3.The technologies of small molecule ligand-target protein interaction and high throughput ligand screening
Rui-fang DONG ; Yuan-zheng XIA ; Ling-yi KONG
Acta Pharmaceutica Sinica 2023;58(11):3242-3253
The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.
4.Label-free target identification for natural products based on proteomics
Rui-fang DONG ; Yuan-zheng XIA ; Ling-yi KONG
Acta Pharmaceutica Sinica 2023;58(8):2000-2015
Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.
5.Experience and thinking on establishing fine course of oral and maxillofacial surgery
lian, GUO ; zhi-yuan, ZHANG ; jia-wei, ZHENG ; xia, CAO ; yuan-jin, XU ; chi, YANG
Journal of Shanghai Jiaotong University(Medical Science) 2008;0(S1):-
Objective To explore the practical ways on establishing fine course of oral and maxillofacial surgery effectively. Methods Relying on the advantages of the discipline,great efforts had been made in step-by-step enhancement of the quality of teachers,teaching contents,teaching methods and administration. Results Through the establishing of fine course,we could improve the curriculum system,enhance the force of education team,and improve the quality of education. Conclusion Establishing fine course of oral and maxillofacial surgery depends on the environment of sharing educational resources,adjusting the curriculum system and establishing an excellent educational team.
6.Effect of methylprednisolone on reperfusion injury in severe uncontrolled hemorrhagic shock.
Fang XIA ; Jing-shan CAO ; Li-ying ZHAN ; Zhong-yuan XIA ; Zheng-yuan XIA ; Hai-bo HUANG
Chinese Journal of Traumatology 2003;6(6):359-362
OBJECTIVETo study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.
METHODSTwelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.
RESULTSInfusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05).
CONCLUSIONSMP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.
Analysis of Variance ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lipid Peroxidation ; Male ; Methylprednisolone ; pharmacology ; Probability ; Random Allocation ; Reference Values ; Reperfusion Injury ; drug therapy ; physiopathology ; Sensitivity and Specificity ; Shock, Hemorrhagic ; drug therapy ; physiopathology ; Survival Rate
7.The significance of the vitamin D anti vitamin D receptor In the initial systemic lupus erythematosus patients
Yijun ZHENG ; Dawei HU ; Sheng CHEN ; Yi TAN ; Chunde BAO ; Jiajing XIA ; Wen AO ; Min YUAN
Chinese Journal of Rheumatology 2009;13(9):595-598
Objective ① To investigate the level of the vitamin D endocrine system in peripheral relationships with bone mineral density (BMD) and the disease activity respectively. Methods The level of the 25-hydroxylate vitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)D3] in plasma from 43 SLE patients and 44 normal controls were detected by enzyme linked immunosorbent assay. Vitamin D receptor (VDR) gene expression was determinied by real-time PCR in peripheral blood. BMD measurements in the lumbar spine (L1-4) and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry before treatment. The relationship between the vitamin D endocrine system and the bone mass were studied. We also discussed the relationship between the vitamin D endocrine system and the disease activity. Results The levels of 25OHD3 and 1,25 (OH)2D3 were lower in the initial SLE patients than normal controls (P<0.01, P<0.01). The expressions of VDR gene were significantly increased in initial SLE compared with normal controls (P<0.01). The initial SLE patients had significantly lower BMD values, and higher frequency of osteopenia (35%) at both sites of measurement compared with matched healthy controls (P<0.01). The initial SLE patients were divided into two groups by BMD, abnormal group and normal group. There were no differences in 25OHD3, 1,25 (OH)D3 and VDR gene expression (P0.05). There was no correlation between the vitamin D endocrine system and BMD in initial SLE patients. There was no correlation between the vitamin D endocrine system and the disease activity either. Conclusion Vitamin D endocrine system may play an important role in SLE, but the level of VDR gene is not correlated with BMD and disease activity.
