Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during Pseudomonas aeruginosa Infection.

The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises 8-oxo-7,8-dihydroguanine lesions induced in DNA by reactive oxygen species, has been linked to the pathogenesis of lung diseases associated with bacterial infections. A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, we report that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during Pseudomonas aeruginosa (PA14) infection, which is mediated by the KRAS-ERK1-NF-κB signaling pathway. Furthermore, SU0268 induces the release of type I IFN by the mitochondrial DNA-cGAS-STING-IRF3-IFN-ß axis, which decreases bacterial loads and halts disease progression. Collectively, our results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection.

Emergency protocol in the dental clinic: Assessing medical emergency training requirements and guidelines for dentists.

BACKGROUND: Medical emergencies are an unavoidable reality affecting dental practices. This review synthesizes and examines the guidelines offered by governmental and professional organizations. TYPES OF STUDIES REVIEWED: Licensing agencies and professional associations were chosen as organizations of focus based on legal authority, high professional regard, or both. International and interprofessional organizational counterparts were chosen as points of comparison. In total, 11 organizations were examined. Guidelines reported were compiled by examination of documents published on official agency websites and in associated peer-reviewed journals. RESULTS: Guidelines for the handling of medical emergencies in the dental clinic vary in level of detail and scope among sources. Licensing agencies provide basic requirements for training, encouraging oral health care providers to develop and integrate their own emergency response plans. Professional associations provide extensive detail on instruction in medical emergency management. Both licensing agencies and professional associations provide lists of emergency medications and equipment, with varying levels of instruction on drug maintenance and organization. Professional associations emphasize regular review of training and office emergency drills. CONCLUSION: Oral health care professionals are provided with basic and required elements of medical emergency training by licensing agencies. They may seek out recommended, but not required, instruction from professional associations. Although guidance is provided, literature on protocol instituted in dental practices is limited. Further research is necessary to determine the oral health care community's approach to emergency management. PRACTICAL IMPLICATIONS: Providers must be prepared to handle medical emergencies that they encounter. Accessible and understandable guidelines are crucial to safe dental practice.

Calling for a united action to defeat COVID-19.

The widespread and lingering pandemic of COVID-19 is partly due to disjointed international countermeasures and policies enforced by different countries. We have been witnessing disparity in policies and measures in different countries and regions: some are in much better control than others. To effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crises, and life and economic losses.