Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. PPARγ is a target for thiazolidinedione (TZD) class of drugs which are widely used for the treatment of type 2 diabetes. Recently, lobeglitazone was developed as a highly effective TZD with reduced side effects by Chong Kun Dang Pharmaceuticals. To identify the structural determinants for the high potency of lobeglitazone as a PPARγ agonist, we determined the crystal structures of the PPARγ ligand binding domain (LBD) in complex with lobeglitazone and pioglitazone at 1.7 and 1.8 Å resolutions, respectively. Comparison of ligand-bound PPARγ structures revealed that the binding modes of TZDs are well conserved. The TZD head group forms hydrogen bonds with the polar residues in the AF-2 pocket and helix 12, stabilizing the active conformation of the LBD. The unique p-methoxyphenoxy group of lobeglitazone makes additional hydrophobic contacts with the Ω-pocket. Docking analysis using the structures of TZD-bound PPARγ suggested that lobeglitazone displays 12 times higher affinity to PPARγ compared to rosiglitazone and pioglitazone. This structural difference correlates with the enhanced affinity and the low effective dose of lobeglitazone compared to the other TZDs.

Taken together, HP-PDT induces apoptotic cell death with autophagy in oral cancer cells. PDT resistance is related to autophagy by PARP-1 regulation in oral cancer cells.

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Background/purpose The value of the temporomandibular joint (TMJ) projections of panoramic radiography for diagnosing TMJ osteoarthritis is not completely elucidated. This study aimed to assess the diagnostic accuracy and reliability of panoramic TMJ radiography to detect bony lesions in patients with TMJ osteoarthritis. Materials and methods This study included 55 TMJs of 44 subjects who were diagnosed with TMJ osteoarthritis. They underwent panoramic radiography (PanRad), lateral (LatTMJ) and frontal (FrnTMJ) projection panoramic TMJ radiography, and cone-beam computed tomography (CBCT). All images were examined by two observers for flattening, erosion, and osteophytes on the condylar head and articular eminence of the TMJ. Results For detecting flattening lesions on the mandibular condyle, the sensitivities of PanRad, LatTMJ, and FrnTMJ were less than 67% and the combination of LatTMJ and FrnTMJ (ComTMJ) had the highest sensitivity for both observers (67.6% and 79.7%, respectively). For erosion lesions, the sensitivity of ComTMJ for observer 1 was the highest, at 84.3%, whereas the specificity of ComTMJ was the lowest, at 37.5%. The sensitivities of all four methods for observer 2 were less than 54% and the specificities ranged from 75.0% to 100%. The overall diagnostic accuracy was highest for ComTMJ (64.3%), followed by LatTMJ (59.5%). The intraobserver reliability was good for one observer and excellent for the other, and the interobserver reliability was fair or moderate. Conclusion Panoramic TMJ radiography demonstrated limited diagnostic accuracy and acceptable reliability in detecting bony lesions of the TMJ, although it was better than conventional panoramic radiography.

Background and Objectives: Bromelain is a mixture of protease obtained from pineapple fruits or stems. Even though the biological mechanism of action of bromelain has not been completely understood, it is well known that bromelain possesses anticancer, anti-inflammatory and immunomodulatory effects. This study investigated the anti-inflammatory effects of bromelain on lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs). Materials and Methods: Cell viability after bromelain treatment was measured using WST-1 assay. We exposed hDPCs to 5 µg/mL of LPS with 2.5 or 5 µg/mL of bromelain. We performed reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay to detect interleukin-1β, interleukin-6, and interleukin-8 levels. Western blots were used to detect intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) levels. Immunofluorescence staining and Western blots were used to determine bromelain’s anti-inflammatory mechanism. We also performed alkaline phosphatase and Alizarin red staining to verify mineralization nodule formation. Results: Bromelain at 2.5, 5, 10, or 20 µg/mL did not affect the viability of hDPCs significantly. LPS increased interleukin-1β, interleukin-6, interleukin-8, ICAM-1 and VCAM-1 expression in hDPCs. Bromelain significantly decreased interleukin-1β, interleukin-6, interleukin-8, ICAM-1, and VCAM-1 levels in hDPCs, which were stimulated by LPS. Bromelain treatment significantly reduced p65 phosphorylation in the cytoplasm and the nucleus. It also significantly decreased phosphorylation levels of extracellular signal-related kinases (ERK) and p38 mitogen-activated protein kinases (p38). Bromelain also promoted ALP activity and mineralized nodule formation. Conclusions: Bromelain inhibits the expression of inflammatory cytokines in LPS-stimulated hDPCs. The inhibitory effect of bromelain on inflammatory mediators is related to decreased NF-κB and the MAPK pathway. Therefore, bromelain might have the potential to be used for regenerative endodontics, including vital pulp therapy.