Transcriptional and functional analysis of plasma exosomal microRNAs in acute viral myocarditis.

AIM: To assess the differential expression profiles of exosome-derived microRNA (miRNA) and reveal their potential functions in patients with acute viral myocarditis (AVMC). MATERIALS & METHODS: Peripheral blood samples were collected from 9 patients diagnosed with AVMC and 9 healthy controls (HC) in the Affiliated Hospital of Qingdao University from July 2021 to September 2022. The exosomal miRNA expression were tested using RNA high-throughput sequencing. We conducted the GO and KEGG functional analysis to predict the potential molecular, biological functions and related signaling pathways of miRNAs in exosomes. Target genes of exosomal miRNAs were predicted and miRNA-target gene network was mapped using gene databases. Differentially expressed exosomal miRNAs were selected and their expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) to verify the sequencing results. RESULTS: P < 0.05 and Fold Change>2 were considered as cut-off value to screen miRNAs that were differently expressed. This study identified 14 upregulated and 14 downregulated exosome-derived miRNAs. GO and KEGG analysis showed that differentially expressed miRNAs may be related to ß-catenin binding, DNA transcription activities, ubiquitin ligase, PI3K-Akt, FoxO, P53, MAPK, and etc.. The target genes of differentially expressed miRNAs were predicted using gene databases. Real-time PCR confirmed the upregulation of hsa-miR-548a-3p and downregulation of hsa-miR-500b-5p in AVMC. CONCLUSIONS: Hsa-miR-548a-3p and hsa-miR-500b-5p could serve as a promising biomarker of AVMC. Exosomal miRNAs may have substantial roles in the mechanisms of AVMC.

The Molecular Mechanisms of Cardiotoxicity Induced by HER2, VEGF, and Tyrosine Kinase Inhibitors: an Updated Review.

AIM: In recent decades, there has been a revolutionary decrease in cancer-related mortality and an increase in survival due to the introduction of novel targeted drugs. Nevertheless, drugs targeting human epidermal growth factor receptor 2 (HER-2), angiogenesis, and other tyrosine kinases also come with unexpected cardiac side effects, including heart failure, hypertension, arterial thrombosis, and arrhythmias, and have mechanisms that are unlike those of classic chemotherapeutic agents. In addition, it is challenging to address some problems, as the existing guidelines need to be more specific, and further large-scale clinical trials and experimental studies are required to confirm the benefit of administering cardioprotective agents to patients treated with targeted therapies. Therefore, an improved understanding of cardiotoxicity becomes increasingly important to minimize the pernicious effects and maximize the beneficial effects of targeted agents. METHODS: "Cardiotoxicity", "targeted drugs", "HER2", "trastuzumab", "angiogenesis inhibitor", "VEGF inhibitor" and "tyrosine kinase inhibitors" are used as keywords for article searches. RESULTS: In this article, we report several targeted therapies that induce cardiotoxicity and update knowledge of the clinical evidence, molecular mechanisms, and management measures.

Head-to-head comparison of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET in the detection of cancer recurrence: a systematic review and meta-analysis.

Background: The comparative diagnostic performance of [68Ga]Ga-fibroblast activation protein inhibitors-04 {[68Ga]Ga-FAPI-04} positron emission tomography (PET) and fluorodeoxyglucose F 18 {[18F]FDG} PET in identifying cancer recurrence remains uncertain. The purpose of our study was to compare the diagnostic performance of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET imaging in cancer recurrence. Methods: Up until March 1, 2024, we searched PubMed, Embase, and Web of Science for pertinent papers. Studies examining the diagnostic utility of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET for cancer recurrence were included. Using a bivariate fixed-effect model and random-effect model, the pooled sensitivity and specificity for [68Ga]Ga-FAPI-04 PET and [18F]FDG PET were reported as estimates with 95% confidence intervals (CIs). The I2 statistic was used to evaluate the heterogeneity among the pooled studies. The included studies' quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) approach. Results: In all, 508 papers were found during the first search; ultimately, 12 studies totaling 224 patients were included. The pooled sensitivity of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET for cancer recurrence were 0.97 (95% CI: 0.90-1.00) and 0.69 (95% CI: 0.60-0.77). The pooled sensitivity of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET for gastrointestinal cancer recurrence were 1.00 (95% CI: 0.97-1.00) and 0.57 (95% CI: 0.42-0.74). The pooled specificity of [68Ga]Ga-FAPI-04 PET and [18F]FDG PET for gastrointestinal cancer recurrence were 0.66 (95% CI: 0.15-1.00) and 0.46 (95% CI, 0.00-1.00). Conclusions: Based on the previous studies, [68Ga]Ga-FAPI-04 PET shows higher sensitivity compared to [18F]FDG PET in detecting tumor recurrence, especially in detecting gastrointestinal cancer recurrence. [68Ga]Ga-FAPI-04 PET shows similar specificity compared to [18F]FDG PET in detecting gastrointestinal cancer recurrence. The detection results, however, came from investigations using modest sample numbers. In this matter, more extensive prospective study is required.

