[Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway].

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.

Effects of Exercise-Based Cardiac Rehabilitation in Patients with Acute Coronary Syndrome: A Meta-Analysis.

BACKGROUND Acute coronary syndrome (ACS) has become an important cause of death from cardiovascular disease. Cardiac rehabilitation (CR) plays an essential role in ACS patients after treatment. Therefore, in order to detect the impact of CR on mortality and major adverse cardiac events in patients with ACS, we conducted this meta-analysis. MATERIAL AND METHODS We searched PubMed, Web of science, and EMBASE databases to obtain published research results from 2010 to August 2018 to determine the relevant research. Random-effects model or fixed-effects model were used to calculate relative risk (RR) and 95% confidence interval (CI). RESULTS Overall, a total of 25 studies with 55 035 participants were summarized in our meta-analysis. The results indicated that the hazard ratio (HR) of mortality significantly lower in the CR group than in the non-CR group (HR=-0.47; 95% CI=(-0.56 to -0.39; P<0.05). Fourteen studies on mortality rate showed exercise was associated with reduced cardiac death rates (RR=0.40; 95% CI=0.30 to 0.53; P<0.05). We found the risk of major adverse cardiac events (MACE) was lower in the rehabilitation group (RR=0.49; 95% CI=0.44 to 0.55; P<0.05). In 11 articles on CR including 8098 participants, the benefit in the CR group was greater than in the control group concerning revascularization (RR=0.69, 95% CI: 0.53 to 0.88; P=0.003). The recurrence rate of MI was reported in 13 studies, and the risk was lower in the CR group (RR=0.63, 95% CI: 0.57-0.70; P<0.05). CONCLUSIONS Our meta-analysis results suggest that CR is clearly associated with reductions in cardiac mortality, recurrence of MI, repeated PCI, CABG, and restenosis.

Long-term prognostic importance of high levels of sST2 in patient with AMI: a meta-analysis.

OBJECTIVE: This meta-study aimed to assess the connection between soluble suppression of tumorigenicity 2 (sST2) and extended clinical outcomes in individuals diagnosed with acute myocardial infarction (AMI). METHODS: We systematically collected pertinent literature from PubMed, Embase and Web of Science. The primary effect measures employed in this research were the hazard ratio and 95% confidence intervals. The quality and publication bias of included studies were evaluated. Subgroup analysis was conducted to explore the diversity in study outcomes. RESULTS: This comprehensive meta-analysis ultimately encompassed thirteen studies, involving a total of 11,571 patients. Elevated levels of sST2 were identified as an adverse prognostic indicator, demonstrating a substantial association not only with overall mortality (combined HR 2.4, 95% CI 1.6-3.5, P < 0.01) but also with major adverse cardiovascular events (MACEs) (HR 2.5, 95% CI 1.5-4.2, P < 0.01). Subgroup analyses revealed that increased sST2 levels were linked to higher rates of all-cause mortality and MACEs in patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and other unselected subcategories of AMI. CONCLUSION: Increased sST2 could predict the long-term prognosis in patients suffering from AMI.

The long noncoding RNA lncMPD2 inhibits myogenesis by targeting the miR-34a-5p/THBS1 axis.

Long noncoding RNAs (lncRNAs) participate in regulating skeletal muscle development. However, little is known about their role in regulating chicken myogenesis. In this study, we identified a novel lncRNA, lncMPD2, through transcriptome sequencing of chicken myoblasts at different developmental stages. Functionally, gain- and loss-of-function experiments showed that lncMPD2 inhibited myoblast proliferation and differentiation. Mechanistically, lncMPD2 directly bound to miR-34a-5p, and miR-34a-5p promoted myoblasts proliferation and differentiation and inhibited the mRNA and protein expression of its target gene THBS1. THBS1 inhibited myoblast proliferation and differentiation in vitro and delayed muscle regeneration in vivo. Furthermore, rescue experiments showed that lncMPD2 counteracted the inhibitory effects of miR-34a-5p on THBS1 and myogenesis-related gene mRNA and protein expression. In conclusion, lncMPD2 regulates the miR-34a-5p/THBS1 axis to inhibit the proliferation and differentiation of myoblasts and skeletal muscle regeneration. This study provides more insight into the molecular regulatory network of skeletal muscle development, identifying novel potential biomarkers for improving chicken quality and increasing chicken yield. In addition, this study provides a potential goal for breeding strategies that minimize muscle damage in chickens.

RRM2 promotes the proliferation of chicken myoblasts, inhibits their differentiation and muscle regeneration.

During myogenesis and regeneration, the proliferation and differentiation of myoblasts play key regulatory roles and may be regulated by many genes. In this study, we analyzed the transcriptomic data of chicken primary myoblasts at different periods of proliferation and differentiation with protein‒protein interaction network, and the results indicated that there was an interaction between cyclin-dependent kinase 1 (CDK1) and ribonucleotide reductase regulatory subunit M2 (RRM2). Previous studies in mammals have a role for RRM2 in skeletal muscle development as well as cell growth, but the role of RRM2 in chicken is unclear. In this study, we investigated the effects of RRM2 on skeletal muscle development and regeneration in chickens in vitro and in vivo. The interaction between RRM2 and CDK1 was initially identified by co-immunoprecipitation and mass spectrometry. Through a dual luciferase reporter assay and quantitative real-time PCR, we identified the core promoter region of RRM2, which is regulated by the SP1 transcription factor. In this study, through cell counting kit-8 assays, 5-ethynyl-2'-deoxyuridine incorporation assays, flow cytometry, immunofluorescence staining, and Western blot analysis, we demonstrated that RRM2 promoted the proliferation and inhibited the differentiation of myoblasts. In vivo studies showed that RRM2 reduced the diameter of muscle fibers and slowed skeletal muscle regeneration. In conclusion, these data provide preliminary insights into the biological functions of RRM2 in chicken muscle development and skeletal muscle regeneration.

