Improving cardiovascular risk prediction with machine learning: a focus on perivascular adipose tissue characteristics.

BACKGROUND: Timely prevention of major adverse cardiovascular events (MACEs) is imperative for reducing cardiovascular diseases-related mortality. Perivascular adipose tissue (PVAT), the adipose tissue surrounding coronary arteries, has attracted increased amounts of attention. Developing a model for predicting the incidence of MACE utilizing machine learning (ML) integrating clinical and PVAT features may facilitate targeted preventive interventions and improve patient outcomes. METHODS: From January 2017 to December 2019, we analyzed a cohort of 1077 individuals who underwent coronary CT scanning at our facility. Clinical features were collected alongside imaging features, such as coronary artery calcium (CAC) scores and perivascular adipose tissue (PVAT) characteristics. Logistic regression (LR), Framingham Risk Score, and ML algorithms were employed for MACE prediction. RESULTS: We screened seven critical features to improve the practicability of the model. MACE patients tended to be older, smokers, and hypertensive. Imaging biomarkers such as CAC scores and PVAT characteristics differed significantly between patients with and without a 3-year MACE risk in a population that did not exhibit disparities in laboratory results. The ensemble model, which leverages multiple ML algorithms, demonstrated superior predictive performance compared with the other models. Finally, the ensemble model was used for risk stratification prediction to explore its clinical application value. CONCLUSIONS: The developed ensemble model effectively predicted MACE incidence based on clinical and imaging features, highlighting the potential of ML algorithms in cardiovascular risk prediction and personalized medicine. Early identification of high-risk patients may facilitate targeted preventive interventions and improve patient outcomes.

MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1.

OBJECTIVE: To discuss the possible effects of microRNA-141 (miR-141) in sepsis-induced cardiomyopathy (SIC) via targeting death-associated protein kinase 1 (DAPK1). METHODS: An SIC mouse model was constructed by abdominal injection of lipopolysaccharide (LPS) and divided into control, LPS, LPS + pre-miR-141, and LPS + anti-miR-141 groups. Hemodynamic indicators and heart function indexes of mice were detected. ELISA was used to determine the serum levels of inflammatory cytokines, while TUNEL staining to observe the apoptosis of myocardial cells of mice, as well as qRT-PCR and Western blotting to clarify the expression of miR-141 and DAPK1. Lastly, in vitro experiment was also conducted on the primary neonatal rat ventricular cardiomyocytes (NRVCMs) to validate the results. RESULTS: Mice in the LPS group, as compared to the control group, had lower left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, and ±dp/dt, but a higher left ventricular end-diastolic pressure, while the serum expression of IL-1ß, IL-6, TNF-α, and cTn-T was up-regulated evidently with the increased apoptotic index of myocardial tissues. However, miR-141 and Bcl-2/Bax were down-regulated with elevated DAPK1 and cleaved caspase-3. The above changes were ameliorated in mice from the LPS + pre-miR-141 group relative to the LPS group, while those in the LPS + anti-miR-141 group were further deteriorated. In vitro experiment showed that miR-141 overexpression could reduce the apoptosis of LPS-induced NRVCMs and the levels of inflammatory cytokines with the increased cell viability. CONCLUSION: MiR-141 could decrease inflammatory response and reduce myocardial cell apoptosis by targeting DAPK1, thereby playing the promising protective role in SIC.

Temperature-sensitive bone mesenchymal stem cells combined with mild hypothermia reduces neurological deficit in rats of severe traumatic brain injury.

