A concise chemoenzymatic total synthesis of neutral Globo-series glycosphingolipids Globo A and Globo B, and Forssman and para-Forssman antigens.

Globo A is a neutral Globo-series glycosphingolipid (GSL) that shows natural properties of a cytotoxicity receptor NKp44 binding ligand. The highly complex heptasaccharide glycan structure of Globo A combined with its biological profile provides a unique target for the development of a synthetic method to facilitate its bioactivity studies. Here, a concise chemoenzymatic route to the synthesis of Globo A and its α1,3-galactose-linked congener Globo B is reported. The key to success was the use of a synthetic azido ß-Globo H sphingosine (Globo H-ßSph) as an acceptor substrate and two glycosyl transferases, an α1,3-N-acetylgalactosaminyltransferase from Helicobacter mustelae (BgtA) and a human blood group B α1,3-galactosyltransferase (h1,3GTB), for stereoselective construction of the terminal α1,3-GalNAc and α1,3-Gal linkages, respectively. The azido-Sph lipid sidechain is further elaborated by reduction and a chemoselective N-acylation to complete the total synthesis of the neutral Globo-series GSLs. In addition, the synthesis of Forssman and para-Forssman antigens were prepared. The strategy may be suitable for accessing other complex GSLs and related lipid-modified GSL derivatives.

The Antibacterial and Remineralization Effect of Silver-Containing Mesoporous Bioactive Glass Sealing and Er-YAG Laser on Dentinal Tubules Treated in a Streptococcus mutans Cultivated Environment.

The aim of this study was to evaluate the remineralization and antibacterial effect of silver-containing mesoporous bioactive glass (MBG-Ag) sealing combined with Er:YAG laser irradiation on human demineralized dentin specimens in a Streptococcus mutans cultivated environment. A total of 48 human dentin specimens were randomly divided into four groups. The characteristics of MBG-Ag and the occlusion efficiency of the dentinal tubules were analyzed using X-ray diffraction patterns, Fourier-transform infrared spectroscopy, scanning electron microscope images and energy dispersive X-ray spectroscopy. Moreover, the antibacterial activity against Streptococcus mutans was evaluated by colony formation assay. The results showed that the dentin specimens with Er:YAG laser irradiation can form a melted occlusion with a size of 3-4 µm. MBG-Ag promoted the deposition of numerous crystal particles on the dentinal surface, reaching the deepest penetration depth of 70 µm. The results suggested that both MBG-Ag and laser have the ability to enhance the remineralization and precipitation of hydroxyapatite crystals. While the results showed that MBG-Ag sealing combined with the thermomechanical subablation mode of Er:YAG laser irradiation-induced dense crystalline deposition, reaching a penetration depth of more than 300 µm, silver nanoparticles without good absorption of the Er:YAG laser resulted in a heterogeneous radiated surface. Er:YAG laser irradiation with a low energy and pulse rate cannot completely inhibit the growth of S. mutans, but MBG-Ag sealing reached the bactericidal concentration. It was concluded that the simultaneous application of MBG-Ag sealing and Er:YAG laser treatment can prevent the drawbacks of their independent uses, resulting in a superior form of treatment for dentin hypersensitivity.

Antibacterial silver-containing mesoporous bioglass as a dentin remineralization agent in a microorganism-challenged environment.

OBJECTIVES: To provide a suitable material capable of treating dentin hypersensitivity with simultaneous active antibacterial activity. METHODS: We developed silver-containing mesoporous bioglass (MBG-Ag) using the sol-gel technique, which loaded silver nanoparticles as promising bacteriostatic agents. The MBG-Ag with a powder-to-liquid ratio of 0.5 g: 0.01 mL were uniformly mixed with 20 %, 30 %, and 40 % phosphoric acid for 5, 10 and 20 min, respectively. Furthermore, we evaluated the occlusion efficiency, depth of penetration, and antibacterial activity of dentin specimens by simulating a Streptococcus mutans (S. mutans) infection on dentin. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the powders and assess tubule occlusion. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the MBG-Ag against S. mutans were determined via time-killing curves and colony formation assays. RESULTS: The MIC ranged from 2.5 to 5 mg/mL, and the MBC ranged from 5 to 10 mg/mL. The highest dentinal tubule occlusion efficiency was over 90 %. The colony formation assay confirmed that 5 mg/mL MBG-Ag mixed with phosphoric acid reached the bactericidal concentration. CONCLUSION: The MBG-Ag 40PA achieved a good occlusion efficiency and deep apatite precipitation in a short time, implying its superiority in clinical applications. CLINICAL RELEVANCE: The MBG-Ag formed in this study is a promising candidate for the treatment of demineralized dentin and confers antibacterial effects on the remineralized dentin surface against S. mutans.

