Efficacy and mechanism of Baicao Fuyanqing suppository on mixed vaginitis based on 16S rRNA and metabolomics.

Background: Mixed vaginitis is the infection of the vagina by at least two different pathogens at the same time, both of which contribute to an abnormal vaginal environment leading to signs and symptoms. Baicao Fuyanqing suppository (BCFYQ) is a Miao ethnomedicine, used to treat various vaginitis. The aim of this study was to investigate the efficacy and possible mechanism of BCFYQ in the treatment of mixed vaginitis based on 16S rRNA high-throughput sequencing and metabonomics. Methods: Escherichia coli and Candida albicans were used to establish mixed vaginitis model in SD rats. Three groups of low, medium and high doses (0.18/0.36/0.64 g.kg-1) were established, and administered vaginally once a day for 6 consecutive days. After the last administration, vaginal pH and IL-1ß, IL-2, IL-13 and IgA levels were measured, and the vaginal tissue was examined pathologically. In addition, the vaginal flora was characterised by 16S rRNA, and endogenous metabolites in the vaginal tissue were detected by UHPLC-Q-Exactive MS. Results: Compared with the model group, BCFYQ can reduce the vaginal pH of rats, make it close to the normal group and improve the damaged vaginal epithelial tissue. The results of ELISA showed that BCFYQ decreased the levels of IL-1 ß and IL-2 and increased the levels of IL-13 and IgA (P<0.05). In addition, BCFYQ may increase the abundance of vaginal flora, especially Lactobacillus. The differential metabolite enrichment pathway suggests that the therapeutic mechanism of BCFYQ is mainly related to lipid metabolism and amino acid metabolism. Conclusion: Our research shows that BCFYQ has a good therapeutic effect on mixed vaginitis. It repairs the damaged vaginal mucosa by regulating the vaginal flora and lipid metabolism disorders to improve the local immune function of the vagina and inhibit the growth and reproduction of pathogens.

Contribution of gene polymorphisms on 3p25 to salivary gland carcinoma, ameloblastoma, and odontogenic keratocyst in the Chinese Han population.

OBJECTIVE: This study aimed to investigate the contribution of gene polymorphisms in 3p25 to salivary gland carcinoma (SGC), ameloblastoma (AM), and odontogenic keratocyst (OKC) in the Chinese Han population. STUDY DESIGN: Sixteen tag-single nucleotide polymorphisms (SNPs) within 5 genes (SYN2, TIMP4, PPARG, RAF1, and IQSEC1) in 3p25 were genotyped in 411 individuals with or without SGC, AM, and OKC. Genotype, clinical phenotype, and bioinformatics analyses were performed to evaluate the function of candidate SNPs. RESULTS: SYN2-rs3773364, TIMP4-rs3755724, PPARG-rs10865710, and PPARG-rs1175544 were related to decreased SGC susceptibility, whereas IQSEC1-rs2600322 and IQSEC1-rs2686742 decreased and increased AM risk, respectively. Stratification analysis revealed that the significance of the identified SNPs was stronger in females or individuals younger than 46 years in SGC. PPARG-rs10865710 and PPARG-rs1175544 were associated with lower lymph node metastasis. SYN2-rs3773364 and PPARG-rs1175544 were associated with favorable SGC patient survival. Functional assessments linked PPARG-rs1175544 to PPARG expression regulation. Linkage disequilibrium analysis revealed a haplotype (SYN2-rs3773364-A, TIMP4-rs3817004-A, and TIMP4-rs3755724-C) associated with decreased susceptibility to SGC. Generalized multifactor dimensionality reduction analysis indicated the gene-gene interactions among IQSEC1, TIMP4, and PPARG in SGC, AM, and OKC progression. CONCLUSIONS: These variants play important roles in the progression of SGC, AM, and OKC in the Chinese Han population and may be considered biomarkers for early diagnosis and prognosis prediction.

A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Genetic associations between gene polymorphisms on 3p25 and oral squamous cell carcinoma.

