Expression of serum inflammatory cytokines and oxidative stress markers and their correlation with coronary artery calcium score in patients with coronary heart disease.

Introduction: The present study was conducted to explore the expression of serum inflammatory cytokines and oxidative stress markers in patients with coronary heart disease (CHD), with an attempt to analyze their relationship with the coronary artery calcium score (CACS) by coronary computed tomography angiography (CCTA). Material and methods: It total 81 patients with coronary heart disease and 81 healthy adults were included as the observation group and the control group, respectively. The levels of serum interleukin (IL)-6 and IL-12 of the two groups were detected by ELISA, and serum superoxide dismutase (SOD) was detected by the hydroxylamine oxidation method. Micro-RNA-497-5p (miR-497-5p) was screened out as a possible new CHD biomarker and its serum level was measured by real-time fluorescence quantitative PCR. The CACS of patients in the observation group was calculated by the Agatston method to analyze the correlation between the abovementioned indexes and CACS. Results: With increase in the number of CHD lesions, the levels of IL-6, IL-12 and miR-497-5p rose gradually while the level of SOD decreased gradually. In the observation group, IL-6, IL-12 and miR-497-5p were positively correlated with CACS while SOD was negatively correlated with CACS. Conclusions: Abnormal expression levels of serum IL-6, IL-12, SOD and miR-497-5p may be able to reveal the severity of the disease, and the combination with CACS is of potential value in terms of evaluating the condition of patients harboring coronary heart disease.

Risk Factors for Pulmonary Infection and Nursing Interventions Post-Tracheostomy in Patients with Spinal Cord Injury.

Objective: We analyzed the characteristics and risk factors for pulmonary infection in patients with spinal cord injury who underwent tracheostomy and propose measures to help in early detection and intervention to reduce mortality and improve prognosis. Methods: We collected data retrospectively from January 1, 2018, to December 31, 2022. The inclusion criteria were: Patients aged 18 years or more with a spinal cord injury who underwent tracheostomy, were treated with mechanical ventilation for over 48 hours, and were diagnosed as having a pulmonary infection. Sputum samples were cultured and analyzed. Results: 101 cases of pulmonary infection were analyzed, and the incidence was 32.17%. Diabetes (OR 2.302, 95% CI 1.285-3.972), hypoproteinemia (OR 1.992, 95% CI 1.125-3.101), administration of glucocorticoids (OR 2.934, 95% CI 1.412-4.661), ASIA grade A (OR 3.672, 95% CI 1.988-5.046), mechanical ventilation for ≥ 6 days (OR 2.108, 95% CI 1.385-4.751), and length of hospital stay for ≥ 20 days (OR 2.137, 95% CI 1.092-3.842) were risk factors for pulmonary infection in patients with spinal cord injury post-tracheostomy. Among 213 pathogenic bacteria, 52 (51.48%) were Gram-negative and 24 (23.76%) were Gram-positive. Klebsiella pneumoniae (15.84%) and Staphylococcus aureus (8.91%) were the most common pathogenic bacteria. The mortality rate of patients with gram-positive infection was higher than that of patients with gram-negative infection. K. pneumoniae and S. aureus were sensitive to cefoperazone, meropenem, and levofloxacin. Conclusion: Pulmonary infection is a complication post-tracheostomy in patients with spinal cord injury. Diabetes, hypoproteinemia, administration of glucocorticoids, mechanical ventilation for ≥ 6 days, length of hospital stay for ≥ 20 days were risk factors for pulmonary infection. Pulmonary infection was mainly caused by gram-negative bacteria. Timely and effective measures for managing risk factors are essential for improving the prognosis of pulmonary infection post-tracheostomy in patients with spinal cord injuries.

DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis.

