and help individuals and groups prepare before entering high-altitude areas. Further external validation, including female and different age groups, is necessary.

miR-155 inhibits oxidized low-density lipoprotein-induced apoptosis of RAW264.7 cells.

Macrophage apoptosis is a prominent feature of advanced atherosclerotic plaques. Here, we examined the hypothesis that the apoptotic machinery is regulated by microRNA-155 (miR-155). Constitutive expression of miR-155 was detected in RAW264.7 cells, which was increased following stimulation with oxidized low-density lipoprotein (OxLDL) in a dose- and time-dependent manner. OxLDL-treated RAW264.7 cells showed a marked time- and dose-dependent increase in apoptosis, which was suppressed in the presence of mimics and increased with antagonists of miR-155. Bioinformatics analysis revealed Fas-associated death domain-containing protein (FADD) as a putative target of miR-155. Luciferase reporter assay and Western blot further disclosed that miR-155 inhibits FADD expression by directly targeting the 3'-UTR region. We propose that miR-155 attenuates the macrophage apoptosis, at least in part, through FADD regulation, since forced expression of FADD blocked the ability of miR-155 to inhibit apoptosis. Our results collectively suggest that miR-155 attenuates apoptosis of OxLDL-mediated RAW264.7 cells by targeting FADD, supporting a possible therapeutic role in atherosclerosis.

Atorvastatin inhibits the 5-lipoxygenase pathway and expression of CCL3 to alleviate atherosclerotic lesions in atherosclerotic ApoE knockout mice.

BACKGROUND: The 5-lipoxygenase (5-LO) pathway and the chemokine CCL3 are involved in the inflammatory processes of atherosclerosis. Statins have shown cholesterol-independent pleiotropic effects on antiimmune and antiinflammatory responses in atherosclerosis. We postulated that this effect may be associated with the 5-LO pathway and CCL3. METHODS AND RESULTS: ApoE knockout mice were randomized into control group (normal diet), atherosclerosis group (high-cholesterol diet), and atorvastatin group (high-cholesterol diet and atorvastatin). Sixteen weeks later, aortic roots were stained with hematoxylin and eosin. Total cholesterol and low-density lipoprotein cholesterol were measured by the enzymatic methods. The gene and protein expressions of 5-LO and CCL3 were detected separately through real-time reverse transcription polymerase chain reaction and western blotting analyses. The serum levels of leukotriene B4 and leukotriene D4 were measured by enzyme-linked immunosorbent assay. All mice have atherosclerotic plaques, mice in the control group have only tiny atherosclerotic plaques, but mice in the atherosclerosis group and atorvastatin group have typical atherosclerotic plaques. The corrected plaque areas (plaque area/luminal area) of the aortas of mice in the atorvastatin group were significantly decreased compared with those of the atherosclerosis group. The serum cholesterol levels of the atorvastatin group were not of significant difference compared with those of the atherosclerosis group. The gene and protein expressions of 5-LO and CCL3 in the aortas, as well as the serum levels of leukotriene B4 and leukotriene D4 in atorvastatin group, were markedly reduced compared with those of the atherosclerosis group. CONCLUSION: These data suggested that atorvastatin significantly alleviated atherosclerotic lesions by inhibiting the 5-LO pathway and down regulating the expression of CCL3 in ApoE-/- mice.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Development of a highly efficient virus-free regeneration system of Salvia miltiorrhiza from Sichuan using apical meristem as explants.

BCAKGROUND: The dry root and rhizome of Salvia miltiorrhiza are used to treat cardiovascular diseases, chronic pain, and thoracic obstruction over 2000 years in Asian countries. For high quality, Sichuan Zhongjiang is regarded as the genuine producing area of S. miltiorrhiza. Given its abnormal pollen development, S. miltiorrhiza from Sichuan (S.m.-SC) relies on root reproduction and zymad accumulation; part of diseased plants present typical viral disease symptoms and seed quality degeneration. This study aim to detected unknown viruses from mosaic-diseased plants and establish a highly efficient virus-free regeneration system to recover germplasm properties. RESULTS: Tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were detected from mosaic-diseased plants. Primary apical meristem with two phyllo podium in 0.15-0.5 mm peeled from diseased plants were achieved 73.33% virus-free rate. The results showed that the medium containing MS, 0.5 mg/L 6-BA, 0.1 mg/L NAA, 0.1 mg/L GA3, 30 g/L sucrose and 7.5 g/L agar can achieve embryonic-tissue (apical meristem, petiole and leaf callus) high efficient organogenesis. For callus induction, the optimal condition was detected on the medium containing MS, 2 mg/L TDZ, 0.1 mg/L NAA by using secondary petiole of virus-free plants under 24 h dark/d condition for 21 d. The optimal system for root induction was the nutrient solution with 1/2 MS supplemented with 1 mg/L NAA. After transplant, the detection of agronomic metric and salvianolic acid B content confirmed the great germplasm properties of S.m.-SC virus-free plants. CONCLUSIONS: A highly efficient virus-free regeneration system of S.m.-SC was established based on the detected viruses to recover superior seed quality. The proposed system laid support to control disease spread, recover good germplasm properties in S.m.-SC.

