Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRGs). However specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. GH modulates homeostasis and tissue repair after injury, but how GH effects nociception in neonates is not known. To determine if GH played a role in modulating sensory neuron function and hyper-responsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-dorsal root ganglion (DRG)-spinal cord preparation. Results show that inflammation of the hairy hindpaw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated via an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that following GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRGs.

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The c9,t11‐conjugated linoleic acid (CLA), which is the minor polyunsaturated fatty acid (PUFA) naturally present in butter, has gained attention due to its important preventive effect against breast cancer in vitro. In this paper, the enrichment of c9,t11‐CLA from butter was optimized and the preventive effect of dietary c9,t11‐CLA against breast cancer in vivo was investigated. Results showed that the concentration of c9,t11‐CLA increased more than 10 times via a one‐step urea complexation. Furthermore, the dietary c9,t11‐CLA showed obvious preventive effect against breast cancer in decreasing the tumor weight and volume, and reducing the tumor incidence up to 50%. In addition, the expression of progesterone receptor and Ki‐67 decreased significantly with the treatment of c9,t11‐CLA. In conclusion, the dietary c9,t11‐CLA enriched from butter showed a preventive effect against breast cancer in vivo via the inhibition of the hormonal receptor and cell proliferation. Practical applications This paper provided new insight into the preparation of specific c9,t11‐CLA isomer. It can be enriched from butter in large‐scale with low‐cost by urea complexation. Meanwhile, the enriched dietary c9,t11‐CLA can be further processed into cancer prevention functional foods.

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Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA, and ITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs, IFNG may play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.