Different Anti-inflammatory Drugs on High-Sensitivity C-Reactive Protein in Patients After Percutaneous Coronary Intervention: A Pilot Randomized Clinical Trial.

ABSTRACT: Colchicine reduces atherothrombotic cardiovascular events in coronary artery disease because of its anti-inflammatory effect. However, the effects of the other anti-inflammatory drugs in coronary artery disease remain unclear. This study included 132 patients aged 18-80 years who completed the planned percutaneous coronary interventions and were treated with aggressive secondary prevention strategies for 4 weeks. The subjects were randomly assigned to 1 of the following treatment groups for 4 weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in high-sensitivity C-reactive protein (hsCRP) levels at the end of 4 weeks. In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male, and 28 (25.69%) were female. The percentage changes in hsCRP after 4 weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups, respectively. Compared with the control group, only the colchicine group showed significantly greater reduction in hsCRP levels ( P = 0.022). In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin, myeloperoxidase, and myeloblastin), platelet aggregation (glycoprotein VI), and endothelial damage (galectin-3) were reduced with colchicine therapy. These results show that of 3 anti-inflammatory drugs only colchicine could reduce hsCRP in patients after percutaneous coronary interventions.

Vascular Calcification: Where is the Cure?

With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

Plasma Level of Elabela in Patients with Coronary Heart Disease and Its Correlation with the Disease Classification.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

Ginsenoside Re enhances the survival of H9c2 cardiac muscle cells through regulation of autophagy.

We examined the effect of ginsenoside Re (G-Re) on autophagy in H9c2 cardiomyocytes cultured in glucose deprivation (GD). Levels of the membrane-bound autophagy-related microtubule-associated protein 1A/1B-light chain 3 (LC3) B-2 were measured via immunoblotting and immunofluorescence was conducted to assess autophagosome formation. GD H9c2 cells were treated with 100 µmol/l G-Re. Cell viability was determined in culture medium. Phosphorylated 5' AMP-activated protein kinase (AMPK)-α and mammalian target of rapamycin (mTOR) levels were measured to explore the mechanisms underlying the effects of G-Re on autophagy in GD cells. G-Re treatment inhibited autophagosome formation and may be beneficial to GD cardiomyocytes.

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients.

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.

Usage patterns and comfort of gardens: a seasonal survey of internal garden microclimate in the aged care homes of Chengdu City.

An increasing number of Chinese elders trade family care for institutional elder care, which poses an acute challenge due to the enormous number of elders. The internal garden of care homes is often the only green space supplied for the elderly. To elucidate the microclimate status of these internal gardens, three microclimate parameters (air temperature (Ta), relative humidity (RH), and solar radiation (SR) were measured in the gardens of eight care homes for the aged in Chengdu City (for 2015 and 2016). The results confirmed that all gardens showed effects of seasonal cooling (from 1.0 ± 0.7 to 2.00 ± 0.8 °C), humidification (from 2.8 ± 1.4 to 4.9 ± 2.0%), and weakening of solar radiation (from 52.3 ± 36.3 to 254.4 ± 124.1 w/m2). Even small internal gardens (130-4000 m2) could yield cooling effects in four seasons. Among garden subareas, the weakest SR, the lowest Ta, and the highest RH were all found in the rest area. Correlation analysis demonstrated that only in summer, the green coverage ratio of the garden significantly affected the microclimate. The observation showed that an average of 29.98% of the elderly used these internal gardens per day. The period of 8:00 am to 10:00 am was the elderly's favorite time to use the gardens. More than 68% of elders preferred to sit in the rest area. Thermal/humidity/radiation sensation votes indicated that the garden microclimate partially deviated from elders' comfortable levels, particularly in winter. The rest area showed the worst comfort level for the elders. A warmer, more humid, and more sun-exposed garden should be supplied to the elderly. Several greening strategies are proposed to improve the garden microclimate for the well-being of the elderly in the care homes.

