Global publication trends and research hotspots of the gut-liver axis in NAFLD: A bibliometric analysis.

Background: Nonalcoholic Fatty Liver Disease(NAFLD)refers to a spectrum of diseases ranging from simple liver steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Bidirectional cross-talk between the gut-liver axis plays an important role in the pathogenesis of NAFLD. To learn more about the gut-liver axis in NAFLD, this study aims to provide a comprehensive analysis from a bibliometric perspective. Method: Literature related to the gut-liver axis in NAFLD from 1989 to 2022 was extracted from the Web of Science Core Collection. Based on Microsoft Excel, CiteSpace and Vosviewer, we conducted to analyze the number of publications, countries/regions, institutions, authors, journals, references, and keywords. Results: A total of 1,891 literature since 2004 was included, with the rapid growth of the number of papers on the gut-liver axis in NAFLD annually. These publications were mainly from 66 countries and 442 institutions. Of the 638 authors analyzed, Bernd Schnabl was the one with the most publications, and Patrice D. Cani was the one with the most co-citations. International Journal of Molecular Sciences is the journal with the most articles published, and Hepatology is the journal with the most citations. The most common keywords are gut microbiota, inflammation, and insulin instance, which are current research hotspots. Short-chain fatty acid, in vitro, randomized controlled trial in clinical, and diabetes mellitus represent the research frontiers in this field and are in a stage of rapid development. Conclusion: This is the first study to conduct a comprehensive bibliometric analysis of publications related to the gut-liver axis in NAFLD. This study reveals that gut microbiota, inflammation, insulin resistance, short-chain fatty acids, and randomized controlled trial will be the hotspots and new trends in the gut-liver axis in NAFLD research, which could provide researchers with key research information in this field and is helpful for further exploration of new research directions.

Neocryptotanshinone protects against myocardial ischemia-reperfusion injury by promoting autolysosome degradation of protein aggregates via the ERK1/2-Nrf2-LAMP2 pathway.

BACKGROUND: Aggrephagy is a critical compensatory mechanism for the elimination of misfolded proteins resulting from stress and depends on the autolysosome degradation of protein aggregates. However, there have been few mechanism research related to aggrephagy in myocardial ischemia/reperfusion (I/R) injury. Neocryptotanshinone (NCTS) is a fat-soluble active compound extracted from Salvia miltiorrhiza, and may be cardioprotective against I/R. However, the efficacy and specific mechanism of NCTS on I/R have not been studied. PURPOSE: The current study aimed to investigate the molecular mechanism of NCTS involved in the therapeutic effect on I/R, with a special emphasis on the up-regulation of the ERK1/2-Nrf2-LAMP2 pathway to increase autolysosomal degradation during aggrephagy. METHODS: A rat model of myocardial I/R injury was constructed by left anterior descending (LAD) ligation-reperfusion. To verify cardiac protection, autolysosome clearance of protein aggregates, and their intracellular biological mechanism, an oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cardiomyocyte model was created. RESULTS: NCTS was found to have a significant cardioprotective effect in I/R rats as evidenced by remarkably improved pathological anatomy, decreased myocardial damage indicators, and substantially enhanced cardiac performance. Mechanistically, NCTS might boost the levels of LAMP2 mRNA and protein, total and Ser40 phosphorylated Nrf2, and Thr202/Tyr204p-ERK1/2 protein. Simultaneously, the cytoplasmic Nrf2 level was reduced after NCTS administration, which was contrary to the total Nrf2 content. However, these beneficial changes were reversed by the co-administration with ERK1/2 inhibitor, PD98059. NCTS therapy up-regulated Rab7 protein content, Cathepsin B activity, and lysosomal acidity, while down-regulating autophagosome numbers, Ubiquitin (Ub), and autophagosome marker protein accumulations through the above signaling pathway. This might indicate that NCTS enhanced lysosomal fusion and hydrolytic capacity. It was also found that NCTS intervention limited oxidative stress and cellular apoptosis both in vivo and in vitro. CONCLUSIONS: We reported for the first time that NCTS promoted the autolysosome removal of protein aggregation both in vivo and in vitro, to exert the therapeutic advantages of myocardial I/R injury. This was reliant on the up-regulation of the ERK1/2-Nrf2-LAMP2 signaling pathway.

