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Comprehensive analysis of cold exposure-associated transcriptional and metabolic changes in the liver
Yuzhu Di, Zhengchao Wen, Xiaomin Liu, Kejiao Zhang, Xiuyun Shen, Chunpeng Shi, Yuqiu Chao, Xiao Wang, Shu Wang, Bo Qu, Yanan Jiang
2025, 5(4): 217-230. doi: 10.1515/fzm-2025-0024
Keywords: cold exposure, liver metabolism, transcriptome, metabolome
  Background  Cold exposure is associated with metabolic alterations. This study aims to investigate the effects and mechanisms of cold exposure on liver metabolism through the integration of transcriptomics and metabolomics.  Methods  Liver tissues from mice exposed to cold were subjected to RNA sequencing and liquid chromatography-mass spectrometry (LC-MS) for transcriptomic and metabolomic profiling, respectively. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were identified. mRNA expression levels were validated by real-time polymerase chain reaction (RT-PCR). Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Reactome enrichment analyses were performed. Finally, transcriptomic and metabolomic data were integrated and analyzed.  Results  Cold exposure altered the transcriptomic and metabolomic profiles in the liver in cold exposed mice. Enrichment analyses were of DEGs and DEMs. Enrichment analyses of DEGs and DEMs revealed that DEGs were involved in pathways such as the PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecules. DEMs were enriched in pathways related to membrane transport, nucleotide metabolism, and the metabolism of cofactors and vitamins. The integration of transcriptomic and metabolomic data identified several pathways potentially associated with cold exposure, such as the PI3K-Akt signaling pathway.  Conclusion  Cold exposure alters liver transcriptomic and metabolomic profiles in mice. The integrative analysis of transcriptomic and metabolomic data highlights the complexity of the liver's response to cold exposure and identifies potential targets for further investigation.
Circulating CCRR serves as potential novel biomarker for predicting acute myocardial infarction
Lina Xuan, Huishan Luo, Shu Wang, Guangze Wang, Xingmei Yang, Jun Chen, Jianjun Guo, Xiaomeng Duan, Xiufang Li, Hua Yang, Shengjie Wang, Hailong Zhang, Qingqing Zhang, Shulei Liu, Yongtao She, Kai Kang, Lihua Sun
2024, 4(3): 137-151. doi: 10.1515/fzm-2024-0015
Keywords: acute myocardial infarction, lncRNA, cardiac conduction regulatory RNA, exosome
  Objective   Cold regions exhibit a high prevalence of cardiovascular disease, particularly acute myocardial infarction (AMI), which is one of the leading causes of death associated with cardiovascular conditions. Cardiovascular disease is closely linked to the abnormal expression of long non-coding RNA (lncRNA). This study investigates whether circulating levels of lncRNA cardiac conduction regulatory RNA (CCRR) could serve as a biomarker for AMI.   Materials and methods   We measured circulating CCRR from whole blood samples collected from 68 AMI patients and 69 non-AMI subjects. An AMI model was established using C57BL/6 mice. Quantitative reverse transcription PCR (qRT-PCR) was used to assess CCRR expression. Exosomes were isolated from cardiomyocytes, and their characteristics were evaluated using electron microscope and nanoparticle tracking analysis. The exosome inhibitor GW4869 was employed to examine the effect of exosomal CCRR on cardiac function using echocardiography. Protein expression was detected using Western blot and immunofluorescence staining.   Results   The circulating level of CCRR was significantly higher in AMI patients (1.93 ± 0.13) than in nonAMI subjects (1.00 ± 0.05, P < 0.001). The area under the ROC curve (AUC) of circulating CCRR was 0.821. Similar changes in circulating CCRR levels were consistently observed in an AMI mouse model. Exosomal CCRR derived from hypoxia-induced cardiomyocytes and cardiac tissue after AMI were increased, a change that was reversed by GW4869. Additionally, CCRR-overexpressing exosomes improved cardiac function in AMI.   Conclusion   Circulating lncRNA CCRR is a potential predictor of AMI. Exosomal CCRR plays a role in the communication between the heart and other organs through circulation.