Apelin as a new therapeutic target for COVID-19 treatment.

BACKGROUND: Apelin is an endogenous neuropeptide that binds to the G-protein-coupled receptor (APJ) and participates in a variety of physiological processes in the heart, lungs, and other peripheral organs. Intriguingly, [Pyr1]-Apelin-13, a highly potent pyroglutamic form of apelin, has the potential to bind to and be degraded by angiotensin-converting enzyme 2 (ACE2). ACE2 is known to operate as a viral receptor in the early stages of severe acute respiratory coronavirus (SARS-CoV-2) infection. AIM: This study aimed to determine if apelin protects against SARS-CoV-2 infection by inhibiting ACE2 binding to SARS-CoV-2 spike protein. DESIGN AND METHODS: To determine whether [Pyr1]-Apelin-13 inhibits ACE2 binding to the SARS-CoV-2 spike protein (S protein), we performed a cell-to-cell fusion assay using ACE2-expressing cells and S protein-expressing cells and a pseudovirus-based inhibition assay. We then analyzed publicly available transcriptome data while focusing on the beneficial effects of apelin on the lungs. RESULTS: We found that [Pyr1]-Apelin-13 inhibits cell-to-cell fusion mediated by ACE2 binding to the S protein. In this experiment, [Pyr1]-Apelin-13 protected human bronchial epithelial cells, infected with pseudo-typed lentivirus producing S protein, against viral infection. In the presence of [Pyr1]-Apelin-13, the level of viral spike protein expression was also reduced in a concentration-dependent manner. Transcriptome analysis revealed that apelin may control inflammatory responses to viral infection by inhibiting the nuclear factor kappa B pathway. CONCLUSION: Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.

Assessment of Pain Onset and Maximum Bearable Pain Thresholds in Physical Contact Situations.

With the development of robot technology, robot utilization is expanding in industrial fields and everyday life. To employ robots in various fields wherein humans and robots share the same space, human safety must be guaranteed in the event of a human-robot collision. Therefore, criteria and limitations of safety need to be defined and well clarified. In this study, we induced mechanical pain in humans through quasi-static contact by an algometric device (at 29 parts of the human body). A manual apparatus was developed to induce and monitor a force and pressure. Forty healthy men participated voluntarily in the study. Physical quantities were classified based on pain onset and maximum bearable pain. The overall results derived from the trials pertained to the subjective concept of pain, which led to considerable inter-individual variation in the onset and threshold of pain. Based on the results, a quasi-static contact pain evaluation method was established, and biomechanical safety limitations on forces and pressures were formulated. The pain threshold attributed to quasi-static contact can serve as a safety standard for the robots employed.