Association of Circulating Neuregulin-4 with Presence and Severity of Coronary Artery Disease.

Neuregulin-4 (Nrg4) is a newly discovered adipokine that is synthesized in many tissues and plays an important role in modulating systemic energy metabolism and in the development of metabolic disorders. However, little is known about the relationship between Nrg4 and coronary artery disease (CAD). In this study, we investigated the association between Nrg4 and the presence and severity of CAD.We enrolled 73 patients diagnosed by coronary angiography (CAG) as having CAD and 32 controls. The CAD group was divided into two subgroups according to their SYNTAX score. Plasma levels of Nrg4 were measured in all participants and compared among different groups. The relationship between Nrg4 and CAD was analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the usefulness Nrg4 in assessing the presence and severity of CAD.Nrg4 levels were negatively associated with the SYNTAX score (r = -0.401, P = 0.000). The patients with a higher SYNTAX score had significantly lower Nrg4 levels as compared with the low SYNTAX score subgroup and the controls (P < 0.05). The Nrg4 levels of the low SYNTAX score subgroup were much lower than controls (P < 0.05). Furthermore, an association between Nrg4 and CAD (odds ratio, 0.279; 95% confidence interval, 0.088-0.882) was observed. Nrg4 had 43.8% sensitivity and 96.9% specificity for identifying CAD, and 73.1% sensitivity and 87.3% specificity for identifying patients who had severe coronary artery lesions.Nrg4 levels were found to be inversely associated with the presence and severity of CAD.

[Association between CMTM5 gene rs723840 single nucleotide polymorphism and high on asprin platelet reactivity].

OBJECTIVE: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR). METHODS: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and ≥ 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene. RESULTS: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264-0.947). CONCLUSION: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity.

[Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabetes and coronary artery disease].

OBJECTIVE: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD). METHODS: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. RESULTS: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687±3 052) ng/g, while the urinary 11dhTxB2 was (1 954±859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05). CONCLUSION: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

[The clinical features of gastrointestinal bleeding complicating aortic stenosis].

OBJECTIVE: To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding. METHODS: Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed. RESULTS: In all the 443 157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%, 474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3 were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg(1 mm Hg = 0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ± 28) g/L and (2.71 ± 2.04)×10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet(PLT) count, prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) fl, (29.39 ± 1.99) pg, (327.57 ± 14.82) g/L, (185.13 ± 22.55)×10(9)/L, (11.4 ± 1.04) s and 1.22 ± 0.44, respectively]. Among all the 14 patients, 13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer, and another of duodenal ulcer, while no definite hemorrhage foci were found in the other 11 patients. A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found. Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5). CONCLUSIONS: Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

[Value of 3-dimensional speckle tracking imaging to quantify regional left ventricular function in patients with coronary artery disease].

