Prognostic value of metabolic syndrome in patients with heart failure and malnutrition.

BACKGROUND: Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. METHODS: We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI < 40 being defined as malnutrition. The follow-up endpoint was cardiovascular death or all-cause death. RESULTS: During the 36-month follow-up, survival rates for cardiovascular and all-cause death were significantly lower in the MS group than in the non-MS group (log-rank P < 0.01). Multivariate Cox proportional hazards regression models showed that MS was independently associated with cardiovascular death (HR:1.759, 95%CI:1.351-2.291, p < 0.001) and all-cause death (HR:1.326, 95%CI:1.041-1.689, p = 0.022) in malnourished patients with HF. MS significantly increased the predictive value of cardiovascular death (AUC:0.669, 95%CI:0.623-0.715, p < 0.001) and all-cause death (AUC:0.636, 95%CI:0.585-0.687, p < 0.001) on the basis of established risk factors. The predictive effect of MS on cardiovascular death was independent of sex, age, functional class and left ventricular ejection fraction. CONCLUSIONS: In malnourished patients with HF, MS is an independent risk factor for cardiovascular and all-cause mortality. MS significantly enhance the predictive value for clinical events in patients.

Design and application of a novel "turn-on" fluorescent probe for imaging sulfite in living cells and inflammation models.

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

AT1R gene rs389566 polymorphism contributes to MACCEs in hypertension patients.

OBJECTIVE: To investigate the possible association between AT1R gene polymorphisms and major adverse cardiovascular and cerebrovascular events (MACCEs) in hypertension patients combined with or without coronary artery disease (CAD) in Xinjiang. METHODS: 374 CAD patients and 341 non-CAD individuals were enrolled as study participants and all of them have a hypertension diagnosis. AT1R gene polymorphisms were genotyped by SNPscan™ typing assays. During the follow-up in the clinic or by telephone interview, MACCEs were recorded. Kaplan-Meier curves and Cox survival analyses were used to explore the association between AT1R gene polymorphisms and the occurrence of MACCEs. RESULTS: AT1R gene rs389566 was associated with MACCEs. The TT genotype of the AT1R gene rs389566 had a significantly higher probability of MACCEs than the AA + AT genotype (75.2% vs. 24.8%, P = 0.033). Older age (OR = 1.028, 95% CI: 1.009-1.0047, P = 0.003) and TT genotype of rs389566 (OR = 1.770, 95% CI: 1.148-2.729, P = 0.01) were risk factors of MACCEs. AT1R gene rs389566 TT genotype may be a predisposing factor for the occurrence of MACCEs in hypertensive patients. CONCLUSION: We should also pay more attention to the prevent of MACCEs in hypertension patients combined with CAD. Especially those elderly hypertensive patients carrying AT1R rs389566 TT genotype requires avoidance of unhealthy lifestyle, better management of blood pressure control and reduce the occurrence of MACCEs.

Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study.

BACKGROUND: Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level. METHODS: The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models. RESULTS: The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01-2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17-3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 µg/mL compared with the day workers. CONCLUSIONS: Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.

Proteome-scale profiling reveals MAFF and MAFG as two novel key transcription factors involved in palmitic acid-induced umbilical vein endothelial cell apoptosis.

BACKGROUND: Vascular endothelial cell apoptosis is the leading risk factor of atherosclerosis (AS). The purpose of our study was to use a new generation high-throughput transcription factor (TF) detection method to identify novel key TFs in vascular endothelial cell apoptosis induced by palmitic acid (PA). METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with 0, 300, or 500 µM PA. Candidate TFs in the three groups were identified by differential expression, pathway enrichment, Western Blot (WB), and RT-qPCR analyses. Apoptosis was assessed by fluorescence-activated cell sorting (FACS) using FITC-annexin V and propidium iodide staining. RESULTS: We established a HUVEC apoptosis model to simulate the process of atherosclerosis onset and identified 51 significant TFs. of the 51 TFs, v-maf musculoaponeurotic fibrosarcoma oncogene family protein G (MAFG) and v-maf musculoaponeurotic fibrosarcoma oncogene family protein F (MAFF), were matched to known AS signalling pathways and were validated by WB and RT-qPCR analyses in our study. Overexpression of MAFG or MAFF in HUVECs significantly inhibited PA-induced early apoptosis. CONCLUSIONS: We identified MAFF and MAFG as novel key TFs in vascular endothelial cell apoptosis.

