Single-cell transcriptome sequencing reveals aberrantly activated inter-tumor cell signaling pathways in the development of clear cell renal cell carcinoma.

BACKGROUND: Aberrant intracellular or intercellular signaling pathways are important mechanisms that contribute to the development and progression of cancer. However, the intercellular communication associated with the development of ccRCC is currently unknown. The purpose of this study was to examine the aberrant tumor cell-to-cell communication signals during the development of ccRCC. METHODS: We conducted an analysis on the scRNA-seq data of 6 ccRCC and 6 normal kidney tissues. This analysis included sub clustering, CNV analysis, single-cell trajectory analysis, cell-cell communication analysis, and transcription factor analysis. Moreover, we performed validation tests on clinical samples using multiplex immunofluorescence. RESULTS: This study identified eleven aberrantly activated intercellular signaling pathways in tumor clusters from ccRCC samples. Among these, two of the majors signaling molecules, MIF and SPP1, were mainly secreted by a subpopulation of cancer stem cells. This subpopulation demonstrated high expression levels of the cancer stem cell markers POU5F1 and CD44 (POU5F1hiCD44hiE.T), with the transcription factor POU5F1 regulating the expression of SPP1. Further research demonstrated that SPP1 binds to integrin receptors on the surface of target cells and promotes ccRCC development and progression by activating potential signaling mechanisms such as ILK and JAK/STAT. CONCLUSION: Aberrantly activated tumor intercellular signaling pathways promote the development and progression of ccRCC. The cancer stem cell subpopulation (POU5F1hiCD44hiE.T) promotes malignant transformation and the development of a malignant phenotype by releasing aberrant signaling molecules and interacting with other tumor cells.

Transcriptome Analysis and Metabolic Profiling Reveal the Key Regulatory Pathways in Drought Stress Responses and Recovery in Tomatoes.

Drought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis-antenna proteins, nitrogen metabolism, plant-pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5'-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.

Study on the Expression Significance of Mb, BChE and cTnI in Myocardial Infarction and Their Relationship with Prognosis.

Objective: Circulating biomarkers can be used as effective prediction tools for AMI diagnosis and prognosis, but their prediction efficiency is limited and still needs to be explored. The study aimed to investigate the changes of myocardial troponin I (cTn I), myoglobin (Mb), and butyryl cholinesterase (BChE) levels in patients with acute myocardial infarction (AMI) and its clinical predictive efficacy. Methods: In this prospective cohort study, fifty patients with AMI who received PCI (AMI group) and 50 healthy subjects who underwent physical examination (reference group) during the same period were included. According to the occurrence of short-term major adverse cardiovascular events (MACE) during 6-month follow-up, they were divided into MACE group and non-MACE group . The difference of Mb, BChE, and cTnI levels was compared, and the ROC curve was drawn to analyze the prediction efficiency. Results: Compared with the reference group or non-MACE group, Mb and cTnI significantly increased and BChE significantly decreased inAMI group and MACE group, respectively (P < .05). The AUC of Mb, cTnI and BChE in diagnosing AMI occurrence and prognosis were all > 0.75, and the sensitivity and specificity were all > 85.00%. cTnI, Mb and BChE have good diagnostic efficacy in disease occurrence and prognosis evaluation of AMI patients. Conclusions: High expression of Mb and cTnI and low expression of BChE can increase the risk of AMI incidence and MACE occurrence and have high diagnostic efficacy, which can be used as sensitive factors in clinical AMI diagnosis and evaluation. Thess provided a theoretical foundation for AMI diagnosis and MACE preventing in AMI patients.

Analysis between high risk of myocardial infarction with non-obstructive coronary artery disease in single center and occurrence of major adverse cardiovascular events.

OBJECTIVE: To investigate and compare the general information, medication, and the occurrence time of major adverse cardiovascular events (MACE) between patients with myocardial infarction with non-obstructive coronary artery myocardial infarction (MINOCA) and those with obstructive coronary artery disease (MICAD). METHODS: A total of 325 acute myocardial infarction (AMI) patients were included (MINOCA: n = 31; MICAD: n = 294). The general information and medication of patients were recorded, including age, gender, prevalence of type 2 diabetes, left ventricular ejection fraction (LVEF), proportion of mitral regurgitation, cTn level, triglyceride level, electrocardiogram (ECG) findings, and drugs used (statins, drugs improving ventricular remodeling, antiplatelet drugs). The above indexes were compared, and statistical analysis was performed at different time points of MACE. RESULTS: MACE occurred significantly more in the MICAD group than in the MINOCA group (38.8% vs. 12.9%; p = .004) after 1 month to 1.5 years of treatment. The earlier the period of MACE occurred in patients with high coronary artery stenosis, it was an independent risk factor for the occurrence of MACE from 1 month to 1 year after surgery (p = .002), while the later the occurrence of MACE in patients with LVEF ≥55% (p = .029). It was not related to gender, cTn, and electrocardiography (ECG) indexes. CONCLUSION: A correlation can be established between the risk factors of MINOCA and the occurrence time of MACE. In addition, MICAD is more commonly seen in male patients and patients with a higher cTn level and lower LVEF.

