Safety and efficacy of brivaracetam in children epilepsy: a systematic review and meta-analysis.

Background: Epilepsy is one of the most common neurological diseases, affecting people of any age. Although the treatments of epilepsy are more and more diverse, the uncertainty regarding efficacy and adverse events still exists, especially in the control of childhood epilepsy.

Methods: We performed a systematic review and meta- analysis following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.

Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer.

DNA ligase (LIG) plays a key role in connecting the 3'-OH end of a DNA strand to the 5'-P end of another DNA strand, resulting in the formation of a phosphodiester bond. It has been reported that LIGs (including LIG1, LIG3 and LIG4) play important roles in the occurrence and progression of many cancers. However, the role of LIGs in breast cancer (BC) is still unclear.

The Alterations and Potential Roles of MCMs in Breast Cancer.

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database.

Tissue microRNA-182 expression level and its potential prognostic value for papillary thyroid carcinoma.

Background: In previous study, qRT-PCR analysis revealed significantly higher miR-182 levels in papillary thyroid carcinoma (PTC) than matched normal tissues. However, the clinical significance and prognostic value of miR-182 have not been investigated in PTC until now.

Methods: 151 pairs of PTC and adjacent normal thyroid tissues were obtained from Affiliated Hospital of Weifang Medical University from February 2008 to January 2015.

New Method for Detecting the Suppressing Effect of Enzyme Activity by Aminopeptidase N Inhibitor.

Aminopeptidase N, also known as CD13, is a transmembrance protease with many functions. CD13 is involved in inflammatory diseases and cancers. A convenient and reliable laboratory test method for detecting the suppressing effects of enzyme activity would be useful for study of CD13 inhibitors.

Discovery of Novel Phosphodiesterase-2A Inhibitors by Structure-Based Virtual Screening, Structural Optimization, and Bioassay.

Phosphodiesterase-2A (PDE2A) is a potential therapeutic target for treatment of Alzheimer's disease and pulmonary hypertension. However, most of the current PDE2A inhibitors have moderate selectivity over other PDEs. In the present study, we described the discovery of novel PDE2A inhibitors by structure-based virtual screening combining pharmacophore model screening, molecular docking, molecular dynamics simulations, and bioassay validation.

Ab Initio QM/MM Study Shows a Highly Dissociated SN2 Hydrolysis Mechanism for the cGMP-Specific Phosphodiesterase-5.

Phosphodiesterases (PDEs) are the sole enzymes hydrolyzing the important second messengers cGMP and cAMP and have been identified as therapeutic targets for several diseases. The most successful examples are PDE5 inhibitors (i.e.

-374T/A polymorphism of the receptor for advanced glycation end products is associated with decreased risk of breast cancer in a Chinese population.

Purpose: we aimed to investigate the receptor for advanced glycation end products (RAGE) -374T/A polymorphism and breast cancer risk in a Chinese population.

Methods: The study subjects included 188 women with histologically confirmed breast cancer and 210 controls. The RAGE genotypes were determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay.

Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent.

Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer's disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs.

Palladium-catalyzed oxidative C-H bond acylation of N-nitrosoanilines with toluene derivatives: a traceless approach to synthesize N-alkyl-2-aminobenzophenones.

A palladium-catalyzed cascade cross-coupling of N-nitroso-anilines and toluene derivatives for the direct synthesis of N-alkyl-2-aminobenzophenones is described. N-nitroso groups in anilines can act as the traceless directing groups while toluene derivatives can serve as effective acyl precursors under mild reaction conditions.

Molecular dynamics-based discovery of novel phosphodiesterase-9A inhibitors with non-pyrazolopyrimidinone scaffolds.

Phosphodiesterase-9A (PDE9A) is a promising therapeutic target for the treatment of diabetes and Alzheimer's disease (AD). The Pfizer PDE9A inhibitor PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013. However, most of the reported PDE9A inhibitors share the same scaffold as pyrazolopyrimidinone, which lacks structural diversity and is unfavorable for the development of novel PDE9A inhibitors.

The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: a modeling study.

Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalafil gives a high selectivity of 1020-fold against PDE6. Till now, their molecular mechanisms of selectivity of PDE5 versus PDE6 have remained unknown in the absence of the crystal structure of PDE6.