Frontiers and hotspots of adipose tissue and NAFLD: a bibliometric analysis from 2002 to 2022.

Background: The annual incidence of non-alcoholic fatty liver disease (NAFLD) continues to rise steadily. In recent years, adipose tissue (AT) has gained recognition as a pivotal contributor to the pathogenesis of NAFLD. Employing bibliometric analysis, we examined literature concerning AT and NAFLD. Methods: Relevant literature on AT in NAFLD from 1980 to 2022 was extracted from the Web of Science Core Collection. These records were visualized using CiteSpace and VOSviewer regarding publications, countries/regions, institutions, authors, journals, references, and keywords. Results: Since 2002, a total of 3,330 papers have been included, exhibiting an annual surge in publications. Notably, the quality of publications is superior in the USA and Europe. Kenneth Cusi stands out as the author with the highest number of publications and H-index. Hepatology is the journal boasting the highest citation and H-index. The University of California System holds the highest centrality among institutions. References specifically delve into physiological processes associated with AT in NAFLD. Currently, lipid metabolism and inflammation constitute the principal research mechanisms in the AT-based regulation of NAFLD, with pertinent keywords including microRNA, T cell, hypoxia, sarcopenia, hepatokine, gut microbiota, and autophagy. The Mediterranean diet is among the most widely recommended dietary approaches for potential NAFLD treatment. Conclusion: This paper represents the inaugural bibliometric study on the effects of AT on NAFLD, offering valuable insights and directions for future research.

Calycosin as a Novel PI3K Activator Reduces Inflammation and Fibrosis in Heart Failure Through AKT-IKK/STAT3 Axis.

Aim: Inflammation and fibrosis have been shown to be critical factors in heart failure (HF) progression. Calycosin (Cal) is the major active component of Astragalus mongholicus Bunge and has been reported to have therapeutic effects on the cardiac dysfunction after myocardial infarction. However, whether Cal could ameliorate myocardial infarction (MI)-induced inflammation and fibrosis and precise mechanisms remain uncertain. The aim of this study is to explore the role of Cal in HF and to clarify the underlying mechanisms. Methods: For in vivo experiments, rats underwent left anterior descending artery ligation for heart failure model, and the cardioprotective effects of Cal were measured by echocardiographic assessment and histological examination. RNA-seq approach was applied to explore potential differential genes and pathways. For further mechanistic study, proinflammatory-conditioned media (conditioned media)-induced H9C2 cell injury model and TGFß-stimulated cardiac fibroblast model were applied to determine the regulatory mechanisms of Cal. Results: In the in vivo experiments, echocardiography results showed that Cal significantly improved heart function. GO and reactome enrichment revealed that inflammation and fibrosis pathways are involved in the Cal-treated group. KEGG enrichment indicated that the PI3K-AKT pathway is enriched in the Cal-treated group. Further experiments proved that Cal alleviated cardiomyocyte inflammatory responses evidenced by downregulating the expressions of phosphorylated IκB kinase α/ß (p-IKKα/ß), phosphorylated nuclear factor kapa B (p-NFκB), and tumor necrosis factor α (TNFα). Besides, Cal effectively attenuated cardiac fibrosis through the inhibitions of expressions and depositions of collagen I and collagen III. In the in vitro experiments, the phosphatidylinositol three kinase (PI3K) inhibitor LY294002 could abrogate the anti-inflammation and antifibrosis therapeutic effects of Cal, demonstrating that the cardioprotective effects of Cal were mediated through upregulations of PI3K and serine/threonine kinase (AKT). Conclusion: Cal inhibited inflammation and fibrosis via activation of the PI3K-AKT pathway in H9C2 cells, fibroblasts, and heart failure in postacute myocardial infarction rats.

