Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence byswitching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse ofcurrent clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drugresistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here,seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether andarteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisininsfailed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistantisolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptomesuggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantlyinhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating thatartemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantlyinhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo causedby both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potentialantifungal compounds against C. albicans infections by targeting at its hyphal development.

Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration in vivo and in vitro

Peri-implantitis are a major problem causing implant failure these days.Accordingly,anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue.Micro-arc oxidation(MAO)treatment is a way to form an oxidation film on the surface of metallic materials.The method shows good osteogenic properties but weak antibacterial effect.Therefore,we developed combined strategies to combat severe peri-implantitis,which included the use of a novel compound,PD,comprising dendrimers poly(amidoamine)(PAMAM)loading dimethylaminododecyl methacrylate(DMADDM)as well as MAO treatment.Here,we explored the chemical properties of the novel compound PD,and proved that this compound was successfully synthesized,with the loading efficiency and encapsulation efficiency of 23.91%and 31.42%,respectively.We further report the two-stage double benefits capability of PD+MAO:(1)in the first stage,PD+MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo;(2)in the second stage,PD+MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo.This study first reports the two-staged,double benefits of PD+MAO,and demonstrates its potential in clinical applications for inhibiting peri-implantitis,especially in patients with severe infection risk.