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Obesity is recognized as not only a major contributing factor to cardiovascular diseases but also an independent risk factor for end-stage renal disease. Previous studies have found that Huoxue Qianyang Qutan Recipe (HQQR) could reduce urinary microalbumin in patients with obesity-related hypertension (OBH). However, the renal protective activity of HQQR in OBH and its molecular targets involved remains ambiguous. In this work, we investigate the mechanism of HQQR against OBH-induced early renal damage using integrating network pharmacology and experimental validation-based strategy. First, via network pharmacology, IL-6 is identified as one of the key targets of HQQR against early renal damage in hypertension, and inhibition of inflammation is a crucial process. Second, in in vivo experiments, HQQR can lower blood pressure, lose weight, and restore metabolic abnormalities in OBH rats, which could be associated with the effects on protecting early renal damage. Finally, in the mechanism, HQQR increases SIRT1 mRNA and protein expression consistent with reduction of NF-κB acetylation and suppressed the p65-mediated inflammatory signaling pathway. As a result, HQQR robustly inhibits OBH-induced renal inflammation by reducing IL-6 mRNA and protein levels in the renal tissue and the release of IL-6 in serum of OBH rats. This study aims to provide a multimethod (network pharmacology-animal experiment) and multilevel (component-target-pathway) strategy for the prevention and treatment of OBH-induced target organ damage by traditional Chinese medicine.

To quantitatively assess the risks of pedestrian evacuation through staircases with different slopes when a flood intrudes into the underground space, a numerical model was designed to simulate flood flow patterns on staircase and escalator under different slope conditions (26.6°, 28.2°, 29.1°, 30°, and 35°). A safety index (F (v2, y)) was employed to assess the risks of pedestrian evacuation through the staircase under different slopes. When the water depth at the staircase entrance (under slopes ranging from 26.6° to 28.2°) was 0.3 m and the unit width discharge was 0.28 m2/s, pedestrians safely evacuated the underground space. However, when the staircase slope was beyond 28.2°, the safety index value was higher than the critical value and the flood caused serious threats to them. Therefore, it is suggested that when the underground space becomes flooded, pedestrians should avoid steep slopes and choose a gentle staircase as a safer escape route. The obtained results provide a theoretical guideline for pedestrian evacuation from a flooded staircase.

Context HuoXue QianYang QuTan Recipe (HQQR) is used to manage hypertension and cardiac remodelling, but the mechanism is elusive. Objective To determine the mechanism of HQQR on obesity hypertension (OBH)-related myocardial fibrosis. Materials and methods OBH models were prepared using spontaneously hypertensive rats (SHRs) and divided (n = 6) into saline, low-dose (19.35 g/kg/d) HQQR, high-dose (38.7 g/kg/d) HQQR, and valsartan (30 mg/kg/d) groups for 10 weeks. Systolic blood pressure (SBP), and Lee’s index were measured. Heart tissues were examined by histology. HQQR’s effects were examined on cardiac fibroblasts (CFs) stimulated with angiotensin II and treated with HQQR, a caspase-1 inhibitor, siNLRP3, and oeNLRP3. Results HQQR(H) reduced SBP (201.67 ± 21.00 vs. 169.00 ± 10.00), Lee’s index (321.50 ± 3.87 vs. 314.58 ± 3.88), and left ventricle mass index (3.26 ± 0.27 vs. 2.71 ± 0.12) in vivo. HQQR reduced percentage of fibrosis area (18.99 ± 3.90 vs. 13.37 ± 3.39), IL-1β (10.07 ± 1.16 vs. 5.35 ± 1.29), and inhibited activation of NLRP3/caspase-1/IL-1β pathway. HQQR also inhibiting the proliferation (1.09 ± 0.02 vs. 0.84 ± 0.01), fibroblast to myofibroblast transition (14.74 ± 3.39 vs. 3.97 ± 0.53), and collagen deposition (Col I; 0.50 ± 0.02 vs. 0.27 ± 0.05 and Col III; 0.48 ± 0.21 vs. 0.26 ± 0.11) with different concentrations selected based on IC50 in vitro (all ps < 0.05). NLRP3 interference further confirmed HQQR inhibiting NLRP3 inflammasome signalling. Conclusion HQQR blunted cardiac fibrosis development in OBH and suppressed CFs proliferation by directly interfering with the NLRP3/caspase-1/IL-1β pathway.