BACKGROUND: To explore the combined influences of temperature-sensitive bone mesenchymal stem cells (tsBMSCs) and mild hypothermia (MH) on neurological function and glucose metabolism in rats with severe traumatic brain injury (TBI). METHODS: SD rats were randomly divided into sham, TBI, TBI + MH, TBI + BMSCs and TBI + MH +tsBMSCs groups. Then, the brain water content, serum-specific proteins (S100ß, NSE, LDH, and CK), and blood glucose at different time points were measured. Furthermore, GLUT-3 expression was detected by Western blotting, and apoptotic rate was determined by TUNEL staining. RESULTS: After TBI rat establishment, the brain injury resulted in significant increases in mNSS scores and brain water content, and upregulations in serum levels of S100ß, NSE, LDH and CK, and blood glucose, with the elevated cell apoptotic rate in the injured cortex. However, these changes were reversed by MH alone, BMSCs alone, or combination treatment of MH and tsBMSCs in varying degrees, and the combination treatment was superior to the treatment with BMSCs or MH alone. CONCLUSION: Combination therapy of tsBMSCs and MH can reduce the neuronal apoptosis in severe TBI rats, with the suppression of serum biomarkers and hyperglycemia, contributing to the recovery of neurological functions. ABBREVIATIONS: tsBMSCs: temperature-sensitive bone mesenchymal stem cells; MH: mild hypothermia; TBI: traumatic brain injury; mNSS: modified Neurological Severity Score.

Peroxiredoxin 1 silencing inhibited the growth and promoted apoptosis of pancreatic cancer cells via targeting FOXO3 gene.

OBJECTIVE: Our study aimed to investigate the interaction between peroxiredoxin 1 (Prx1) and forkhead box O3 (FOXO3) and to explore the role of PI3K/AKT pathway in the development of pancreatic cancer. MATERIAL AND METHODS: Human pancreatic normal cells HPDE6-C7 and pancreatic cancer cells PANC-1 were randomly divided into control group, Prx1-silencing (si-Prx1) group, Prx1/FOXO3 dual-silencing (si-Prx1/FOXO3) group, and negative control group. Cell proliferation assay, clone formation assay, and cell apoptosis assay were performed to investigate the effects of Prx1 silencing and FOXO3 silencing on the proliferation and apoptosis ability of pancreatic cancer cells. qRT-PCR and Western blot were performed to study the Prx1 and FOXO3 mRNA in the two cells and FOXO3 protein expression in PANC-1 cells. RESULT: We found Prx1 silencing could inhibit growth and promote apoptosis of PANC-1 cells. And Prx1 silencing could decrease the Prx1 mRNA level and increase FOXO3 mRNA level. To further explore the role of Prx1 in PI3K/AKT, we study the cell proliferation and apoptosis ability after adding the PI3K inhibitor and PI3K activator. We observed that PI3K inhibitor could inhibit tumor cell growth and promote cell apoptosis. And PI3K inhibitor also downregulated Prx1 protein expression. CONCLUSION: We concluded that the Prx1 silencing inhibited the growth and promoted apoptosis of pancreatic cancer cells via modulation of PI3K/AKT pathway by targeting FOXO3 gene.

Protective effect of Fructus corni polysaccharide on hippocampal tissues and its relevant mechanism in epileptic rats induced by lithium chloride-pilocarpine.

The aim of the present study was to investigate the potential effect of Fructus corni polysaccharide (PFC) on the hippocampus tissues in epileptic rats induced by lithium chloride-pilocarpine, and to explore the underlying mechanism. The epileptic rat models were established using lithium chloride-pilocarpine treatment. According to the dosage of PFC, the rat models were divided into three groups: The low-dose (100 mg/kg/day), middle-dose (200 mg/kg/day) and high-dose (300 mg/kg/day) groups. The intervention for rat models lasted for 24 days. Subsequently, the production levels of reactive oxygen species (ROS) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), the mitochondrial membrane potential and the expressions of mitogen-activated protein kinase [P-38, Janus kinase (JNK) and extracellular signal-regulated kinase 1/2], cytochrome-C and caspase-3 in hippocampal tissues were detected. In addition, the structure of the CA-1 region of the hippocampus was also observed. Compared with the control group, the production levels of ROS were increased and the mitochondrial membrane potential was decreased in the hippocampus tissues of rats in the model group. In addition, in the model group, it was observed that MDA content was increased, SOD activity was decreased, and the expressions of phosphorylated (p)-p38, p-JNK, cytochrome-c and caspase-3 were increased, compared with the control group. Furthermore, those abnormal variations of the indicators were reversed by the intervention of PFC. These findings suggest that PFC can ameliorate the secondary damage to the hippocampi of epileptic rats, and that the anti-oxidation and -apoptosis effects of PFC may be associated with the mechanism that provides a protective effect for hippocampal tissues.

