Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Mad2 and p27 expression profiles in colorectal cancer and its clinical significance.

AIM: To investigate the expression of tumor suppressor gene p27 and spindle checkpoint gene Mad2 and to demonstrate their expression difference in colorectal cancer and normal mucosa and to evaluate its clinical significance. METHODS: Immunohistochemical staining was used for detection of expression of Mad2 and p27 in colorectal cancer and its corresponding normal mucosa. RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P<0.01, chi(2) = 7.5), and it was related to the differentiation of adenocarcinoma, lymph node metastasis and survival period after excision (P<0.05, chi(2) = 7.72, chi(2) = 4.302, chi(2) = 6.234). The rate of p27 positive expression in adenocarcinomas and normal mucosa was 40% and 80% respectively. There was a significant difference in p27 expression between adenocarcinomas and normal mucosa (P<0.001, chi(2) = 13.333), which was related to the differentiation degree of adenoca rcinoma and lymph node metastasis (P<0.05, chi(2) = 8.901 chi(2) = 4). The positive expression of p27 was not correlated with survival period after excision. CONCLUSION: Defect of spindle checkpoint gene Mad2 and mutation of p27 gene are involved mainly in colorectal carcinogenesis and associated with prognosis of colorectal cancer.

Mad2 and p53 expression profiles in colorectal cancer and its clinical significance.

AIM: To investigate the expression of tumor suppressor gene p53 and spindle checkpoint gene Mad2, and to demonstrate their expression difference in colorectal cancer and normal mucosa and to evaluate its clinical significance. METHODS: Western blot and immunohistochemistry methods were used to analyze the expression of Mad2 in colorectal cancer and its corresponding normal mucosa. The expression of p53 was detected by immunohistochemistry method in colorectal cancer and its corresponding normal mucosa. RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P<0.001), and it was not related to the differentiation of adenocarcinoma and other clinical factors (P>0.05). The ratio of Mad2 protein in cancer tissue (C) to that in its normal mucosa tissue (N) was higher than 2, which was more frequently observed in patients with lymph gland metastasis (P<0.05). p53 protein expression was not observed in normal mucosa. The rate of p53 positive expression in adenocarcinomas was 52.6 %. There was a significant difference between adenocarcinomas and normal mucosa(P<0.001), which was not related to the differentiation degree of adenocarcinoma and other clinical factors (P>0.05). CONCLUSION: Defect of spindle checkpoint gene Mad2 and mutation of p53 gene are involved mainly in colorectal carcinogenesis and C/N>2 is associated with prognosis of colorectal cancer.