A bibliometric analysis of myocardial ischemia/reperfusion injury from 2000 to 2023.

Background: Myocardial ischemia/reperfusion injury (MIRI) refers to the more severe damage that occurs in the previously ischemic myocardium after a short-term interruption of myocardial blood supply followed by restoration of blood flow within a certain period of time. MIRI has become a major challenge affecting the therapeutic efficacy of cardiovascular surgery. Methods: A scientific literature search on MIRI-related papers published from 2000 to 2023 in the Web of Science Core Collection database was conducted. VOSviewer was used for bibliometric analysis to understand the scientific development and research hotspots in this field. Results: A total of 5,595 papers from 81 countries/regions, 3,840 research institutions, and 26,202 authors were included. China published the most papers, but the United States had the most significant influence. Harvard University was the leading research institution, and influential authors included Lefer David J., Hausenloy Derek J., Yellon Derek M., and others. All keywords can be divided into four different directions: risk factors, poor prognosis, mechanisms and cardioprotection. Conclusion: Research on MIRI is flourishing. It is necessary to conduct an in-depth investigation of the interaction between different mechanisms and multi-target therapy will be the focus and hotspot of MIRI research in the future.

Gut-derived short-chain fatty acids bridge cardiac and systemic metabolism and immunity in heart failure.

Heart failure (HF) represents a group of complex clinical syndromes with high morbidity and mortality and has a significant global health burden. Inflammation and metabolic disorders are closely related to the development of HF, which are complex and depend on the severity and type of HF and common metabolic comorbidities such as obesity and diabetes. An increasing body of evidence indicates the importance of short-chain fatty acids (SCFAs) in regulating cardiac function. In addition, SCFAs represent a unique class of metabolites and play a distinct role in shaping systemic immunity and metabolism. In this review, we reveal the role of SCFAs as a link between metabolism and immunity, which regulate cardiac and systemic immune and metabolic systems by acting as energy substrates, inhibiting the expression of histone deacetylase (HDAC) regulated genes and activating G protein-coupled receptors (GPCRs) signaling. Ultimately cardiac efficiency is improved, cardiac inflammation alleviated and cardiac function in failing hearts enhanced. In conclusion, SCFAs represent a new therapeutic approach for HF.

Heart failure with preserved ejection fraction and non-alcoholic fatty liver disease: new insights from bioinformatics.

AIMS: Heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) are related conditions with an increasing incidence. The mechanism of their relationship remains undefined. Here, we aimed to explore the potential mechanisms, diagnostic markers, and therapeutic options for HFpEF and NAFLD. METHODS AND RESULTS: HFpEF and NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were screened for functional annotation. A protein-protein interaction network was constructed based on the STRING database, and hub genes were analysed using GeneMANIA annotation. ImmuCellAI (Immune Cell Abundance Identifier) was employed for analysis of immune infiltration. We also used validation datasets to validate the expression levels of hub genes and the correlation of immune cells. To screen for diagnostic biomarkers, we employed the least absolute shrinkage and selection operator and support vector machine-recursive feature elimination. Drug signature database was used to predict potential therapeutic drugs. Our analyses identified a total of 33 DEGs. Inflammation and immune infiltration played important roles in the development of both diseases. The data showed a close relationship between chemokine signalling pathway, cytokine-cytokine receptor interaction, calcium signalling pathway, neuroactive ligand-receptor interaction, osteoclast differentiation, and cyclic guanosine monophosphate-protein kinase G signalling pathway. We demonstrated that PRF1 (perforin 1) and IL2RB (interleukin-2 receptor subunit beta) proteins were perturbed by the diseases and may be the hub genes. The analysis showed that miR-375 may be a potential diagnostic marker for both diseases. Our drug prediction analysis showed that bosentan, eldecalcitol, ramipril, and probucol could be potential therapeutic options for the diseases. CONCLUSIONS: Our findings revealed common pathogenesis, diagnostic markers, and therapeutic agents for HFpEF and NAFLD. There is need for further experimental studies to validate our findings.

