The Gut Mycobiome Characterization of Gestational Diabetes Mellitus and Its Association With Dietary Intervention.

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The active interface between gut microbiota and diet contributes to metabolic homeostasis in GDM. However, the contributions of gut mycobiome have been neglected. Here, we profiled the gut fungi between GDM and healthy subjects at two time points and investigate whether variations in gut mycobiome correlate with key features of host metabolism and diet management in this observational study. We identified that Hanseniaspora, Torulaspora, Auricularia, Alternaria, and Candida contributed to GDM patient clustering, indicating that these fungal taxa are associated with abnormal blood glucose levels, and the causality needs to be further explored. While Penicillium, Ganoderma, Fusarium, Chaetomium, and Heterobasidion had significant explanatory effects on healthy subject clustering. In addition, spearman analysis further indicated that blood glucose levels were negatively correlated with polysaccharide-producing genera, Ganoderma, which could be reshaped by the short-term diet. The Penicillium which was negatively correlates with metabolic parameters, also exhibited the antimicrobial attribute by the fungal-bacterial interaction analysis. These data suggest that host metabolic homeostasis in GDM may be influenced by variability in the mycobiome and could be reshaped by the diet intervention. This work reveals the potential significance of the gut mycobiome in health and has implications for the beneficial effects of diet intervention on host metabolic homeostasis through regulating gut fungal abundance and metabolites.

The Gut Microbial Signature of Gestational Diabetes Mellitus and the Association With Diet Intervention.

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The link between microbiota and diet management contributes to metabolic homeostasis in GDM. Therefore, it is crucial to understand the structure of the gut microbiota in GDM and to explore the effect of dietary management on the microbiota structure. In this study, we analyzed the composition of the gut microbiota between 27 GDM and 30 healthy subjects at two time points using Illumina HiSeq 2500 platform. The taxonomy analyses suggested that the overall bacteria clustered by diabetes status, rather than diet intervention. Of particular interest, the phylum Acidobacteria in GDM was significantly increased, and positively correlated with blood glucose levels. Moreover, Partial least-squares discriminant analysis (PLS-DA) revealed that certain genera in the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Lentisphaerae characterized the GDM gut microbiota. Correlation analysis indicated that blood glucose levels and BMI index were correlated with the relative abundance of SCFAS-producing genera. Through the comparison between the GDM and healthy samples with or without diet intervention, we discovered that the role of short-term diet management in GDM processes is associated with the change in the Firmicutes/Bacteroidetes ratio and some specific taxa, rather than an alternative gut microbial pattern. Our study have important implications for understanding the beneficial effects of diet intervention on the specific gut microbiota and thus possibly their metabolism in pregnant women with GDM.

[Expression, roles and therapy target values of CD24 in oral squamous cell carcinoma].

OBJECTIVE: To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy. METHODS: Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues. Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells, oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA) and CD24 antibody on CD24 expression, and the proliferation and tumorsphere formation capacity of these two cell lines. RESULTS: CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05), as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05). CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05). Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05). Among them ATRA at least involved partially in the proliferation by down-regulating the CD24 expression (P<0.05), while CD24 antibody blocking had no effect on the CD24 expression. CONCLUSION: CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells. Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target.

[Expression of nuclear transcription factor kappaB in hamster buccal pouch carcinogenesis].

OBJECTIVE: To study the expression and significance of p65 which is an important subtype of nuclear transcription factor kappaB (NF-kappaB) and its inhibitory protein IkappaBalpha in malignant transformation of hamster buccal mucosa. METHODS: The animal model of malignant transformation in hamster buccal mucosa induced by DMBA (0.5%) was established. Twelve paired specimens including normal buccal mucosa, epithelial hyperplasia, epithelial dysplasia and squamous cell carcinoma (SCC) were subjected to Western blot for the analysis of p65. The expression of IkappaBalpha was observed in 22 normal buccal epithelia, 20 hyperplasia epithelia, 35 dysplasia epithelia and 23 SCC by immunohistochemical evaluation. RESULTS: In normal buccal epithelia and hyperplasia epithelia, the expression of p65 was not obvious, and there was no significant difference between them (P > 0.05). The expression of IkappaBalpha existed at large, but mostly localizing in cell cytoplasmic staining in the basal cell layer and bottom of spinocelluar layer. With the occurrence of epithelia dysplasia, the expression of p65 gradually increased, comparing with normal buccal epithelia and hyperplasia epithelia (P < 0.01). But the positive intensity of IkappaBalpha was dramatically decreased (P < 0.05). In SCC, p65 expressed at a higher level comparing with normal buccal mucosa and dysplasia (P < 0.01), while the staining of IkappaBalpha was feedbackly higher comparing with dysplasia (P < 0.01) and even with normal buccal mucosa (P < 0.01). CONCLUSION: NF-kappaB p65 is strongly activated in malignant transformation of hamster buccal mucosa. The abnormal expression of p65 and IkappaBalpha, especially the ascending expression of p65 as well as the descending expression of IkappaBalpha in dysplasia may be an early event during oral carcinogenesis, and can be used as biomarkers for supervising oral malignancy.