Association of serum complement C1q with cardiovascular outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To determine the association of serum complement C1q levels with cardiovascular outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), and evaluate the value of C1q modified by high-sensitivity C-reactive protein (hs-CRP) levels as an independent predictor. METHODS: As a single-center prospective observational study, we analyzed 1701 patients who had received primary or elective PCI for ACS at Beijing Anzhen Hospital, Capital Medical University, Beijing, China between June 1, 2016 and November 30, 2017. The associations of C1q modified by hs-CRP with major adverse cardiovascular events (MACE) were determined in survival analysis. RESULTS: Patients with the lowest C1q tertile had the highest cumulative risk of MACE (log-rank P = 0.007). In fully adjusted Cox regression models, stratifying the total population according to hs-CRP dichotomy, C1q was significantly associated with MACE in patients with hs-CRP levels less than 2 mg/L but not in those with 2 mg/L or more (P interaction = 0.02). In patients with hs-CRP levels less than 2 mg/L, with the lowest C1q tertile as reference, the risk of MACE was reduced by 40.0% in the middle C1q tertile [hazard ratio (HR) = 0.600, 95% CI: 0.423-0.852, P = 0.004] and by 43.9% in the highest C1q tertile (HR = 0.561, 95% CI: 0.375-0.840, P = 0.005). CONCLUSIONS: Serum complement C1q is significantly associated with cardiovascular outcomes in patients with ACS undergoing PCI, only when hs-CRP levels are less than 2 mg/L. This finding implicates the usefulness of C1q for the risk stratification in ACS patients with reduced systemic inflammation.

Protective effect of quercetin against phthalates induced hepatotoxicity in rats.

Humans are increasingly exposed to ubiquitous phthalates (PEs), e.g. butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), which are widely used plasticizers in polymer products. This study was aimed to investigate the effect of phytochemical quercetin (Que) on hepatotoxicity caused by the mixture of the 3 commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty male Sprague-Dawley rats were randomly divided into control group, MPEs group, and MPEs combined Que at Low-, Median-, and High-dose groups; rats in MPEs group were orally administered with 900 mg/kg/d MPEs, whereas rats in MPEs combined Que groups were simultaneously treated with 900 mg/kg/d MPEs and respectively 10, 30, and 90 mg/kg/d Que. The intervention last 30 days. Compared with control group, serum ALT, AST, LDH and AKP, and hepatic MDA, SOD, CAT and GPx were significantly increased, whereas, serum albumin and total protein were significantly decreased in MPEs group (P < 0.05); hepatic histopathological observation showed numerous inflammatory cells infiltration, hepatocyte ballooning degeneration, and numerous residual erythrocytes in the central vein in MPEs group. Western-blot analysis showed that hepatic Keap1 was downregulated, whereas Nrf2 and HO-1 were upregulated in MPEs group (P < 0.05). However, the alterations of these parameters were alleviated in MPEs combined Que at Median- and High-dose groups. The results indicated that MPEs-induced hepatic oxidative stress, and caused hepatic injuries; whereas, Que inhibited MPEs' hepatotoxicity, which might relate to Que's ability of quenching free radicals directly, and restored the regulation of Nrf2 signaling pathway.

Cobalt-Nickel Phosphate Composites for the All-Phosphate Asymmetric Supercapacitor and Oxygen Evolution Reaction.