The Transcriptome Analysis of Circular RNAs Between the Doxorubicin- Induced Cardiomyocytes and Bone Marrow Mesenchymal Stem Cells- Derived Exosomes Treated Ones.

AIM: To analyze the sequencing results of circular RNAs (circRNAs) in cardiomyocytes between the doxorubicin (DOX)-injured group and exosomes treatment group. Moreover, to offer potential circRNAs possibly secreted by exosomes mediating the therapeutic effect on DOX-induced cardiotoxicity for further study. METHODS: The DOX-injured group (DOX group) of cardiomyocytes was treated with DOX, while an exosomes-treated group of injured cardiomyocytes were cocultured with bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BEC group). The high-throughput sequencing of circRNAs was conducted after the extraction of RNA from cardiomyocytes. The differential expression of circRNA was analyzed after identifying the number, expression, and conservative of circRNAs. Then, the target genes of differentially expressed circRNAs were predicted based on the targetscan and Miranda database. Next, the GO and KEGG enrichment analyses of target genes of circRNAs were performed. The crucial signaling pathways participating in the therapeutic process were identified. Finally, a real-time quantitative polymerase chain reaction experiment was conducted to verify the results obtained by sequencing. RESULTS: Thirty-two circRNAs are differentially expressed between the two groups, of which twenty-three circRNAs were elevated in the exosomes-treated group (BEC group). The GO analysis shows that target genes of differentially expressed circRNAs are mainly enriched in the intracellular signalactivity, regulation of nucleic acid-templated transcription, Golgi-related activity, and GTPase activator activity. The KEGG analysis displays that they were involved in the autophagy biological process and NOD-like receptor signaling pathway. The verification experiment suggested that mmu_circ_0000425 (ID: 116324210) was both decreased in the DOX group and elevated in BEC group, which was consistent with the result of sequencing. CONCLUSION: mmu_circ_0000425 in exosomes derived from bone marrow mesenchymal stem cells (BMSC) may have a therapeutic role in alleviating doxorubicin-induced cardiotoxicity (DIC).

pT1-2 gastric cancer with lymph node metastasis predicted by tumor morphologic features on contrast-enhanced computed tomography

PURPOSE: To investigate the value of tumor morphologic features of pT1-2 gastric cancer (GC) on contrast-enhanced computed tomography (CT) in assessing lymph node metastasis (LNM) with reference to histopathological results. METHODS: Eighty-six patients seen from October 2017 to April 2019 with pT1-2 GC proven by histopathology were included. Tumor volume and CT densities were measured in the plain scan and the portal-venous phase (PVP), and the percent enhancement was calculated. The correlations between tumor morphologic features and the N stages were analyzed. The diagnostic capability of tumor volume and enhancement features in predicting the LN status of pT1-2 GCs was further investigated using receiver operating characteristic (ROC) analysis. RESULTS: Tumor volume, CT density in the PVP, and tumor percent enhancement in the PVP correlated significantly with the N stage (rho: 0.307, 0.558, and 0.586, respectively). Tumor volumes were significantly lower in the LNM- group than in the LNM+ group (14.4 mm3 vs. 22.6 mm3, P = 0.004). The differences between the LNM- and LNM+ groups in the CT density in the PVP and the percent enhancement in the PVP were also statistically significant (68.00 HU vs. 87.50 HU, P < 0.001; and 103.06% vs. 179.19%, P < 0.001, respectively). The area under the ROC curves for identifying the LNM+ group was 0.69 for tumor volume and 0.88 for percent enhancement in the PVP, respectively. The percent enhancement in the PVP of 145.2% and tumor volume of 17.4 mL achieved good diagnostic performance in determining LNM+ (sensitivity: 71.4%, 82.1%; specificity: 91.4%, 58.6%; and accuracy: 84.9%, 66.3%, respectively). CONCLUSION: Tumor volume and percent enhancement in the PVP of pT1-2 GC could improve the diagnostic accuracy of LNM and would be helpful in image surveillance of these patients.

Rotenone nanoparticles based on mesoporous silica to improve the stability, translocation and insecticidal activity of rotenone.

Nanotechnology has been widely applied for pesticide carriers, which is an important way to improve the utilization, stability, and sustained release of pesticides. Mesoporous silica nanoparticles (MSNs) are a nanomaterial with adjustable particle and pore sizes, with a high specific surface area and good biocompatibility. Rotenone is a non-systemic botanical insecticide that is easily degraded in the environment. We used a modified soft-template method to prepare MSNs, in which rotenone was loaded using the solvent evaporation method. The prepared rotenone nanopesticide based on mesoporous silica showed considerable drug loading rates of 33.2%. Moreover, the prepared rotenone nanoparticles showed improved photostability and sustained release behavior, which improved the translocation of rotenone in tomato plants. Finally, the rotenone nanoparticles displayed superior insecticidal activity compared to traditional preparations. In summary, the rotenone nanopesticide improved the persistence and utilization rates of rotenone. These findings are of significance in reducing pesticide usage, mitigating environmental pollution, and ensuring food safety.

