CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway.

CD9 is a member of the tetraspanin protein family, which has been widely studied in inflammation and cancer, but not in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 was increased in transaortic constriction (TAC) myocardial tissue. Knockdown of CD9 alleviated damage to cardiac function in the TAC model and reduced heart weight, cardiomyocyte size, and degree of fibrosis, and vice versa. Mechanistically, co-immunoprecipitation results showed that CD9 and GP130 can bind to each other in cardiomyocytes, and knockdown of CD9 can reduce the protein level of GP130 and the phosphorylation of STAT3 in vivo and in vitro, and vice versa. GP130 knockdown reversed the aggravating effects of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy by regulating the GP130/STAT3 signaling pathway and may serve as a therapeutic target for pathological cardiac hypertrophy.

Effect of KNDC1 overexpression on the senescence of human umbilical vein endothelial cells.

Kinase non-catalytic C-lobe domain containing 1 (KNDC1) exists in dendrites, guanine nucleotide exchange factor complexes and neuronal cell bodies as a putative protein­protein interaction module that regulates a number of signaling pathways. Previous studies have demonstrated that the knockdown of KNDC1 delays human umbilical vein endothelial cell (HUVEC) senescence. However, the effect of KNDC1 overexpression on HUVEC function remains unclear. In the present study, an adenovirus vector carrying KNDC1 was constructed and then transfected into endothelial cells to observe cell senescence. Furthermore, the effect of KNDC1 overexpression on HUVEC senescence was investigated in vitro and the underlying molecular mechanism was investigated. Senescence­associated ß­galactosidase staining was used to determine cellular senescence and reactive oxygen species (ROS) were monitored to detect the level of cell oxidative stress. The mRNA transcription level and protein expression were analyzed by reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that KNDC1 overexpression possibly inhibited HUVEC activity and function and promoted HUVEC senescence. Mechanistic studies demonstrated that KNDC1 triggered a p53­ROS positive feedback loop, which serves a crucial role in regulating senescence. In conclusion, to the best of the authors' knowledge, this is the first time that KNDC1­adenovirus vector inhibition of HUVEC proliferation by activating the p53 signaling pathway has been reported. Theoretically, the results of the present study also support KNDC1 as a therapeutic target for future anti-senescence.

Short-term efficacy and safety of three different antiplatelet regimens in diabetic patients treated with primary percutaneous coronary intervention: a randomised study.

BACKGROUND AND AIM: This study aimed to investigate the efficacy and safety of dual and triple antiplatelet therapy (DAPT and TAPT) in patients with diabetes and acute ST segment elevation myocardial infarction (D-STEMI), who had undergone primary percutaneous coronary intervention (PCI). METHODS: We designed a phase IV, single-centre, randomised, double-blind, placebo-controlled study. The D-STEMI patients (n = 258) were randomly divided into three groups. Control group A (85 patients), was treated with aspirin and clopidogrel; group B (87 patients) received aspirin, clopidogrel, and tirofiban; and group C (86 patients) were treated with aspirin, ticagrelor, and tirofiban. Patients in all three groups received oral DAPT, and patients in groups B and C received intravenous tirofiban when primary PCI was performed. RESULTS: Compared to the findings in group A, the post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow in groups B and C increased significantly (TIMI grade 3 in groups A, B, C: 74%, 91%, and 98%, respectively; TIMI myocardial perfusion grade [TMPG] grade 3 in groups A, B, C: 59%, 86%, and 97%, respectively), and the incidence of major adverse cardiac events (MACE) decreased significantly (p < 0.05). Compared to the findings in group B, the rate of TMPG 3 in group C was significantly higher (p < 0.05) and the incidence of MACE was significantly lower (p < 0.05). Patients in group B exhibited minor bleeding; however, the incidence of mild to moderate bleeding in group C increased significantly (p < 0.05). CONCLUSIONS: TAPT effectively improved the TIMI blood flow and TMPG and reduced the occurrence of MACE. Ticagrelor was more effective than clopidogrel in TAPT; however, when using the combination of aspirin, ticagrelor, and tirofiban, close monitoring is required for possible bleeding complications.

Impact of Admission Glucose on Non-Diabetic Patients with ST-Segment Elevation Myocardial Infarction Treated with Percutaneous Coronary Intervention: A Meta-Analysis.