Recently, design of cost-effective multifunctional electromaterials for supercapacitors and oxygen evolution reaction (OER) and enhancing their functionalities have become an emphasis in energy storage and conversion. Herein, a series of cheap and functional phosphate composites with different ratios of cobalt and nickel are synthesized using a simple polyalcohol refluxing method, and their excellent capacity and OER properties are systematically studied. Notably, owing to the different major role of Co and Ni elements in the phosphate composites for capacity and OER, the optimal electroconductibility, structural adjustment, electrochemical active sites, and activities for capacity and OER are obtained from the composites with the different ratios of Co/Ni. In addition, using high-capacity BiPO4 (BPO) as the negative electrodes, the new type of all-phosphate asymmetric supercapacitor (CNPO-40//BPO) shows a high energy density and reaches 36.84 W h kg-1 at a power density of 254.52 W kg-1. Its cyclic stability is also more excellent than that of the CNPO-40//AC device using commercial activated carbon as the negative electrodes. This study is beneficial to the more in-depth research on efficient dual-function electromaterials in capacity and OER and provides a high-efficient way to improve the practicality of asymmetric supercapacitors using the high-capacity Bi-based electromaterials as the negative electrodes.

Identification and characterization of a novel 5 bp deletion in a putative insulin response element in the lipoprotein lipase gene.

Our aim was to identify an insulin response element (IRE) in the lipoprotein lipase (LPL) gene. We identified a 19 bp sequence as a putative IRE in LPL non-coding exon 10 using bioinformatics. Upon sequencing the IRE region, a novel 5 bp deletion was identified in Hispanics (N=406) with a carrier frequency of 4.2% but not in non-Hispanic whites (N=604) or Africans. Electrophoretic mobility shift assay revealed binding sites for regulatory factor(s) in muscle cell nuclear extracts with putative IRE sequence. Antibody supershift assay using human aorta smooth muscle cell nuclear extract revealed that Elk-1 specifically binds to putative IRE. TaqMan real-time RT-PCR of the 5 bp deletion, the mutant and wild type cDNA expressed in COS-1 and human muscle cells revealed that the 5 bp deletion was associated with modest reduction in LPL expression. There was also a slight reduction in LPL translation in the deletion mutant. Our data suggest the presence of an IRE in the 3'UTR of the LPL gene.

The effect of the expression of angiotensin II on extracellular matrix metalloproteinase inducer (EMMPRIN) in macrophages is mediated via the AT1/COX-2/PGE2 pathway.

AIM: To explore the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in THP-1 macrophages induced by angiotensin II (Ang II) and the mechanism of EMMPRIN expression. METHODS: THP-1 cells were cultured and induced into macrophages, then stimulated with 10(-6) mol/L Ang II. Levels of EMMPRIN gene and its protein were measured by real-time polymerase chain reaction and western blotting. Prostaglandin E(2) (PGE(2)) expression was assayed by enzyme-linked immunosorbent assay. Antagonists of the angiotensin type-1 receptor (AT(1)R) and angiotensin type-2 receptor (AT(2)R) were used to inhibit the effect of Ang II, and PGE(2) added to detail the mechanism of Ang II-induced EMMPRIN expression. RESULTS: Ang II clearly induced the expression of EMMPRIN mRNA and protein in macrophages; this expression peaked at 12 h and declined after 24 h. The tendency of enhancement of the levels of cyclooxygenase-2 (COX-2) and PGE(2) was coincident with EMMPRIN expression. AT(1)-receptor antagonists and COX-2 inhibitors inhibited the effect of Ang II, but AT(2)-receptor antagonists did not. CONCLUSION: Ang II can up-regulate EMMPRIN expression in THP-1 macrophages via the AT(1)/COX-2/PGE(2) signal transduction pathway, and the effect can be inhibited by losartan and NS-398.

Aqua-(1H-benzimidazole-κN)(pyridine-2,6-dicarboxyl-ato-κO,N,O)copper(II) 0.75-hydrate.

The title complex, [Cu(C(7)H(3)NO(4))(C(7)H(6)N(2))(H(2)O)]·0.75H(2)O, consists of discrete monomeric units. The Cu(II) atom is coordinated by two carboxyl-ate O atoms and the N atom from a dipicolinate unit and by an N atom from a benzimidazole ligand. The distorted square-pyramidal geometry is completed by a longer axial bond to the O atom of a water mol-ecule. The mol-ecular structure and packing are stabilized by classical O-H⋯O and N-H⋯O hydrogen bonds, also including a disordered crystal water molecule.