Up-regulation of PYK2/PKCα-dependent haem oxygenase-1 by CO-releasing molecule-2 attenuates TNF-α-induced lung inflammation.

BACKGROUND AND PURPOSE: Haem oxygenase-1 (HO-1) could provide cytoprotection against various inflammatory diseases. However, the mechanisms underlying the protective effect of CO-releasing molecule-2 (CORM-2)-induced HO-1 expression against TNF-α-induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown. EXPERIMENTAL APPROACH: CORM-2-induced HO-1 protein and mRNA expression, and signalling pathways were determined by Western blot and real-time PCR, coupled with respective pharmacological inhibitors or transfection with siRNAs. The effect of CORM-2 on TNF-α-induced increase in leukocyte counts in BAL fluid and VCAM-1 expression in lung was determined by cell counting and Western blot analysis. KEY RESULTS: CORM-2 attenuated the TNF-α-induced pulmonary haematoma, VCAM-1 expression and increase in leukocytes through an up-regulation of HO-1 in mice; this effect of CORM-2 was reversed by the HO-1 inhibitor zinc protoporphyrin IX. Furthermore, CORM-2 increased HO-1 protein and mRNA expression as well as the phosphorylation of PYK2, PKCα and ERK1/2 (p44/p42 MAPK) in HPAEpiCs; these effects were attenuated by their respective pharmacological inhibitors or transfection with siRNAs. Inhibition of PKCα by Gö6976 or Gö6983 attenuated CORM-2-induced stimulation of PKCα and ERK1/2 phosphorylation but had no effect on PYK2 phosphorylation. Moreover, inhibition of PYK2 by PF431396 reduced the phosphorylation of all three protein kinases. Finally, PYK2/PKCα/ERK1/2-mediated stimulation of activator protein 1 was shown to play a key role in CORM-2-induced HO-1 expression via an up-regulation of c-Fos mRNA. CONCLUSIONS AND IMPLICATIONS: CORM-2 activates a PYK2/PKCα/ERK1/2/AP-1 pathway leading to HO-1 expression in HPAEpiCs. This HO-1/CO system might have potential as a therapeutic target in pulmonary inflammation.

Using positive images to manage resistance-to-care and combative behaviors in nursing home residents with dementia: A pilot study.

This pilot study attempted to reduce resistance-to-care (RTC) and combative behaviors in nursing home residents with dementia by eliciting their positive affect. Four female residents with dementia were recruited from a nursing facility. Each resident was involved in one intervention trial and one control trial. The response of the residents was assessed by the Agitated Behavior Scale and the Observational Measurement of Engagement Tool. The distress level of the certified nursing assistants (CNAs) delivering the care was reported through the Distress Thermometer. Results showed that the residents displayed fewer behavioral symptoms in the intervention trial than in the control trial. The CNAs reported less distress in the intervention trial than in the control trial. These preliminary findings suggest that it might be feasible to use positive images to reduce residents' behavioral symptoms and decrease the distress of CNAs.

Hypertrophic osteopathy associated with disseminated metastases of renal cell carcinoma in the dog: a case report.

A 6-year-old, mixed breed, intact male dog showed signs of left carpal joint swelling and weakness of the forelimbs one month before presentation. The symptoms gradually progressed to bilateral carpal and tarsal joint swelling and tetraparalysis. There were a number of radiographically identified lytic-proliferative bone lesions noted on the axial skeleton. Hypertrophic osteopathy of the metacarpi and all distal long bones was also evident. Because of the deteriorating quality of life and guarded prognosis, the patient was euthanized and a complete necropsy was performed. Renal cell carcinoma, with metastasis to the lung, thoracic vertebrae, ribs, and the right adrenal gland, was diagnosed. To our knowledge, renal cell carcinoma with bone metastases and hypertrophic osteopathy has not been reported in dogs.