BACKGROUND: Impaired admission glucose (AG) is thought to significantly increase the risk of both early and late death with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients. However, several earlier studies contradict these relationships. Through our meta-analysis, we aimed to evaluate such a relation between impaired AG, the risk of death and STEMI. METHODS: We accessed PubMed, EMBASE, Web of Science, and the Cochrane Library and systematically searched their databases to identify all related prospective cohort studies. The relative risks (RRs) with their 95% confidence interval (CI) were pooled quantitatively. RESULTS: The pooled, unadjusted relative risks of early outcome events indicated that patients who had glucose concentrations ≥ the range of 6.1-11.1 mmol/L, had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. For late outcome events, the pooled unadjusted RR indicated patients who had glucose concentrations ≥ the range 7.8-11.1 mmol/L, and had a 2.69-fold (95% CI, 2.16-3.34) higher late mortality based on full participants, whereas patients had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on based on in-hospital or 30-day survivors. CONCLUSIONS: In conclusion, the present meta-analysis demonstrated that impaired admission glucose may be an effective prognostic marker for significantly increased risk of early death. Regarding the long-term outcomes based on full population or early survival, high admission glucose also has a distinct but poorer prognostic impact on long-term mortality than early mortality. KEY WORDS: Admission glucose • Meta-analysis • Myocardial infarction • Non-diabetic.

Efficacy and safety of different doses of tirofiban combined with ticagrelor on diabetic patients with AMI receiving in emergency percutaneous coronary intervention (PCI).

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of dual antiplatelet drugs combined with different doses of tirofiban on diabetic patients with acute myocardial infarction (AMI) receiving emergency percutaneous coronary intervention (PCI). METHODS: 158 diabetic patients with AMI undergone emergency PCI were randomly divided into three groups: Group A (53 cases) as the control group-dual anti-platelet agents (aspirin + ticagrelor); Group B (52 cases)-dual anti-platelet agents + conventional dose of tirofiban [10 µg/kg by PCI and 0.15 µg/(kg·min) by continue venous pump for 24 h]; Group C (53 cases)-dual antiplatelet agents + half-dose tirofiban [10 µg/kg by PCI and 0.075 µg/(kg·min) by continue venous pump for 24 h]. RESULTS: Compared with group A, thrombolysis in myocardial infarction 3 (TIMI3) blood flow and TIMI myocardial perfusion grade 3 (TMPG3) myocardial perfusion of patients in group B and group C after PCI was significantly higher (P < 0.05), the average day of hospitalization was significantly shorter (P < 0.05), reinfarction during hospitalization, post-infarction angina, severe arrhythmia, the incidence of cardiac function above KillipIII level was significantly lower (P < 0.05). And the differences between group B and C was not statistically significant (P > 0.05). Severe bleeding and moderate incidence of bleeding in group B was significantly higher than that in group A and group C (P < 0.05). CONCLUSIONS: Based on combination of dual the anti-platelet agents and ticagrelor for diabetic patients with AMI receiving PCI, the combination of half-dose tirofiban can effectively improve TIMI flow and TMPG myocardial tissue perfusion, and reduce the incidence of major adverse cardiac events (MACE) and severe bleeding.

Predictors of visual and anatomical outcomes for neovascular age-related macular degeneration treated with bevacizumab.

The present study aimed to evaluate the predictive factors for visual and anatomical outcomes in neovascular age-related macular degeneration (AMD) patients treated with intravitreal bevacizumab (IVB). A total of 113 patients with neovascular AMD received IVB treatment. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and total macular volume (TMV) were assessed before the injection, and at 1, 2, 3 and 9 months after surgery. Changes in BCVA and these optical coherence tomography (OCT) outcomes from baseline were compared, and independent predictors were evaluated by logistic regression models. During the treatment, logarithm of the minimum angle of resolution (logMAR) significantly decreased from 1.12 to 0.83, and reductions in OCT parameters were earlier and larger. Baseline BCVA was associated with the changes in BCVA and CRT, whereas baseline OCT features significantly affected their own changes. Larger baseline logMAR and OCT features were more likely to experience a greater proportion of ≥50 µm reduction in CRT (P<0.05). The BCVA decreases were positively associated with the reductions in CRT (r=0.34, P<0.01) and TMV (r=0.41, P<0.01). Among patients with neovascular AMD, IVB resulted in earlier significant decreases in TMV and CRT, suggesting that these OCT anatomical outcomes may be considered as more sensitive responders to evaluate the treatment effects of bevacizumab.

Comparison of primary coronary percutaneous coronary intervention between Diabetic Men and Women with acute myocardial infarction.

OBJECTIVE: This study aimed to explore the short-term efficacy and safety of primary percutaneous coronary intervention (PCI) in female diabetic patients complicated with acute myocardial infarction (AMI). METHODS: A total of 169 diabetic patients with AMI who underwent primary PCI were selected and divided into group A (52 females) and group B (117 males). The clinical data, characteristics of coronary artery lesions, lengths of hospital stay, and incidences of complications were then compared between two groups. RESULTS: The average age, history of hyperlipidemia, double branch lesions, triple branch lesions, and left main lesions were significantly higher in group A than in group B (P < 0.05). Smoking history, PCI history, and pre-infarction angina were distinctly lower in group A than in group B (P < 0.05). Thrombolysis in myocardial infarction 3 (TIMI3) flow and TIMI myocardial perfusion grade 3 (TMPG3) after PCI were markedly lower in group A than in group B (P < 0.001). Group A had a higher incidence of complications, such as severe arrhythmia, cardiac function Killip III/IV, cardiogenic shock, major, moderate and mild bleed event, as well as a 30-day mortality rate, compared with group B (P < 0.05). CONCLUSION: In summary, our study demonstrated that female diabetic patients with AMI had lower TIMI3 flow and TMPG3 following PCI than male patients, while there was higher incidence of complications and 30-day mortality rate. Therefore, more attention should be paid to the therapy of diabetic women with acute myocardial infarction as well as the control of risk factors.

