Endothelial dysfunction is a key pathophysiological step in early stage diabetes mellitus (DM) macrovascular complications and is also crucial in the inflammatory mechanisms of macrovascular complications. However, there is currently no effective intervention to improve endothelial dysfunction associated with DM macrovascular complications. Astragaloside IV (AS-IV), which can be extracted from the traditional Chinese medicine Astragalus membranaceus , has potential therapeutic effects on DM and its complications. The present study evaluated the effect of AS-IV on high glucose-induced human umbilical vein endothelial cell (HUVEC) injury and its possible mechanism. The result indicated that AS-IV has a significant protective effect on high glucose-induced HUVEC injury. AS-IV could significantly promote cell proliferation, reduce apoptosis and decrease the protein and mRNA expression levels of tumor necrosis factor-α and interleukin-1β in HUVECs. Furthermore, AS-IV could decrease the expression of phosphorylated c-Jun NH 2 -terminal kinase (JNK) phosphorylated apoptosis signal-regulating kinase 1, cytochrome c, cleaved-caspase-9, cleaved-caspase-3 and the relative ratio of B-cell lymphoma-2 associated X protein/B-cell lymphoma-2 in HUVECs. In conclusion, the present study demonstrated that AS-IV could suppress apoptosis and inflammatory reactions promoted by high glucose conditions in HUVECs by inhibiting the JNK signaling pathway. These findings suggest that AS-IV could inhibit the process of endothelial dysfunction in diabetic macrovascular complications.

Background Universal salt iodization program was introduced to China to eliminate iodine deficiency disorders in 1995. In 2012, Fujian Province decreased the concentration of iodized table salt according to the national unified requirement. This study aimed to assess the effect on iodine status after the adjustment, providing evidence for further adjustment in Fujian Province. Methods Sampling units were selected by multistage cluster sampling method. In each sampling unit, table salt was collected from 30 households. A total of 2,471 people in 2009 and 4,806 people in 2017 provided urine samples and were included in this cross-sectional analysis. Median iodized salt concentration and median urine iodine concentration were present by median and interquartile range. Results Median iodized salt decreased from 29.8 mg/kg in 2009 to 23.9 mg/kg in 2017. The median urinary iodine concentrations for school-age children in 2017 in coastal urban area, non-coastal urban area, coastal rural area and non-coastal rural area were 163.6µg/L (interquartile range = 100.1–252.0µg/L), 198.9µg/L (interquartile range = 128.0-294.0µg/L), 181.8µg/L (interquartile range = 114.1–257.0µg/L) and 218.2µg/L (interquartile range = 148.1-306.5µg/L), respectively. The median urinary iodine concentrations for adults in 2017 in these areas were 151.1µg/L (interquartile range = 98.3-231.7µg/L), 168.7µg/L (interquartile range = 109.6–242.0µg/L), 167.7µg/L (interquartile range = 105.7-245.7µg/L) and 182.7µg/L (interquartile range = 117.1-258.9µg/L). The median urinary iodine concentrations for pregnant women in 2017 in these areas were 157.7µg/L (interquartile range = 106.9-223.8µg/L), 141.5µg/L (interquartile range = 97.7-207.6µg/L), 127.3µg/L (interquartile range = 90.0-184.5µg/L) and 144.8µg/L (interquartile range = 99.9-184.5µg/L). The median urinary iodine concentrations for lactating women in 2017 in these areas were 122.7µg/L (interquartile range = 84.1–172.0µg/L), 123.7µg/L (interquartile range = 70.7-184.7µg/L), 105.8µg/L (interquartile range = 67.1-152.3µg/L) and 110.2µg/L (interquartile range = 74.1-170.3µg/L). Conclusions The overall urinary iodine concentrations among school-age children, adults and lactating women dramatically decreased after implementing the new standard. Almost all of them were iodine adequate, suggesting we reached the expected aim of iodized salt adjustment. However, pregnant women were iodine insufficient after adjustment. Therefore, we should continue the surveillance of iodine status of populations and focus on the additional iodine supplement strategies for pregnant women.

Objective. To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN). Methods. Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the “YQHXTLF Pharmacodynamic Component-DPN Target” regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software. Results. A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets. Conclusion. YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action.

Background: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in the world with complicated pathogenesis. This study aimed to identify differentially expressed genes (DEGs) and molecular pathways in T2DM using bioinformatics analysis. Materials and Methods: To explore potential therapeutic targets for T2DM, we analyzed three microarray datasets (GSE50397, GSE38642, and GSE44035) acquired from the Gene Expression Omnibus (GEO) database. DEGs between T2DM islet and normal islet were picked out by the GEO2R tool and Venn diagram software. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify the pathways and functional annotation of DEGs. Then, protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Results: In total, we identified 36 DEGs in the three datasets, including 32 up-regulated genes and four down-regulated genes. The improved functions and pathways of the DEGs enriched in cytokine-cytokine receptor interaction, pathways in cancer, PI3K-Akt signaling pathway, and Rheumatoid arthritis. Among them, ten hub genes with a high degree of connectivity were selected. Furthermore, via the re-analysis of DAVID, four genes (IL6, MMP3, MMP1, and IL11) were significantly enriched in the Rheumatoid arthritis pathway. Conclusion: Our study, based on the GEO database, identified four significant up-regulated DEGs and provided novel targets for diagnosis and treatment of T2DM.

Background Urinary iodine concentration (UIC) is routinely used to evaluate the population iodine status while the uniform method for the individual level assessment is uncertain. Objectives To explore the 24-h urinary iodine excretion (UIE) in five different periods of the day and the corresponding prediction equations respect by the use of creatinine-corrected UIC. Methods We collected 24-h, spot and fasting urine in five periods of the day to estimate 24-h UIE by the six different prediction equations. We compared the estimated creatinine-corrected UIC to the collected 24-h UIE and identified the most suitable equations in each period of the day. Results Among the six different prediction equations, the equation of Kawasaki T was the best to estimate the 24-h UIE by fasting urine among Chinese adults. Among the five periods of time, the equation of Knudsen N was the best to estimate the 24-h UIE in the non-morning period. Conclusion Urinary iodine status at the individual level could be estimated by different creatinine-based equations at different periods of the day.