Environmental toxicology of bisphenol A: Mechanistic insights and clinical implications on the neuroendocrine system.

Bisphenol A (BPA) is a widely used environmental estrogen found in a variety of products, including food packaging, canned goods, baby bottle soothers, reusable cups, medical devices, tableware, dental sealants, and other consumer goods. This substance has been found to have detrimental effects on both the environment and human health, particularly on the reproductive, immune, embryonic development, nervous, endocrine, and respiratory systems. This paper aims to provide a comprehensive review of the effects of BPA on the neuroendocrine system, with a primary focus on its impact on the brain, neurons, oligodendrocytes, neural stem cell proliferation, DNA damage, and behavioral development. Additionally, the review explores the clinical implications of BPA, specifically examining its role in the onset and progression of various diseases associated with the neuroendocrine metabolic system. By delving into the mechanistic analysis and clinical implications, this review aims to serve as a valuable resource for studying the impacts of BPA exposure on organisms.

The 40 kDa Linear Polyethylenimine Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection by Blocking Its Attachment to Permissive Cells.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in pigs worldwide. The causative agent is the PRRS virus (PRRSV). In this study, we explored polyethylenimine (PEI), a cationic polymer with different forms (linear or branched), to inhibit the replication of PRRSV. Our results demonstrate that the linear but not the 40 kDa branched PEI, or the 25 kDa linear PEI, were well tolerated in cultured cells and exhibited a broad-spectrum inhibition of heterogeneous PRRSV-2 isolates in both MARC-145 cells and primary porcine pulmonary alveolar macrophages (PAMs). Further analysis suggests that PEI could prevent the attachment of PRRSV virions to the susceptible cells. Notably, PEI had a minimal effect on PRRSV internalization in MARC-145 cells, whereas PEI promoted the internalization of PRRSV virions in PAMs, which suggests that these two types of cells might have different internalization processes of PRRSV virions. In conclusion, our data demonstrate that PEI could be used as a novel inhibitor against PRRSV.

Oral Microbiome Alterations Associated with Early Childhood Caries Highlight the Importance of Carbohydrate Metabolic Activities.

Globally, dental caries is the most prevalent chronic oral disease and affects roughly half of all children. The aim of this report was to use metagenomic analyses to investigate the relationship between the oral microbiome and caries in preschool children. A total of 25 preschoolers, aged 3 to 5 years old with severe early childhood caries (ECC), and 19 age-matched, caries-free children as controls were recruited. Saliva samples were collected from the participants and were subjected to metagenomic analyses, whereby the oral microbial communities were investigated. The metagenomic analyses revealed substantial microbiota differences between the two groups, indicating apparent shifts of the oral microbiome present in the ECC group. At the species level, the ECC-enriched microbes included Prevotella amnii, Shuttleworthia satelles, Olsenella uli, and Anaeroglobus geminatus Interestingly, Actinomyces odontolyticus and Actinomyces graevenitzii exhibited apparent differences at the strain level but not the species level between the ECC and control groups. Functional examination showed that the ECC group displayed extensive alterations in metabolic genes/pathways/modules, including enriched functions in sugar metabolism. Finally, an SVM (support vector machine) classifier comprising seven species was developed and generated a moderately good performance in predicting caries onset (area under the receiver operating characteristic curve [AUC] = 78.33%). Together, these findings indicate that caries is associated with considerable changes in the oral microbiome, some of which can potentially be exploited as therapeutic targets or diagnostic markers. (This study has been registered at ClinicalTrials.gov under registration no. NCT02341352.)IMPORTANCE Dental caries is a highly prevalent oral disease that can lead to severe dental damage and may greatly compromise the quality of life of the affected individuals. Previous studies, including those based on 16S rRNA gene, have revealed that the oral microbiota plays a prominent role in development of the disease. But the approach of those studies was limited in analyzing several key microbiome traits, including species- or strain-level composition and functional profile. Here, we performed metagenomic analyses for a cohort of preschool children with or without caries. Our results showed that caries was associated with extensive microbiota differences at various taxonomic and functional levels. Some caries-associated species had not been previously reported, some of which may have significant clinical implications. A microbiome gene catalogue from children with caries was constructed for the first time. The results demonstrated that caries is associated with alterations of the oral microbiome, including changes in microbial composition and metabolic functional profile.

A metagenomic study of the gut microbiome in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease. METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD. RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ. CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

Tongue Coating and the Salivary Microbial Communities Vary in Children with Halitosis.

Halitosis is a common symptom mainly caused by microbial activities in the oral cavity. Here, we used 16S rRNA gene pyrosequencing and metagenomic sequencing to examine oral microbial compositions and their functional variations in children with halitosis. We found that the tongue coating of subjects with halitosis had greater bacterial richness than those of healthy subjects. The relative abundance and prevalence of Leptotrichia wadei and Peptostreptococcus stomatis were higher in tongue coating samples from children with halitosis than those from children without halitosis; Prevotella shahii had higher relative abundance and prevalence in saliva samples from children with halitosis. We present the first comprehensive evaluation of the co-occurrence networks of saliva and tongue coating communities under healthy and halitosis conditions, and investigated patterns of significant differences between these communities. Moreover, we observed that bacterial genes associated with responses to infectious diseases and terpenoid and polyketide metabolism were enriched in subjects with halitosis, but not in healthy subjects. Hydrogen sulphide (H2S)-related metabolic pathways suggested that there was higher microbial production and less usage of H2S in subjects with halitosis. Thus, the mechanism of halitosis was implied for the first time via metagenomic sequencing.