OBJECTIVE: To assess left ventricular (LV) strain by 3-dimensional speckle tracking imaging (3D-STI) in patients with coronary heart disease (CHD). METHODS: All subjects underwent invasive coronary angiography.2-dimensional and 3-dimensional echocardiography were performed in 52 subjects with suspected CHD. Longitudinal strain (LS) , circumferential strain (CS) , radial strain (RS) and area strain (AS) in 17 LV segments were acquired by 3D-STI respectively. RESULTS: According to coronary angiography results, 35 (76.1%)subjects were diagnosed as CHD, and 138 coronary branches were divided into the control group(25 branches, 18.1%), the mild stenosis group (31 branches, 22.5%), the moderate stenosis group (43 branches, 31.2%) and the severe stenosis group (39 branches, 28.2%).3D-STI was performed with reliable tracking quality in 46(88.5%) out of the 52 subjects initially enrolled in this study. 3D-STI showed:(1)LS was similar between mild stenosis group and the control group (P > 0.05) and significantly reduced in the moderate stenosis group compared with the control group(P < 0.05), and LS in some segments (MAS, AA, A, BAL, MAL, AL, BIS, MIS and AI) of moderate stenosis group were significantly decreased compared with the mild stenosis group (P < 0.05). LS of all segments in the severe stenosis group decreased significantly compared with the control group, the mild stenosis group and the moderate stenosis (P < 0.05). (2)RS was similar between mild stenosis group and the control group (P > 0.05) . RS in some segments (BAS,MA and BI) was significantly decreased in the moderate stenosis group compared with the control group(P < 0.05). RS was significantly decreased in the severe stenosis group compared with the control group and the mild stenosis group (except for AS,AL,MIS,MI and AI) (P < 0.05). (3) CS was similar between mild stenosis group and the control group (P > 0.05) and was significantly reduced in some segments (BAS,AS,BIL and BI) of the moderate stenosis group compared with the control group(P < 0.05). CS was significantly decreased in the severe stenosis group compared with the control group, the mild stenosis group and the moderate stenosis(P < 0.05). (4) AS was significantly decreased in the mild stenosis group compared with the control group(P < 0.05, except for BIL,MAL and BIS) and in all segments of the moderate stenosis group compared with the control group and the mild stenosis group(P < 0.05). AS was significantly decreased in the severe stenosis group compared with the control group, the mild stenosis group and the moderate stenosis(P < 0.05). The progressive decrease in AS was observed from the control group to the mild stenosis group, the moderate stenosis group and the severe stenosis group (P < 0.05). In addition, AS was negatively correlated with coronary artery Gensini score (r = -0.71, P < 0.01) . CONCLUSION: LV strain can be reliably quantified by 3D-STI. AS is a more sensitive parameter to detect coronary artery disease at early phase.

Ginsenoside Rg1 inhibits autophagy in H9c2 cardiomyocytes exposed to hypoxia/reoxygenation.

Ginsenoside Rg1 promotes antioxidative protection and intracellular calcium homeostasis in cardiomyocytes hypoxia/reoxygenation (H/R) model. However, the pharmacological effects of G-Rg1 on autophagy in cardiomyocytes have not been reported. In this study, we employed H9c2 cardiomyocytes as a model to investigate the effects of G-Rg1 on autophagy in cardiomyocytes under H/R stress. Our results showed that H/R induced increased level of LC3B-2, an autophagy marker, in a time-dependent manner in association with decreased cell viability and cellular ATP content. H/R-induced autophagy and apoptosis were further confirmed by morphological examination. 100 µmol/l Rg1-inhibited H/R induced autophagy and apoptosis, and this was associated with the increase of cellular ATP content and the relief of oxidative stress in the cells. Mechanistically, we found that Rg1 inhibited the activation of AMPKα, promoted the activation of mTOR, and decreased the levels of LC3B-2 and Beclin-1. In conclusion, our data suggest that H/R induces autophagy in H9c2 cells leading to cell injury. Rg1 inhibits autophagosomal formation and apoptosis in the cells, which may be beneficial to the survival of cardiomyocytes under H/R.

Paeonol alleviates placental inflammation and apoptosis in preeclampsia by inhibiting the JAK2/STAT3 signaling pathway.

Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti-apoptosis and anti-inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl-phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme-linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF-α, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bax, Bcl-2, and caspase-3) were tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules. Here, Pae repressed the inflammatory response in the placenta of PE-like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF-α, IL-6, and IFN-γ and the increased concentrations and mRNA levels of IL-4. Apoptosis in the placentas of PE-like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved-caspase-3 and the upregulated Bcl-2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC-39100) reversed Pae treatment-mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

Combined effects of cyclooxygenase-1 and cyclooxygenase-2 selective inhibitors on ovarian carcinoma in vivo.