Association between CCN1 gene polymorphism and acute coronary syndrome in Chinese Han and Uygur populations.

BACKGROUND: CCN1 plays a crucial role in the modulation of cardiovascular diseases. However, whether CCN1 genetic variants are involved in the susceptibility of ACS remains unknown. Hence, the present study investigates the association between CCN1 polymorphisms and ACS among Han and Uygur populations in Xinjiang, China. RESULTS: In this case-control study, 1234 Han (547 ACS patients and 687 controls) and 932 Uygur (471 ACS patients and 461 controls) were genotyped using SNPscanTM for three single-nucleotide polymorphisms (SNPs, rs6576776, rs954353, and rs3753794) of the human CCN1 gene. In the Uygur population, we found that the detected frequencies of the C allele (25.3% vs. 18.3%, P<0.001) and CC genotype (6.4% vs. 3.0%, P=0.001) of rs6576776 were significantly higher in the ACS patients than in the control participants. Differences in rs6576776 regarding the dominant model (CC+CG vs. GG, 44.2% vs. 55.8%, P=0.001) and the recessive model (CC vs. CG+GG, 6.4% vs. 93.6%, P=0.016) were observed between the two groups. The frequencies of the GGC and AGC haplotypes in those with ACS were significantly higher than those in the control group (all P<0.05) in the Uygur population. After adjusting for hypertension, diabetes, lipids and smoking, all of which indicate that the rs6576776 C allele is associated with higher risk of ACS (odds ratio (OR)=1.798, 95% confidence interval (CI), 1.218-2.656, P=0.003). In Han population, neither the distribution of genotypes and alleles of the CCN1 gene three SNPs nor the distribution of haplotypes constructed with the three SNPs exhibited a significant difference between the ACS patients and control participants. CONCLUSIONS: Our study document that the CCN1 gene rs6576776 C allele is associated with higher susceptibility of ACS and that the frequencies of GGC and AGC haplotypes are higher among the Uygur ACS patients.

Relaxin mitigates microvascular damage and inflammation following cardiac ischemia-reperfusion.

Microvascular obstruction (MVO) and leakage (MVL) forms a pivotal part of microvascular damage following cardiac ischemia-reperfusion (IR). We tested the effect of relaxin therapy on MVO and MVL in mice following cardiac IR injury including severity of MVO and MVL, opening capillaries, infarct size, regional inflammation, cardiac function and remodelling, and permeability of cultured endothelial monolayer. Compared to vehicle group, relaxin treatment (50 µg/kg) reduced no-reflow area by 38% and the content of Evans blue as a permeability tracer by 56% in jeopardized myocardium (both P < 0.05), effects associated with increased opening capillaries. Relaxin also decreased leukocyte density, gene expression of cytokines, and mitigated IR-induced decrease in protein content of VE-cadherin and relaxin receptor. Infarct size was comparable between the two groups. At 2 weeks post-IR, relaxin treatment partially preserved cardiac contractile function and limited chamber dilatation versus untreated controls by echocardiography. Endothelial cell permeability assay demonstrated that relaxin attenuated leakage induced by hypoxia-reoxygenation, H2O2, or cytokines, action that was independent of nitric oxide but associated with the preservation of VE-cadherin. In conclusion, relaxin therapy attenuates IR-induced MVO and MVL and endothelial leakage. This protection was associated with reduced regional inflammatory responses and consequently led to alleviated adverse cardiac remodeling.

Arsenic trioxide suppresses cell growth and migration via inhibition of miR-27a in breast cancer cells.

Accumulating evidence has demonstrated that arsenic trioxide (ATO) exhibits its anti-cancer activities in a variety of human malignancies. Recent studies have revealed that ATO regulated multiple microRNAs (miRNAs) in human cancers. However, the exact mechanism of ATO-mediated tumor suppressive function has not been fully elucidated. In the present study, we explore whether ATO governed oncogenic miR-27a in breast cancer cells by multiple methods such as MTT assay, RT-PCR, Wound healing assay, Western blotting analysis, migration, Transwell invasion assay, and transfection. Our results showed that ATO inhibited cell growth, migration, invasion, and induced cell apoptosis in breast cancer cells. Further molecular analysis dissected that ATO inhibited miR-27a expression in breast cancer cells. Moreover, inhibition of miR-27a suppressed cell growth, migration, invasion, and trigged cell apoptosis, whereas overexpression of miR-27a enhanced cell growth, motility, and inhibited apoptosis in breast cancer cells. Notably, we found that miR-27a inhibitor treatment potentiates ATO-induced breast cancer cell growth inhibition, apoptosis and motility inhibition. However, overexpression of miR-27a partly abrogated ATO-mediated anti-tumor activity. Our findings provide a novel anti-tumor mechanism of ATO involved in miR-27a for the treatment of breast cancer.

