1.EFFECT OF FISH OIL ON SERUM LIPIDS IN RATS
Hua DING ; Wenkai YANG ; Xiaopeng DANG
Chinese Pharmacological Bulletin 1987;0(02):-
An EPA and DHA enriched fish oil ( containing EPA 0.24 g/L, DHA 0.47g/L ) was administered by gastric intubation at the dose of O.2ml/100g wt for a period of one month in the hyperlipoprotein-emia rats caused by high lipid and cholesterol feeding. The administration of fish oil resulted in reduction in TG ( Triglyceride ) ; TC ( Total Cholesterol ) and VLDL-C + LDL-C levels in serum. Levels of HDL2-C and ratio of HDL2/HDL3 were elevated although there was no significant change in level of HDL-C. The study suggests that oral administration of EPA and DHA enriched fish oil might reduce the developoment of atherosclerosis.
2.Renal protection of erythropoietin and its mechanism in diabetic rats
Jianzhong DANG ; Ruhan JIA ; Yafang TU ; Shengshun XIAO ; Guohua DING
Chinese Journal of Nephrology 2011;27(8):597-601
Objective To investigate the renoprotective effect of erythropoietin(EPO) in streptozotocin-induced diabetic rats and to explore the possible mechanism.Methods The SD rats were randomly divided into there groups: normal control rats, diabetic, diabetic treated with EPO(NC, DM, DE groups).The rats were sacrificed after 8 weeks treatment.Renal morphology was observed by light microscopy.The expression of erythropoietin receptor(EPOR) in kidney was detected by immunofluorescence and Western blotting.The expression of p47phox, transforming growthfactor (TGF)β1andfibronectin (FN)proteininkidneywasdetectedby immunohistochemistry and Western blotting.The activity of antioxidants including total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde(MDA) in kidney were also measured.Results EPO treatment notably attenuated renal pathologic and functional changes.The expression of EPOR was found in kidney,but there was no difference among groups(P>0.05).Compared with normal rats, diabetic rats showed an elevated expression of p47phox, TGF-β1, FN proteins and MDA levels in kidney as well as reduced activities of SOD, GSH-Px and T-AOC (all P<0.01).Compared with diabetic rats, EPO could decrease the protein expression of p47phox,TGF-β1and FN in kidney (all P<0.05).Meanwhile, elevated MDA level in the kidney was decreased as well as decreased SOD, GSH-Px,T-AOC activities were significantly remitted in DE group(all P<0.01).Conclusion EPO can amelioraterenaldamagevia theinhibition of oxidativestressandTGF-β1andFNprotein expression in streptozotocin-induced diabetic rats.
3.Posterior pedicle screw flxation for adjacent two-segment thoracic and lumbar vertebral fractures
Min YANG ; Zhujun XU ; Guozheng DING ; Lijun DONC ; Gengding DANG
Chinese Journal of Trauma 2012;28(6):500-504
Objective To investigate the clinical outcomes of three kinds oi internal fixations via posterior approach for treating adjacent two-segment thoracic and lumbar vertebral fractures.Methods A retrospective analysis was done on data of 34 patients with adjacent two-segment thoracic and lumbar vertebral fractures treated between 2003 and 2010.The treatments included three different pedicle screw fixations via posterior approach,ie,fixation with four verlebrae and four screws (Group Ⅰ,n = 14),fixation with four vertebrae and six screws ( Group Ⅱ,n = 11 ),fixation with four vertebrae and eight screws ( Group Ⅲ,n = 9).The changes of spinal Cobb' s angle before and after operation and at the last final follow-up were statistically analyzed.Oswestry disability index (ODI) score,Denis pain scale and Denis work scale at the final follow-up were evaluated.Also,the recovery of neurological function was observed.Results The duration of follow-up was average 24 months (range,10-48 months).The neurological function of all the patients recovered to some degree.Two patients had pedicle screw breakage and one had spontaneous fusion of the collaprsed vertebra in Group Ⅰ.The Cobb' s angles of the three groups were decreased immediately after operation,but all obtained some degree of enhancement at the final follow-up.In Group Ⅰ,the mean Cobb's angle was (7.5 ±3.0)° postoperatively and then improved to ( 13.7 ±5.1 )°at the final follow-up,with correction loss of (6.2 ±2.1)°.In Group Ⅱ,the average Cobb's angle was( 1.4 ± 1.5) ° postoperatively and later increased to (4.5 ± 2.4)° at the final follow-up,with correction loss of (3.1 ± 1.1 )°.In Group Ⅲ,the mean Cobb' s angle was ( 0.0 ± 1.1 )° postoperatively but was increased to ( 1.3 ± 1.2 )° at the last follow -up,with correction loss of ( 1.3 ± 0.0 1 )°.The three groups showed statistical difference regarding the correction loss of Cobb' s angle ( P < 0.05 ).Group Ⅱ and Group Ⅲ showed no significant differences in aspects of ODI score and Denis work and pain scale at the final follow-up,but the differences were significant when Group Ⅰ was compared with Group Ⅱ and Group Ⅲ (P < 0.05 ).Conclusions The posterior transvertebral pedicle screw fixation with 4 vertebrae and 8 screws for adjacent two-segment thoracic and lumbar vertebral fractures is beneficial to gaining well reduction and fixation,maintaining deformity correction,preserving motion segment and releasing pain.The operation,a simple and convenient technique,has the prospect of clinical application.