Background. This study aimed to explore the function of modified Yuejuwan (MYJ) on THP-1 macrophage-derived foam cells. Methods. First, human THP-cells were obtained, and then, grouping was made to the following: control group, foaming group, foaming group +0.2 mg/mL Jiawei Yueju pill, foaming group +0.5 mg/mL Jiawei Yueju pill, and foaming group +1 mg/mL Jiawei Yueju pill. An Oil Red O staining assay was used to examine the uptake of oxidatively modified low-density lipoprotein (oxLDL). The secretion of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR (qRT-PCR) and Western blot were used to quantify genes and proteins expression levels. Results. Our results indicated that MYJ inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and cholesteryl ester (CE) in foam cells. Moreover, the secretion of IL-1β and TNF-α also downregulated in foam cells after treatment of MYJ. Furthermore, we found that tripartite motif-containing 37 (TRIM37) was significantly upregulated in foam cells. Knockdown of TRIM37 promoted cholesterol efflux and presented an anti-inflammation effect in foam cells. Furthermore, TRIM37 positively mediated the translocation of NF-κB to nuclear. It negatively regulated its ubiquitination in foam cells after interacting with TRAF2. Importantly, MYJ profoundly suppressed the function of TRIM37 in foam cells and functioned as a TRIM37 inhibitor. Conclusions. This study demonstrated that MYJ might alleviate oxLDL-induced foam cell formation by inhibiting the TRIM37/TRAF2/NF-κB pathway activity. MYJ was a potential agent in preventing atherosclerosis and indicated its potential signaling pathway in foam cells.

Continuous and irreversible cardiac hypertrophy can induce cardiac maladaptation and cardiac remodeling, resulting in increased risk of developing cardiovascular diseases. The present study was conducted to investigate the therapeutic effect of Huoxue Qianyang Qutan recipe (HQQR) on angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from the cardiac tissue of neonatal rats, followed by flow cytometry detection to confirm the proportion of primary cardiomyocytes. Cell Counting Kit-8 assay and immunofluorescence detection were performed to examine the effect of Ang II and HQQR on cardiomyocyte hypertrophy. Reactive oxygen species (ROS) and a series of metabolic indicators were quantified to investigate the effect of HQQR on Ang II-induced cardiomyocyte hypertrophy. Mitochondrial electron transport chain complex activity and related coding gene expression were determined to explore the effect of HQQR on mitochondrial function. HQQR significantly inhibited Ang II-induced cardiomyocyte hypertrophy and restored Ang II-induced ROS accumulation, metabolic indicators, and membrane potential levels. HQQR also regulated the mitochondrial function related to the sirtuin 1 pathway in Ang II-induced cardiomyocytes by increasing the activity of the mitochondrial electron transport chain complex and affecting the expression of genes encoding mitochondrial electron transport chain complex subunits. HQQR could alleviate Ang II-induced cardiomyocyte hypertrophy by modulating oxidative stress, accumulating ROS and increasing mitochondrial electron transport chain activity.

This work presents an experiment involving detailed fluvial flood propagation process. Comparing to the existing flood experiments which collect hydrodynamical data just at gauges, flood evolution process in river channel and flood plain is measured and temporal–spatial data are provided. In the experiment, three inflow patterns are considered to reflect the different severity of the floods. The flood propagation and inundation are captured by using an array of surveillance cameras. The images are pre‐processed by applying camera calibration method to correct the barrel distortion. A deep learning technique is introduced to automatically identify inundated area. The inundation process is therefore obtained by identifying image series. In addition to the spatial data, the water level evolutions at three gauges are also monitored to supply detailed hydrodynamic information at gauges. The repeatability of the experiments and reliability of the deep learning technique are verified. The experimental data including spatial and point hydrodynamic features for flood events can be used to systematically validate numerical model and calibrate parameters.

