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.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.
6.Effects of Shenxiong Xintong Pill on Cardiac Hemodynamics
Yuanpeng ZHOU ; Yi YAN ; Xinjie PENG ; Wei XU
Traditional Chinese Drug Research & Clinical Pharmacology 1993;0(03):-
Objective: To study the effect of Shenxiong Xintong Pill(SXP) on cardiac hemodynamics. Methods: Parameters of cardiac hemodynamics were examined in anesthetic chest-opened dogs medicated with various doses of SXP. Results: After intraduodenal administration of SXP of 2.0g/kg, the coronary blood flow was raised, coronary resistance decreased, heart rate slowed and the left ventricular diastolic end pressure fallen in the dogs. No obvious changes were found in the contraction , works and ejection of left ventricle. Conclusion: The mechanism of SXP in relieving angina pectoris was probably related to the dilatation of coronary artery and increase of coronary flow with the increase supply of oxygen.
7.IL-1β promotes glial scar formation after spinal cord injury in rats by JAK2-STAT3
Jingxian LIU ; Yongzhi XIA ; Fugui WANG ; Wei TANG ; Yi YAN
Basic & Clinical Medicine 2017;37(5):668-675
Objective To investigate the mechanism of IL-1β in promoting glial scar formation after spinal cord injury.Methods The experimental model of SCI was created by extradural compression of the spinal cord using an aneurysm clip.Rats were randomly divided into model group, sham operation group, IL-1β inhibitor IL-1RA group, IL-1β group and IL-1β+JAK2-STAT3 inhibitor AG490 group, according to different interventions, then were given normal saline, IL-1RA, IL-1β and IL-1β+AG490 every 10 μL respectively, sham group received only laminectomy.The motion function of the hindlimbs of rats was measured by Basso Beattie Bresnahan(BBB) scores and the expression of GFAP, vimentin and p-STAT3 were detected by Western blot technique, immunofluorescence assay and immunohistochemistry technique at corresponding time points(at the 8th, 12th hour, 1st, 3rd, 7th and 14th day after SCI).Results The expression trend of p-STAT3(at the 8th and 12th hour after SCI),GFAP and vimentin(at the 7th and 14th day after SCI)was: the expressions of p-STAT3, GFAP and vimentin in the model group were significantly higher compared with the sham group(P<0.01), the expression of p-STAT3,GFAP andvimentin in the IL-1RA group were significantly lower compared with the model group(P<0.05) whereas significantly higher compared with the sham group(P<0.05);the expressions of p-STAT3, GFAP and vimentin in the IL-1β+AG490 group were significantly lower compared with the model group(P<0.05)whereas significantly higher compared with the sham group(P<0.05), the expressions of p-STAT3, GFAP and vimentin in the IL-1β group were significantly higher compared with the model group(P<0.05).Conclusions IL-1β can improve glial scar formation via JAK2-STAT3 signal.Inhibition of IL-1β or JAK2-STAT3 can reduce glial scar formation and promote functional recovery of spinal nerve.
8.Study on Anti-inflammatory and Analgesic Activities of Volatile Oil from Piper Puberulum in Guizhou
Yan YANG ; Yu WEI ; Yuhe WANG ; Yi SU
China Pharmacist 2016;19(10):1837-1839,1840
Objective:To study the anti-inflammatory and analgesic effects of the volatile oil from Piper puberulum ( Benth. ) Max-im. in Guizhou. Methods:Fifty KM mice were randomly divided into five groups (10 ones in each), the model control group (sa-line), low concentration volatile oil group (0. 125 ml/100 ml), medium concentration volatile oil group (0. 25 ml/100ml), high con-centration volatile oil group (0. 5 ml/100 ml) and aspirin group (3 mg·ml-1). Mouse ear swelling induced by xylene and skin capil-lary permeability were used to evaluate anti-inflammatory activity of the volatile oil from Piper puberulum ( Benth. ) Maxim. in Guizhou. Acetic acid-induced abdominal eonstrietion test and hot-plate test were applied to evaluate anti-analgesic activity of the vola-tile oil from Piper puberulum ( Benth. ) Maxim. In Guizhou. Results:Compared with that in the model group, the mouse ear swelling in the medium concentration volatile oil group, high concentration volatile oil group and aspirin group was significantly reduced ( P<0. 05). The skin capillary permeability in the high concentration volatile oil group and aspirin group was significantly reduced (P<0. 05 or P<0. 01). Compared with that in the model group, the writhing times in the medium concentration volatile oil group, high concentration volatile oil group and aspirin group were significantly reduced (P<0. 05 or P<0. 01). The pain threshold in the high concentration volatile oil group was effectively reduced (P<0. 05 or P<0. 01). Conclusion: The volatile oil from Piper puberulum ( Benth. ) Maxim. in Guizhou has promising anti-inflammatory and analgesic activities.
9.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.
10.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.