Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development / 国际口腔科学杂志·英文版

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance 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 and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

A novel variation of B allele is responsible for ABweak phonetype / 中国输血杂志

Objective To investigate the molecular basis of ABO gene in a patient with serologic ABO blood group discrepancy.Methods Serologic blood group identification,Coombs' test and antibody screening were detected with DG Gel Confirm cards,Neutral cards,Coombs cards by WADiana/8XT Compact Analyzer (from Diagnostic Grifols,S.A).The enhancer,promoter,exon 1 ～ 7 and their adjacent intron region of ABO gene were amplified by using polymerase chain reaction (PCR) method.Results The patient's red blood cells was determined as weak B phenotype showing two groups in gel and mixed field in tube with monoclonal anti-B,and A phenotype with monoclonal anti-A.DNA sequencing showed nine variants in ABO gene.One heterozygous variation in exon 6 (297A＞G) and eight heterozygous variations in exon 7 (467C＞T,526C ＞G,657C＞T,703G＞A,796C＞A,803G＞C,829G＞T 930G＞A) were identified and 829G＞T was the novel variant.Compared with Blood Group Antigen Gene Mutation Database,genotype of the patient was weak expression of A102/B101.Conclusion The novel variation of B allele is the main reason of Bweak phonetype in A102/B101 genotype.Serological and molecular biological detection help to understand the characteristics of blood group phenotype and genotype,provide the guidance for clinical transfusion strategies.