Potential Mechanisms Between HF and COPD: New Insights From Bioinformatics.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are closely related in clinical practice. This study aimed to investigate the co-genetic characteristics and potential molecular mechanisms of HF and COPD. HF and COPD datasets were downloaded from gene expression omnibus database. After identifying common differentially expressed genes (DEGs), the functional analysis highlighted the critical role of extracellular matrix and ribosomal signaling pathways in both diseases. In addition, GeneMANIA's results suggested that the 2 diseases were related to immune infiltration, and CIBERSORT suggested the role of macrophages. We also discovered 4 TFs and 1408 miRNAs linked to both diseases, and salbutamol may positively affect them.

Investigating the cardioprotective effects of Fuzheng Yangxin recipe based on network pharmacology and experimental evaluation.

Background: Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF. Materials and methods: The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium. Results: We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function. Conclusion: FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.

Mechanisms of Cardiorenal Protection With SGLT2 Inhibitors in Patients With T2DM Based on Network Pharmacology.

Purpose: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardiorenal protective effects regardless of whether they are combined with type 2 diabetes mellitus, but their specific pharmacological mechanisms remain undetermined. Materials and Methods: We used databases to obtain information on the disease targets of "Chronic Kidney Disease," "Heart Failure," and "Type 2 Diabetes Mellitus" as well as the targets of SGLT2 inhibitors. After screening the common targets, we used Cytoscape 3.8.2 software to construct SGLT2 inhibitors' regulatory network and protein-protein interaction network. The clusterProfiler R package was used to perform gene ontology functional analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analyses on the target genes. Molecular docking was utilized to verify the relationship between SGLT2 inhibitors and core targets. Results: Seven different SGLT2 inhibitors were found to have cardiorenal protective effects on 146 targets. The main mechanisms of action may be associated with lipid and atherosclerosis, MAPK signaling pathway, Rap1 signaling pathway, endocrine resistance, fluid shear stress, atherosclerosis, TNF signaling pathway, relaxin signaling pathway, neurotrophin signaling pathway, and AGEs-RAGE signaling pathway in diabetic complications were related. Docking of SGLT2 inhibitors with key targets such as GAPDH, MAPK3, MMP9, MAPK1, and NRAS revealed that these compounds bind to proteins spontaneously. Conclusion: Based on pharmacological networks, this study elucidates the potential mechanisms of action of SGLT2 inhibitors from a systemic and holistic perspective. These key targets and pathways will provide new ideas for future studies on the pharmacological mechanisms of cardiorenal protection by SGLT2 inhibitors.

Guanxinning Injection Combined With Ischemic Postconditioning Attenuate Myocardial Ischemic Reperfusion Injury in Chronic Renal Failure Rats by Modulating Mitochondrial Dynamics.

Purpose: Salvia miltiorrhiza Bge. (Danshen, DS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) have been widely used in traditional Chinese medicine to prevent and treat myocardial ischemia and renal insufficiency, and their extracts (Guanxinning injection, GXN) have been reported to exhibit antioxidant, anti-inflammatory, and anti-ischemia-reperfusion injury properties. It is well-established that ischemic postconditioning (IPOC) can protect against myocardial ischemia-reperfusion (I/R) injury in rats with chronic renal failure (CRF). However, little is known on whether GXN combined with IPOC may affect myocardial I/R injury in CRF rats. We sought to observe the effect of GXN combined with IPOC on myocardial I/R injury in CRF rats by quantifying changes in the expression of proteins related to mitochondrial dynamics. Materials and Methods: In a survey, 90 Wistar rats were randomly divided into 6 groups (15 rats per group): CRF group, I/R group, comorbid group (CRF + I/R), IPOC group, IPOC + GXN group and the sham group. Changes in blood myocardial injury markers, urea, and creatinine were analyzed. Heart tissues were harvested for histomorphometry and western blotting when rats were sacrificed. Myocardial infarction area was measured by Evans blue and Triphenyltetrazolium chloride solution staining. The expressions of mitochondrial fission relative proteins (DRP1 and FIS1) and mitochondrial fusion relative proteins (OPA1 and MFN1) were detected by western blotting. Results: IPOC could significantly decrease myocardial injury markers and myocardial area of necrosis (AN)/area at risk (AAR) of the comorbid model rats. Further results showed that GXN combined with IPOC could significantly reduce CK-MB levels and myocardial AN/AAR in comorbid model rats compared with the IPOC group. Meanwhile, both IPOC and IPOC + GXN significantly reduced DRP1 levels and increased the MFN1 and OPA1 protein levels in the comorbid model rats. However, compared with the IPOC group, MFN1 and OPA1 protein levels increased significantly in the IPOC + GXN group. Conclusion: Extracts of DS and CX combined with IPOC exert a protective effect against myocardial I/R injury in rats with CRF, mediated by increased expression of mitochondrial fusion proteins (MFN1 and OPA1).

