Machine learning-based mRNA signature in early acute myocardial infarction patients: the perspective toward immunological, predictive, and personalized.

Patients diagnosed with stable coronary artery disease (CAD) are at continued risk of experiencing acute myocardial infarction (AMI). This study aims to unravel the pivotal biomarkers and dynamic immune cell changes, from an immunological, predictive, and personalized viewpoint, by implementing a machine-learning approach and a composite bioinformatics strategy. Peripheral blood mRNA data from different datasets were analyzed, and CIBERSORT was used for deconvoluting human immune cell subtype expression matrices. Weighted gene co-expression network analysis (WGCNA) in single-cell and bulk transcriptome levels was conducted to explore possible biomarkers for AMI, with a particular emphasis on examining monocytes and their involvement in cell-cell communication. Unsupervised cluster analysis was performed to categorize AMI patients into different subtypes, and machine learning methods were employed to construct a comprehensive diagnostic model to predict the occurrence of early AMI. Finally, RT-qPCR on peripheral blood samples collected from patients validated the clinical utility of the machine learning-based mRNA signature and hub biomarkers. The study identified potential biomarkers for early AMI, including CLEC2D, TCN2, and CCR1, and found that monocytes may play a vital role in AMI samples. Differential analysis revealed that CCR1 and TCN2 exhibited elevated expression levels in early AMI compared to stable CAD. Machine learning methods showed that the glmBoost+Enet [alpha=0.9] model achieved high predictive accuracy in the training set, external validation sets, and clinical samples in our hospital. The study provided comprehensive insights into potential biomarkers and immune cell populations involved in the pathogenesis of early AMI. The identified biomarkers and the constructed comprehensive diagnostic model hold great promise for predicting the occurrence of early AMI and can serve as auxiliary diagnostic or predictive biomarkers.

CircUsp9x/miR-599/stim1 axis regulates proliferation and migration in vascular smooth muscle cells induced by oxidized-low density lipoprotein.

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS.

Identification of prognostic and diagnostic signatures for cancer and acute myocardial infarction: multi-omics approaches for deciphering heterogeneity to enhance patient management.

Patients diagnosed with cancer face an increased risk of cardiovascular events in the short term, while those experiencing acute myocardial infarction (AMI) have a higher incidence of cancer. Given limitations in clinical resources, identifying shared biomarkers offers a cost-effective approach to risk assessment by minimizing the need for multiple tests and screenings. Hence, it is crucial to identify common biomarkers for both cancer survival and AMI prediction. Our study suggests that monocyte-derived biomarkers, specifically WEE1, PYHIN1, SEC61A2, and HAL, hold potential as predictors for cancer prognosis and AMI. We employed a novel formula to analyze mRNA levels in clinical samples from patients with AMI and cancer, resulting in the development of a new risk score based on expression profiles. By categorizing patients into high-risk and low-risk groups based on the median risk score, we observed significantly poorer overall survival among high-risk patients in cancer cohorts using Kaplan-Meier analysis. Furthermore, calibration curves, decision curve analysis (DCA), and clinical impact curve analyses provided additional evidence supporting the robust diagnostic capacity of the risk score for AMI. Noteworthy is the shared activation of the Notch Signaling pathway, which may shed light on common high-risk factors underlying both AMI and cancer. Additionally, we validated the differential expression of these genes in cell lines and clinical samples, respectively, reinforcing their potential as meaningful biomarkers. In conclusion, our study demonstrates the promise of mRNA levels as biomarkers and emphasizes the significance of further research for validation and refinement.

Nanoengineering of a biocompatible organogel by thermal processing.

The formation of most organogels requires the compatibility of both the gelator and solvent. It is very desirable if the rheological properties of a gel can be manipulated to achieve the desired performance. In this paper, a novel organogel was developed and its rheological properties and fiber network were engineered by controlling the thermal processing conditions. The gel was formed by the gelation of 12-hydroxystearic acid as a gelator in benzyl benzoate. It was observed that the degree of supercooling for gel formation has a significant effect on the rheological properties and fiber network structure. By increasing supercooling, the elasticity of the gel was enhanced, and the correlation length of the fibers was shortened, leading to the formation of denser fiber networks. The good biocompatibility of both the gelator and solvent makes this gel a promising vehicle for a variety of bioapplications such as controlled transdermal drug release and in vivo tissue repair.

Molecular simulation of protein adsorption and desorption on hydroxyapatite surfaces.