4.Effects of erythropoietin on renal tubular cells apoptosis induced by high glucose
Jianzhong DANG ; Ruhan JIA ; Yafang TU ; Shengshun XIAO ; Guohua DING
Chinese Journal of Nephrology 2010;26(7):537-542
Objective To investigate whether erythropoietin (EPO) can inhibit the proapoptotic effect of high glucose on rat proximal tubular epithelial cells, and the possible mechanisms in which EPO exerts its anti-apoptotic role. Methods Rat proximal tubular epithelial cells (NRK-52E) were divided into 5 groups: normal control group, osmolarity control group, high glucose group, high glucose with EPO (50 U/ml) group and high glucose with EPO (100 U/ml) group. The expression of EPO receptor (EPOR) in NRK-52E cells was examined by immunocytochemistry. The effect of high glucose on the expression of EPOR was detected by Western blotting. The rate of apoptosis was evaluated by flow cytometry Annexin V-FITC/PI double stains. The intracellular ROS was detected using fluorescent probe CM-H2DCFDA. The expression of bcl-2, bax and caspase-3 mRNA were examined by RT-PCR. Results The expression of EPOR was demonstrated in NRK-52E cells, and high glucose could up-regulate the expression of EPOR. High glucose could induce oxidative stress in NRK-52E cells, and up-regulate the mRNA expression of bax and caspase-3, down-regulate the mRNA expression of bcl-2. These effects of high glucose on NRK-52E cells could be reversed by EPO. Conclusion EPO inhibits NRK-52E cells apoptosis induced by high glucose through attenuating oxidative stress,up-regulating theexpression of bcl-2 mRNA and down-regulating the expression of bax and caspase-3 mRNA, which may be mediated by EPOR.
5.Integrated medicinal chemistry: new modalities and methodologies in drug discovery
Shu-jing XU ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(10):2889-2901
New drug research and development is a technology-intensive industry with high investment, high cycle and high risk. In recent years, with the rapid development of modern disciplines such as omics technology, bioinformatics, high-throughput and high-content screening, and artificial intelligence, the research and development of small-molecule drugs has presented a new paradigm characterized by "integrated medicinal chemistry". This review summarizes new enabling drug discovery technologies, the emergence of new subfields formed through integration innovations and practical chemistry toolbox in the field of medicinal chemistry.
6.Universal strategies and methodologies in broad-spectrum antiviral drug discovery
Shu-jing XU ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(5):1289-1300
Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.
7.Performance Investigation of Ion Trap with Various Collision gas and Pressures
Fuxing XU ; Qiankun DANG ; Hangyu DING ; Zhengxu HUANG ; Yuanyuan WANG ; Zhen ZHOU ; Chuanfan DING
Chinese Journal of Analytical Chemistry 2017;45(4):587-592
Ion trap performances are investigated based on digital ion trap technique with different collision gases at different pressures. Collision gases of helium (4 amu), nitrogen (28 amu) and argon (40 amu) with various pressures are adopted in ion excitation and dissociation stages to investigate the ion trap performances, including mass resolution, signal intensity, tandem mass spectrometric analysis ability and low-mass cut off (LMCO) effect. It is found that when heavy gas of argon is used, energy can be efficiently transferred and LMCO effect is decreased with higher ion capture and dissociation efficiencies but with low mass resolution. Higher mass resolution is realized with helium as collision gas. Furthermore, at the same gas pressure, heavy gas is beneficial to abundant fragment ions and structural information of precursor ion.