Adsorption of Pb(2+) from aqueous solution using spinel ferrite prepared from steel pickling sludge.

In this paper, spinel ferrite with high crystallinity and high saturation magnetization was successfully prepared from steel pickling sludge by adding iron source and precipitator in the hydrothermal condition. The obtained spinel ferrite was characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), vibrating sample magnetometer (VSM), and Zeta potential methods and investigated as an adsorbent for removal of Pb(2+) from aqueous solution. Batch experiments were performed by varying the pH values, contact time, temperature and initial metal concentration. The result of pH impact showed that the adsorption of Pb(2+) was a pH dependent process, and the pH 5.8 ± 0.2 was found to be the optimum condition. The achieved experimental data were analyzed with various kinetic and isotherm models. The kinetic studies revealed that Pb(2+) adsorption onto spinel ferrite followed a pseudo-second order model, and the Langmuir isotherm model provided the perfect fit to the equilibrium experimental data. At different temperatures, the maximum Pb(2+) adsorption capacities calculated from the Langmuir equation were in the range of 126.5-175.4 mg/g, which can be in competition with other adsorbents. The thermodynamic results showed that the spinel ferrite could spontaneously and endothermically adsorb Pb(2+) from aqueous solution. The regeneration studies showed that spinel ferrite could be used five times (removal efficiency (%) >90%) by desorption with HNO3 reagent.

[Grape seed proanthocyanidins extract inhibits pancreatic cancer cell growth through down-regulation of miR-27a expression].

OBJECTIVE: To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms. METHODS: The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects. RESULTS: GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 µg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 µg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination. CONCLUSION: GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.

Relationship Between Athletes' History of Stressors and Sport Injury: A Systematic Review and Meta-Analysis.

A history of stressors in athletes represents psychosocial factors that may lead to sport injury. However, empirical studies have provided varying results for the relationship between stress history and sport injury. We examined prior literature on the stress history - sport injury relationship within a systematic review and, by meta-analysis, we offered a pooled estimate of the strength of this relationship. We searched seven major academic databases (Sportdiscus, Psyinfo, Academic Search Premier, Ovid, Scopus, Web of Science, and PubMed) from January 2000 to September 2023 and identified 19 empirical studies that examined injuries in sports contexts for meta-analysis. In 19 empirical studies of moderate to high publication quality, we found moderate heterogeneity (Q(17) = 98.61; p < .001), low sensitivity (I2 77.82-83.77), and low publication bias (Z-value = 7.74; p < .001). Further, using a random effect estimate-r, we found a low but significant correlation between stress history and sport injury, yielding a small overall effect size (ES) of r = .12. Furthermore, moderation analyses found adolescents (r = .14), contact-sport athletes (r = .09), non-elite athletes (r = .13), and non-European athletes (America r = .16; Asia r = .14; Oceania r = .14) to have a relatively higher ES than their counterparts in this stress history/sport injury relationship. We concluded that inevitable life stressors may lead to many negative consequences for athletes, such that sports professionals should provide stress management educational programs to enhance athletes' health and well-being.

Prognostic Nutritional Index (PNI) as a Predictor in Patients with Metabolic Syndrome and Heart Failure.