Expression of circular RNA has-circ-0009158 and identification of associated miRNA-mRNA network in hepatocellular carcinoma.

Primary hepatocellular carcinoma (HCC) affects people all over the world. Circular RNAs are involved in the growth and development of several malignancies and regulate a number of biological processes. However, the roles of has-circ-0009158 in HCC remain unknown. This study explored the expression and associated miRNA-mRNA network of has-circ-0009158 in HCC. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-circ-0009158 in the HCC tissues of 143 patients and four human HCC cell lines. Then, the potential relationship of hsa-circ-0009158 expression with clinical characteristics and prognosis of patients was analyzed using the GO and KEGG databases. Correlated miRNA-mRNA networks were forecasted using the TCGA database and Cytoscape software. The hsa-circ-0009158 expression was significantly upregulated in HCC tissues and cell lines (P<0.001). The multivariate Cox analysis revealed that HCC patients were associated with high hsa-circ-0009158 expression. The bioinformatics analysis screened 1 miRNA, and 248 mRNAs associated with the circRNA in HCC. A pathway analysis suggested that the differentially expressed genes (DEGs) may be linked to the development and growth of HCC tumors. Ten hub genes (MELK, NCAPG, BUB1B, BIRC5, CDCA8, CENPF, BUB1, CDK1, TTK, TPX2) were identified from the PPI network based on the 248 genes. Additionally, the 10 hub genes that were verified had an association between high expression levels and low overall survival rates. As a result, the high expression of hsa-circ-0009158 was found to be a separate risk factor for recurrence and a poor prognosis in HCC patients.

Comprehensive analysis of CPSF4-related alternative splice genes in hepatocellular carcinoma.

BACKGROUND: An important stage in controlling gene expression is RNA alternative splicing (AS), and aberrant AS can trigger the development and spread of malignancies, including hepatocellular carcinoma (HCC). A crucial component of AS is cleavage and polyadenylation-specific factor 4 (CPSF4), a component of the CPSF complex, but it is unclear how CPSF4-related AS molecules describe immune cell infiltration in the total tumor microenvironment (TME). METHODS: Using RNA-sequencing data and clinical data from TCGA-LIHC from the Cancer Genome Atlas (TCGA) database, the AS genes with differential expression were found. The univariate Cox analysis, KM analysis, and Spearman analysis were used to identify the AS genes related to prognosis. Screening of key AS genes that are highly correlated with CPSF4. Key genes were screened using Cox regression analysis and stepwise regression analysis, and prognosis prediction models and the topography of TME cell infiltration were thoroughly analyzed. RESULTS: A model consisting of seven AS genes (STMN1, CLSPN, MDK, RNFT2, PRR11, RNF157, GHR) was constructed that was aimed to predict prognostic condition. The outcomes of the HCC samples in the high-risk group were considerably worse than those in the lower risk group (p < 0.0001), and different risk patient groups were formed. According to the calibration curves and the area under the ROC curve (AUC) values for survival at 1, 2, and 3 years, the clinical nomogram performs well in predicting survival in HCC patients. These values were 0.76, 0.70, and 0.69, respectively. Moreover, prognostic signature was markedly related to immune infiltration and immune checkpoint genes expression. CONCLUSION: By shedding light on the function of CPSF4 and the seven AS genes in the formation and progression of HCC, this research analysis contributes to the development of more useful prognostic, diagnostic, and possibly therapeutic biomarkers.

Docosahexaenoic acid affects endothelial nitric oxide synthase in caveolae.

n-3 Polyunsaturated fatty acids are assumed to play an important role in the prevention and treatment of atherosclerosis. Endothelial nitric-oxide synthase (eNOS) is responsible for cardiovascular homeostasis involving in regulation of vascular function, and the subcellular localization is critical for its activation. Here we determined the effect of docosahexaenoic acid (DHA, 22:6 n-3) on distribution of eNOS and its activity. DHA treatment markedly altered lipid environment of caveolae microdomains, which was coincided with selective displacement of caveolin-1 and eNOS from caveolae. Akt was not detected in caveolae fractions and CaM was distributed in both of caveolin-1-enriched membranes and non-caveolar fractions, whose distribution was unaffected by DHA. These data demonstrated for the first time that DHA altered caveolae microenvironment not only by modifying membrane lipid composition, but also by changing distribution of major structural proteins. DHA-induced alterations in caveolae lipid/protein environment may be an important mechanism in the development of pathogenesis of atherosclerosis.