LIMD2 is the Signature of Cell Aging-immune/inflammation in Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is an age-dependent cardiovascular disease in which cell aging, immunity, and inflammatory factors alter the course; however, cell aging-immune/inflammation signatures in AMI have not been investigated. METHODS: Based on the GEO database to obtain microRNA (miRNA) sequencing, mRNA sequencing and single-cell sequencing data, and utilizing the Seurat package to identify AMI-associated cellular subpopulations. Subsequently, differentially expressed miRNAs and mRNAs were screened to establish a network of competing endogenous RNAs (ceRNAs). Senescence and immunity scores were calculated by single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms, and the Hmisc package was used to screen for genes with the highest correlation with senescence and immunity scores. Finally, protein-protein interaction (PPI) and molecular docking analyses were performed to predict potential therapeutic agents for the treatment of AMI. RESULTS: Four cell types (Macrophage, Fibroblast, Endothelial cells, CD8 T cells) were identified in AMI, and CD8 T cells exhibited the lowest cell aging activity. A ceRNA network of miRNAs-mNRA interactions was established based on the overlapping genes in differentially expressed miRNAs (DEmiRNAs) target genes and differentially expressed mRNAs (DEmRNAs). Twenty-four marker genes of CD8 T cells were observed. LIMD2 was identified as cell aging-immune/inflammation-related hub gene in AMI. This study also identified a potential therapeutic network of DB03276-LIMD2-AMI, which showed excellent and stable binding status between DB03276-LIMD2. CONCLUSION: This study identified LIMD2 as a cell aging-immune/inflammation-related hub gene. The understanding of the pathogenesis and therapeutic mechanisms of AMI was enriched by the ceRNA network and DB03276-LIMD2-LAMI therapeutic network.

Mechanism of angiotensin-converting enzyme inhibitors in the treatment of dilated cardiomyopathy based on a protein interaction network and molecular docking.

Background: Dilated cardiomyopathy (DCM) is a severe manifestation or intermediate stage of cardiovascular disease progression with a significantly poor prognosis. Based on a protein interaction network and molecular docking, the present study determined the genes and mechanism of action of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of DCM, providing a direction for future studies on ACEI drugs for DCM. Methods: This is a retrospective study. DCM samples and healthy controls were downloaded from the GSE42955 dataset, and the targets of the potential active ingredients were obtained from PubChem. Hub genes in ACEIs were analyzed by constructing network models and a protein-protein interaction (PPI) network using the STRING database and Cytoscape software. Molecular docking was performed using Autodock vina software. Results: Twelve DCM samples and five control samples were finally included. A total of 62 intersected genes were obtained by intersecting the differentially expressed genes with six ACEI target genes. PPI analysis identified 15 intersecting hub genes from these 62 genes. Enrichment analysis showed that the hub genes were associated with T helper type 17 (Th17) cell differentiation as well as the nuclear factor kappa-B (NF-kappa B), interleukin 17 (IL-17), mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) (PI3K-Akt), and Toll-like receptor signaling pathways. Molecular docking indicated that the compound Benazepril to produce favorable interactions with TNF proteins with a relatively higher score (-8.3). Conclusions: This study primarily revealed that the preventive and curative effects of ACEI treatment on DCM could be realized through multiple targets and pathways, and its mechanism of action is related to genes such as TNF, vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), Cyclin D1 (CCND1), and AKT serine/threonine kinase 1 (AKT1), with immune- and inflammation-related signaling pathways involvement.

The effects of Xuebijing injection combined with ulinastatin as adjunctive therapy on sepsis: An overview of systematic review and meta-analysis.

