Activation of GDNF-ERK-Runx1 signaling contributes to P2X3R gene transcription and bone cancer pain.

Bone cancer pain is a common symptom in cancer patients with bone metastases and its underlying mechanisms remain unknown. Here, we report that Runx1 directly upregulates the transcriptional activity of P2X3 receptor (P2X3R) gene promoter in PC12 cells. Knocking down Runx1 in dorsal root ganglion (DRG) neurons suppresses the functional upregulation of P2X3R, attenuates neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats, whereas overexpressing Runx1 promotes P2X3R gene transcription in DRG neurons, induces neuronal hyperexcitability and pain hypersensitivity in naïve rats. Activation of GDNF-GFRα1-Ret-ERK signaling is required for Runx1-mediated P2X3R gene transcription in DRG neurons, and contributes to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. These findings indicate that the Runx1-mediated P2X3R gene transcription resulted from activation of GDNF-GFRα1-Ret-ERK signaling contributes to the sensitization of DRG neurons and pathogenesis of bone cancer pain. Our findings identify a potentially targetable mechanism that may cause bone metastasis-associated pain in cancer patients.

In vitro damage to hairs by Trichophyton mentagrophytes and Microsporum canis / 中华皮肤科杂志

Objective To observe the in vitro damage to hairs by Trichophyton mentagrophytes and Microsporum canis using light microscopy and scanning electron microscopy ( SEM ), and to compare the differences in the duration needed for the two fungi to damage hairs in different age groups. Methods We collected healthy hairs from different age groups, and performed hair perforation test in vitro. The damage to the hairs was observed by SEM and light microscopy. Results Both T. mentagrophytes and M. canis could damage the hairs. The duration needed for T. mentagrophytes to damage the hairs was significantly shorter than that for M. canis in all age groups ( P