Purpose: There is a lack of research on nutritional status and poor prognosis in patients with metabolic syndrome and heart failure. This study evaluated the relationship between nutritional status as defined by the PNI and adverse outcomes in patients with metabolic syndrome and heart failure. Methods: A total of 1048 heart failure patients with metabolic syndrome admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2019 were consecutively. PNI was used to assess their nutritional status. Results: A total of 51.0% of the patients were in the nonmalnutrition group (PNI≥45), 27.9% were in the mild malnutrition group (40≤PNI<45), and 21.1% of patients were in the malnutrition group (PNI<40). At 36 months of follow-up, after adjusting for other confounding factors, malnutrition (PNI<40) was independently associated with all-cause death (HR: 1.787, 95% CI: 1.451-2.201, P<0.001) and cardiovascular death (HR: 1.837, 95% CI: 1.467-2.301, P<0.001). PNI showed additional prognostic predictive value when included in the established risk factor model, both for all-cause death (AUC: 0.620, 95% CI: 0.579-0.661, P<0.001) and cardiovascular death (AUC: 0.596, 95% CI: 0.555-0.636, P<0.001). Conclusion: In patients with metabolic syndrome and heart failure, malnutrition assessed by PNI is an independent predictor for all-cause death and cardiovascular death, and PNI is negatively correlated with the occurrence of adverse outcomes.

Liraglutide alleviates myocardial ischemia‒reperfusion injury in diabetic mice.

Diabetic patients are prone to acute myocardial infarction. Although reperfusion therapy can preserve the viability of the myocardium, it also causes fatal ischemia‒reperfusion injury. Diabetes can exacerbate myocardial ischemia‒reperfusion injury, but the mechanism is unclear. We aimed to characterize the effects of liraglutide on the prevention of ischemia‒reperfusion injury and inadequate autophagy. Liraglutide reduced the myocardial infarction area and improved cardiac function in diabetic mice. We further demonstrated that liraglutide mediated these protective effects by activating AMPK/mTOR-mediated autophagy. Liraglutide markedly increased p-AMPK levels and the LC3 II/LC3 I ratio and reduced p-mTOR levels and p62 expression. Pharmacological inhibition of mTOR increased cell viability and autophagy levels in high glucose and H/R-treated H9C2 cells. Overall, our study reveals that liraglutide acts upstream of the AMPK/mTOR pathway to effectively counteract high glucose- and H/R-induced cell dysfunction by activating AMPK/mTOR-dependent autophagy, providing a basis for the clinical prevention and treatment of ischemia‒reperfusion in diabetes.

Metabolic Score for Insulin Resistance (METS-IR) Predicts Adverse Cardiovascular Events in Patients with Type 2 Diabetes and Ischemic Cardiomyopathy.

Purpose: This study aimed to evaluate the association between metabolic score for insulin resistance (METS-IR) and adverse cardiovascular events in patients with ischemic cardiomyopathy (ICM) and type 2 diabetes mellitus (T2DM). Methods: METS-IR was calculated using the following formula: ln[(2 × fasting plasma glucose (mg/dL) + fasting triglyceride (mg/dL)] × body mass index (kg/m2)/(ln[high-density lipoprotein cholesterol (mg/dL)]). Major adverse cardiovascular events (MACEs) were defined as the composite outcome of nonfatal myocardial infarction, cardiac death, and rehospitalization for heart failure. Cox proportional hazards regression analysis was used to evaluate the association between METS-IR and adverse outcomes. The predictive value of METS-IR was evaluated by the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: The incidence of MACEs increased with METS-IR tertiles at a 3­year follow­up. Kaplan‒Meier curves showed a significant difference in event-free survival probability between METS-IR tertiles (P<0.05). Multivariate Cox hazard regression analysis adjusting for multiple confounding factors showed that when comparing the highest and lowest METS-IR tertiles, the hazard ratio was 1.886 (95% CI:1.613-2.204; P<0.001). Adding METS-IR to the established risk model had an incremental effect on the predicted value of MACEs (AUC=0.637, 95% CI:0.605-0.670, P<0.001; NRI=0.191, P<0.001; IDI=0.028, P<0.001). Conclusion: METS-IR, a simple score of insulin resistance, predicts the occurrence of MACEs in patients with ICM and T2DM, independent of known cardiovascular risk factors. These results suggest that METS-IR may be a useful marker for risk stratification and prognosis in patients with ICM and T2DM.

Interactive effects of dispositional mindfulness and PETTLEP imagery training on basketball shooting performance: A randomized controlled trial.

