NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root of Salvia miltiorrhiza Bge., a traditional Chinese medicine that has been used for the treatment of several cardiovascular diseases for many years. This study was aimed to test the potential role of Tan C against macrophage foam cell formation and to explore the underlying mechanism. Firstly, we observed that Tan C markedly suppressed oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation. Then, we found that Tan C was an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Nrf2 and Sirt1 synergistically activated the transcription of anti-oxidant peroxiredoxin 1 (Prdx1) after Tan C treatment. More important, we demonstrated that silencing of Prdx1 promoted oxLDL-induced macrophage foam cell formation. Prdx1 upregulated adenosine triphosphate-binding cassette (ABC) transporter A1 (ABCA1) expression and decreased intracellular lipid accumulation. Furthermore, Tan C ameliorated oxLDL induced macrophage foam cell formation in a Prdx1-dependent manner. These observations suggest that Tan C protects macrophages from oxLDL induced foam cell formation via activation of Prdx1/ABCA1 signaling and that Prdx1 may be a novel target for therapeutic intervention of atherosclerosis.

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In birds, the sperm storage tubules ( SST ) are dispersed in uterovaginal junction ( UVJ ) and highly correlated with differential capacity of sperm storage ( SS ) in and among species with unspecified mechanisms. Here, the SS duration of 252 egg layer breeders was evaluated in 5 rounds with 3 phenotypic traits to screen high- and low-SS individuals, respectively, followed with transcriptome of UVJ tissues and metabolome of serum (high-SS vs. low-SS) to decipher the candidate genes and biochemical markers correlated with differential SS capacity. Histological characterization suggested slightly higher density of SST in UVJ (high-SS vs. low-SS). Transcriptome analyses identified 596 differentially expressed genes (336 upregulated vs. 260 downregulated), which were mainly enriched in gene ontology terms of homeostasis, steroid and lipid metabolism and hormone activity, and 12 significant pathways ( P < 0.05) represented by calcium, steroid, and lipid metabolism. Immunohistochemical staining of GNAQ, ST6GAL1, ADFP, and PCNA showed similar distribution in UVJ tissues between 2 groups. Several candidates ( HSD11B2 , DIO2 , AQP3 , GNAQ, NANS, ST6GAL1 ) combined with 4 (11β-prostaglandin F2α, prostaglandin B1, 7α-hydroxytestosterone, and N-acetylneuraminic acid) of 40 differential metabolites enriched in serum metabolome were considered as regulators and biomarkers of SS duration in egg layer breeders. The integrated transcriptome and metabolome analyses of chicken breeder hens will provide novel insights for exploration and improvement of differential SS capacity in birds.

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The apocrine sweat gland is a unique skin appendage in humans compared to mouse and chicken models. The absence of apocrine sweat glands in chicken and murine skin largely restrains further understanding of the complexity of human skin biology and skin diseases, like hircismus. Sheep may serve as an additional system for skin appendage investigation owing to the distributions and histological similarities between the apocrine sweat glands of sheep trunk skin and human armpit skin. To understand the molecular mechanisms underlying morphogenesis of apocrine sweat glands in sheepskin, transcriptome analyses were conducted to reveal 1631 differentially expressed genes that were mainly enriched in three functional groups (cellular component, molecular function and biological process), particularly in gland, epithelial, hair follicle and skin development. There were 7 Gene Ontology (GO) terms enriched in epithelial cell migration and morphogenesis of branching epithelium that were potentially correlated with the wool follicle peg elongation. An additional 5 GO terms were enriched in gland morphogenesis (20 genes), gland development (42 genes), salivary gland morphogenesis and development (8 genes), branching involved in salivary gland morphogenesis (6 genes) and mammary gland epithelial cell differentiation (4 genes). The enriched gland-related genes and two Kyoto Encyclopedia of Genes and Genomes pathway genes (WNT and TGF-β) were potentially involved in the induction of apocrine sweat glands. Genes named BMPR1A, BMP7, SMAD4, TGFB3, WIF1, and WNT10B were selected to validate transcript expression by qRT-PCR. Immunohistochemistry was performed to localize markers for hair follicle (SOX2), skin fibroblast (PDGFRB), stem cells (SOX9) and BMP signaling (SMAD5) in sheepskin. SOX2 and PDGFRB were absent in apocrine sweat glands. SOX9 and SMAD5 were both observed in precursor cells of apocrine sweat glands and later in gland ducts. These results combined with the upregulation of BMP signaling genes indicate that apocrine sweat glands were originated from outer root sheath of primary wool follicle and positively regulated by BMP signaling. This report established the primary network regulating early development of apocrine sweat glands in sheepskin and will facilitate the further understanding of histology and pathology of apocrine sweat glands in human and companion animal skin.