Predictive Value of a Combination of the Age, Creatinine and Ejection Fraction (ACEF) Score and Fibrinogen Level in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Background: The purpose of this study was to explore whether consideration of FIB levels might improve the predictive value of the ACEF score in patients with ACS. Methods: A total of 290 patients with ACS were enrolled in this study. The clinical characteristics and MACE were recorded. Results: Multivariate logistic regression analysis revealed that the FIB level (odds ratio=7.798, 95%CI, 3.44–17.676, P<0.001) and SYNTAX score (odds ratio=1.034, 95%CI, 1.001–1.069, P=0.041) were independent predictors of MACE. On the basis of the regression coefficient for FIB, the ACEF-FIB was developed. The area under the ROC of the ACEF-FIB scoring system in predicting MACE after PCI was 0.753 (95%CI 0.688–0.817, P<0.001), a value greater than those for the ACEF score, SYNTAX score and Grace score (0.627, 0.637 and 0.570, respectively). Conclusion: ACEF-FIB had better discrimination ability than the other risk scores, according to ROC curve analysis, net reclassification improvement and integrated discrimination improvement

The clinical utilization of SNIP1 and its pathophysiological mechanisms in disease

Smad intranuclear binding protein 1 (SNIP1), a highly conserved nuclear protein, functions as a transcriptional regulator and exerts a significant influence on disease progression. In addition, the N-terminal domain of SNIP1 facilitates its interaction with Smad4, a signaling protein associated with the TGF-β family, and RelA/p65, a transcription factor connected to NF-κB. This interaction further enhances the transcriptional activation of c-Myc-dependent genes. Presently, the primary emphasis in research is directed towards targeting the catalytic domain of SNIP1, as it holds promise as a potential therapeutic target for various diseases. While the significance of SNIP1 in pathological mechanisms remains uncertain, this review aims to comprehensively examine the existing literature on the association between SNIP1 and proteins implicated in the regulation of diverse clinical conditions, including cancer, inflammation, and related diseases

Declined plasma microfibrillar-associated protein 4 levels in acute coronary syndrome

Abstract Background Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. Methods We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan–Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. Results Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174–0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = − 0.311 and − 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan–Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009). Conclusions MFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted

Protective Effect of Resveratrol Improves Systemic Inflammation Responses in LPS-Injected Lambs

Highly intensive livestock production often causes immune stress to animals, which makes them more susceptible to infections. The aim of this study was to examine whether resveratrol (Res) alleviates inflammation in lambs. In Experiment 1, 16 male lambs were injected with lipopolysaccharides (LPS) at an initial dose of 0.25, 1.25, and 2.5 &mu;g/kg body weight (BW) for 9 days. Average daily gain and blood parameters were measured and clinical symptoms were recorded. In Experiment 2, 20 male lambs were injected intravenously with LPS (0 mg/kg) + Res (0 mg), LPS (2.5 &mu;g /kg) + Res (0 mg, 82.5 mg, 165 mg, 330 mg), 4 h after LPS injection. Jugular blood was collected from each lamb to determine white blood cell (WBC) counts and the expression of inflammatory genes. In Experiment 1, all LPS-treated lambs showed clinical signs of sickness including rhinorrhea, lethargy, and shivering, and systemic inflammatory responses of increased inflammatory genes levels and cortisol concentration. The lambs had increased respiratory and heart rates and rectal temperature and decreased average daily gain and feed intake. In Experiment 2, resveratrol significantly reduced WBCs and the expression levels of several genes associated with inflammation response (TLR4, NF-&kappa;B, c-jun) and inhibited the signaling cascades of NF-&kappa;B and MAPKs by down-regulating the expression levels of inflammatory cytokines (IL-1&beta;, IL-4, IL-6, TNF-&alpha;, IFN-&gamma;) induced by LPS. Resveratrol attenuated the LPS-evoked inflammatory responses in lambs by suppressing expression levels of inflammatory cytokines, and blocking NF-&kappa;B and MAPK signaling pathways

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy

Nerve growth factor protects against cadmium-induced hypertension in mice via vascular remodeling

Purpose: To investigate the effect of nerve growth factor (NGF) on cadmium ion (Cd2+)-induced hypertension in a mouse model, and the mechanism of action involved. Methods: Hypertension was induced in mice by administration of cadmium chloride (CdCl2) at a dose of 100 mg/L in deionised water. Then, NGF was administered daily for 45 days via the intragastric route. Immunohistochemical technique employing Vectastain ABC kit was used for determination of the levels of matrix metalloproteinases in mice aorta. Results: Treatment with NGF significantly and dose-dependently alleviated Cd-induced increase in blood pressure in mice (p &lt; 0.05). The Cd-induced elevation in mean arterial pressure (MAP) in mice was also reduced on treatment with NGF at doses of 5 and 10 mg/kg. At the two doses of NGF, vascular responsiveness was enhanced in Cd-administered mice. Exposure to NGF dose-dependently reversed Cd-mediated suppression of eNOS expression and elevation in iNOS level. Moreover, NGF at doses of 5 and 10 mg/kg, reversed Cd-mediated enhancement in nitrate/nitrite levels in urine samples, and reversed Cd-induced elevation in vascular smooth muscle cell (VSMC) count and collagen content in mice arterial wall. The NGF treatment also significantly (p &lt; 0.05) reduced Cd-induced increases in levels of MMP’s. Conclusion: The present study demonstrates that NGF increased vascularity and arterial stiffness, and protected against Cd-induced hypertension in mice. Moreover, NGF treatment elevated eNOS expression, suppressed iNOS level and inhibited MMP expression in mice exposed to Cd. Thus, NGF has anti-hypertensive potential and may be beneficial in the treatment of hypertension

Retinol exerts therapeutic effect on myocardial infarction through regulation of immune inflammatory cells and Cx43 expression

Purpose: To investigate the effect of retinol on cardiac fibroblast proliferation in vitro and on fibrosis formation in mice in vivo. Methods: Proliferative potential of fibroblasts was determined using cell counting kit-8 assay. Acute myocardial infarction (AMI) was induced in mice via ligation of the left side coronary artery. In myocardial tissues, concentration of TNF-α was determined using enzyme-linked immunosorbent assay (ELISA) assay. Results: Exposure to retinol significantly suppressed cardiac fibroblast proliferation under ischemia, when compared to untreated fibroblasts (p &lt; 0.05). However, exposure of cardiac fibroblasts to retinol did not produce toxicity at a dose of 10 μM under normal conditions. In contrast, exposure to normal levels of oxygen, glutamine and glucose significantly reversed the inhibitory potential of retinol against fibroblasts during ischemia (p &lt; 0.05). Treatment of mice with retinol at a dose of 5 mg/kg reversed the AMI-mediated increase in hydroxyproline level in myocardial tissues. Retinol treatment of AMI mice caused significant elevation in the number of CD31+ capillaries in myocardial tissues. Increase in TNF-α by AMI in cardiac tissues of mice was reversed by treatment with retinol at a dose of 5 mg/kg. The retinol treatment also caused significant reversal of AMI-induced down-regulation of Cx43 protein (p &lt; 0.05). Conclusion: Retinol enhanced the proliferation of fibroblasts under ischemic conditions and prevented fibrosis in mice with AMI. Moreover, retinol targeted TNF-α production and upregulated Cx43 expression in myocardial tissues of mice with AMI. Thus, retinol may be useful for the management of myocardial infarction