Using highly sensitive methods relying on 16S ribosomal RNA-based oligonucleotide probes, we confirmed the strong association of 7 putative periodontopathogens with AP patients in a Korean population. With the exceptions of Fusobacterium sp. and B. forsythus, all the periodontopathogens were significantly more associated with the healthy sites of periodontitis subjects than in the healthy sites of periodontally healthy subjects.

No abstract

The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) occurs by various mechanisms and appears to be almost inevitable, even in patients with lung cancer who initially respond well to EGFR-TKIs. Consequently, considerable efforts have been made to develop more effective EGFR-TKIs. Therefore, an understanding of the mechanisms behind TKI resistance is essential for improving EGFR-TKI therapeutic efficacy in non-small cell lung cancer (NSCLC) patients. In this study, we discovered that overexpression of antioxidant-responsive element (ARE)-containing Nrf2 target genes by increased transactivation of Nrf2 occurred because of an acquired Keap1 mutation in the gefitinib-resistant (GR) NSCLC cell line we established. These GR cells also acquired cross-resistance to the irreversible EGFR-TKIs, afatinib and osimertinib, and showed increased viability, invasiveness, proliferation, and tumorigenicity both in vitro and in vivo. These results were confirmed by the fact that inhibition of Nrf2 activity, either by treatment with brusatol or by inducing expression of exogenously introduced wild-type Keap1, suppressed tumor cell proliferation and tumorigenicity in vitro and in vivo. Our data suggest that disruption of the Keap1-Nrf2 pathway is one of the mechanisms by which EGFR-TKI resistance occurs, a fact that must be considered when treating patients with EGFR-TKI.-Park, S.-H., Kim, J. H., Ko, E., Kim, J.-Y., Park, M.-J., Kim, M. J., Seo, H., Li, S., Lee, J.-Y. Resistance to gefitinib and cross-resistance to irreversible EGFR-TKIs mediated by disruption of the Keap1-Nrf2 pathway in human lung cancer cells.

Curiosity has been regarded as a key intrinsic motivational drive for facilitating human exploratory behaviors in many domains, such as psychology, education, and sport. However, no attempt has been made to measure curiosity in a sport context. The purpose of this study was to develop an effective and efficient sport fan exploratory curiosity scale (SFECS). A total of 657 participants were recruited and completed surveys. Various statistical analyses were used to examine the reliability and validity of the scale. The analyses resulted in a reliable and valid scale with three factors (Excitement, New Sport Events, Sport Facility) and a total of 10-items. The SFECS was useful in predicting various sport fan behaviors. Future research should be done in an effort to further refine the scale and to examine the role of curiosity in various practical areas in a sport context.

No abstract

Cutaneous leishmaniasis (CL) is caused by several species of the protozoan parasite , affecting an estimated 10 million people worldwide. Previously reported strategies for the development of topical CL treatments have focused primarily on drug permeation and formulation optimization as the means to increase treatment efficacy. Our approach aims to identify compounds with antileishmanial activity and properties consistent with topical administration. Of the test compounds, five benzoxaboroles showed potent activity (50% effective concentration [EC] < 5 μM) against intracellular amastigotes of at least one species and acceptable activity (20 μM< EC < 30 μM) against two more species. Benzoxaborole compounds were further prioritized on the basis of the evaluation of progression criteria related to skin permeation, such as the partition coefficient and solubility. An MDCKII-hMDR1 cell assay showed overall good permeability and no significant interaction with the P-glycoprotein transporter for all substrates except LSH002 and LSH031. The benzoxaboroles were degraded, to some extent, by skin enzymes but had stability superior to that of-hydroxybenzoate compounds, which are known skin esterase substrates. Evaluation of permeation through reconstructed human epidermis showed LSH002 to be the most permeant, followed by LSH003 and LSH001. Skin disposition studies following finite drug formulation application to mouse skin demonstrated the highest permeation for LSH001, followed by LSH003 and LSH002, with a significantly larger amount of LSH001 than the other compounds being retained in skin. Finally, the efficacy of the leads (LSH001, LSH002, and LSH003) against was tested LSH001 suppressed lesion growth upon topical application, and LSH003 reduced the lesion size following oral administration.

No abstract

Trehalnse and LEA proteins, representative low MW chemicals that are synthesized under dehydralJon, are known to protect plants from drouBht ~ To compare their effectiveness on enhancin 8 tolerance against various abiotic stresses, we generated tranSl~=nic Chinese cabbase plants overexpressin 8 E. co//trehalose-6-phosphate m/nthase 8erie (ors4) or hot pepper (Capsicum annuum) LEA protein &ene (CaLEA). Both trampnic planl3 exhibited altered phenotype includin 8 stuntedgrowth and aberrant root developmenL When subjected to drousht , salt or heat sb~ss, these plants showed remarkably improved tolerance aj~dnst those stresses compared with nonlTansformants. After dehydra~n b~atment, leaf turgidity and fresh weight was better maintained in both transl~=nic plant~ Cat~-plants performed somewhat better under dehydrated condition, When ~eated with 250 mM NaCI, both ot~4-plants and CaZEA.plants remained equally healthier than nonl]'ansformants in maintaining leaf turgidity and delaying necrosis. Furthermore, leaf Chl content and Fv/Fm was maintained comiderably higher in both tram~enic plant~= than nontransformant~ After heat-treatment at 45~ both Irans~.nk plants appeared much less damased in external shape and PSII funclion, but LEA proteins were more protective. Our results iedicate that although bolh trehalose and LEA proteins are in proteclJng plants against various abiotic stresses, LEA proteins seem to be more promising in generatJn 8 sbess-tolerant ITansl~enic plants.