Imaging manifestations of idiopathic granulomatous lobular mastitis on cone-beam breast computed tomography.

PURPOSE: To evaluate the imaging manifestations of idiopathic granulomatous mastitis (IGM) on cone-beam breast computed tomography (CBBCT). METHODS: We retrospectively evaluated the clinical data of 22 female patients (mean age, 34.73 ± 10.41 years; range 20-58 years) with IGM pathologically confirmed by biopsy or resection. The non-contrast-enhanced CBBCT features, contrast-enhanced CBBCT features, contrast enhancement rate, time-density curve (TDC) and Breast Imaging-Reporting and Data System category of IGM were assessed. The contrast enhancement rates of IGM lesions at 60 s, 120 s and 180 s after injection of contrast agent were compared using ANOVA. RESULTS: All 22 patients with IGM showed non-mass enhancement on CBBCT. Approximately 40.9% (9/22) of IGM lesions displayed diffuse patchy or focal nodular enhancement on CBBCT, 31.8% (7/22) showed mammary duct dilation, 13.6% (3/22) showed pseudocystic appearance, and 13.6% (3/22) manifested as honeycomb cysts. Among the 22 patients, 72.7% (16/22) displayed type I TDC (persistently enhancing pattern) and 27.3% showed type II TDC (plateau pattern) on contrast-enhanced CBBCT. CONCLUSIONS: IGM mainly manifests as non-mass enhancement on CBBCT, with persistently enhancing or plateau TDC. CBBCT efficiently displays detailed features of IGM with high-density resolution and hemodynamic characteristics.

Study on toxicity effects of environmental pollutants based on metabolomics: A review.

In the past few decades, the toxic effects of environmental pollutants on non-target organisms have received more and more attention. As a new omics technology, metabolomics can clarify the metabolic homeostasis of the organism at the overall level by studying the changes in the relative contents of endogenous metabolites in the organism. Recently, a large number of studies have used metabolomics technology to study the toxic effects of environmental pollutants on organisms. In this review, we reviewed the analysis processes and data processes of metabolomics and its application in the study of the toxic effects of environmental pollutants including heavy metals, pesticides, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers and microplastics. In addition, we emphasized that the combination of metabolomics and other omics technologies will help to explore the toxic mechanism of environmental pollutants and provide new research ideas for the toxicological evaluation of environmental pollutants.

Glucose control independent mechanisms involved in the cardiovascular benefits of glucagon-like peptide-1 receptor agonists.

Patients with type 2 diabetes mellitus (T2DM) face a high risk of developing cardiovascular diseases. However, traditional hypoglycemic drugs have limited effects on macrovascular complications of the disease. Clinical trials have confirmed that glucagon-like peptide-1 receptor agonists (GLP-1RAs), in addition to their capability of controlling blood glucose, can also decrease the risk of cardiovascular events in T2DM. The protective influence of GLP-1RAs on coronary heart disease and heart failure has been proven in recent clinical studies. Therefore, the international guidelines recommend GLP-1 RAs as the first-line therapy for patients with T2DM having cardiovascular disease. Notwithstanding the widespread clinical application of GLP-1RAs, the underlying mechanisms through which GLP-1RAs exert cardiovascular benefits in patients with DM remain unclear. In this review, we systematically summarize the mechanisms of action of GLP-1RAs responsible for producing favorable effects on the cardiovascular system, beyond their capability of blood glucose regulation. GLP-1RA-mediated cardiovascular protection is manifested through multiple mechanisms, including oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and vascular/cardiac remodeling. The understanding of these mechanisms will facilitate the development of new and promising therapeutic modalities for T2DM. Furthermore, we have identified several promising targets for future research in this area.

Uptake, translocation and subcellular distribution of chlorantraniliprole and tetrachlorantraniliprole in maize.

This study aimed to investigate the uptake, translocation, and subcellular distribution of chlorantraniliprole (Cap) and tetrachlorantraniliprole (Tca) in maize (Zea mays L.) plants using a hydroponic experiment. Tca mainly accumulated in the roots and stems, while Cap showed better acropetal translocation capacity than Tca. The uptake of Cap was positively correlated with Tca uptake, particularly at the effect of plant transpiration force. Transpiration inhibitor treatments significantly reduced the acropetal translocation of Cap and Tca. The absorption of Cap and Tca in the dead and fresh roots showed a good linear relationship and mainly occurred via the apoplastic pathway. Regarding subcellular distribution, the cell wall was the dominant storage compartment for Cap and Tca. In the protoplast, Cap mainly accumulated in cell soluble fractions, while Tca accumulated in the organelles. This study provides information for the accurate application of maize pest management and is of great significance to environmental risk and food safety assessments.