High-intensity Focused Ultrasound-A New Choice to Conduct Pulmonary Artery Denervation.

This research aimed to explore whether high-intensity focused ultrasound (HIFU) could conduct pulmonary artery denervation (PADN). HIFU was performed in pulmonary arteries of 6 normotensive rabbits at dose of 250W, 6 times for each rabbit, and an additional 6 rabbits served as controls. Then ATEPH was induced in both groups by intravenous infusion of autogeneic thrombus. Hemodynamics and ultrasonography parameters were measured by right heart catheter and echocardiography pre- and post-establishment of ATEPH models in both groups. Histological analysis and immunohistochemistry of tyrosine hydroxylase (TH) were also performed. After PADN procedures, 5 rabbits were successfully conducted PADN, of which ablation zone was also observed in right auricle or right lung in 4 rabbits. Ablation zone was detected only in right lung in 1 rabbit. Compared with control group, milder right heart hemodynamic changes were found in PADN group, accompanied by improved ultrasound parameters in PADN group. HIFU can acutly damage SNs around pulmonary artery successfully, which may be a new choice to conduct PADN. However, the accuracy of HIFU with PADN needs to be improved.

Beyond traditional methods: Unveiling the skin whitening properties of Rhein-Embedded PROTACs.

Proteolysis Targeting Chimeras (PROTAC) technology has emerged as a promising approach for targeted protein degradation. In this study, we focused on tyrosinase (TYR), a key enzyme involved in melanin synthesis and pigmentation. For this target, we designed and synthesized a series of PROTACs (D3-D9), employing Rhein as the target protein-ligand. Through some experimental tests, we made a significant discovery. Preliminary experimental results show that the most promising compound (D6) demonstrated the ability to degrade MITF and inhibit the expression and TYR in B16-F10 cells, effectively suppressing melanogenesis in zebrafish. Notably, at equivalent concentrations, the whitening effect of D6 surpassed that of its precursor Rhein and was even comparable to that of the well-established whitening agent, ß-arbutin. Validating experiments further revealed that the action of D6 was reliant on the E3 ligand, indicating its capacity to degrade TYR and MITF through the ubiquitination pathway. Whether D6 acts directly on TYR or MITF needs to be further explored. These compelling results underscore the tremendous whitening potential of D6, suggesting its suitability as a valuable lead for whitening agents and its potential to expand the range of whitening cosmetic products.

The progress of pulmonary artery denervation.

Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disease characterized by increased pulmonary arterial pressure and pulmonary arterioles remodeling. Some studies have discovered the relationship between sympathetic nerves (SNs) and pathogenesis of PAH. This review is aimed to illustrate the location and components of SNs in the pulmonary artery, along with different methods and effects of pulmonary artery denervation (PADN). Studies have shown that the SNs distributed mainly around the main pulmonary artery and pulmonary artery bifurcation. And the SNs could be destroyed by three ways: the chemical way, the surgical way and the catheter-based way. PADN can significantly decrease pulmonary arterial pressure rapidly, improve hemodynamic varieties, and then palliate PAH. PADN has been recognized as a prospective and effective therapy for PAH patients, especially for those with medication-refractory PAH. However, further enlarged clinical studies are needed to confirm accurate distribution of SNs in the pulmonary artery and the efficacy of PADN.