The Infant Microbiome and Its Impact on Development of Food Allergy.

The prevalence of food allergy (FA) has been increasing over the past few decades; recent statistics suggest that FA has an impact on up to 10% of the population and 8% of children. Although the pathogenesis of FA is unclear, studies suggest gut microbiome plays a role in the development of FA. The gut microbiome is influenced by infant feeding method, infant diet, and maternal diet during lactation. Breastfeeding, Mediterranean diet, and probiotics are associated with commensal gut microbiota that protect against FA. This area of research is essential to discovering potential preventive methods or therapeutic targets against FA.

HIF-3α1 promotes colorectal tumor cell growth by activation of JAK-STAT3 signaling.

Hypoxic environment is critical in colorectal cancer (CRC) development. Most studies have mainly focused on hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxic transcription factors in CRC development and progression. However, the role of HIF-3α in CRC is not clear. Here we found that HIF-3α protein was increased in colorectal tumors from both mouse models and human patients. Moreover, increased HIF-3α expression was correlated with decreased survival. Overexpression of a long isoform of HIF-3α, HIF-3α1, increased cell growth in two CRC cell lines. Surprisingly, overexpressed HIF-3α1 was localized to the cytosol and increased phosphorylated signal transducer and activator of transcription 3 (p-STAT3). STAT3 inhibition effectively reduced p-STAT3 levels and cell growth induced by HIF-3α1. The activation of p-STAT3 was independent of the transcriptional activity of HIF-3α1. However, the inhibition of the upstream regulator Janus kinase (JAK) abolished HIF-3α1-induced p-STAT3 and cell growth. Together, these results demonstrated that HIF-3α1 promotes CRC cell growth by activation of the JAK-STAT3 signaling pathway through non-canonical transcription-independent mechanisms.