Multi-omics reveals aging-related pathway in natural aging mouse liver.

Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.

Exosomes from human umbilical cord mesenchymal stem cells protect aortas in Db/db mice characterized by combination of metabolomics and proteomics.

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications.

Value of CT Density Measurements in Distinguishing Parathyroid Adenoma,Thyroid,and Lymph Node / 中国医学科学院学报

Objective To explore the value of multi-phase contrast-enhanced computed tomography in the differential diagnosis of parathyroid adenoma,lymph node,and thyroid. Methods The enhanced multi-slice CT (MSCT) results of 21 parathyroid adenoma patients were analyzed,and their postoperative pathological specimens were examined. During the MSCT,the plain CT scan was recorded,along with the density of thyroid adenoma,lymph nodes,and thyroid at 35 s and 65 s (D0,D35,D65) following the injection of contrast medium. Results During the D0 phase,there was significant difference in CT values between the parathyroid adenoma and thyroid parenchyma[(45?12) HU vs.(90?15)HU,P=0.007]. According to ROC curve,75 HU,with 95.2% sensitivity and specificity,was the critical value for distinguishing the density of parathyroid adenoma and that of thyroid parenchyma. At 35 s following the injection of contrast medium,there was significant difference in the enhancement degree between parathyroid adenoma and lymph node[(182?39) HU vs.(80?20)HU,P=0.004]. According to ROC curve,111 HU,with 95.2 % sensitivity and specificity,was the critical value for distinguishing the density of parathyroid adenoma and that of lymph node 35 s following the injection of contrast medium. At 35 s to 65 s following the injection of contrast medium,the parathyroid adenoma experienced a decline in density,which was dramatically different from parathyroid adenoma,however,lymph node experienced a rise in density. Conclusion Enhanced CT measurements at different time points enable the differentiation among parathyroid adenomas,lymph nodes,and thyroid.