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Donkeys, with high economic value for meat, skin and milk production, are important livestock. However, the current insights into reproduction of donkeys are far from enough. To obtain a deeper understanding, the differential expression analysis and weighted gene co-expression network analysis (WGCNA) of transcriptomic data of testicular and epididymis tissues in donkeys were performed. In the result, there were 4313 differentially expressed genes (DEGs) in the two tissues, including 2047 enriched in testicular tissue and 2266 in epididymis tissue. WGCNA identified 1081 hub genes associated with testis development and 6110 genes with epididymal development. Next, the tissue-specific genes were identified with the above two methods, and the gene ontology (GO) analysis revealed that the epididymal-specific genes were associated with gonad development. On the other hand, the testis-specific genes were involved in the formation of sperm flagella, meiosis period, ciliary assembly, ciliary movement, etc. In addition, we found that eca-Mir-711 and eca-Mir-143 likely participated in regulating the development of epididymal tissue. Meanwhile, eca-Mir-429, eca-Mir-761, eca-Mir-200a, eca-Mir-191 and eca-Mir-200b potentially played an important role in regulating the development of testicular tissue. In short, these results will contribute to functional studies of the male reproductive trait in donkeys.

It is known that lipopolysaccharide (LPS) triggers inflammatory response after intracerebroventricular (ICV) injection and elevates the expression of hepcidin through the interleukin 6/janus kinase 2/transducer and activator of the transcription 3 (IL-6/JAK2/STAT3) signaling pathway in the brain. This study was conducted to determine whether LPS ICV injection can regulate peripheral hepatic hepcidin expression and iron metabolism. Here, we studied the hepcidin expression in the liver, as well as serum iron and transferrin saturation, after LPS ICV injection. We also demonstrated the role of the IL-6/JAK2/STAT3 pathway in hepcidin expression in the livers of IL-6 knockout (IL-6–/– mice) and IL-6+/+ mice. AG490 was used to verify the effect of the IL-6/JAK2/STAT3 pathway on hepatic hepcidin expression. Our present study demonstrated that LPS ICV injection up-regulated hepatic hepcidin expression. This finding provides further evidence for highlighting the importance of the central inflammation on hepatic hepcidin expression and peripheral iron metabolism.

BackgroundLPS triggers inflammation response in periphery, whether the infection in CNS induced by LPS ICV injection affected the peripheral iron metabolism was unknown , The current study was to find out whether LPS injected to the brain could regulate hepcidin expression in liver and peripheral iron metabolism. MethodsWide type mice (IL-6+/+) and IL-6-/- mice of 8-week-old were performed on ICV injection with LPS. After 6h, hepcidin expression in liver, as well as serum iron and transferrin saturation was detected and calculated, we also tested the IL-6/JAK2/STAT3 pathway in hepcidin regulation in liver of IL-6 knockout (IL-6-/- mice) and IL-6+/+ mice, AG490 as an inhibitor of JAK2 was used to confirm the effect of IL-6/JAK2/STAT3 pathway on hepcidin expression in liver. ResultsHepcidin mRNA, IL-6 mRNA and protein expression in the liver of IL-6-/- mice was significantly lower than IL-6+/+ mice after LPS administration. IL-6 deficiency abolished the decrease of serum iron, transferrin saturation induced by LPS injection. IL-6 deficiency also abolished the decrease of Fpn1, increase of pSTAT3 and Ft-L protein in liver. AG490 significantly reduced the pSTAT3 protein and abolished the changes of Fpn1 and Ft-L expression induced by LPS in liver. ConclusionThese finding provided further evidence that the effect of central inflammation on the hepatic hepcidin expression and peripheral iron metabolism.

Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). Here, we investigate the role of Clk1 in neuroinflammation and consequentially dopaminergic (DA) neuron survival. Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. Mechanistic studies demonstrated that mTOR/HIF-1α and ROS/HIF-1α signaling pathways were involved in Clk1 deficiency-induced aerobic glycolysis. The increase in neuronal cell death was observed following treatment with conditioned media from Clk1 deficient microglia. Increased DA neuron loss and microgliosis were observed in Clk1+/− mice after treatment with MPTP, a rodent model of Parkinson’s disease (PD). This increase in DA neuron loss was due to an exacerbated microglial inflammatory response, rather than direct susceptibility of Clk1+/− DA cells to MPP+, the active species of MPTP. Exaggerated expressions of proinflammatory genes and loss of DA neurons were also observed in Clk1+/− mice after stereotaxic injection of LPS. Our results suggest that Clk1 regulates microglial metabolic reprogramming that is, in turn, involved in the neuroinflammatory processes and PD.

Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.