The purpose of this study was to examine the interactive effects of dispositional mindfulness and visualized PETTLEP imagery training on basketball mid-range shooting performance and retention. Seventy-three participants (M age = 20.32 ± 1.09) with high/low dispositional mindfulness (high n = 35; low n = 38) selected out of 302 college students were randomly assigned into the following six groups: (a) high mindfulness internal imagery (H-II, n = 13); (b) high mindfulness external imagery (H-EI, n = 11); (c) high mindfulness control (H-CO, n = 11); (d) low mindfulness internal imagery (L-II, n = 13); (e) low mindfulness external imagery (L-EI, n = 12); and (f) low mindfulness control (L-CO, n = 13). Participants engaged in a pretest to measure their basketball shooting performance, then participated in a 6-week (3 times/per-week) intervention, plus a posttest and retention test. A three-way 2 (high/low mindfulness) X 3 (treatments: internal-, external imagery, and control) X 3 (measurement time: pretest, posttest, and retention) mixed ANOVA statistical analysis found dispositional mindfulness interacted with treatments and measurement time. The main effects showed high dispositional mindfulness performed better than low dispositional mindfulness, and internal imagery training performed better than external imagery training on mid-range basketball performance at retention. The 3-way interaction indicated that when using either internal or external imagery, high dispositional mindfulness performed better than low mindfulness on retention but not posttest. For 2-way interaction, high dispositional mindfulness performed better than low dispositional mindfulness on retention but not posttest. Our results extended current knowledge on sport imagery and dispositional mindfulness and gained several theoretical implications for researchers. The limitations, future research directions, and practical implications were also discussed.

Pre-competition mental energy and performance relationships among physically disabled table tennis players.

Energy is essential to human daily functioning and performance. However, the association of mental energy with athletes' performance has rarely been examined. We attempted to examine the pre-competition mental energy-performance relationships by two studies. Study 1 administered Athletic Mental Energy Scale (AMES, Lu et al., 2018) to nine elite physically-disabled table tennis players one day before competition in 5 international tournaments. Then, we collected their subjective performance after each competition. In Study 2, we sampled 77 National-level physically-disabled table tennis players and examined the pre-competition mental energy-performance relationship as the procedure in Study 1. Results from Study 1 provided initial findings of how pre-competition mental energy is associated with performance and portrayed in elite physically-disabled table tennis players. Results from Study 2 further confirmed the pre-competition mental energy- performance relationships. We suggested future studies to examine the mental energy-performance relationships in physically-disabled and abled athletes and different sports.

Targeted activation of ERK1/2 reduces ischemia and reperfusion injury in hyperglycemic myocardium by improving mitochondrial function.

Background: Diabetes can increase the risk of coronary heart disease, and also increase the mortality rate of coronary heart disease in diabetic patients. Although reperfusion therapy can preserve the viable myocardium, fatal reperfusion injury can also occur. Studies have shown that diabetes can aggravate myocardial ischemia-reperfusion injury, ERK1/2 can reduce myocardial ischemia-reperfusion injury, but its mechanism in hyperglycemic myocardial ischemia-reperfusion injury is unclear. This study sought to explore the mechanism of extracellular signal-regulated kinase 1/2 (ERK1/2) in hyperglycemic myocardial ischemia reperfusion (I/R) injury. Methods: H9C2 cardiomyocytes were treated with high-glucose (HG) medium plus I/R stimulation to establish a hyperglycemia I/R model in vitro. The cells were treated with LM22B-10 (an ERK activator) or transfected with the constitutive activation of the mitogen-activated protein kinase 1 (CaMEK) gene. Myocardial cell apoptosis, mitochondria functional-related indicators, the oxidative stress indexes, and the expression levels of ERK1/2 protein were detected. Results: The HG I/R injury intervention caused an increase in the ratio of apoptotic cardiomyocytes (P<0.05), but the phosphorylation level of the ERK1/2 protein did not increase further. Administering LM22B-10 or transfecting the CaMEK gene significantly activated the phosphorylation levels of ERK1/2 protein and reduced the proportion of cardiomyocyte apoptosis (P<0.05). HG I/R injury increased mitochondrial fission and reduced membrane potential. The intervention reduced the number of punctate mitochondria, increased the average network structure size and median branch length (P<0.01), increased the median network structure size and average branch length (P<0.05), and reduced the colocalization of Drp1 (Dynamin-Related protein1)/TOMM20 (Mitochondrial outer membrane translocation enzyme 20) (P<0.05) and Drp1 with serine 616 phosphorylation (Drp1s616) phosphorylation (P<0.01), thereby reducing mitochondrial fission, increasing membrane potential and mitochondrial function. HG I/R injury increased the level of oxidative stress, while administering LM22B-10 or transfecting the CaMEK gene reduced the level of oxidative stress (P<0.01). Conclusions: Targeting the activation of ERK1/2 protein phosphorylation reduced mitochondrial fission, increased membrane potential and mitochondrial function, reduced oxidative stress and myocardial cell apoptosis, and alleviated hyperglycemia myocardial I/R injury.

