1.Expression of Jagged2/Notch3 signaling molecules in pulmonary hyper-tensive rats induced by monocrotaline
Cheng CHANG ; Peng JIN ; Wei ZHENG ; Huali KANG ; Mengyang DENG ; Shuangfei LI ; Xiaojing WU
Chinese Journal of Pathophysiology 2015;(1):12-17
AIM:To study the expression of Jagged 2/Notch3 signaling molecules in pulmonary vascular wall of pulmonary hypertensive rats induced by monocrotaline .METHODS: SD rats were randomly divided into normal control group (C group,n=15), solvent control group (S group,n=15) and monocrotaline model groups (M group,n=15).The model of pulmonary hypertension was established by a single subcutaneous injection of monocrotaline (50 mg/kg).The rats in S group were given a single subcutaneous injection of the same dose of solvent .After 4 weeks, the pulmonary vascular remodeling was assessed by HE staining , and the mean pulmonary artery pressure ( mPAP) and right ventricular systolic pressure (RVSP) were determined by right heart catheterization .The expression of Jagged2/Notch3 /Hes5 molecules in the pulmonary vascular wall was detected by immunohistochemical method and real -time PCR.RESULTS:Compared with S group and C group , the percentage of medial wall thickness of smaller arteries in model group increased significantly (P<0.01).The levels of mPAP and RVSP in M group were significantly higher than those in S group and C groups (P<0.01).The results of real-time PCR showed that the expression of Jagged 2, Notch3 and Hes5 was significantly increased in M group compared with S group and C group .The data from immunohistochemical detection indicated that Jagged 2 mainly expressed in the intima of small lung artery , Notch3 and Hes5 mainly expressed in the medial smooth muscle cells .Com-pared with S group and C group , the expression of Jagged 2 and Notch3 was significantly increased in the lung small arteries of M group.CONCLUSION:The activation of Jagged2/Notch3 signaling pathway might play an important role in the for-mation of pulmonary hypertension .
2.Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery.
Jing CHEN ; Peng JI ; Giri GNAWALI ; Mengyang CHANG ; Feng GAO ; Hang XU ; Wei WANG
Acta Pharmaceutica Sinica B 2023;13(6):2736-2746
The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.
3.Correlative analysis advance of chemical constituents of Polyporus umbellatus and Armillaria mellea.
Jing-Wen HUANG ; Chang-Jiang-Sheng LAI ; Yuan YUAN ; Min ZHANG ; Jun-Hui ZHOU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2017;42(15):2905-2914
Medicinal Polyporus umbellatus is the dry sclerotia of P. umbellatus, with the effect of diuresis; Armillaria mellea is a parasitic fungus which can infect plants up to 300 genera, with sedative, anticonvulsant and some other biological activities. As the medicinal value of P. umbellatus and A. mellea is increasingly wide concerned, the market quantity demanded of them is gradually increased and the demand outstrips the supply. The symbiotic A. mellea and P. umbellatus are both the medicinal and edible fungi with diverse activities, including hypoglycemic action, improve immunity and antitumor and so on. The growth of the sclerotia forming from the mycelium of P. umbellatus is related to the infection of the symbiotic A. mellea and their secondary products. In this study, by comparing the chemical constituents of the mycelium and sclerotia of P. umbellatus and A. mellea, we found that they all produced steroids and nitrogen-containing heterocycles. The sclerotia of P. umbellatus and A. mellea also produced triterpenes secondary metabolites. In addition, the mycelium and infected sclerotia of P. umbellatus mainly produced different steroids, and the sclerotia produced some other special secondary metabolites, such as long-chain fatty acids, ceramides, phenol and so on. By analyzing above all kinds of differences, speculated that these may be caused by the infection of the symbiotic A. mellea which mainly produced sesquiterpenes, diterpenes and other secondary metabolites. The contents and types of compounds of P. umbellatus and A. mellea are closely related to their symbiosis and reproduction, therefore, many symbiosis mechanisms should be found by utilizing more molecular biology technology to elucidate this complex symbiotic infection and provide scientific basis for improving the yield and quality of P. umbellatus and A. mellea.