Background De Winter syndrome accounts for approximately 2% of all patients with acute anterior myocardial infarction admitted to the emergency department, and is characterized by severe stenosis of the left anterior descending coronary artery (LAD). The ECG changes are not recognized by ECG software, and poor understanding of the syndrome among physicians may lead to misdiagnosis, delayed reperfusion, and mortality. Case presentation A 51-year-old male patient presented with a newly developed ECG pattern suggestive of de Winter Syndrome. Coronary angiography revealed anterior myocardial infarction. Based on the ECG and clinical manifestations, the patient was diagnosed with de Winter syndrome and underwent timely percutaneous coronary intervention to revascularize the left anterior descending artery (LAD). The patient showed good outcomes and no complications at 4 months after the operation. Conclusions This case highlights the importance of being aware of the possibility of de Winter syndrome in patients with symptoms of myocardial infarction but atypical ECG in order to conduct early revascularization and treatments.

Shengxian decoction (SXT) is a traditional Chinese medicine that is clinically used for treating cardiovascular diseases. It is known for its beneficial effect on cardiomyocyte injuries, some of which can be induced by anticancer agents including doxorubicin (DOX). To determine the molecular mechanisms involved in the cardioprotective effects of SXT, DOX‑induced H9c2 cells were analyzed for apoptosis and expression levels of apoptosis biomarkers. Cell viability and apoptosis were measured by CCK‑8 and flow cytometry. Triggering receptors expressed on myeloid cells 1 (TREM1), cleaved caspase‑3, survivin and NF‑κBp65 expression levels were measured by reverse transcription‑quantitative PCR and/or western blotting. A total of 30 adult male Sprague‑Dawley rats were randomly allocated into five groups (n=6 each); control group receiving 0.9% saline, 1 DOX group receiving 2.5 mg/kg of DOX and 3 DOX + SXT groups, receiving a DOX dose equivalent to the DOX‑only group and either 0.4, 0.8 or 1.6 g/kg of SXT. It was found that DOX increased apoptosis and NF‑κB activation of H9c2 cells by increasing TREM1 expression and that SXT inhibited apoptosis and NF‑κB activation of H9c2 cells induced by DOX or Trem1 overexpression. SXT also significantly reversed DOX‑induced cardiotoxicity in rats. The results suggested that the protective effects of SXT against DOX‑induced apoptosis may be attributed to its downregulation of TREM1.

Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling.

BACKGROUND Accumulating evidence suggests that cardiotoxicity is one of the main manifestations of aconitine (AC) poisoning. However, the molecular mechanism of AC-induced cardiotoxicity remains unclear, there is little direct evidence for therapeutic targets and drugs of AC-induced cardiotoxicity. MATERIAL AND METHODS Zebrafish were exposed to AC to evaluate cardiotoxicity by calculating the heart rates and observing the changes of cardiac and vascular structure. RNA-seq (RNA sequencing) and bioinformatics analysis were used to obtain differentially expressed genes (DEGs). The anti-AC cardiotoxicity compound was identified via connectivity map (CMAP) analysis and molecular docking. RESULTS AC-induced cardiotoxicity in zebrafish predominantly included arrhythmias, extended sinus venous and bulbus arteriosus (SV-BA) distance, and larger pericardial edema aera. A total of 1380 DEGs were identified by RNA-seq and bioinformatics analysis. cyclin-dependent kinase-1 (CDK1) was screened as the hub gene and the most potential therapeutic target due to its significant downregulation in cardiotoxicity based on protein-protein interaction (PPI) and drug-gene interaction (DGIdb) network analysis. Cell cycle signal pathway was the most significant pathways identified in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, the expression of CDK1 was validated in the Gene Expression Omnibus (GEO) database GSE71906, GSE65705, and GSE95140. Finally, heptaminol was identified as a novel anti-AC cardiotoxicity compound via CMAP analysis and molecular docking. CONCLUSIONS Totally, hub genes and key pathways identified in this study can aid in the understanding of the molecular changes in AC-induced cardiotoxicity. Meanwhile, we provide a systematic method to explore drug toxicity prevention and treatment.