8.An experimental investigation of therapeutic effect of Oxalis comiculata L. extracts on rats with alcoholic liver disease
Liang DING ; Lina ZHANG ; Zhiyong DANG ; Jianhong SHI ; Hui GUO ; Hui YANG ; Yingjian HOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2013;(5):257-260
Objective To investigate the therapeutic action and molecular mechanisms of Oxalis comiculata L. extracts on rats with alcoholic liver disease. Methods Forty-two male Sprague Dawley(SD)rats were randomly divided into normal control group(n=10),model group(n=8),moderate dose oxalis group(n=8),high dose oxalis group(n=8)and prednisone group(n=8). The model of rat with alcoholic liver disease was established by liquor gavage;after 12 weeks,moderate dose oxalis group,high dose oxalis group and prednisone group were given the total extract of oxalis 3.5 g?kg-1?d-1,7 g?kg-1?d-1 or prednisolone acetate 0.9 mg?kg-1?d-1,respectively,the remaining two groups were given the same amount of normal saline by gavage daily for 6 weeks. Levels of indexes of liver function,superoxide dismutase(SOD),malondialdehyde(MDA),antidiuretic hormone(ADH)and aldehyde dehydrogenase(ALDH)in rats were detected. The pathological changes of liver tissues in rats were observed under light microscope;tumor necrosis factor-α(TNF-α) expression level was detected by immunohistochemical staining. Results Compared with the normal control group, the levels of aspartate aminotransferase (AST), alanine aminotransferase(ALT),alkaline phosphatase(AKP),γ-glutamyl transferase(GGT),MDA were increased significantly,while the levels of SOD,ADH and ALDH were obviously reduced in model group. Compared with the model group,AST,ALT,AKP,GGT and MDA contents were decreased significantly,while the levels of SOD, ADH and ALDH were markedly increased in the drug groups,and the changes of levels of AST,ALT,AKP,GGT, SOD,ADH in high dose oxalis group were the most obvious〔AST(U/L):117.38±22.75 vs. 201.62±17.95,ALT (U/L):33.51±11.64 vs. 59.14±9.52,AKP(U/L):95.19±24.85 vs. 169.39±37.21,GGT(U/L):46.54±14.55 vs. 89.37±12.49,SOD(U/mg):137.03±12.03 vs. 80.64±13.45,ADH(U/L):3.48±0.71 vs. 2.05±0.91,P<0.05 or P<0.01〕,and the most significant changes of MDA and ALDH were in oxalis moderate dose group〔MDA (mmol/mg):2.05±0.64 vs. 3.17±0.61,ALDH(U/L):7.59±1.95 vs. 5.71±1.33,both P<0.05〕. In normal control group,no obvious lesion was seen in the rat liver tissues. In the model group,fatty degeneration of liver cells with formation of bullae was found,while in the moderate and high dose oxalis groups,cells with macrovesicular steatosis were significantly decreased. Immunohistochemical staining showed that the expression of TNF-α in the cytoplasm and part of cell membrane of macrophage was significantly decreased in liver tissues in oxalis moderate and high dose groups. Conclusion These results show that the Oxalis comiculata L. extracts possess certain therapeutic effect on alcoholic liver disease.
9.Clinical observation of curative effect of high intensity focused ultrasound treatment in liver metastasis of colorectal cancer
Hongbo LI ; Dongqing ZHENG ; Yuanqing HU ; Daming DING ; Guiyuan ZHANG ; Jianbo DANG
Chinese Journal of Primary Medicine and Pharmacy 2010;17(19):2608-2609
Objective To investigate the clinical efficacy and safety of the high-intensity focused ultrasound therapy in patients with colorectal liver metastases. Methods 28colorectal lesions in 16 patients with liver metastases after HIFU treatment lines observed patient vital signs,the main organ,imaging studies (CT or MRI,etc. ) ,complications and prognosis of cancer cases. Results All patients with stable vital signs after treatment, liver, kidney function was normal,6-month follow up, six more than 80% reduced lesion size,lesion size decreased in 18 of 30% to 50% ,4tumor volume did not change significantly; 16 patients, 1 patient was lost. 15 cases were followed uPfor 6 to 24 months,5 patients were transferred because of lesions disseminated in death within 6 months after surgery, calculated with the Kaplan-Meier median survival time was 13 months; 1 patient skin burning streak marks, healed after 1 week after treatment. 1 patient treatment areas of the chest skin, mild subcutaneous edema. Conclusion The treatment of patients with liver metastasis of colon cancer lesions was a non-invasive, safe and effective treatment.
10.Bioinorganic chemistry strategies in antiviral drug discovery
Shu-jing XU ; Xu-jie ZHANG ; Dang DING ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(3):576-592
Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.