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.

The dynamic landscape of parasitemia dependent intestinal microbiota shifting and the correlated gut transcriptome during Plasmodium yoelii infection.

Malaria, caused by Plasmodium, is a global life-threatening infectious disease. However, the dynamic interactions between intestinal microbiota and host immunity during the infections are still unclear. Here, we investigated the change of intestinal microbiome and transcriptome during Plasmodium yoelii infection in mice. The mice were infected with P. yoelii through the intraperitoneal injection. The intestinal contents and tissues were collected at different time points along with the malaria procession and they were subjected to the microbiome and transcriptome sequencing and analysis respectively. The dynamic landscape of parasitemia-dependent intestinal microbiota and related host immunity were identified: (1) The diversity and composition of the intestinal microbiota represented a significant correlation with the Plasmodium infection; (2) Up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways, especially, naive CD4+ T cell differentiation to Th1/2 cells in the early immune response and Th17 cells in the later immune stage, T cell receptor (TCR) and B cell receptor (BCR) activation in the whole host immunity; (3) Host immune cells presented parasitemia phase-specific characteristics against P. yoelii infection; (4) There were significant associations between the parasitemia phase-specific microbiotas and the host immune response. Th1 cell differentiation was positively correlated with genera Moryella and specie Erysipelotrichaceae bacterium canine oral taxon 255, while negatively correlated with genera Ruminiclostridium. Th17 cell differentiation was related to the colonization of family Peptococcaceae, genera Lachnospiraceae FCS020 group, and specie Eubacterium plexicaudatum ASF492 and the reduction of family Bacteroidales BS11 gut group, genera Sutterella, and specie Parabacteroides distasonis str. 3776 D15 I. BCRs and TCRs were highly related with the family Bacteroidales BS11 gut group, genera Moryella, and specie Erysipelotrichaceae bacterium canine oral taxon 255, but negatively related with the genera Ruminiclostridium. Our results indicated a remarkable dynamic landscape and correlation of the parasitemia-dependent shifting of intestinal microbiota and immunity, suggesting the essential roles of intestinal microbiome on the modulation of host immunity against Plasmodium infection.

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.