XU Wen-qing

The identity of the maturation inducer capable of mediating the differentiation of human myeloid leukemic HL-60 calls to terminal monocytic cells was investigated. One of such inducers from T cells was purified as a 54.3-kD peptide. The amino acid sequence of a tryptic peptide and the enzyme cleavage sites revealed 100% homology to neuroleukin or phosphoglucose isomerase (PGI). Neuroleukin mediates differentiation of neurons and is homologous to PGI, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate. The 54.3-kD inducer was shown to have PGI enzymatic activity. Separately purified PGI by substrate-elution exhibited identical specificity as the maturation inducer for HL-60 cell differentiation. They mediated a reduction of proliferating S and G2M cells, and the mature monocytic calls acquired complement receptors, phagocytic capacity, and adherence morphology. The magnitude of differentiation was dosage dependent on the inducer, with a bell-shaped curve. At the excess dose range cells did not undergo differentiation and remained in a proliferating cycle. Abnormally elevated PGI enzyme activities were detected in the plasma of acute myelogenous leukemia patients. Whether they represent an excess of the differentiation regulator in patients and are important in leukemogenesis remain to be investigated.

Compared to adrenocortical adenoma (ACA), adrenocortical carcinoma (ACC) has very poor prognosis and limited treatment options. Also conventional methods to distinguish ACC from ACA can be difficult. At this time, no molecular pathological markers are reliable enough to distinguish either tumor. Recently, increasing data have indicated miRNAs to be crucial regulators in the tumor‑related processes. In the present study, we found that miR-205 expression is significantly suppressed in ACC tissues compared with ACAs, and that this induces apoptosis and impairs proliferation of ACC SW-13 cells in vitro as well as inhibits tumor growth in vivo. Using bioinformatic predictions, Bcl-2 was identified to be a target of miR-205 via 3'-untranslated region (3'UTR) interactions, which was confirmed by luciferase assay, qRT-PCR, immunohistochemical assay and western blotting showing that mRNA and protein expression of Bcl-2 were negatively related to miR-205. Further investigation into the mechanism found that activation of Bcl-2 cleaved Bax, releasing caspase-9 and -3 that are involved in the intrinsic apoptosis pathway, eventually inducing SW-13 cell apoptosis. In conclusion, miR-205 suppresses the growth of ACC SW-13 cells via targeting the anti-apoptotic gene Bcl-2.

Recent advances in the structural modification of ligustrazine and studies on the bioactivities of ligustrazine derivatives are reviewed in this article. Due to its rapid metabolism and short half-life, ligustrazine is not suitable for application in clinical practice. Derivatives of ligustrazine were therefore designed and synthesized, including ether, amine, amide, hydrocarbon and deuterated derivatives of ligustrazine and ester and alcohol derivatives of 2-hydroxymethyl-3,5,6-trimethylpyrazine, an active metabolite of ligustrazine. Some of these compounds present better cerebro- arid cardiovascular activities and more favorable pharmacokinetic properties compared to the parent compound.

One of the most promising approaches for the discovery of new antidiabetic agents is represented by the exploitation of peroxisome proliferator-activated receptor (PPAR) ligands. New agents that selectively target PPARs and molecules with combined activity on several PPARs (i.e., PPARa and PPARy) have been identified as potentially superior therapeutic agents for metabolic diseases. These include: 1) PPARa agonists, which exert significant antidyslipidemic and antiatherosclerotic effects; 2) PPARy agonists, which are effective in treating type 2 diabetes; 3) selective partial PPARy agonists with robust antidiabetic efficacy and fewer adverse effects than currently available agonists; 4) PPARy antagonists, which are powerful tools to study PPARy signaling pathways; 5) dual PPARa/y agonists, which beneficially affect carbohydrate and lipid metabolism; 6) PPARδ agonists, which may have beneficial effects on circulating lipids and obesity; and 7) pan-PPARaα/γ/δ agonists with excellent antidiabetic activity. The advances in antidiabetic agents targeting PPARs are summarized in this review.