BACKGROUND: Xuebijing injection (XBJ) has increasingly been used for sepsis in China. We aimed to evaluate the methodological quality and summarize the evidence regarding the effectiveness of XBJ combined with ulinastatin (UTI) for sepsis from systematic reviews/meta-analyses (SRs/MAs). METHODS: From the inception to May 23, 2021, eight databases were searched to screen the SRs/MAs of XBJ combined with UTI in the treatment of sepsis. Methodology Quality of Systematic Reviews 2 (AMSTAR-2) was used to evaluate the quality of the methods. Grading of Recommendation,Assessment, Development, and Evaluation (GRADE) was used in the assessment of evidence quality. RESULTS: Seven SRs/MAs on XBJ combined with UTI treatment for sepsis were included. The AMSTAR-2 showed that the methodological quality of all included SRs/MAs was rated as critically low. According to the evaluation results of GRADE, 30% (13/44), 30% (13/44), and 40% (18/44) were rated to be of moderate, low, and critically low quality, respectively. Descriptive analysis results showed that XBJ combined with UTI was an effective treatment modality for sepsis. CONCLUSIONS: All included SRs/MAs showed that XBJ combined with UTI was more effective than UTI alone in the treatment of sepsis on the basis of conventional treatment, but the reliability of the results was limited due to the disadvantages of lower methodological quality and higher risk of bias in the included SRs/MAs. Further high-quality clinical studies and SRs/MAs are recommended to verify whether XBJ combined with UTI is more effective than UTI alone.

Efficacy and safety of Shengmai injection as an adjunctive therapy on sepsis: A protocol for systematic review and meta-analysis.

INTRODUCTION: Sepsis is a common life-threatening, acute and severe disease with high morbidity and mortality, which seriously endangers patient health. Shengmai injection (SMI) is typically used as an alternative treatment for sepsis patients. This investigation aimed at designing a comprehensive recollection and meta-analytical exercise for evaluating efficacy and safety-profile for employing SMI against sepsis. METHODS: Multiple research literature repositories, both localized and global, were examined for randomized controlled trials of sepsis treated by SMI - from repository inception to December 2021 as a timeframe. Primary outcome measures contained 28-day all-cause mortality, while secondary outcome measures consisted of Sequential Organ Failure Assessment scorings, acute Physiology and Chronic Health Evaluation II scorings, ICU-based hospitalization length, mechanical ventilation timespan, ICU mortality rate, and adverse effects/events. RevMan V.5.3 was employed for data analyses. Two reviewers evaluated bias risks/investigation quality through Cochrane Collaboration risk of bias tool / Grades of Recommendations Assessment Development and Evaluation, separately. RESULTS: Such a comprehensive reviewing protocol review protocol systematically and objectively analyzes the effectiveness and safety-profile of SMI for therapy against sepsis, together with providing scientific grounds for clinic-based employment for SMI. PROSPERO REGISTRATION NUMBER: CRD42021245247.

Evaluation of the safety and efficacy of Zhenwu decoction as adjuvant therapy for the treatment of heart failure with reduced ejection fraction: A protocol for systematic review and meta-analysis.

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) demonstrates a substanital threat to global public health. Several Chinese studies have been conducted to date evaluating the clinical efficacy of Zhenwu decoction (ZWD) as a treatment for HFrEF. The present systematic review will be conducted to more comprehensively evaluate the impact of ZWD on HFrEF outcomes. METHODS: For this systematic review, all randomized controlled trials (RCTs) reporting on the effectiveness of ZWD as a treatment for HFrEF published as of December 30, 2021 in the Embase, PubMed, Springer, Web of Science, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure, and the Wan-Fang databases will be identified without any language or publication restrictions. Two researchers will independently choose investigations, extract information, and gauge research quality. Primary outcomes of interest will include all-cause mortality and HF-associated mortality. Secondary outcomes will include the incidence of adverse events, ultrasonic cardiographic indices (including left ventricular ejection fraction and left ventricular mass index), New York Heart Association grade, N-terminal pro-b-type natriuretic peptide, B-type natriuretic peptide, and 6-minute walking distance. RevMan v 5.3 will be used to conduct meta-analyses where possible, with descriptive or subgroup analyses otherwise being conducted. Data will be given as risk ratios for categorical variables and mean difference for continuous variables. RESULTS: This comprehensive protocol will aid in the systematic and objective evaluation of the efficacy and safety of ZWD as a treatment for HFrEF, providing a scientific basis for the clinical utilization of ZWD.

A Dual-Label Time-Resolved Fluorescence Immunoassay for the Simultaneous Determination of Cardiac Troponin T and Myoglobin.