In vitro evidence of baicalein's inhibition of the metabolism of zidovudine (AZT).

BACKGROUND: Herb-drug interaction (HDI) has been regarded as a key factor limiting the clinical application of herbs and drugs. AIMS: Potential baicalein-zidovudine (AZT) interaction was predicted in the present study. METHODS: In vitro evaluation of baicalein's inhibition towards human liver microsomes (HLMs)-catalyzed metabolism of zidovudine (AZT) was performed. Dixon and Lineweaver-Burk plots were used to determine the inhibition kinetic type, and second plot with the slopes from Lineweaver-Burk plot versus the concentrations of baicalein was employed to calculate the inhibition parameter (Ki). In combination with the in vivo concentration of baicalein, in vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo baicalein-AZT interaction. RESULTS: Competitive inhibition of baicalein towards AZT metabolism was demonstrated, and the Ki value was calculated to be 101.2 µM. The value of AUCi/AUC was calculated to be 2. CONCLUSION: Potential baicalein-AZT interaction was indicated in the present study, indicating the need for monitoring when AZT is co-administrated with baicalein or baicalein-containing herbs.

Poly-l-lactic acid/amorphous calcium phosphate bioabsorbable stent causes less inflammation than poly-l-lactic acid stent in coronary arteries.

AIM: Poly-l-lactic acid (PLLA) based bioabsorbable stents with or without amorphous calcium phosphate (ACP) were implanted and compared the inflammation in coronary arteries. METHODS: 6 PLLA and 6 PLLA/ACP based paclitaxel-eluting stents were randomly implanted into the coronary arteries of 12 healthy mini-pigs. The segments with stent were used to evaluate inflammation score and endothelialization score by hematoxylin-eosin staining. RESULTS: At the 28th day after stent implantation, no in-stent restenosis or stent thrombosis was found in both PLLA and PLLA/ACP group. Histological analysis indicated that the inflammation score in PLLA/ACP group was less than that of in PLLA group (2.20±0.42 vs. 2.80±0.48, P<0.05). Consist with that, the expression of NF-κB was lower in PLLA/ACP group. The results from immunohistochemistry showed that the expressions of endothelial nitric oxide synthase (eNOS) and CD 31 in PLLA/ACP group were dramatically higher than those in PLLA group respectively. The serum levels of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in PLLA/ACP group were significantly higher than those in PLLA group respectively (509.86±49.37 pg/ml vs. 322.04±35.16 pg/ml and 139.46±7.52 µmol/L vs. 29.55±16.55 µmol/L, P<0.05). CONCLUSION: The application of ACP helps to reduce the inflammation caused by PLLA, and is also helpful in endothelial formation and function for PLLA-based bioabsorbable stent.

Influence of racemic higenamine on the sinus node.

The aim of this study was to explore the mechanism of racemic higenamine in the treatment of sick sinus syndrome (SSS). A total of 40 New Zealand rabbits were randomly divided into normal sinus node and damaged sinus node (SND) groups, and each group was randomly divided into treatment and control groups (n=10). The SND model was established by formaldehyde wet dressing of the sinus node area. The treatment groups were administered an intravenous infusion of 0.04 mg/kg racemic higenamine via the marginal ear vein within 5 min. The electrophysiological indicators of sinoatrial function, including the sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), total sinoatrial conduction time (TSACT) and sinus cycle length (SCL), were determined before and 20 min after medication and the changes in these indicators were evaluated. The two control groups were administered 10 ml physiological saline. Following the administration of racemic higenamine, the SNRT, CSNRT, TSACT and SCL in the normal sinus node and SND groups were significantly shortened compared with those in the control groups (P<0.01). The electrophysiological influence of racemic higenamine on sinoatrial function in the SND group was significantly greater than that in the normal sinus node group (P<0.01), and its effect in the treatment of arrhythmia caused by a damaged sinus node was statistically significant (P<0.05). The main electrophysiological mechanism of racemic higenamine in the treatment of SSS was the enhancement of sinus node self-discipline and improvement of sinoatrial and atrioventricular conduction function.