Gene expression profiling in the lung tissue of cynomolgus monkeys in response to repeated exposure to welding fumes

Many in the welding industry suffer from bronchitis, lung function changes, metal fume fever, and diseases related to respiratory damage. These phenomena are associated with welding fumes; however, the mechanism behind these findings remains to be elucidated. In this study, the lungs of cynomolgus monkeys were exposed to MMA-SS welding fumes for 229 days and allowed to recover for 153 days. After the exposure and recovery period, gene expression profiles were investigated using the Affymetrix GeneChip® Human U133 plus 2.0. In total, it was confirmed that 1,116 genes were up-or down-regulated (over 2-fold changes, P < 0.01) for the T1 (31.4 ± 2.8 mg/m3) and T2 (62.5 ± 2.7 mg/m3) dose groups. Differentially expressed genes in the exposure and recovery groups were analyzed, based on hierarchical clustering, and were imported into Ingenuity Pathways Analysis to analyze the biological and toxicological functions. Functional analysis identified genes involved in immunological disease in both groups. Additionally, differentially expressed genes in common between monkeys and rats following welding fume exposure were compared using microarray data, and the gene expression of selected genes was verified by real-time PCR. Genes such as CHI3L1, RARRES1, and CTSB were up-regulated and genes such as CYP26B1, ID4, and NRGN were down-regulated in both monkeys and rats following welding fume exposure. This is the first comprehensive gene expression profiling conducted for welding fume exposure in monkeys, and these expressed genes are expected to be useful in helping to understand transcriptional changes in monkey lungs after welding fume exposure

Bacterial microbiome of breast milk and child saliva from low-income Mexican-American women and children

BACKGROUND: The childhood salivary microbiome, which plays an important role in healthy development, may be influenced by breast milk consumption. The composition of the milk microbiome and the role it plays in the establishment of the infant microbiome are not well understood. METHODS: Here, we sequenced the bacterial 16S rRNA gene to characterize microbial communities in breast milk and 5-year-old child saliva from ten low-income, Mexican-American mother-child pairs with a high prevalence of obesity. RESULTS: Members of the genus Streptococcus dominated both milk and salivary microbial communities in most subjects. Staphylococcus was observed predominately in milk samples while Prevotella was more prevalent in child saliva. No statistically significant relationships were observed between maternal and child microbiomes or between child microbiome and BMI. However, pre-pregnancy BMI was correlated with both lower Streptococcus abundance (r = −0.67) and higher microbial diversity (r = 0.77) in breast milk (P < 0.05 for both). Diversity estimates were notably similar to data from other low-income cohorts or children. CONCLUSION: These findings contribute to the currently-limited state of knowledge regarding the breast milk and salivary microbiomes in mother-child pairs and may inform future studies seeking to elucidate the relationship between early-life microbial exposures and pediatric health

Infant colic: mechanisms and management

Infant colic is a commonly reported phenomenon of excessive crying in infancy with an enigmatic and distressing character. Despite its frequent occurrence, little agreement has been reached on the definition, pathogenesis or the optimal management strategy for infant colic. This Review aims to delineate the definitional entanglement with the Rome IV criteria, which were published in 2016, as the leading, most recent diagnostic criteria. Moreover, neurogenic, gastrointestinal, microbial and psychosocial factors that might contribute to the pathophysiology of infant colic are explored. This Review underlines that a comprehensive medical history and physical examination in the absence of alarm symptoms serve as guidance for the clinician to a positive diagnosis. It also highlights that an important aspect of the management of infant colic is parental education and reassurance. Management strategies, including behavioural, dietary, pharmacological and alternative interventions, are also discussed. Owing to a lack of large, high-quality randomized controlled trials, none of these therapies are strongly recommended. Finally, the behavioural and somatic sequelae of infant colic into childhood are summarized

Central nervous system myeloid cells as drug targets: current status and translational challenges

Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic