1.Research progress of natural products for the treatment of hyperuricemia and gout
Zhi-jiao ZHANG ; Rui-peng LIANG ; Tong ZHAO ; Shu-jing XU ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(6):1679-1688
Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.
2.A preliminary study of the relationship of MR delayed enhancement with cardiac troponin Ⅰ in hypertrophic cardiomyopathy
Jun-Yan SUN ; Zhao-Qi ZHANG ; Yi HE ; Teng-Yong JIANG ; Yu LI ; Zhan-Ming FAN ; Yong-Mei WANG ;
Chinese Journal of Radiology 2001;0(08):-
Objective To study the relationship of MR delayed enhancement with cardiac troponin I in hypertrophic cardiomyopathy(HCM)and to evaluate their values on assessing HCM condition and prognosis.Methods Thirty-five HCM patients who were diagnosed by echocardiography were enrolled.All patients were performed MR scan and cTn Ⅰ test of blood.The relationships of MR delayed enhancement, myocardial hypertrophy and cTn Ⅰ were analyzed.Results(1)DE was found in 25 of total 35 HCM patients(71.4%).19 of 35 HCM patients(54.3%)had abnormal increased eTn Ⅰ value.The medians of cTn Ⅰ in patients with DE and without DE(110,5 ?g/ml,respectively)had statistics significance (P
3.Effect of portal vein blocking on permeability of the intestinal mucosa in pigs
Jian-Yong ZHAO ; Jia-Hong DONG ; Guo-Qing ZHAN ; Huai-Zhi WANG ; Zhan-Yu YANG
Journal of Third Military Medical University 2001;23(4):432-433
Objective To study the effect of portal vein blocking on the permeability of the intestinal mucosa in pigs. Methods Healthy Rongchang pigs were divided into 3 groups: ① sham operation group(SO), ② portal vein clamping for 45 min group (PVC-45'), ③ portal vein clamping for 60 min group (PVC-60'). Urine lactulose/mannitol(L/M) ratio was measured after portal vein blocking. Results The L/M ratio was increased significantly (P<0.05) in PVC-45' and 60' groups than in SO group, with that of PVC-60' higher than that of PVC-45' group, but not significantly. Conclusion The increase of intestinal mucosal permeability after portal vein blocking is an early and important index for the damage of the intestinal mucosa barrier.
4.Advances in the research of HIV-1 envelope glycoprotein gp120 inhibitors
Ming-hui XIE ; Zhao WANG ; Yan-ying SUN ; Xiang-yi JIANG ; Peng ZHAN ; Xin-yong LIU ; Dong-wei KANG
Acta Pharmaceutica Sinica 2023;58(3):616-628
From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.
5.Research progress and medicinal chemistry strategies of URAT1 inhibitors
Xiao-yu SHI ; Tong ZHAO ; Jian ZHANG ; Rui-peng LIANG ; Zhi-jiao ZHANG ; Xin-yong LIU ; Peng ZHAN
Acta Pharmaceutica Sinica 2022;57(10):2960-2971
The urate transporter 1 (URAT1) which controls urate reabsorption is a membrane transporter in the apical membrane of human renal proximal tubule epithelial cells. It was found that about 90% of patients suffer from hyperuricemia due to insufficient uric acid excretion. Therefore, the development of URAT1 inhibitors that can reduce the level of serum uric acid
6.Related risk factors analysis of pancreatic fistula after radical resection of gastric cancer and establishment of risk prediction scoring model
Ping'an DING ; Zhidong ZHANG ; Peigang YANG ; Yuan TIAN ; Shixin ZHAN ; Honghai GUO ; Yang LIU ; Dong WANG ; Yong LI ; Qun ZHAO
Cancer Research and Clinic 2021;33(2):104-108
Objective:To investigate the risk factors of pancreatic fistula after radical resection of gastric cancer, and to establish a risk prediction scoring model for pancreatic fistula.Methods:The clinico-pathological data of 312 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from January 2019 to January 2020 were retrospectively analyzed. Multiple factor logistic regression model was used to analyze the risk factors of pancreatic fistula after radical resection of gastric cancer, and a risk prediction scoring model based on the risk factors was established. Hosmer-Lemeshow test was used to detect the goodness of fit of regression equation, and receiver operating characteristics (ROC) curve was used to evaluate the distinction degree of regression equation.Results:Among 312 patients with gastric cancer, 27 cases (8.65%) had pancreatic fistula after radical resection of gastric cancer. Multiple factor logistic regression analysis showed that male patients ( OR = 5.312, 95% CI 1.532-18.420, P = 0.008), age ≥ 60 years old ( OR = 4.928, 95% CI 1.493-16.250, P = 0.009), preoperative diabetes mellitus ( OR = 3.062, 95% CI 1.091-8.589, P = 0.034), lesion location in the gastric body-gastric antrum ( OR = 3.121, 95% CI 1.052-9.251, P = 0.040), intraoperative omental bursa resection ( OR = 6.209, 95% CI 2.084-18.478, P = 0.001), intraoperative lymph node dissection at D2+ station ( OR = 3.114, 95% CI 1.044-9.281, P = 0.042), intraoperative combined organ resection ( OR = 5.063, 95% CI 1.473-17.400, P = 0.010), preoperative TNM stage Ⅲ ( OR = 4.973, 95% CI 1.189-20.792, P = 0.028) were independent risk factors for pancreatic fistula after radical resection of gastric cancer. A risk prediction equation of pancreatic fistula after radical resection of patients with gastric cancer was established: P = -8.619+1.670X 1+1.595X 2+1.119X 3+1.138X 4+1.826X 5+1.136X 6+1.622X 7+1.604X 8; factor X was set as a binomial assignment (0 or 1); X1-X8 were listed as follows respectively: gender (the male was 1), age (≥60 years old was 1), preoperative diabetes history (yes was 1), lesion location (gastric body-gastric antrum was 1), intraoperative resection of omental bursa or not (yes was 1), intraoperative lymph node dissection at D2+ station or not (yes was 1), intraoperative combined organ resection or not (yes was 1), preoperative TNM stage (stage Ⅲ was 1). The goodness of fit of regression equation was high ( P = 0.395). The area under the curve of ROC by using risk prediction scoring model to judge pancreatic fistula was 0.916 (95% CI 0.872-0.960, P<0.01). The probability of pancreatic fistula in patients with score ≥ 5 was 40.90%, and the probability of pancreatic fistula in patients with score < 5 was 3.35%. Conclusions:The occurrence of pancreatic fistula after radical resection of gastric cancer is closely related to a variety of risk factors. By establishing a risk prediction scoring model for pancreatic fistula after radical resection of gastric cancer, it is helpful to effectively identify patients with high risk of pancreatic fistula after radical surgery during the perioperative period.
7.Clinical observation on the paraumbilical skin flaps application in the repair of the wounds of 39 patients with severe burns.
Qiang WANG ; Yu-ling ZHAO ; Quan-bin CAO ; Zhan-jie YANG ; Dian-yong ZHU
Chinese Journal of Burns 2006;22(4):266-268
OBJECTIVETo evaluate the effectiveness of paraumbilical skin flaps for the repair of the severe burn wounds.
METHODSPedicled, island, or free paraumbilical skin flaps, as well as combined transplantation of several kinds of flaps were used to repair the wounds of 39 patients with severe burns. The largest paraumbilical skin flap was 55 x 27 cm(2) in area, with the end approaching the armpit midline of the axilla on the same side, and extending 10cm from the abdominal midline. The survival, color, elasticity of the flaps, degree of deformity resulted from scar contracture, and the condition of donor area were observed.
RESULTSAll the paraumbilical skin flaps survived, without obvious infection subsequent to complete debridement of the wounds. The flaps exhibited good color and elasticity, without scar contracture after 1 to 46 months in 33 patients. No obvious scar formation was observed in the donor area.
CONCLUSIONParaumbilical skin flap is an ideal one for the early repair of deep burn wounds, because it can cover a large area, and can be transferred in different ways according to the area and the position of the wounds.
Adolescent ; Adult ; Burns ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Skin Transplantation ; methods ; Surgical Flaps ; Thorax ; Umbilicus ; Wound Healing
8.Optimization of transfection efficiency of small interfering RNA in purified human prolactinoma cells.
Qing-Hu MENG ; Yong-Mei SONG ; Jiang ZHAO ; Chun-Jiang YU ; Qi-Min ZHAN
Chinese Medical Journal 2011;124(12):1862-1869
BACKGROUNDControl of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA (siRNA) was optimized in human prolactinoma cells.
METHODSFirst, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin (PRL) secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfection efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR.
RESULTSThe siRNA of 100 pmol with Lipofectamine 2000 of 5 µl for 1 × 10(6) cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%.
CONCLUSIONIt is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.
Adolescent ; Adult ; Cell Line, Tumor ; Cell Separation ; Female ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms ; pathology ; therapy ; Prolactinoma ; pathology ; therapy ; RNA, Small Interfering ; genetics ; Transfection
9.The study in primary cultured astrocytes following fluid percussion injury.
Tao HE ; Shu-wang YANG ; Yun GUP ; Zhan-kao ZHAO ; Xu-yi CHEN ; Yong-liang ZHANG
Chinese Journal of Applied Physiology 2010;26(1):46-50
OBJECTIVETo investigate the morphology alterations and proteomics changes in primary astrocytes following fluid percussion injury.
METHODSPrimary cultures of astrocytes were prepared from cerebral hemispheres of 1-3 d-old SD rats, then, astrocytes were randomly divided into control group and injury group which were subjected to (0.2 +/- 0.01) MPa fluid percussion injury. The changes of protein expression pattern in astrocytes between injury and control groups were monitored with two dimensional gel electrophoresis.
RESULTSAstrocytes' s abnonmalities of morphology after injury were apparent. The fluid percussion injury caused astrocytes edema, shrinkage, cell junction disconnection and necrosis at 2 h after injury. 24 h and 48 h after injury, most part of astrocytes's dendrites and soma became hypertrophy and showed a higher rate of cell proliferation. The dynamic proteomics changes were identified and total different 13 spots were detected in this study from the 2DE gels. The different displayed 5 spots were identified via MALDI-TOF: cofilin 1, destrin, phosphoglycerate mutase 1, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10, annexin 1.
CONCLUSIONThe obvious alteration of morphology and protein expression pattern in primary cultured astrocytes could be induced after fluid percussion injury. The differential proteins detected were probably related to stress responses.
Animals ; Animals, Newborn ; Astrocytes ; cytology ; metabolism ; Brain Injuries ; metabolism ; physiopathology ; Cerebral Cortex ; cytology ; Female ; Male ; Primary Cell Culture ; methods ; Proteins ; metabolism ; Proteome ; analysis ; Proteomics ; methods ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological ; physiology
10.Experimental study on the mechanism of icariin improving human osteoblasts proliferation and the expression of OPG protein.
Hai-ling GUO ; Yong-fang ZHAO ; Xiang WANG ; Yu XU ; Hong-sheng ZHAN
China Journal of Orthopaedics and Traumatology 2011;24(7):585-588
OBJECTIVETo establish the human osteoblasts culture system in vitro, observe the effects of icariin on human osteoblasts proliferation and expression of OPG protein, and to explore the mechanism of promoting bone formation about human osteoblast in icariin.
METHODSThe femoral cancellous bone pieces were obtained from the operation. The enzyme digestion method was used for culturing. The third passage of human osteoblast was taken for experiments. The cells were divided into four groups, the control group was treated with 15% NCS-DMEM-F12 (1:1), the experimental groups were respectively treated with 10(-6), 10(-8), 10(-10) mol/L icariin. The MTT method was used to observe the proliferation of human osteoblast on 1, 3, 5, 7, 9 d; in 8, 10, 12 d, western blot was used to determine the expression of OPG protein on human osteoblast.
RESULTS1) Results of MTT: the icariin promoted the proliferation of human osteoblast. There was a concentration-response relation,while with the concentration of icariin increased, the ability was more obvious. There was statistically difference between 10(-6) mol/L icariin group (0.402 +/- 0.033) and the control group (0.268 +/- 0.031) (P<0.05). In the timely research, as the time prolong, the number of human osteoblast were more. At the fifth day, the human osteoblast entered rapid growth period, and access the growth platform stage; the icariin began to promote the proliferation of human osteoblast from the fifth day, which almost maintained to the 7th day and the 9th day, and most obvious in the 9th day. There was statistically difference between 10(-6) mol/L icariin group (0.402 +/- 0.033) and the control group (0.268 +/- 0.031) at the 9th day. (The results of OPG protein expression: in the control group, the expression of OPG protein was detected at the 8th day (1.01 +/- 0.08), and reached the expression peak (1.80 +/- 0.10), there was statistically different (P<0.05). In the different days and different concentration icariin groups, the expressions of OPG protein were all inferior to the control group. While the concentration decreasing, the expression was less. There were statistically difference (P<0.05). At the day 12, there was no significant difference of OPG protein expression between the 10(-6) mol/L icariin group and the 10(-8) mol/L icariin group (P>0.05).
CONCLUSIONThe effect of icariin promoting the proliferation of human osteoblast maybe is one of the mechanisms of improving the bone formation on human osteoblast.
Animals ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Humans ; Osteoblasts ; cytology ; drug effects ; metabolism ; Osteogenesis ; drug effects ; Osteoprotegerin ; metabolism