1.Experimental study on the effects of GuiJi cream in anti-fissure and permeability of skin
Gang WANG ; Xiaoli CHENG ; Youlin ZHANG ; Xiuhua ZHANG ; Mingquan CHANG ; Jiong LI ; Taoyang LI
International Journal of Traditional Chinese Medicine 2011;33(10):890-892
Objective To study the effect of Guiji cream in the treatment of fissure and permeability of skin.Methods The models of fissure Japonic rabbits were established to observe the effects of skin cream on inhibiting fissure.Rabbits back area was divided into 6 blocks and given different medicines in six different groups:GuiJi cream group of low dosage,middle dosage and high dosage (0.05、0.1、0.2 g/m-2 crude drug of Bletilla colloid respectively),urea frost cream group(0.1 g/m-2),normal saline group and control group.Observe the changes of skin surface symptoms every day.The permeability test was performed on 36 KM mouse and randomly divided into control group,GuiJi cream group and urea frost cream group(0.2 g/m-2).Apply drugs to the back and observe the permeability change of cilia capillary,and auricle swelling degree in mice of each group.Results The curative criteria for Guiji groups was 3.8~4.1,the inhibition rate of auricular swelling was 75%.GuiJi cream could inhibit xylene-induced ear edema (P<0.05) ; the Inhibition rate of vascular permeability was 45.08%,The ear swelling induced by xylene and increased capillary permeability induced by acetic acid in mice were inhibited significantly (P<0.05) by Guiji cream which had obvious effects on fissure as well as the permeability.Conclusion Guiji chapped skin cream played significant functions in treating fissure and acting anti-inflammatory.
2.KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.
Cancan ZHENG ; Xiaomei YU ; Taoyang XU ; Zhichao LIU ; Zhili JIANG ; Jiaojiao XU ; Jing YANG ; Guogeng ZHANG ; Yan HE ; Han YANG ; Xingyuan SHI ; Zhigang LI ; Jinbao LIU ; Wen Wen XU
Acta Pharmaceutica Sinica B 2023;13(10):4217-4233
Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.