[Metabolomics study of Danggui Buxue Tang on treatment of type 2 diabetes mice using UHPLC-Q-TOF-MS].

In this paper, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS)-based metabolomics approach was used to explore the mechanism of Danggui Buxue Tang(DBT) in treating type 2 diabetes mellitus(T2 DM). T2 DM mice model was induced by high-sugar and high-fat fodder and streptozotocin(STZ). The routine indexes such as body weight, blood glucose, plasma insulin, IL-6 and related organ indexes were determined. The UHPLC-Q-TOF-MS technique was used to analyze the metabolism profile of serum samples between the control group and model group, and multiple statistical analysis methods including principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to screen and identify biomarkers. Metabolic profiling revealed 16 metabolites as the most potential biomarkers distinguishing mice in model group from those in control group. The metabolomics pathway analysis(MetPA) was used to investigate the underlying metabolic pathways. Seven major metabolic pathways such the valine, leucine and isoleucine biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, fatty acid metabolism and biosynthesis of unsaturated fatty acid. Eleven metabolites such as taurocholic acid and palmitic acid were down-regulated in T2 DM mice, and five metabolites such as L-leucine and leukotriene E4 were up-regulated. Moreover, the sixteen biomar-kers of each administration group had a trend of returning to mice in control group. The significantly-altered metabolite levels indicated that DBT can improve the progression of type 2 diabetes by increasing insulin sensitivity, regulating sugar and lipid metabolism disorders, and relieving inflammation.

Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARα partially through the ubiquitin-proteasome pathway.

PML/retinoic acid receptor alpha (RARα), as a hallmark of acute promyeloid leukemia (APL), is directly related to the outcome of clinical APL remedy. It is reported that arsenicals can effectively degrade PML/RARα, such as arsenic trioxide and realgar. However, the high toxicity or insolubility have hampered their clinical applications. Realgar transforming solution (RTS) was produced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significant anti-cancer ability on chronic myeloid leukemia through oncoprotein degradation. The capacity of RTS on treating APL is what is focused on in this study. The results showed that RTS had a noticeable sensitivity in NB4 cell, and RTS remarkably down-regulated PML/RARα expression and induced cell differentiation. Further, RTS could accumulate PML/RARα into the nuclear bodies and then execute degradation, which could be reversed by proteasome inhibitor MG132. The results also exhibited that the reduction of RTS-induced PML/RARα expression accompanied by the elevation of ubiquitin and SUMO-1 protein expression. Finally, PML and SUMO-1 had been demonstrated to be co-localized after RTS treatment by immunofluorescence co-localization assay and immunoprecipitation assay. In conclusion, these results suggested that RTS-induced cell differentiation may attribute to the PML/RARα degradation partially through the ubiquitin-proteasome pathway.

A novel classification system for the evaluation and reconstruction of oral defects following oncological surgery.

Accurate evaluation of oral tissue defects following oncological surgery is necessary for the subsequent reconstruction. However, there is currently no effective classification system for oral defects in the clinical setting. The present study therefore developed a clinical classification system for the evaluation and reconstruction of oral defects. A retrospective cohort study was performed. A two-dimensional classification system based on coronal computed tomography/magnetic resonance imaging was developed and validated by 145 cases with oral defects. Oral defects could be classified into 6 types (I-VI) horizontally and 2 classes (a and b) vertically. The proportion of the various types was as follows: Type I, 35.9%; type II, 21.4%; type III, 23.4%; type IV, 4.8%; type V, 2.1%; and type VI, 12.4%. Among them, 91 cases (62.8%) were class a and 54 cases (37.2%) were class b. Type Ia-Va represented the unilateral 1-5 subsites involving superficial oral defects without mandibular continuity destruction (88 cases, 60.7%). Type Ib-Vb (+M) represented the unilateral 1-5 subsites involving deep oral defects with segmental mandibular continuity destruction (38 cases, 26.2%). Type I-V (+S) represented the unilateral through and through oral defects with cheek skin involvement (10 cases, 6.9%). Type VI represented bilateral oral defects (18 cases, 12.4%). The present classification system for the evaluation of the oral defects was simple and practical, and could identify the common types of oral defects and guide the reconstruction.