1.Advances in the role of kynurenine 3-monooxygenase in disease and its target drugs
Acta Pharmaceutica Sinica 2024;59(5):1101-1112
Kynurenine 3-monooxygenase (KMO) is a key rate-limiting enzyme in the downstream catabolism of kynurenine pathway (KP). Under the catalysis of KMO, the intermediate product kynurenine is metabolized into various active metabolites, including 3-hydroxykynurenine (3-HK), quinolinic acid (QA) and nicotinamide adenine dinucleotide (NAD+). More and more studies have shown that abnormal KMO expression activity mediates KP metabolic disorders, and is involved in the occurrence and development of nervous system diseases, autoimmune diseases, infectious diseases and tumors, suggesting that KMO can be used as a potential and effective drug therapeutic target. This article focuses on the role of KMO in the pathological mechanism of various diseases, and summarizes the existing KMO inhibitors to provide methods and ideas for targeted KMO therapy.
2.Effects of Keratinocyte Growth Factor 2(KGF-2) on Keratinocyte Growth, Migration and on Excisional Wound Healing
Xia CHEN ; Wei HU ; Wangui WEI ; Yan SHEN ; Yan CHEN ; Shengli YANG ; Yi GONG
Progress in Biochemistry and Biophysics 2009;36(7):854-862
Keratinocyte growth factor 2 (KGF-2) is a member of the FGF family that is mainly synthesized by mesenchymal cells and acta predominantly on epithelial cells in a paracrine manner. It is known to play an important role in fetal limb and lung development; skin wound healing and prostatic epithelial cell growth. The KGF-2 coding sequence were isolated from human kidney cDNA library, revealing that the Kgf-2 gene is also expressed in the kidney apparatus. Purified from prokaryotic E. coli cells, the effects of the recombinant KGF-2 protein in cultured keratinocyte were analyzed by using MTT assay and in situ TUNEL assay. Interestingly, results revealed that KGF-2 promoted keratinocyte cell growth by stimulating cell proliferation and attenuating cell apoptosis. These findings supported a few evidences that KGF-2 could contribute to alveolar epithelial cells against apoptosis. Cell migration assays for the first time revealed that KGF-2 could stimulate keratinocyte cell migration in vitro. In addition, in the pilot animal test, recombinant KGF-2 incorporated within the hydrogel dressing exhibited significantly stimulatory effect on cutaneous wound healing. These combined effects implicate a potential therapeutic application of human recombinant KGF-2 in the future.
3.A model-based meta-analysis to compare urate-lowering response rate of febuxostat and allopurinol in gout patient.
Yi SUN ; Liang LI ; Tian-Yan ZHOU ; Wei LU
Acta Pharmaceutica Sinica 2014;49(12):1674-1683
This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Allopurinol
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therapeutic use
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Febuxostat
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Gout
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blood
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drug therapy
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Gout Suppressants
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therapeutic use
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Humans
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Thiazoles
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therapeutic use
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Uric Acid
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blood
5.Specific allergic food Intolerance and correlated factors in Qingdao areas
Yan WANG ; Ying ZHANG ; Jing ZHOU ; Wei WANG ; Yi ZHANG
Chinese Journal of Health Management 2012;06(3):154-157
ObjectiveTo study specific allergic IgG antibody test and its impact factors.MethodsA total of 1770 Qingdao residents were recruited in this cross-sectional study from January to October 2011.ELISA was used to test specific allergic IgG antibodies.Logistic regression was used for multifactor analysis.Results Of 1770 participants,9 individuals had insufficient data,resulting in a response rate of 99.5%.Identification rate of specific allergic IgG antibody was 60.0% (1056/1761 ),and the most commonly seen allergic foods were crab (49.4% ),egg (44.80% ),ling (38.0% ),shrimp ( 30.4% ) and soy ( 22.2% ).Intolerance to crab,egg,shrimp,creamery,com,and tomato showed gender difference ( x2 =18.978,P<0.05 ).Serum level of allergic IgG antibody was increased with age [20 - 40 years:( 118.61 ±45.67) U/ml; 41-60 years:(166.57 ±55.82) U/ml; >60 years:(183.67 ±49.34) U/ml; x2=13.597,P<0.01].In logistic regression,difference between individuals with normal body weight and obesity population ( OR =1.897,95% CI 1.215 - 2.578 ) or between those with or without allergic history ( OR =0.780,95% CI 0.648 - 0.912) was found.Conclusions Impact factor of food intolerance includes gender,age,constitution and body mass index.Six kinds of food intolerance are more common in women.41 -60 year group shows peak of food intolerance.No exposure to allergic food and antianaphylaxis may reduce the risk of food intolerance.
