1.Upregulated SKP2 Empowers Epidermal Proliferation Through Downregulation of P27 Kip1
Lipeng TANG ; Bowen ZHANG ; Guanzhuo LI ; Xinmin QIU ; Zixin DAI ; Hongying LIU ; Ying ZHU ; Bing FENG ; Zuqing SU ; Wenhui HAN ; Huilin HUANG ; Qiuping LI ; Zihao ZHANG ; Maojie WANG ; Huazhen LIU ; Yuchao CHEN ; Yanmei ZHANG ; Dinghong WU ; Xirun ZHENG ; Taohua LIU ; Jie ZHAO ; Chutian LI ; Guangjuan ZHENG
Annals of Dermatology 2024;36(5):282-291
Background:
Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear.
Objective:
This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis.
Methods:
We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo.
Results:
We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo.
Conclusion
Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.
2.Constitutional types of Chinese medicine of primary bile reflux gastritis among different season:a cross-sectional study
Dinghong XIAO ; Xiaohua WU ; Zhiping HUANG ; Weiying NI ; Wei YANG ; Yingying SHANG ; Zhaoping GUO
International Journal of Traditional Chinese Medicine 2018;40(6):490-493
Objective To investigate the constitutional types of Chinese medicine of primary bile reflux gastritis among different seasons. Methods Data of gastroscopy center during August 2015 to July 2016 were analyzed. A total of 603 patients were diagnosed as primary bile reflux gastritis. After gastroscopy, the standardized constitution in Chinese medicine questionnaire was used to evaluation the scores of all kinds of constitutional types. The Constitutional types of Chinese medicine of primary bile reflux gastritis among different seasons were analyzed. Results Among all seasons, the positive detection rate showed significant difference (χ2=13.041, P=0.005), and summer group showed the highest among the four seasons (23.38% vs. 17.63%,χ2=12.414, P<0.001). Among all seasons, constitutional types of Chinese medicine of primary bile reflux gastritis had significant difference (χ2=37.441, P<0.001). Damp-heated type had significant difference among seasons (χ2=8.472, P=0.037), especially during the summer (χ2=5.847, P=0.016). Conclusions The summer may have more primary bile reflux gastritis chance to be diagnosed as primary bile reflux gastritis. Yang-deficiency type, Gentleness type, Qi-deficiency type and damp-heat type were more common in primary bile reflux gastritis patients.
3.In silico pharmacology of Chinese herbs for chronic kidney diseases.
Wei ZHU ; Dinghong WU ; Xiaohui QIU ; Wen XU
China Journal of Chinese Materia Medica 2010;35(23):3211-3215
Tonifying herbs and evil expelling herbs of traditional Chinese medicine (TCM) for chronic kidney diseases in molecular level were studied by computer aided drug design, including analysis of molecular similarity, predictive ADME simulation and predictive toxic simulation. It was found that this technology could distinguish the structure diversity of compounds from TCM, and screen the lead compounds rapidly.
Chronic Disease
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therapy
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Drugs, Chinese Herbal
;
adverse effects
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chemistry
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pharmacology
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Humans
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Kidney Diseases
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drug therapy
4.Quality Standard of Dibiling
Dinghong WU ; Yanfen CHEN ; Shanghong ZHU
China Pharmacy 2001;0(12):-
OBJECTIVE:To establish the quality standard of Dibiling.METHODS:Rhizoma Coptidis in the formulation was identified qualitatively by TLC,and the content of ephedrine hydrochloride was determined by RP - HPLC.RESULTS: The TLC spots of Rhizoma Coptidis were clear and distinctive.The linear range of ephedrine hydrochloride was 0.088~3.520?g(r = 0.996 0) with an average recovery rate of 100.82%(RSD = 1.19%,n = 6).CONCLUSION:The established standard is applicable for the quality control of Dibiling.
5.Determination of Protocatechuic Acid in Pterospermum heterophyllum by RP-HPLC
Hua LIN ; Dinghong WU ; Buqing LOU
China Pharmacy 2001;0(07):-
OBJECTIVE:To establish an HPLC method for determination of protocatechuic acid in Pterospermum heterophyllum.METHODS: The separation was performed on Agilent TC C18(250 mm?4.6 mm,5.0 ?m)column.Moblie phase consisted of acetonitrile-0.1% glacial acetic acid solution(pH 3.16,10 ∶ 90)with flow rate of 1.0 mL?min-1 and detection wavelength of 260 nm.The column temperature was set at 35℃ and injection volume was 10 ?L.RESULTS:The linear range of protocatechuic acid was 0.007 76~0.310 4 ?g(r=0.999 7) with an average recovery of 97.68% (RSD=1.51%,n=6).CONCLUSION:The method is simple,accurate and reproducible for the quality control of P.heterophyllum.

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