Preclinical Evidence of Paeoniflorin Effectiveness for the Management of Cerebral Ischemia/Reperfusion Injury: A Systematic Review and Meta-Analysis.

Background: Vessel recanalization is the main treatment for ischemic stroke; however, not all patients benefit from it. This lack of treatment benefit is related to the accompanying ischemia-reperfusion (I/R) injury. Therefore, neuroprotective therapy for I/R Injury needs to be further studied. Paeonia lactiflora Pall. is a commonly used for ischemic stroke management in traditional Chinese medicine; its main active ingredient is paeoniflorin (PF). We aimed to determine the PF's effects and the underlying mechanisms in instances of cerebral I/R injury. Methods: We searched seven databases from their inception to July 2021.SYRCLE's risk of bias tool was used to assess methodological quality. Review Manager 5.3 and STATA 12.0 software were used for meta-analysis. Results: Thirteen studies, including 282 animals overall, were selected. The meta-analyses showed compared to control treatment, PF significantly reduced neurological severity scores, cerebral infarction size, and brain water content (p = 0.000). In the PF treatment groups, the apoptosis cells and levels of inflammatory factors (IL-1ß) decreased compared to those in the control groups (p = 0.000). Conclusion: Our results suggest that PF is a promising therapeutic for cerebral I/R injury management. However, to evaluate the effects and safety of PF in a more accurate manner, additional preclinical studies are necessary.

Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure.

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.

Effect of arotinolol on chronic heart failure: A systematic review and meta-analysis of randomized controlled trials.

Background: Heart failure is the end stage of all cardiovascular diseases, which brings a heavy burden to the global health network. Arotinolol, as a new type of ß Receptor blocker, has a good antihypertensive effect. Many clinical trials have observed the clinical efficacy of arotinolol in the treatment of essential hypertension. However, so far, there has been no systematic evaluation on the efficacy and safety of arotinolol in the treatment of chronic heart failure. Objective: The purpose of this review was to systematically evaluate the clinical efficacy of arotinolol in patients with chronic heart failure. Methods: Randomized controlled trials (RCTs) of arotinolol in the treatment of chronic heart failure were retrieved from seven databases according to the Cochrane manual, including CNKI (China National Knowledge Infrastructure), Wan fang database, VIP database, PubMed, Sinomed, EMBASE, and the Cochrane Library databases. The main outcomes were the effective rate, left ventricular ejection fraction (LVEF), blood pressure, heart rate, cardiac index, stroke volume (SV), brain natriuretic peptide (BNP), hypersensitive C-reactive protein (Hs-CRP), left ventricular end diastolic volume (LVEDV), left ventricular end diastolic diameter (LVEDD), and adverse events (AEs). Results: A total of 17 trials met the qualification criteria, which included 1,717 patients with heart failure. Most trials had uncertain risks in terms of random sequence generation, allocation hiding, patient loss, and result evaluation. Meta analysis showed that arotinolol significantly improved the treatment efficiency of patients with heart failure (standardized mean difference (SMD) = 4.07, 95% confidence interval (CI) [2.89, 5.72], p = 0.00, I 2 = 0), LVEF (SMD = 1.59, 95% CI [0.99, 2.19], p = 0.000 0, I 2 = 95.8%), cardiac index (SMD = 0.32, 95% CI [0.11, 0.53], p = 0.03), I 2 = 0), SV (SMD = 2.00, 95% CI [1.57, 2.34], p = 0.000, I 2 = 64.2%), lower BNP (SMD = -0.804, 95% CI [-0.97, -0.64], p = 0.000, I 2 = 94.4%), and LVEDV (SMD = -0.25, 95% CI [-0.45, -0.05], p = 0.015, I 2 = 0). There was no statistical significance for blood pressure (SMDsystolic pressure = -0.09, 95% CI [-0.69, 0.51], p = 0.775, I 2 systolic pressure = 90.2%; SMDdiastolic pressure = -0.16, 95% CI [-0.79, 0.48], P = 0.632, I 2 diastolic pressure = 91.2%), heart rate (SMD = -0.12, 95% CI [-1.00, 0.75], P = 0.787, I 2 = 96.1%), Hs-CRP (SMD = -1.52, 95% CI [-3.43, 0.40], P = 0.121, I 2 = 98.3%), and LVEDD (SMD = -0.07, 95% CI [-0.90, 0.76], P = 0.870, I 2 = 96.5%). Conclusion: Arotinolol can safely and effectively improve the effective rate of patients with chronic heart failure, increase LVEF, increase CI and SV, and reduce BNP and LVEDV. However, because of the low overall quality of the included randomized controlled trials, these findings need to be considered carefully. More high-quality randomized controlled trials are needed for further verification, to provide a more scientific basis for the safety and effectiveness of arotinolol in the clinical treatment of heart failure. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371214], identifier [CRD:420223371214].