6.Curative Effect of Desmopressin Acetate Combined with Bladder Training Therapy on Primary Nocturnal Enuresis in Children
yi-yan, RUAN ; wei-ling, QIN ; xian-ming, GUO
Journal of Applied Clinical Pediatrics 1992;0(05):-
Objective To observe the curative effect and recurrence rate of desmopressin acetate(DDAVP) combined with bladder training therapy on primary nocturnal enuresis(PNE) in chlidren.Methods One hundred children with PNE were randomly divided into control group and observation group(50 cases in each group).Children in control group were treated with simple DDAVP,and patients in observation group were treated with bladder training while DDAVP was using.The course of treatment were 3 months.The therapeutic effect between the 2 groups when the treatment was finished was compared and then followed up all the cases for 3 months to compare the near-term and long-term recurrence rate between the 2 groups.SPSS 13.0 software was used to analyze the data.Results The total effective rate in control group was 72.9%,and the near-term recurrence rate and the long-term recurrence rate were 22.9% and 54.3%,respectively.The total effective rate in observation group was 91.3%,and the near-term recurrence rate and the long-term recurrence rate were 11.9% and 28.6%,respectively.The total effective rate was significantly higher in observation group than that in control group(Z=-1.972,P=0.049).The near-term recurrence rate in 2 groups had no significant difference(?2=1.632,P=0.201).The long-term recurrence rate was extremely lower in observation group than that in control group(?2=5.249,P=0.022).Conclusions There is significant curative effect that DDAVP combined with bladder training therapy on PNE in children,and it can lower the long-term recurrence rate.
7.Change of trace elements and body comprehensive immune state of patients with viral keratitis
Yan, JIANG ; Wei-Cai, FU ; Yi-Kang, DAI
International Eye Science 2015;(2):259-261
AlM:To study and investigate the change situation of trace elements and body comprehensive immune state of patients with viral keratitis.METHODS:Sixty-two patients with viral keratitis in our hospital from December 2011 to February 2014 were selected as observation group, 62 healthy persons with health education at the same time were the control group, then the serum and tear Zn, Cu, cellular immunity and erythrocyte immunity of two groups were compared, and the detection results of observation group with different types and severity degree were compared.RESULTS:The serum and tear Zn of observation group was all lower than that in control group, serum and tear Cu was higher than that in control group, cellular immunity and erythrocyte immunity indexes were all worse than that in control group, the detection results of observation group with mild, moderate and severe infection had significant differences (P<0. 05), while the detection results of observation group with herpes simplex keratitis and herpes zoster keratitis had no significant differences (P>0. 05).CONCLUSlON: The change of trace elements and body comprehensive immune state of patients with viral keratitis are obvious, and the severity degree for the detection levels of keratitis are greater.
8.Nasogastric enteral nutrition for severe acute pancreatitis:meta-analysis of clinical trials
Zhongfang YAN ; Yumei QI ; Wei LU ; Yi XIE
Chinese Journal of Clinical Nutrition 2009;17(5):271-274
Objective To assess the safety and effectiveness of nasegastric enteral nutrition (NGEN) in patients with severe acute pancreatitis (SAP).Methods A meta-analysis of all the relevant clinical trials was performed.Clinical trials were identified from the following electronic databases:Medline,EMBASE,the Cochrane Controlled Trials Register,and Chinese Bio-medicine Database.The search was undertaken in October 2008.The literature quality was evaluated with Cochrane Handbook 5.0.The statistical analysis was performed by RevMan 4.2 software.Results Four trials involving 157 patients were included.The combined results showed that no significant differences in the safety and tolerance between nasogastric and conventional routes in patients with SAP.Conclusions Currently available data show early NGEN appears to be effective,safe,and tolerable in patients with SAP.However,more large-scale high-quality trials are required to further elucidate this topic.
9.Protective effect of catechin on renal microvessels in 5/6 nephrectomized rats and its mechanism.
Yan CAO ; Xiaojie HE ; Wei XIANG ; Zhuwen YI
Journal of Integrative Medicine 2009;7(6):557-62
To investigate the effects of catechin on angiotensin-converting enzyme (ACE) activity, angiotensin II(Ang II) content and microvessel density (MVD) in renal tissues of 5/6 nephrectomized rats.
10.Reversal of Multidrug Resistance by IFN-? in KBv200 Cell Lines
Yan LIANG ; Xiyin WEI ; Kai LI ; Yi YANG ; Ruifang NIU
Chinese Journal of Cancer Biotherapy 1995;0(03):-
Objective: To explore the effects of various concentrations IFN-? on human oral epidermic cancer cell line KB and its multidrug resistant counterpart KBv200.Methods: The toxicity of IFN-? and/or VCR was assayed by MTT method; intracellular rhodamin123 concentration and p-glycoprotein expression were measured by flow cytometry; mdr-1 mRNA was assayed by RT-PCR. Results: High-dose IFN-?(10 000 IU/ml) had significant antiproliferative effects on KB/KBv200 cell lines. Low-dose IFN-? did not have any significant effect on growth of KB/KBv200 cells, but did increase the cytotoxic effect of VCR and the accumulation of Rhodamine123 in KBv200 cell line and had no effect on parent VCR-sensitive KB cell line. IFN-? down-regulated expression of P-gp and mdr-1mRNA . Conclusions: IFN-? has significant effect on the reversal of multidrug resistance of KBv200 cell line via a mechanism of P-gp and mdr1 mRNA down-regulation.