Aim and Objective: Maxingyigan (MXYG) decoction is a traditional Chinese medicine (TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction against COVID-19. Methods: A network pharmacology strategy involving drug-likeness evaluation, prediction of oral bioavailability, network analyses, and virtual molecular docking was used to predict the mechanism of action of MXYG against COVID-19. Results: Thirty-three core COVID-19-related targets were identified from 1023 gene targets through analyses of protein–protein interactions. Eighty-six active ingredients of MXYG decoction hit by 19 therapeutic targets were screened out by analyses of a compound–compound target network. Via network topology, three “hub” gene targets (interleukin (IL-6), caspase-3, IL-4) and three key components (quercetin, formononetin, luteolin) were recognized and verified by molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19 through anti-inflammatory and immunity-based actions involving activation of T cells, lymphocytes, and leukocytes, as well as cytokine–cytokine-receptor interaction, and chemokine signaling pathways. Conclusion: The hub genes of COVID-19 helped to reveal the underlying pathogenesis and therapeutic targets of COVID-19. This study represents the first report on the molecular mechanism of MXYG decoction against COVID-19.

Objective Endoplasmic reticulum (ER) stress is involved in hypertension related cardiac remodeling. We aimed to evaluate the effects of Huoxue Qianyang (HXQY) decoction on cardiac remodeling in obese spontaneously hypertensive rats (SHRs), and explore its impacts on the activating transcription factor 6 (ATF6)-C/EBP homologous protein (CHOP) ER stress signaling pathway. Methods Twenty-seven obese SHRs were randomly divided into Obese SHR, Obese SHR + HXQY and Obese SHR + Valsartan groups, and treated with the indicated drugs for 8 weeks. Nine age-matched male SHRs were used as controls. Systolic blood pressure (SBP), body weight (BW), and the left ventricular mass index (LVMI) were measured weekly or at end point. Then, angiotensin II (Ang II), fasting glucose (FPG) and fasting insulin (FIN), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglyceride (TG) levels were evaluated with commercial kits. Apoptotic cardiomyocytes were detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression levels of GRP78, ATF6, PERK/pPERK and CHOP were assessed by quantitative PCR and Western blot. Results Treatment with HXQY decoction resulted in significantly reduced SBP, BW, LVMI, Ang II, TC and LDL-C levels, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) score in obese SHRs. Apoptosis in heart tissues of obese SHRs was significantly attenuated after HXQY decoction administration, paralleling reduced expression of GRP78, ATF6, PERK/pPERK and CHOP at both mRNA and protein levels. Conclusion Cardiac remodeling in obese SHRs is ameliorated by intervention with HXQY decoction in association with inhibited ATF6−CHOP ER stress signaling pathway.

Given that ankylosing spondylitis (AS) occurs in approximately 5 out of 1,000 adults of European descent and the unclear pathogenesis, the aim of the research was to further predict the molecular mechanism of this disease. The Affymetrix chip data GSE25101 were available from Gene Expression Omnibus database. First of all, differentially expressed genes (DEGs) were identified by Limma package in R. Moreover, DAVID was used to perform gene set enrichment analysis of DEGs. In addition, miRanda, miRDB, miRWalk, RNA22 and TargetScan were applied to predict microRNA-target associations. Meanwhile, STRING 9.0 was utilized to collect protein–protein interactions (PPIs) with confidence score >0.4. Then, the PPI networks for up- and down-regulated genes were constructed, and the clustering analysis was undergone using ClusterONE. Finally, protein-domain enrichment analysis of modules was conducted using DAVID. Total 145 DEGs were identified, including 103 up-regulated and 42 down-regulated genes. These DEGs were significantly enriched in phosphorylation (p = 1.21E−05) and positive regulation of gene expression (p = 1.25E−03). Furthermore, one module was screened out from the up-regulated network, which contained 39 nodes and 205 edges. Moreover, the nodes in the module were significantly enriched in ribosomal protein (RPL17, ribosomal protein L17 and MRPL22, mitochondrial ribosomal protein L22) and proteasome (PSMA6, proteasome subunit, alpha type 6, PSMA4)-related domains. Our findings that might explore the potential pathogenesis of AS and RPL17, MRPL22, PSMA6 and PSMA4 have the potential to be the biomarkers for the disease.