The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.
Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Unfortunately, its wide therapeutic application is often hindered by multidrug resistance (MDR), low water solubility and toxicity. In our previous study, new derivatives of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were synthesized and exhibited better inhibitory activity compared with the drug etoposide itself. To expose the binding interactions between the eukaryotic topoisomerase II and the active heterocyclic compounds, docking studies were performed, using the software Discovery Studio 2.1, based on the crystal structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was conducted on a selected set of 31 fused heterocyclic compounds with variation in structure and activity. The structural analyses indicate coordinate and hydrogen bonding interactions, van der Waals interactions and hydrophobic interactions between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible for the preference of inhibition and potency. Collectively, the results demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant anti-tumour drug candidates that should be further studied.
We describe a cryptococcal infection localized in the parotid gland of an otherwise healthy 72-year-old woman. The patient presented with a painful, approximately 4.5 cm diameter mass in the anterior region of her right ear. Her symptoms were mild and uncharacteristic. The patient had previously fallen on her face in her garden, causing the loss and breakage of her dentures. Since the soil of the garden contained chicken droppings, it is quite likely that the oral prothesis became contaminated on contacting the soil. The fungus probably entered the parotid gland through the traumatization of the posterior lateral wall of her oral cavity by her broken denture. Numerous intra- and extracellular cryptococcal yeast cells were observed in both histopathological and mycological slide preparations. The yeastlike fungus was recovered in cultures inoculated with tissue collected through three biopsies of her parotid region. The isolates were identified as Cryptococcus neoformans by classical mycology methods and found to be susceptible, in vitro, to fluconazole, amphotericin B and flucytosine. Fluconazole treatment (400 mg/d, for 6 months) was started and the patients facial swelling resolved and the pain significantly reduced within 5 weeks of the initiation of treatment. While fungal infection of the parotid gland have been reported, to our knowledge, this is the first description of a non-disseminated primary parotid infection due to C. neoformans.
Quantitative structure-activity relationship (QSAR) studies have been performed on heterocyclic urea derivatives (n ¼ 86) as transient receptor potential vanilloid (TRPV1) antagonists. The whole data set was divided into a training set (81% of the dataset) and a test set (remaining 19%) randomly. Models with genetic function approximation (GFA) and partial least-squares (PLS) algorithms, developed from the training set were used to assess the predictive potential of the models using test set compounds. Obtained nonlinear and linear QSAR models were developed by using constitutional, chemical and topological descriptors, Num. Rings, Mol. Vol. and PHI to relate to TRPV1 antagonist activity. It demonstrated that, the nonlinear GFA model had obvious superiority over the linear PLS model basing on good stability and predictive ability which were verified by internal validation (cross-validation by LOO) and external validation (r 2 ¼ 0.765, q 2 ¼ 0.736; for training set r 2 ¼ 0.940, q 2 ¼ 0.873; for test set). The generated GFA model was also reasonable and effective to discern the QSAR of heteroaromatic urea compounds as TRPV1 antagonists with in vitro activity in blocking capsaicin activation of TRPV1 in animal pain models. In future, the proposed model can be used to predict the biological activity of drug molecule and also to design new drug molecule(s) for TRPV1.
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