Ligandomics: a paradigm shift in biological drug discovery

As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adverse effects, wide therapeutic indices, and low safety-related attrition rates. Therefore, ligandomics represents a paradigm shift to address the bottleneck of target discovery for biologics development

Recognition of host proteins by Helicobacter cysteine-rich protein C

Tetratricopeptide- and sel1-like repeat (SLR) proteins modulate various cellular activities, ranging from transcription regulation to cell-fate control. Helicobacter cysteine-rich proteins (Hcp) consist of several SLRs that are cross-linked by disulfide bridges and have been implicated in host/pathogen interactions. Using pull-down proteomics, several human proteins including Nek9, Hsp90, and Hsc71 have been identified as putative human interaction partners for HcpC. The interaction between the NimA-like protein kinase Nek9 and HcpC has been validated by ELISA and surface plasmon resonance. Recombinant Nek9 is recognized by HcpC with a dissociation constant in the lower micromolar range. This interaction is formed either directly between Nek9 and HcpC or via the formation of a complex with Hsc71. The HcpC homologue HcpA possesses no affinity for Nek9, suggesting that the reported interaction is rather specific for HcpC. These results are consistent with previous observations where Nek9 was targeted upon bacterial or viral invasion. However, further experiments will be required to show that the reported interactions also occur in vivo

On the causes of persistent apical periodontitis: a review.

Apical periodontitis is a chronic inflammatory disorder of periradicular tissues caused by aetiological agents of endodontic origin. Persistent apical periodontitis occurs when root canal treatment of apical periodontitis has not adequately eliminated intraradicular infection. Problems that lead to persistent apical periodontitis include: inadequate aseptic control, poor access cavity design, missed canals, inadequate instrumentation, debridement and leaking temporary or permanent restorations. Even when the most stringent procedures are followed, apical periodontitis may still persist as asymptomatic radiolucencies, because of the complexity of the root canal system formed by the main and accessory canals, their ramifications and anastomoses where residual infection can persist. Further, there are extraradicular factors -- located within the inflamed periapical tissue -- that can interfere with post-treatment healing of apical periodontitis. The causes of apical periodontitis persisting after root canal treatment have not been well characterized. During the 1990s, a series of investigations have shown that there are six biological factors that lead to asymptomatic radiolucencies persisting after root canal treatment. These are: (i) intraradicular infection persisting in the complex apical root canal system; (ii) extraradicular infection, generally in the form of periapical actinomycosis; (iii) extruded root canal filling or other exogenous materials that cause a foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue healing of the lesion. This article provides a comprehensive overview of the causative factors of non-resolving periapical lesions that are seen as asymptomatic radiolucencies post-treatment