Ergosterol peroxide (EP) has been extensively studied for its antitumor activities. However, its further development has been restricted due to its limited intracellular accumulation and poor aqueous solubility. In this study, a novel triphenylphosphonium cation (TPP+) moiety was coupled to ergosterol peroxide to precisely target it at tumor cell mitochondria. The synthesized Mito-EP derivatives Mito-EP-3a-3d displayed stronger cytotoxicity than the EP parent and exhibited selectively cytotoxic effects between cancer cells and normal gastric epithelial (GES-1) cells. The most potent compound, Mito-EP-3b, was 9.7-fold more efficacious than ergosterol peroxide in the MCF-7 (breast cancer) cell line and showed good selectivity (SI = IC50GES-1/IC50MCF-7 = 4.04, IC50: concentrations to inhibit 50% of cell growth). Furthermore, Mito-EP-3b was able to decrease the mitochondrial membrane potential and induced reactive oxygen species production, accompanied by activating the expression of cytochrome c and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. Overall, the above results incentivize the further study of Mito EP-3b derivatives as potent anticancer agents.

A series of novel betulin-28-hydrazone derivatives (7a-7o) were synthesized. All compounds were evaluated for their in vitro cytotoxicities in four human carcinoma cells (HepG2, MCF-7, HCT-116 and A549). Among them, compound 7l displayed the most potent cytotoxicity with an IC50 (concentration of the tested compound that inhibits 50% of cell growth) value of 7.37 ± 0.38 μM against MCF-7 cells. The preliminary cellular mechanism studies indicated that compound 7l could induce MCF-7 cells apoptosis. The above findings indicated that compound 7l may be used as a lead compound for antitumor agents with improved efficacy.

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1β, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1β, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination.

ABSTRACT Objective The aim of this study was to investigate the incidence and risk factors for lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC). Subjects and methods 356 patients diagnosed with PTC who underwent total thyroidectomy and central lymph node dissection and lateral lymph node dissection between January 2005 and December 2011 were enrolled. The relation between LLNM and clinicopathological features such as gender, age, tumor size, tumor spread, psammoma bodies, tumor multifocality, extrathyroidal extension (ETE), unilateral or bilateral disease, tumor primary location and central lymph node metastases (CLNM) was analyzed. Results The rate of LLNM was 75.0%. In the univariate analysis, it was significantly associated with age, tumor size, tumor spread, extrathyroidal extension, primary tumor location and central lymph node metastasis (p < 0.05). In contrast, in the multivariate analysis, it was significantly associated with primary tumor location, central lymph node metastasis (p < 0.05) and tumor size > 1.5 cm with p = 0.05 but was unrelated to the other factors. Conclusion Patients with PTC, with the primary tumor located in the upper part of the lobe and positive central compartment lymph node metastasis with a tumor size > 1.5 cm diameter are more likely to have LLNM. Therefore, more meticulous evaluations including the lateral lymph nodes should be performed before surgery.