DNA methyltransferase 1 (DNMT1) shows close link with heart disease. This study aimed to define the role DNMT1 plays in heart failure and determine the underlying mechanism. Expression of microRNA (miR)-152-3p, DNMT1, E26 transformation specific-1 (ETS1) and ras homolog gene family member H (RhoH) was determined by RT-qPCR and/or western blot analysis. The interaction between miR-152-3p and ETS1 was predicted and verified. Methylation of the miR-152-3p promoter region was assessed using methylation-specific PCR. H9c2 cells were chosen for in vitro assays to examine the regulatory role of DNMT1 in autophagy and mitophagy with respect to miR-152-3p/ETS1/RhoH. Doxorubicin (DOX)-induced rat models of heart failure were employed for in vivo validation. DNMT1 expression was upregulated in the heart tissues of DOX-induced rats, where it showed an inverse correlation with miR-152-3p expression. Moreover, DNMT1 was shown to enhance methylation of the miR-152-3p promoter region and suppress its expression, leading to inhibition of mitophagy in H9c2 cells. In addition, DNMT1 enhanced expression of ETS1, which further elevated RhoH expression. Moreover, ETS1-elevated RhoH reduced cell viability and promoted autophagy and mitophagy in H9c2 cells upon treatment with DOX. Next, in vivo results demonstrated that depletion of DNMT1 protected rats from heart failure in a miR-152-3p/ETS1/RhoH-dependent manner. Overall, these findings indicate that DNMT1 may inhibit expression of miR-152-3p by promoting the methylation of miR-152-3p and enhancing the expression of ETS1, thereby inducing RHOH transcriptional activation and inhibiting mitochondrial autophagy, ultimately promoting the development of heart failure.

[Relationship between NF-kappa B binding activity and expression of PPAR gamma-mRNA in the livers of rats with fatty liver disease].

OBJECTIVE: To investigate the changes of NF-kappa B binding activity, the expression of PPARr and their correlation in the liver of rats with fatty liver disease (FLD) induced by different pathogenic factors and to investigate the molecular mechanism of the inflammation in FLD. METHODS: 40 Wistar rats were randomly divided into 4 groups of ten each: normal group, alcohol group, fat-rich diet group, alcohol adding fat-rich diet group. The rats were sacrificed at the end of the 16th week from the starting day of the experiment. Serum and liver specimens were collected. Histological specimens were stained with HE, SudanIV, and Masson and then studied microscopically. The ultrastructural changes were also checked under an electron microscope. NF-kappa B binding activity and the expression of PPARr mRNA were determined by electrophoretic mobility shift assay (EMSA) and RT-PCR respectively. The correlations between NF-kappa B binding activity and the expression of PPARr and the biochemical indexes were analyzed. RESULTS: Steatosis, inflammation, necrosis and fibrosis were present in livers of the rats of all the experimental groups, and were most severe in the alcohol adding fat-rich diet group. NF-kappa B binding activity was markedly increased in the livers of the alcohol group (142+/-16.32) and of the alcohol adding fat-rich diet group (238+/-19.14) in comparison to the livers of the normal (73+/-9.24, F = 6.36, 17.93) and those of the fat-rich diet group (84+/-10.38, F = 5.96, 16.20). Binding activity was higher in the alcohol adding fat-rich diet group than that in the simple alcohol group, but there was no difference between those of the fat-rich diet and normal groups. The level of PPARr mRNA was lower in the livers of the alcohol, fat-rich diet, alcohol adding fat-rich diet groups (0.2530+/-0.069, 0.3647+/-0.082, 0.1226+/-0.054) than that of the controls (0.8097+/-0.094) (F = 15.43, 7.24, 21.45). NF-kappa B binding activity was correlated positively with the level of serum TNF alpha (r = 0.527, 0.639) and the content of MDA in the liver homogenates (r = 0.723, 0.537), but negatively with the expression of PPARr in the livers of the alcohol and the alcohol adding fat-rich diet groups (r = -0.568, -0.891). CONCLUSION: The enhanced nuclear factors NF-kappa B binding activity and decreased expression of PPARr play a pivotal role in the inflammatory response of FLD induced by alcohol and fat-rich diet. It may provide a new idea for treating FLD effectively.

Peroxisome proliferator activated receptor-gamma in pathogenesis of experimental fatty liver disease.

AIM: To study the expression of peroxisome proliferator activated receptor-gamma (PPARgamma) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARgamma in the pathogenesis of FLD to provide the basis for using PPARgamma ligand to treat patients with FLD. METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFalpha) in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan IV, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope. The expression of PPARgamma in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARgamma and biochemical indexes, and liver histology were analyzed. RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups, especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARgamma was decreased remarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43+/-1.48) was significantly lower than that in normal group (18.34+/-3.73), alcohol group (8.82+/-2.52) and fat-rich diet group (11.73+/-2.51) (all P<0.01). The level of PPARgamma mRNA was also lower in the livers of model rats (group B-D) than in livers of controls. The expression of PPARgamma in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFalpha and the content of MDA in liver homogenates, but not with steatosis or serum ALT. CONCLUSION: Decreased expression of PPARgamma may play an important role in the development of hepatocellular inflammation, necrosis and fibrosis of rats with FLD. Thus, activating PPARgamma by its ligand can be anticipated to provide a therapy target for FLD.