Identification of Potential Bioactive Ingredients and Mechanisms of the Guanxin Suhe Pill on Angina Pectoris by Integrating Network Pharmacology and Molecular Docking.

The Guanxin Suhe pill (GSP), a traditional Chinese medicine, has been widely used to treat angina pectoris (AP) in Chinese clinical practice. However, research on the bioactive ingredients and underlying mechanisms of GSP in AP remains scarce. In this study, a system pharmacology approach integrating gastrointestinal absorption (GA) evaluation, drug-likeness (DL) evaluation, target exploration, protein-protein-interaction analysis, Gene Ontology (GO) enrichment analysis, network construction, and molecular docking was adopted to explore its potential mechanisms. A total of 481 ingredients from five herbs were collected, and 242 were qualified based on GA and DL evaluation. Target exploration identified 107 shared targets between GSP and AP. Protein-protein interaction identified VEGFA (vascular endothelial growth factor A), TNF (tumor necrosis factor), CCL2 (C-C motif chemokine ligand 2), FN1 (fibronectin 1), MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), IL10 (interleukin 10), CXCL8 (C-X-C motif chemokine ligand 8), IL6 (interleukin 6), and INS (insulin) as hub targets for GSP, which were involved in the inflammatory process, ECM proteolysis, glucose metabolism, and lipid metabolism. GO enrichment identified top pathways in the biological processes, molecular functions, and cell components, explaining GSP's potential AP treatment mechanism. Positive regulation of the nitric oxide biosynthetic process and the response to hypoxia ranked highest of the biological processes; core targets that GSP can regulate in these two pathways were PTGS2 and NOS2, respectively. Molecular docking verified the interactions between the core genes in the pathway and the active ingredients. The study lays a foundation for further experimental research and clinical application.

Efficacy and safety of Qishen granules for chronic heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: Qishen granules (QSG) is a famous traditional Chinese Medicine (TCM) formula used to treat chronic heart failure (CHF). The objective of this protocol is to clarify the efficacy and safety of QSG for treating CHF. METHODS: Six databases will be electronically searched up to November 1, 2020 for randomized controlled trials (RCTs) in English and Chinese languages. Two independent reviewers will complete tasks of literature retrieval and data extraction. After that, the Cochrane Collaboration risk of bias tool will be utilized to assess methodological quality. The primary outcomes are left ventricular ejection fraction, left ventricular fractional shortening, and N-terminal B-type natriuretic peptide. The secondary outcomes consist of composite cardiac events, adverse effects, and quality of life. Meta-analysis will be performed using the Revman version 5.3. RESULTS: This study will provide a high-quality synthesis of current evidence of QSG for CHF from primary and secondary outcomes. CONCLUSION: This study will provide evidence for the effectiveness and safety of QSG in the treatment of CHF. PROSPERO REGISTRATION NUMBER: CRD42020150442.

Long non-coding RNA SNHG16 regulates cell behaviors through miR-542-3p/HNF4α axis via RAS/RAF/MEK/ERK signaling pathway in pediatric neuroblastoma cells.

Neuroblastoma (NB) is an extracranial solid tumor in children with complex mechanism. Increasing reports indicated that long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) account for the pathogenesis of NB. Nevertheless, the precise functions of SNHG16 needed to be further exposed in NB progression. Our data revealed that SNHG16 and hepatocyte nuclear factor 4 α (HNF4α) were up-regulated, but miR-542-3p was down-regulated in NB. Knockdown of SNHG16 or HNF4α could impede cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro. Interestingly, the role of SNHG16 detetion in cell behaviors was rescued by HNF4α overexpression in NB cells. Mechanically, SNHG16 modulated the progression of tumor growth via miR-542-3p/HNF4α axis in NB. Also, SNHG16 knockdown inactivated rat sarcoma/effector of RAS/mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases (RAS/RAF/MEK/ERK) signaling pathway through HNF4α. Therefore, SNHG16/miR-542-3p/HNF4α axis modified NB progression via RAS/RAF/MEK/ERK signaling pathway, might highlight a novel therapeutic approach for NB.