Admission glucose and risk of early death in non-diabetic patients with ST-segment elevation myocardial infarction: a meta-analysis.

BACKGROUND: Impaired admission glucose (AG) is considered to significantly increase risk on both early and late death of the patients with ST-segment elevation myocardial infarction (STEMI), especially for non-diabetic patients; however, some reports contradict the relationship. We therefore conducted a meta-analysis to clarify this issue. MATERIAL/METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched to identify all related prospective cohort studies. The relative risks (RR) with their 95% confidence interval (CI) were pooled quantitatively. RESULTS: The pooled RR of early outcome events indicated patients with glucose concentrations ≥6.1-11.1 mmol/L had a 4.38-fold (95% CI, 3.23-5.94) higher early mortality. The pooled RR of late outcome events indicated that the patients with glucose concentrations ≥7.8-11.1 mmol/L had a 1.65-fold (95% CI, 1.33-2.04) higher late mortality based on in-hospital or 30-day survivors. CONCLUSIONS: High AG may be a helpful prognostic marker of significantly increased risk on early death in non-diabetic patients with STEMI, and has an explicit but prognostic adverse impact on long-term mortality but not early mortality in these patients.

Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis.

The purpose of this meta-analysis was to evaluate the relationship between blood lutein and zeaxanthin concentration and the risk of age-related cataract (ARC). MEDLINE, EMBASE, ISI and Cochrane Library were searched to identify relevant studies up to April 2013. Meta-analysis was conducted to obtain pooled relative risks (RRs) for the highest-versus-lowest categories of blood lutein and zeaxanthin concentrations. One cohort study and seven cross-sectional studies were included in the meta-analysis. There were significant inverse associations between nuclear cataract and blood lutein and zeaxanthin concentrations, with the pooled RRs ranging from 0.63 (95% confidence interval (CI): 0.49, 0.77) for zeaxanthin to 0.73 (95% CI: 0.59, 0.87) for lutein. A stronger association between nuclear cataract and blood zeaxanthin might be noted for the studies conducted in the European Nations. Blood lutein and zeaxanthin were also noted to lead towards a decrease in the risk of cortical cataract and subcapsular cataract; however, these pooled RRs were not statistically significant, with the exception of a marginal association between lutein and subcapsular cataract. Our results suggest that high blood lutein and zeaxanthin are significantly associated with a decrease in the risk of nuclear cataract. However, no significant associations were found for ARC in other regions of the lens.

A dose-response meta-analysis of dietary lutein and zeaxanthin intake in relation to risk of age-related cataract.

BACKGROUND: Lutein and zeaxanthin are thought to have beneficial effects on protecting the lens against cataract formation, but findings from epidemiologic studies have been inconsistent. We aimed to conduct a meta-analysis of prospective cohort studies to examine the association between dietary lutein and zeaxanthin intake and risk of age-related cataract (ARC). METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library databases up to March 2013. Reference lists from retrieved articles were also reviewed. The adjusted relative risks (RRs) from each study were extracted to calculate a pooled estimate with its 95 % confidence interval (CI). The dose-response relationships were assessed by using generalized least-squares trend estimation. RESULTS: Six prospective cohort studies were identified involving 4,416 cases and 41,999 participants. For the comparison between the highest and the lowest categories of dietary lutein and zeaxanthin intake, significant inverse association were found for nuclear cataract (RR: 0.75; 95 % CI: 0.65, 0.85), but not for cortical cataract (RR: 0.85; 95 % CI: 0.53, 1.17) and for posterior subcapsular cataract (RR: 0.77; 95 % CI: 0.40, 1.13). Dose-response analysis showed that every 300 µg/d increment in dietary lutein and zeaxanthin intake was associated with a 3 %, 1 %, or 3 % reduction in the risk of nuclear cataract (RR: 0.97; 95 % CI: 0.94, 0.99), cortical cataract (RR: 0.99; 95 % CI: 0.95, 1.02), or posterior subcapsular cataract (RR: 0.97; 95 % CI: 0.93, 1.01) respectively. CONCLUSIONS: Dietary lutein and zeaxanthin intake is associated with a reduced risk of ARC, especially nuclear cataract in a dose-response manner, indicating a beneficial effect of lutein and zeaxanthin in ARC prevention.