Metabonomics: A Useful Tool to Reveal Underlying Relationships between Altered Chinese Medicine Syndromes and Ultrafiltration in Treatment of Heart Failure.

OBJECTIVE: To reveal the underlying relationships between Chinese medicine (CM) syndromes and ultrafiltration (UF) in the treatment of heart failure based on a metabonomic approach. METHODS: Seventeen acute decompensated heart failure (ADHF) patients were enrolled, and their CM syndromes before and after UF were collected. In addition, their venous plasma collected before and after UF was used for liquid chromatographmass spectrometer-based metabonomic analysis. Both reversed phase liquid chromatography and hydrophilic interaction liquid chromatography were used to analyze the plasma samples. Partial least-squares to latent structure-discriminant analyses were used for data analysis. RESULTS: An obvious difference was observed pre- and post-treatment. A total of 17 potential biomarkers associating with alterd syndromes with UF including hypoxanthine, 1-methylhistidine, phytosphingosine, O-decanoyl-R-carnitine, etc. were screened out, showing a significant change after UF. The major adjusted metabolic pathways were purine metabolism, histidine metabolism, leucine and isoleucine metabolism, arginine and proline metabolism, carnitine shuttle, sphingolipid metabolism and phospholipid metabolism. CONCLUSIONS: Metabonomic approach is a useful tool to identify potential biomarkers of altered syndromes link to UF and could provide a theoretical basis for further research on the therapeutic mechanism of UF combined with CM.

Down-Regulation of PpBGAL10 and PpBGAL16 Delays Fruit Softening in Peach by Reducing Polygalacturonase and Pectin Methylesterase Activity.

ß-galactosidases are cell wall hydrolases that play an important role in fruit softening. However, PpBGALs mechanism impacting on ethylene-dependent peach fruit softening was still unclear. In this study, we found that PpBGAL4, -6, -8, -10, -16, and -17 may be required for ethylene-dependent peach softening and PpBGAL10, -16 may make a main contribution to it among 17 PpBGALs. Utilization of virus-induced gene silencing (VIGS) showed that fruits were firmer than those of the control at 4 and 6 days after harvest (DAH) when PpBGAL10 and PpBGAL16 expression was down-regulated. Suppression of PpBGAL10 and PpBGAL16 expression also reduced PpPG21 and PpPME3 transcription, and polygalacturonase (PG) and pectinmethylesterases (PME) activity. Overall, total cell wall material and protopectin slowly declined, water-soluble pectin slowly increased, and cellulose and hemicellulose was altered significantly at 4 DAH, relative to control fruit. In addition, PpACO1 expression and ethylene production were also suppressed at 4 DAH because of inhibiting PpBGAL10 and PpBGAL16 expression. These results suggested that down-regulation of PpBGAL10 and PpBGAL16 expression delays peach fruit softening by decreasing PG and PME activity, which inhibits cell wall degradation and ethylene production.