Protein adsorption and desorption on material surfaces play a key role in the biocompatibility of medical implants, biomineralization and protein separation. In this report, the adsorption and desorption behavior of the 10th type III module of fibronectin (FN-III(10)) with different orientations on hydroxyapatite (HAP) (001) surface were systematically studied by molecular dynamics (MD) and steered MD simulations. These studies show that the electrostatic energy plays a dominant role in the interaction between the model protein and the HAP surface. The values of the interaction energy not only relates to the number of adsorbed sites but also the type. The charged -COO(-) and -NH(3)(+) are the strongest groups that interact with the surface, while other groups like charged guanido group, neutral amino and hydroxyl groups have considerable interactions with the surface. The effects of these groups on interaction energy were quantitatively investigated.

Up-regulation of ASIC3 expression by ß-estradiol.

Sex differences occur in nociceptive pain, and estrogens are involved in the sex differences. Our previous study shows sex differences exist in acidosis-induced nociception in rats, with females being more sensitive than males to acetic acid. However, the mechanisms underlying the sex differences remain unclear. We report here17ß-estradiol (E2) up-regulates expression of acid-sensing ion channel 3 (ASIC3), which can mediate the acidosis-induced events. The recombinant plasmid of pCDNA3.1-ASIC3-GFP and pCDNA3.1-estrogen receptor α (ERα) were cotransfected to 293 T cells by lipid transfection method. And western blot assays showed expression of ASIC3. We found that E2 markedly increases ASIC3 protein expression in a dose- and time- dependent manner in 293 T cells expressing ASIC3 and ERα. The up-regulating effect of E2 on ASIC3 protein expression is almost completely blocked by the addition of MPP, a specific ERα antagonist. We also observed that sex differences occur in ASIC3 expression in rat dorsal root ganglia (DRG) and in acetic acid-induced nociceptive responses. ASIC3 protein expression in female rat DRG is higher than those in male rat DRG. And female rats are more sensitive to acetic acid-induced nociception than males. ASIC3 protein expression in DRG decreases significantly after ovariectomy, but not after orchiectomy. These results suggest that E2 up-regulates ASIC3 expression through ERα, which may contribute to sex differences in acetic acid-induced nociception.

miR-190 protects cardiomyocytes from apoptosis induced by H2O2 through targeting MAPK8 and regulating MAPK8/ERK signal pathway.

MicroRNAs (miRs) have been demonstrated to regulate physiological and pathological processes. Numerous miRsprotect against cardiomyocyte injury induced by oxidative stress. However, the function of miR-190 still remains unclear. Here, we determined the expression level of miR-190 in H9c2 cells under H2O2 treatment and found that miR-190 expression was significantly inhibited by H2O2. Further study indicated that miR-190 significantly reduced cell apoptosisand the LDH and MDA levels of H9c2 cells induced by H2O2. Luciferase activity assay, quantitative real-time-PCR, and Western blot demonstrated that miR-190 directly targets MAPK8. Rescue experiment confirmed this hypothesis. Further study has revealed that miR-190 protects H9c2 cells from oxidative stress injury through inhibiting the MAPK8/ERK signal pathway. In conclusion, these data suggest that miR-190 protects against oxidative stress injury of H9c2 cells induced by H2O2 through inhibiting MAPK8 expression and the MAPK8/ERK pathway. Our findings provide a potential therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.

Impact evaluation of CONSORT and STRICTA guidelines on reporting quality for randomized controlled trials of acupuncture conducted in China.

OBJECTIVE: To evaluate and compare the reports' qualities of acupuncture randomized controlled trials (RCTs) conducted in China before and after the implementation of two guidelines, i.e., the Consolidated Standards of Reporting Trials (CONSORT) statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). METHODS: Proportions of studies that reported CONSORT and STRICTA items were compared for the years before and after implementation of these two guidelines. In addition, the total score of each item's reporting were calculated and reported differences during different date ranges were compared. RESULTS: For CONSORT items (maximum score 8), there was evidence of a slight improvement in reporting between 1994-1995 and 1999-2000 combined (2.5±0.6) and 2004-2005 and 2009-2010 combined (3.0±0.9; difference 0.4, 95% confidence interval, 0.3 to 0.6, P<0.01). For STRICTA items (maximum score 17), there was evidence that a slight improvement in reporting between 1994-1995 and 1999-2000 combined (8.6±2.1) and 2004-2005 and 2009-2010 combined (10.1±1.8; difference 1.5, 95% confidence interval, 1.1 to 1.9, P<0.01). CONCLUSION: Quality of reporting for RCTs of acupuncture treatment conducted in China have generally improved since the introduction of the STRICTA and CONSORT guidelines.