Bioinformatics analysis of immune cell infiltration patterns and potential diagnostic markers in atherosclerosis.

This study aimed to investigate efficient diagnostic markers and molecular mechanisms of atherosclerosis and to analyze the role of immune infiltration through bioinformatics analysis. Expression profile datasets (GSE28829 and GSE43292) of patients with atherosclerosis and healthy controls were downloaded from the GEO database. Glutamine (GLN) metabolism-associated genes were obtained from the Molecular Signatures Database (MSigDB). The limma package in R was used to identify differentially expressed genes (DEGs). Significant modules were filtered using Weighted Gene Co-expression Network Analysis (WGCNA). MSigDB sets were subjected to Gene Set Enrichment Analysis and Gene Set Variation Analysis. The biological functions of DEGs were examined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. STRING and Cytoscape software were used to identify hub genes and functional modules through protein-protein interaction (PPI) network analysis. The xCell software was adopted to assess the composition patterns of immune and stromal cells. Correlation analyses were performed for key genes and immune cell subtypes. We identified 308 DEGs and GLN-associated genes. Functional enrichment analysis showed that these genes were strongly enriched in muscle contract, muscle tissue development, cutile fiber, mycobacterial, and actin binding. Enriched KEGG pathways comprised dilated cardiomyopathy, hypertrophic cardiomyopathy, and the cAMP signaling pathway. In the PPI network analysis, 27 genes were identified as hub genes. The area under the curve (AUC) values of 27 biomarkers were relatively high, indicating high diagnostic values. The atherosclerosis group exhibited a markedly higher degree of infiltration than the control group. This study identified 27 GLN-associated genes as potential biomarkers for the diagnosis of atherosclerosis. It provides a new perspective on immune responses that facilitates exploration of the molecular mechanisms of atherosclerosis.

Dioscin ameliorates doxorubicin-induced heart failure via inhibiting autophagy and apoptosis by controlling the PDK1-mediated Akt/mTOR signaling pathway.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway.

Transcriptome-Based Identification of the Muscle Tissue-Specific Expression Gene CKM and Its Regulation of Proliferation, Apoptosis and Differentiation in Chicken Primary Myoblasts.

Skeletal muscle is an essential tissue in meat-producing animals, and meat-producing traits have been a hot topic in chicken genetic breeding research. Current research shows that creatine kinase M-type-like (CKM) is one of the most abundant proteins in skeletal muscle and plays an important role in the growth and development of skeletal muscle, but its role in the development of chicken skeletal muscle is still unclear. Via RNA sequencing (RNA-seq), we found that CKM was highly expressed in chicken breast muscle tissue. In this study, the expression profile of CKM was examined by quantitative real-time PCR (qPCR), and overexpression and RNA interference techniques were used to explore the functions of CKM in the proliferation, apoptosis and differentiation of chicken primary myoblasts (CPMs). It was shown that CKM was specifically highly expressed in breast muscle and leg muscle and was highly expressed in stage 16 embryonic muscle, while CKM inhibited proliferation, promoted the apoptosis and differentiation of CPMs and was involved in regulating chicken myogenesis. Transcriptome sequencing was used to identify genes that were differentially expressed in CPMs after CKM disruption, and bioinformatics analysis showed that CKM was involved in regulating chicken myogenesis. In summary, CKM plays an important role in skeletal muscle development during chicken growth and development.

Uncovering the molecular mechanisms of Curcumae Rhizoma against myocardial fibrosis using network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis leads to cardiac remodeling and dysfunction. Curcumae Rhizoma has been utilized in clinical trials to treat a variety of cardiovascular illnesses, although its role in myocardial fibrosis is unknown. AIM OF THE STUDY: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with Curcumae Rhizoma. MATERIALS AND METHODS: The chemical components in the aqueous extract from Curcumae Rhizoma were identified using GC-MS analysis. A prediction network describing the relationship between Curcumae Rhizoma and MF was established based on information collected from multiple databases. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate Curcumae Rhizoma targets acting on MF, which were further validated by vivo experiments. RESULTS: There were 444 targets obtained from the 39 active ingredients in Curcumae Rhizoma, and 5691 disease targets related to MF were identified. Then, 41 key targets were determined with the PPI interaction network, which was structured from 324 overlapping gene targets. GO and KEGG analyses revealed that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 signaling pathways might play crucial roles in the therapeutic mechanism of MF. According to the results of molecular docking, the binding activity between core components and targets was marvelous (affinity < -6 kcal/mol). Take it a step further, the experimental validation data affirmed that Curcumae Rhizoma substantially decreased myocardial fibrosis and recovered cardiac function in the ISO-induced rats. The associated proteins expression data implied that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways might be vital in the anti-fibrosis effect of Curcumae Rhizoma. CONCLUSION: The findings suggested that Curcumae Rhizoma diminished myocardial fibrosis by suppressing fibrosis multiplication and collagen deposition through inhibiting p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways, which might be a promising therapeutic medicament for alleviating myocardial fibrosis.