Serum and exosomal hsa_circ_0000907 and hsa_circ_0057362 as novel biomarkers in the early diagnosis of diabetic foot ulcer.

OBJECTIVE: Diabetic foot ulcer (DFU) is a serious chronic complication leading to disability and death in patients suffering from diabetes. Currently, there is no effective marker for its early diagnosis. The aim of this study is to analyze the difference of circRNA expression profiles between DFU and normal human wounds (NHW) and to screen serum biomarkers for the early diagnosis of DFU. MATERIALS AND METHODS: Differentially expressed circRNAs were screened by bioinformatics analysis, using GSE114248 chip data downloaded from GEO database, including 5 pairs of tissue samples from DFU patients and NHW cases. Accordingly, 20 cases of DFU (Wagner grade 0~2), 20 non-DFU diabetes and 20 healthy controls were selected in the screening test, and the total RNAs of serum and serum-derived exosomes were extracted. The screened circRNAs were verified in the third largest cohort, and the ROC curves were drawn to assess the diagnostic efficiency. RESULTS: As discovered by experiment, there were a total of 67 circRNAs presented differential expressions between the two groups, with 28 circRNAs upregulated and 39 circRNAs downregulated in DFU group. Two types of circRNAs, hsa_circ_0000907 and hsa_circ_0057362, were selected as candidate biomarkers in current study and validated in a large cohort. The AUCs of serum hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.9389 and 0.8792, respectively, and the AUCs of exosomal hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.8783 and 0.8481, respectively. Furthermore, the expressions of serum hsa_circ_0000907 and hsa_circ_0057362 were negatively correlated with ankle brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) in DFU patients. CONCLUSIONS: Serum and exosomal hsa_circ_0000907 and hsa_circ_0057362, especially hsa_circ_0000907, have novel diagnostic capabilities in the early diagnosis of DFU.

Effects of diet restriction and carnitine on carbon tetrachloride toxicity in the rat.

Male Sprague Dawley rats were fed a semisynthetic diet ad libitum, 55% of ad libitum (45% restriction), or supplemented with 1% L-carnitine for 68 days. The LD50 dose of CCl4 was orally administered, and mortality and hepatic lipids were determined. The CCl4-induced mortality was significantly increased by feed restriction but not by carnitine. Carnitine prevented hepatic lipid accumulation caused by CCl4 under these conditions.

Effects of levels of feed restriction on in vivo and in vitro alterations in drug metabolism and associated enzymes.

The objective of this study was to determine if 15% and 30% feed restriction would enhance drug metabolism similar to that caused by 45% feed restriction. Four groups of weanling male Sprague-Dawley rats were subjected to 0%, 15%, 30%, and 45% feed restriction for 28 days. Feed restriction of 45% significantly enhanced hepatic DNA, microsomal protein, cytochrome P-450, aniline hydroxylase, p-chloromethylaniline-N-demethylase, and decreased hexobarbital sleeping time. The feed restriction of 15% and 30% did not significantly alter the above parameters of drug metabolism. The activities of NADPH-generating enzymes were enhanced by all levels of feed restriction. Thus it is concluded that 15% and 30% feed restriction did not enhance in vivo or in vitro drug metabolism to the extent enhanced by 45% restriction for the same length of time.