Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer’s disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations.Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK’s Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results.Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis.Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.
Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.
Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein–protein interaction networks and herb–ingredient–target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway, advanced glycosylation end product (AGE)–RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.
The aim of this study was to gain insight into the progress and dynamics of psycho-cardiological disease research and track its hot spots. We have analyzed psycho-cardiological disease-related literature extracted from the Web of Science (WOS) Core Collection from 2001 to 2021 with the help of Cite Space. As a result, we have included 5,032 records. Then, we have analyzed connected networks for the country, author, subject category, keywords, and cited reference. We have summarized the findings in four aspects. First, the annual quantitative distribution of publications is on the rise, although there is a slight drop. Second, in terms of country analysis, the United States, England, Australia, Germany, and Italy are the main research forces in psycho-cardiological diseases. At the same time, several academic entities represented by Andrew Steptoe and Roland von Känel, MD, have been formed based on the early consciousness of physical and mental health in these countries. Besides, China is also more concerned about it due to the rapid population aging process and the largest population. Third, the psycho-cardiological disease is multidisciplinary, including psychology, psychiatry, clinical medicine, such as cardiovascular system and neurology, public environmental and occupational health, and pharmacology. Finally, the results of keyword analysis and co-cited references indicate the hot spots and frontiers in psycho-cardiological disease. The hot spots in psycho-cardiological disease include three aspects. The first aspect includes psychosocial factors, such as depression, lack of social support, and low economic and social status; the second aspect includes priority populations, such as Alzheimer’s disease dementia caregivers, elderly, and patients with cancer, and the third aspect includes interventions, such as exercise therapy and diet. In addition, there are three future research frontiers. The first is a psycho-cardiological disease in patients with COVID-19; the second is cardiac rehabilitation, especially exercise therapy and health behavior evaluation; and the final is evidence-based medical evaluation, such as systematic reviews and meta-analyses.
BackgroundThe global community has been affected by the coronavirus disease 2019 (COVID-19), which emerged in December 2019. Since then, many studies have been conducted on cardiovascular diseases (CVDs) and COVID-19. The aim of this study was to perform a bibliometric and visual analysis of the published relationship between CVDs and COVID-19.Methods1,890 publications were retrieved from the Web of Science Core Collection database on January 5, 2022. Microsoft Office Excel and CiteSpace were then used to carry out scientometric analysis on the relevant literature according to seven aspects: document type, countries/regions, institutions, authors, journals, references, and keywords.ResultsThe research on CVDs and COVID-19 is currently in a period of rapid development, with China, USA, England, and Italy leading the field. There is active cooperation between most countries and institutions. Harvard Medical School stands out among the many institutions not only for the largest number of publications, but also for their high quality. Banerjee A, Solomon SD and Narula J are three representative authors in this field. Frontiers in Cardiovascular Medicine was the journal with the highest number of published studies, and The Lancet was the most cited journal. Two documents with a high degree of significance in this field were identified. Popular research topics in this field are specific diseases, such as acute coronary syndrome and heart failure; pathogenesis related to ACE2, insulin resistance and pericyte; the specific therapeutic drug chloroquine; and clinical characteristics, physical activity, and mental health. ACE2 and NF-κB will be the focus of future research.ConclusionsThis study provides useful information for the research of CVDs and COVID-19, including potential collaborators, popular research topics, and a reference for more extensive and in-depth research in the future.
Cardiovascular disease is a group of diseases with high mortality in clinic, including hypertension, coronary heart disease, cardiomyopathy, heart valve disease, heart failure, to name a few. In the development of cardiovascular diseases, pathological cardiac remodeling is the most common cardiac pathological change, which often becomes a domino to accelerate the deterioration of the disease. Therefore, inhibiting pathological cardiac remodeling may delay the occurrence and development of cardiovascular diseases and provide patients with greater long-term benefits. Resveratrol is a non-flavonoid polyphenol compound. It mainly exists in grapes, berries, peanuts and red wine, and has cardiovascular protective effects, such as anti-oxidation, inhibiting inflammatory reaction, antithrombotic, dilating blood vessels, inhibiting apoptosis and delaying atherosclerosis. At present, the research of resveratrol has made rich progress. This review aims to summarize the possible mechanism of resveratrol against pathological cardiac remodeling, in order to provide some help for the in-depth exploration of the mechanism of inhibiting pathological cardiac remodeling and the development and research of drug targets.
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