8.Expression of interleukin-33 and vascular endothelial growth factor-C in gastric cancer and its clinical significance
Bingxiang XIA ; Fan LI ; Jian XU ; Zhenhua YUAN ; Suwen ZHENG ; Yewei ZHANG
Chongqing Medicine 2017;46(15):2056-2059,2062
Objective To investigate the expression of interleukin-33(IL-33)and vascular endothelial growth factor C(VEGF-C)in gastric cancer tissues and serum,and to explore the relationship between these two indicators and gastric cancer lymph node metastasis.Methods The levels of IL-33 and VEGF-C in the tissues of gastric mucosa and serum were detected by immunohistochemical SP method and enzyme-linked immunosorbent assay(ELISA)in 98 patients with gastric cancer and 36 healthy subjects.Results The expression rates of IL-33 and VEGF-C in gastric cancer were 67.35%and 74.49%,which were significantly higher than the rates in normal gastric tissue(47.22%and 61.11%).The difference was statistically significant(P<0.01).The expression of IL-33 and VEGF-C was correlated with the degree of tumor differentiation,tissue infiltration,lymph node metastasis,distant metastasis and clinical stage(P<0.05).The positive rates of IL-33 and VEGF-C in gastric cancer lymph node metastasis group were higher than those in non-lymph node metastasis group(P<0.05).The serum concentrations of IL-33 and VEGF-C in patients with gastric cancer were(50.24±13.08)pg/mL and(210.73±58.35)pg/mL,respectively,which were higher than those in healthy control group(P<0.05);the expressions of serum concentration of IL-33 and VEGF-C in the cases with lymph node metastasis were higher than those without lymph node metastasis and the difference was statistically significant(P<0.05).Conclusion High levels of IL-33 in gastric carcinoma patients might induce the secretion of VEGF-C,promote lymph node metastasis,and be applied as an important index of the appraisal to the prognosis of gastric cancer.
9.Influence of WeChat platform-based continuing nursing on the compliance of antiviral therapy in chronic hepatitis B patients
Ying WANG ; Xu XIA ; Siying REN ; Yulei XUE ; Lina LIU ; Zheng YUAN
Chinese Journal of Practical Nursing 2017;33(15):1139-1142
Objective To evaluate the influencing factors of compliance and the compliance changes before and after intervention on chronic hepatitis B patients who oral nucleos(t)ide analogue (NA), by using the continuing care service items provided by WeChat platform. Methods A total of 67 patients with chronic hepatitis B were selected from January 2013 to June 2015. WeChat health care teams and WeChat groups were established to conduct continuing care intervention for 6 months by providing services, such as authoritative scientific diagnosis and treatment information, online consulting service, expert outpatient appointment, etc. Results The score of Morisky Medication Adherence Scale (MMAS-8) in patients of different culture levels of illiteracy (4.75 ± 2.20) points, primary school or junior high school graduate (5.73±1.87) points,high school or vocational school graduate (6.31±1.45) points,university diploma and above (7.24 ± 1.23) points were significant difference (χ2=22.113, P < 0.01). The score in patients previous used of nucleoside drugs (5.76±1.89) points was lower than that in patients not previous used of nucleoside drugs (6.62±1.60) points, and there was a significant difference between the two groups(Z=-2.636, P<0.01). Significant difference (χ2=10.844, P<0.01) was shown between groups of≥3 kinds drugs combined with the score 7.02 ± 1.08, 1-2 kinds drugs combined with the score 7.02 ± 1.08 and no combined medication with score 6.04±1.95. Different medical insurance types of free of charge (7.60±0.48) points,residents medical insurance (6.54 ± 1.52) points,new rural cooperative (5.17 ± 2.34) points and self-paying medical service (5.93±1.91) points showed significant difference(χ2=15.630, P<0.01). The scores in other diseases showed no significant difference (Z=0.401, P > 0.05) both in combination or non-combination. Compared to 6.45 ± 1.69 of pre-intervention, the total compliance score 6.86 ± 1.53 showed significant increased after intervention (Z=-2.551, P < 0.05), and the number of people with high compliance after the intervention increased while the number of people with middle and low compliance after the intervention decreased, and significant differencewas observed in two groups (χ2=9.521, P<0.01). Conclusions After the intervention of continuing care based on WeChat platform, the patients' compliance with nucleoside antiviral drugs were significant improvement than those of pre-intervention.