The present study was designed to investigate the combined effects of cyclooxygenase (COX)-1 and COX-2 selective inhibitors on human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 3 mg/kg SC-560 (a COX-1 selective inhibitor) alone, 25 mg/kg celecoxib (a COX-2 selective inhibitor) alone, or SC-560/celecoxib by gavage, twice a day for three weeks. To test the mechanism of inhibition of tumor growth by COX selective inhibitors, the index of proliferating cells in tumor tissues was determined by immunostaining and the index of apoptotic cells by the terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. The inhibitory rate on tumor growth in the combination group was 35.54% which is significant statistically compared with that of the control group (P < 0.05). In the combination group, the index of cell proliferation and apoptosis were 12.40% and 51.03% respectively, which are significant statistically compared with those of the control group (22.56%, 19.07%, all P < 0.05). These studies indicate that synergism between two COX inhibitors and inhibitor combination treatment has particular potential for chemoprevention of ovarian cancer growth.

[Aspirin response and related factors in aged patients].

OBJECTIVE: To explore clinical and laboratory factors associated aspirin response, and the association between gastrointestinal bleeding and aspirin response in aged patients. METHODS: A total of 136 patients aged 60 and over [mean age (74.9 ± 7.0) years] with ischemic heart disease and at high risk for ischemic heart disease were included. Arachidonic acid induced platelet aggregation (AA-Ag) was measured before and at 7(th) day after taking aspirin (100 mg/d). Patients were followed for 6 months and incidence of gastrointestinal bleeding was obtained. RESULTS: Post-treatment AA-Ag was significantly reduced compared to baseline (13.29% ± 5.52% vs. 73.20% ± 7.32%, P < 0.05). A heterogeneous distributed post-treatment AA-Ag was observed (range 0.42% to 30.50%). Post-treatment AA-Ag was positively correlated with baseline AA-Ag (r = 0.493, P < 0.01). The level of post-treatment AA-Ag was significantly higher in the fourth quartile group at baseline than in the others quartile groups at baseline. Patients aged 80 years and over had significantly lower post-treatment AA-Ag (10.25% ± 4.68%) compared with patients of 60 - 69 years (13.96% ± 5.20%) and of 70 - 79 years (13.73% ± 5.48%, all P < 0.01). The incidence of patients in the lowest quartile of post-treatment AA-Ag was significantly higher in patients ≥ 80 years (38.24%) than in patients of 60 - 69 years (11.1%) and of 70 - 79 years (24.0%). Multiple variable analysis revealed post-treatment AA-Ag was significantly influenced by baseline AA-Ag, ≥ 80 years old, diabetes mellitus and acute coronary syndrome. We observed 4 (2.9%) mild gastrointestinal bleeding during follow up. Post-treatment AA-Ag was in the lowest quartile in 3 patients with mild gastrointestinal bleeding. CONCLUSIONS: Increased baseline platelet reactivity as well as diabetes mellitus and acute coronary syndrome are associated with low aspirin response in the aged patients. Aspirin response is significantly higher in very old patients.

[Effects of mixed-tocopherols and eicosapentaenoic acid on oxidized LDL-induced oxidative damage and inflammatory cytokine secretion in human umbilical vein endothelial cells].

OBJECTIVE: To observe the influence of either alone or combined mixed-tocopherols combined with eicosapentaenoic acid (EPA) and α-Tocopherol use on oxidized LDL (oxLDL) induced 8-hydroxy-2'-deoxyguanosine (8-OHDG) and interleukin-6 (IL-6) secretion by human umbilical vein endothelial cells (HUVECs) and to explore the potential mechanism. METHOD: Cultured HUVECs in vitro were incubated with oxLDL, oxLDL + α-tocopherol, oxLDL + mixed-tocopherols, oxLDL + EPA, oxLDL + α-tocopherol + EPA, oxLDL + mixed-tocopherols + EPA for 24 hours, respectively. Secretion of 8-OHDG and IL-6 were detected by cell enzyme linked immunosorbent assay (ELISA). The expressions of superoxide dismutase (SOD), protein kinase C-δ (PKC-δ), phosphorylated PKC-δ (p-PKC-δ) were analyzed by Western blot. RESULTS: 8-OHDG and IL-6 secretion of HUVECs was significantly increased significantly after incubated with oxLDL for 24 hours which could be significantly attenuated in the presence of tocopherols and EPA (alone or in combination, all P < 0.05) while the strongest inhibition effects were seen with combined use of mixed-tocopherols and EPA. Moreover, combination of mixed-tocopherols and EPA could also significantly increase SOD activity and decrease PKC activity (all P < 0.05). However, the protein expression of SOD and PKC-was similar among groups. CONCLUSION: Combined mixed-tocopherols + EPA use enhanced the inhibiting effects on the secretion of 8-OHDG and IL-6 in oxLDL stimulated HUVECs which might be linked with increased SOD activity and reduced p-PKC activity.