NFKB1 Gene Mutant Was Associated with Prognosis of Coronary Artery Disease and Exacerbated Endothelial Mitochondrial Fission and Dysfunction.

Endothelial apoptosis is the core pathological change in atherosclerotic cardiovascular disease, including coronary artery disease (CAD). Determining the molecular mechanisms underlying endothelial apoptosis is important. Nuclear factor kappa B (NF-κB) is a crucial transcription factor for controlling apoptosis. Our previous study demonstrated that the -94 ATTG ins/del mutant in the promoter of NFKB1 gene (rs28362491) is a risk factor for CAD. In the present study, we found that NFKB1 rs28362491 polymorphism was positively associated with increased major adverse cardiac and cerebrovascular events (MACCEs) in CAD patients. After adjusting for confounding factors including age, smoking, hypertension, glucose, and low-density lipoprotein cholesterol, the mutant DD genotype was an independent predictor of MACCEs (OR = 2.578, 95%CI = 1.64-4.05, P = 0.003). The in vitro study showed that mutant human umbilical vein endothelial cells (DD-mutant HUVECs) were more susceptible to high-glucose/palmitate-induced apoptosis, which was accompanied by decreased p50 expression and increased expression of cleaved caspase-3, Cytochrome c, and phospho-p65 (P < 0.05). The mitochondrial membrane potential was significantly lower, while increasing levels of mtROS and more opening of the mPTP were observed in DD-mutant HUVECs (P < 0.05). Furthermore, the percentage of cells with fragmented or spherical mitochondria was significantly higher in DD-mutant HUVECs than in wild-type cells (genotype II HUVECs) (P < 0.05). In addition, after stimulation with high glucose/palmitate, the NFKB1 gene mutant significantly increased the expression of Drp1, which indicated that the NFKB1 gene mutant affected the expression of mitochondrial morphology-related proteins, leading to excessive mitochondrial fission. In conclusion, the mutant DD genotype of the NFKB1 gene was an independent predictor of worse long-term prognosis for CAD patients. DD-mutant HUVECs exhibited abnormal activation of the NF-κB pathway and increased Drp1 expression, which caused excessive mitochondrial fission and dysfunction, ultimately leading to increased apoptosis.

Long-term prognostic value of macrophage migration inhibitory factor in ST-segment elevation myocardial infarction patients with metabolic syndrome after percutaneous coronary intervention.

Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease and negatively affecting the prognosis of patients with ST elevation myocardial infarction (STEMI). Macrophage migration inhibitory factor (MIF) is a multipotent cytokine involved in various cardiovascular and inflammatory diseases. In this prospective study, we investigate the value of MIF in the long-term prognosis of STEMI combined with MetS after emergency PCI. Circulating MIF levels were measured at admission, and major adverse cardiovascular and cerebrovascular events (MACCE) were monitored during the follow-up period of 4.9 (3.9-5.8) years. MACCE occurred in 92 patients (22.9%), which was significantly higher in MetS (69/255, 27.1%) than in the non-MS subgroup (23/146, 15.8%, P < 0.05). Patients with MetS developed MACCE had the highest admission MIF level. Kaplan-Meier survival analysis using the cutoff value of admission MIF (143 ng/ml) showed that patients with a higher MIF level had a greater incidence of MACCE than those with lower MIF levels in both the MetS (P < 0.0001) and non-MetS groups (P = 0.016). After adjustment for clinical variables, the value of MIF ≥ 143 ng/ml still had the predictive power for the MetS group [HR 9.56, 95% CI (5.397-16.944),P < 0.001]; nevertheless, it was not the case in the non-MetS group. Our findings indicated that MetS is a critical risk factor for adverse clinical outcomes in patients with STEMI, and a high admission MIF level has predictive power for the long-term MACCE, which is superior in STEMI patients with MetS and better than other traditional predictors.