OBJECTIVES: To evaluate the association of SYN2, PPARG, RAF1, TIMP4, and IQSEC1 polymorphisms in 3p25 with oral squamous cell carcinoma (OSCC) in the Chinese Han population. SUBJECTS AND METHODS: Genomic DNA was extracted from 494 subjects with or without OSCC. Basic information on the subjects, clinical data, and prognoses were collected. Fifteen candidate single nucleotide polymorphisms (SNPs) were selected and genotyped. The statistical analyses included descriptive statistics, logistic regression, survival, and functional annotation was performed. RESULTS: IQSEC1-rs2686742 correlated with OSCC occurrence. In addition, RAF1-rs1051208, PPARG-rs10865710, PPARG-rs3856806, IQSEC1-rs2686742, PPARG-rs1175544, IQSEC1-rs9211, and IQSEC1-rs2600322 were significantly associated with the clinical characteristics of patients with OSCC. The log-rank test showed that IQSEC1-rs2600322 may play an important role in the survival of patients with OSCC. The Cox regression analysis suggested that PPARG-rs10865710, PPARG-rs7649970, IQSEC1-rs9211, IQSEC1-rs2600322, and IQSEC1-rs12487715 influenced survival outcomes. The functional annotation indicated that the transcript levels of IQSEC1 were upregulated in head and neck squamous cell carcinoma tissues, whereas PPARG gene transcription was downregulated. CONCLUSIONS: IQSEC1-rs2686742 may be closely associated with OSCC onset. Multiple SNPs in IQSEC1 and PPARG genes correlated with the clinical characteristics of OSCC, among which PPARG-rs10865710, IQSEC1-rs9211, and IQSEC1-rs2600322 were associated with cancer prognosis.

Fermented Rosa Roxburghii Tratt Juice Alleviates High-Fat Diet-Induced Hyperlipidemia in Rats by Modulating Gut Microbiota and Metabolites.

Hyperlipidemia endangers human health and has become a significant public health problem. This study aimed to investigate the mechanism of the hypolipidemic effects of Fermented Rosa roxburghii Tratt juice (FRRT) on hyperlipidemic rats and a new hypolipidemic intervention strategy was disclosed. The study revealed 12 weeks FRRT treatment significantly decreased the body weight, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), while high-density lipoprotein cholesterol (HDL-c) increased. We integrated the 16S rDNA sequencing and metabolomic profiling to evaluate the changes in the gut microbiota and metabolites. Significant changes in microbial composition accompanied marked changes in 56 feces metabolites. The results showed that FRRT could decrease the ratio of Firmicutes to Bacteroidetes, while increase the abundance of some bacterial genera (Prevotella, Paraprevotellaceae_Prevotella, Ruminococcus, Oscillospira). Metabolomics analysis displayed that the metabolisms of bile acid, amino acid and lipid were significantly affected by FRRT. Correlation analysis suggest that the reductions in serum lipids by FRRT are associated with the gut microbial community and their associated metabolites (amino acid metabolites, bile acid metabolites, and lipid metabolites). This study confirmed FRRT could be used as a new dietary and therapeutic strategy to dyslipidemia by improving the gut microbiota dysbiosis, metabolomic disorders and regulating the dyslipidemia. Our study also extended the understanding of the relationship between gut microbiota, metabolites, and lipid-lowering functions.

The pharmaceutical excipient PEG400 affect the absorption of baicalein in Caco-2 monolayer model by interacting with UDP-glucuronosyltransferases and efflux transport proteins.

The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert substances in clinical safety evaluations. However, a large number of studies have shown that pharmaceutical excipients regulate the metabolism and transport of drugs in the body and improve the bioavailability. The pharmaceutical excipient polyethylene glycol 400 (PEG400) as a good solubilizer and surfactant has the potential to improve the bioavailability of drugs. The combined action of UDP-glucuronosyltransferases (UGTs) and efflux transport proteins is responsible for the intestinal disposition and poor bioavailability of baicalein. Our aim is to study the effect of PEG400 on the absorption of baicalein on the Caco-2 monolayer, and confirm the interaction of PEG400 with UGTs (UGT1A8 and UGT1A9) and efflux transports. We initially found that baicalein in the Caco-2 monolayer would be metabolized into glucuronide conjugates BG and B6G under the action of UGT1A8 and UGT1A9 on the endoplasmic reticulum membrane, and then mainly excreted to different sides by acting of MRP and BCRP. The addition of PEG400 significantly accelerated the metabolism of B in Caco-2 cells and increased the penetration of BG and B6G. Furthermore, PEG400 also significantly decreased the efflux ratio of BG and B6G, which was the evidence of the interaction with the efflux transporters. In the in vitro intestinal microsome regeneration system, low concentration PEG400 decreased the Km value of UGT1A8 and UGT1A9 (key enzymes that mediate the production of BG and B6G); high concentration PEG400 enhanced the Vmax value of UGT1A8 and UGT1A9. In conclusion, our results determined that PEG400 interacted with some UGTs and efflux transporters, which were the main factors affecting the absorption of baicalein.