Association Between Low-Dose Aspirin and Uric Acid in the Elderly: An Observational Retrospective Cross-Sectional Study.

PURPOSE: Uric acid is an independent factor for arteriosclerotic cardiovascular disease (ASCVD). Although aspirin is one of the most widely used agent in patients with ASCVD, there were only a few studies focusing on the effects of low-dose aspirin on uric acid metabolism with controversial results. The present study aimed to investigate an association between low-dose aspirin treatment for more than one month and serum uric acid (SUA) with its urinary excretion in elderly patients. PATIENTS AND METHODS: This paper presents an observational retrospective cross-sectional study to determine the association between continuous daily taking low-dose aspirin (50-100mg) for more than one month and SUA with fraction excretion of uric acid (FEUA) in elderly patients. A total of 506 inpatients equal or over 60 in Department of Geriatrics of Peking University First Hospital were enrolled from 2017 to 2020. About 41.9% of them were taking aspirin for more than one month, while others were not taking this medicine. The correlation between aspirin use and SUA or FEUA was analyzed, and group-comparison was performed in different dosage groups of aspirin. RESULTS: After correcting confounding factors, there is no remarkable correlation between taking low-dose aspirin and SUA or FEUA, but a decreasing trend (coefficients=-4.946) of SUA in hyperuricemia patients with low-dose aspirin was observed despite no obvious difference (P=0.534). Whether SUA or FEUA has no significant difference between 50mg/d and 100mg/d aspirin subjects. CONCLUSION: SUA and urinary uric acid excretion are not associated with using of 50-100mg/d aspirin for more than one month in elderly patients with ASCVD or at risk.

Identification of Potential Inhibitors Against the TGF-ß/BMPs-Activin Receptor- like Kinase 1 Signal Pathway.

INTRODUCTION: In many diseased states, especially fibrosis and cancer, TGF-ß family members are overexpressed and the outcome of signaling is diverted toward disease progression. As the result of activin receptor-like kinase 1 (ALK1) plays a key role in TGF-ß signaling, discovering inhibitors of ALK1 to block TGF-ß signaling for a therapeutic benefit has become an effective strategy. METHODS: In this work, ZINC15894217 and ZINC12404282 were identified as potential ALK1 inhibitors using molecular docking, molecular dynamics simulation and MM/PBSA calculations studies. The analysis of energy decomposition found that Val208, Val216, Lys229, Gly283, Arg334 and Leu337 acted as crucial residues for ligand binding and system stabilizing. RESULTS: In addition, these compounds displayed excellent pharmacological and structural properties, which can be further evaluated through in vitro and in vivo experiments for the inhibition of ALK1 to be developed as drugs against fibrosis and tumor. CONCLUSION: Overall, our study illustrated a time- and cost-effective computer aided drug design procedure to identify potential ALK1 inhibitors. It would provide useful information for further development of ALK1 inhibitors to improve disease related to TGF-ß signal pathway.

Cyclin D1 expression and the inhibitory effect of celecoxib on ovarian tumor growth in vivo.