The aim of this study was to establish a dual-label time-resolved fluorescence immunoassay (TRFIA) for the simultaneous determination of cardiac troponin T (cTnT) and myoglobin (MYO) for the early diagnosis of acute myocardial infarction. The sandwich immunoassay was used to detect the concentration of cTnT and MYO in serum. cTnT and MYO in serum were captured by anti-cTnT and anti-MYO antibodies immobilized on microtiter wells and then banded together with another anti-cTnT and anti-MYO labeled with europium(III) Sm3+ and samarium(III) Eu3+ chelates, followed by fluorescence measurement using time-resolved fluorometry. The performance of this TRFIA was evaluated using the clinical serum and compared with the commercial assays. The linear correlation coefficients ( R2) of the cTnT and MYO standard curves were 0.9993 and 0.9995, respectively. The sensitivity for cTnT detection was 2.21 pg/mL (linear dynamic range was 3.24-963.71 pg/mL), and the average recovery was 100.57%. The sensitivity for MYO detection was 3.24 ng/mL (linear dynamic range was 4.95-976.85 ng/mL), and the average recovery was 99.79%. High correlation coefficients ( R2) were obtained between the commercial assays and dual-label TRFIA ( R2 = 0.999). The present dual-label TRFIA has high sensitivity, specificity, and accuracy in clinical sample analysis. It is a good alternative to the single-label diagnostic methods.

[Effect of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis].

OBJECTIVE: To investigate the effects of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis. METHODS: A prospective single-blind randomized controlled trial was conducted. 60 septic patients were divided into three groups with the method of random number table, 20 cases in the control group, 20 in the Chinese herb group, and 20 in corticoid group. All of them received routine treatment. Patients in Chinese herb group were given Sini decoction in addition (decoction of monkshood 15 g, dried ginger 15 g, honey-fried licorice 10 g) 100 mL/d orally or by nasal feeding, while patients in corticoid group were given hydrocortisone 200 mg/d intravenously instead, both for 7 days. Before the treatment, 3 days and 14 days after treatment, blood was collected to determine the levels of adrenocorticotropic hormone (ACTH) and cortisol, and the result of ACTH stimulating test was observed. At the same time, acute physiology and chronic health evaluation II (APACHEII) score was recorded, and 3-day shock recovery rate and 28-day death rate were also compared among these groups. RESULTS: None of the three groups showed different result in ACTH stimulating test (χ(2)=1.101, P=0.605). ACTH in three groups was gradually decreased. Compared with that before treatment, ACTH in Chinese herb group and corticoid groups began to decrease obviously on day 3 (29.90±3.31 ng/L vs. 33.10±3.31 ng/L, 28.20±2.45 ng/L vs. 33.30±3.84 ng/L, both P<0.01), while in control group declined ACTH appeared later (on day 14) compared with before treatment (29.40±5.63 ng/L vs. 33.50±4.89 ng/L, P<0.05). No obvious difference in ACTH level was showed between the Chinese herb group and the cortical group (both P>0.05). Cortisol level in both Chinese herb and cortical groups showed a raise-fall biphase trend while there was no change in the control. The cortical levels on day 3 in Chinese herb and cortical groups were much higher than that before treatment (343.04±31.20 µg/L vs. 294.70±42.10 µg/L, 331.25±42.80 µg/L vs. 280.36±38.10 µg/L, both P<0.01) and that of control group (291.61±41.50 µg/L, both P<0.01), though no significant statistical difference was observed between two groups (both P>0.05). APACHEII score on day 14 in control, Chinese herb and cortical groups was significantly lower than that before treatment (16.8±5.1 vs. 20.1±4.3, 13.4±3.2 vs. 18.3±3.8,15.1±2.5 vs. 19.5±4.0, all P<0.01), and the score was much lower in Chinese herb group comparing with that of control group (P<0.05). No statistical difference was observed among control, Chinese herb and cortical groups in lowering 28-day death rate [35.0% (7/20), 25.0% (5/20), 20.0% (4/20)] and improving 3-day shock recovery rate [40.0% (8/20), 70.0% (14/20), 60.0% (12/20), all P>0.05]. CONCLUSIONS: Sini decoction could elevate cortisol while lower ACTH at the early stage of sepsis. Sini decoction could also effectively improve symptoms and hypothalamic-pituitary-adrenal axis function in septic patients without affecting death rate.