Expression and significance of T-cell immunoglobulin mucin molecule 3 and its ligand galectin-9 in patients with adenomyosis.

The T cell immunoglobulin mucin molecule 3 (TIM-3), as a negative regulatory immune checkpoint, plays an important role in cellular immunity by binding to its ligand galectin-9 (Gal-9). Under abnormal conditions, this pathway can regulate the depletion of T cells and suppress the immune response. Abnormal expression of TIM-3 and Gal-9 has been confirmed in a variety of cancers, recurrent miscarriages, chronic infectious diseases and autoimmune diseases. More and more studies have shown that immune factors play an important role in the pathogenesis of adenomyosis. However, few studies have attempted to explore their expression in adenomyosis. The ectopic and eutopic endometrium were collected from 15 women with adenomyosis and 13 women without adenomyosis. TIM-3/Gal-9 expression in endometrial tissue was detected using immunohistochemistry, western blot analysis and real-time PCR. We observed TIM-3/Gal-9 expression in both eutopic and ectopic endometria, with elevated expression in adenomyosis. These data suggest that TIM-3/Gal-9 may be involved in the development and progression of adenomyosis.

Access to 8-Azachromones via Activation of C-H in N-Oxides.

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

E804 induces growth arrest, differentiation and apoptosis of glioblastoma cells by blocking Stat3 signaling.

Glioblastoma, the most common type of primary malignant brain tumor, is a devastating disease associated with a median survival of approximately 12 months. Here, we have tested E804, the commercially available indirubin derivatives, against U251 and U87 glioblastoma cells. Treatment with E804 significantly inhibits the growth of human glioblastoma cells lines via induction of differentiation and apoptosis. Differentiation induction is coupled with increased expression of glial fibriliary acidic protein, a marker for mature astrocytes. Apoptosis is associated with activation of Caspase 3 and reduction of Bcl-xL and Mcl-1. Furthermore, we demonstrate that E804 reduces signal transducer and activator of transcription-3 (Stat3) signaling to a remarkable extent, suggesting that inactivation of Stat3, at least in part, mediates the effects of this indirubin derivative. Consistently, reduction of Stat3 activity promotes E804-mediated anti-tumor effects, whereas overexpression of Stat3C mutant recues cell apoptosis induced by E804. Taken together, our results indicate that E804 can effectively suppress tumor cell growth, induce tumor cell differentiation and apoptosis mediated partially by Stat3 signaling pathway, suggesting that E804 could be useful for a potential anti-glioblastoma therapeutic approach.

Stereoselective Four-Component Synthesis of Functionalized 2,3-Dihydro-4-Nitropyrroles.

We report a metal-free and stereoselective four-component reaction between α-ketoamides, amines, aromatic aldehydes and ß-nitroalkenes or ß-pivaloxy-nitroalkanes to obtain 2,3-dihydro-4-nitropyrroles functionalized in every position. The heterocycles accessible using this reaction may have utility in the synthesis of pharmacologically active compounds.

Health orientation and disease state as predictors of online health support group use.

What are the antecedents to the usage of online health-based support groups? This article draws on the motivation literature to posit the role of disposition-specific and situation-specific motivations in shaping the use of online health support groups. Based on 2 different nationally representative studies, it examines the role of situation-specific and disposition-specific motivations as predictors of online health community participation. Study results point out that intrinsic health orientation is a positive predictor of participation in an online health community. In addition, disease-specific motivation in the realm of perceived susceptibility to a disease or being detected with a disease triggers online community participation in disease-specific groups. The study results provide theoretical and practical guidelines for future scholarship.