The report aims to investigate the relationship between the expression of cyclin D1 and Cyclooxgenase-2 (COX-2), thus to explore the molecular mechanisms of the antitumor efficacy of Celecoxib, a COX-2 inhibitor. Human ovarian SKOV-3 carcinoma cell xenograft-bearing mice were treated with Celecoxib by infusing gaster (i.g.) twice/day for 21 days. The mRNA levels of COX-2 and cyclin D1 were determined by RT-PCR. The expression of cyclin D1 at the protein level was detected by immunohistochemistry, while COX-2 protein expression was determined by Western blot. A high-dose of Celecoxib (100 mg/kg) significantly inhibited tumor growth (P < 0.05), and the expression of cyclin D1 was reduced by 61%. Celecoxib decreased the proliferation cell index by 40% (P < 0.001) and increased apoptotic index by 52% (P < 0.05) in high-dose Celecoxib treated group. Our results suggest that the antitumor efficacy of Celecoxib against ovarian cancer in mice may in part be mediated through suppression of cyclin D1, which may contribute to its ability to suppress proliferation.

[Effects of n-3 polyunsaturated fatty acids on hemorheology and coagulation in atherosclerotic rats].

OBJECTIVE: To investigate the effect of n-3 polyunsaturated fatty acids (n-3PUFAs) on the hemorheology and coagulation function of high-fat induced atherosclerotic rats and understand the underlying mechanism. METHODS: Twenty-four Wistar rats were assigned randomly into 3 groups: normal control, model and n-3PUFAs treatment (n = 8 in each). The rats in model and treatment groups were injected with a single dose of vitamin D(3) (600,000 U/kg) and fed with a high-fat diet. Basic chow was provided for normal control group. After a 6-week high-fat diet, the rats in treatment group were treated with n-3PUFAs at 250 mg×kg(-1)×d(-1) by gastric tube. The serum lipid, aortal morphological changes, hemorheology, coagulation, nitric oxide (NO), total antioxidant capacity (T-AOC) and malonaldehyde (MDA) were detected after a 6-week n-3PUFAs diet. RESULTS: Compared with control group, model group rat total cholesterol (TC), low density cholesterol (LDL-C), plasma viscosity, whole blood viscosity, fibrinogen (FIB) and MDA concentrations were higher (all P < 0.05), but activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), erythrocyte deformation index(DI), plasma NO and T-AOC were lower (all P < 0.05). Compared with model group, n-3PUFAs could reduce blood lipid levels, inhibit atherosclerotic plaque formation, decrease plasma viscosity [(1.58 ± 0.23) mPa·s vs (1.81 ± 0.16) mPa·s], whole blood viscosity [(4.76 ± 0.42) mPa·s vs (5.47 ± 0.41) mPa·s, (4.24 ± 0.32) mPa·s vs (4.91 ± 0.39) mPa·s, (4.04 ± 0.29) mPa·s vs (4.58 ± 0.33) mPa·s] and FIB [(2.45 ± 0.12)g/L vs (2.65 ± 0.13) g/L], lower MDA content [(10.1 ± 0.7) µmol/ml vs (11.2 ± 0.6) µmol/ml], prolong APTT, PT and TT [(29.04 ± 0.49)s vs (26.46 ± 0.25) s, (13.86 ± 0.55) s vs (10.71 ± 0.34) s, (23.05 ± 0.24) s vs (20.90 ± 0.68) s], increase erythrocyte DI (0.35 ± 0.01 vs 0.31 ± 0.02), plasma NO [(3.9 ± 0.7) nmol/ml vs (2.8 ± 0.7) nmol/ml] and T-AOC levels [(8.0 ± 0.6) U/ml vs (6.7 ± 0.6) U/ml]of atherosclerotic rats (all P < 0.05). CONCLUSION: n-3PUFAs may improve hemorheology and coagulation of atherosclerotic rats, reduce oxidative stress, improve endothelial function and inhibit atherosclerotic plaque formation.