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.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.
4.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.
5.Impact on evaluation of clinical efficacy of traditional Chinese medicine for level in soft targets of processing technology.
Ming-Yi SHAO ; Ming WEI ; Bo-Hua YAN
China Journal of Chinese Materia Medica 2014;39(7):1315-1317
Traditional Chinese medicine (TCM) is a very practical subject, which has its unique theoretical system and clinical characteristics. In the course of clinical practice, the exact clinical efficacy is the key of existence and development. But the existing evaluation system is difficult to objectively evaluate the clinical efficacy of TCM. Therefore, how to objectively evaluate the clinical efficacy and get definitive evidence is the focus of the evaluation of clinical efficacy of TCM. Relative to modern medicine, TCM is more concerned about the changes of feelings and clinical symptoms of the patient in the course of the evolution of the disease. Soft targets mainly used for the evaluation of the clinical efficacy of symptoms and functional activity of the disease. The level in soft targets of processing technology is often used methods in clinical evaluation. But it has often produced the phenomenon which the results of the evaluation is mutual contradiction, which will ultimately affect the effect of evaluation of clinical efficacy of TCM. In order to better evaluate the clinical efficacy of TCM, in the process of adoption of soft targets, it clearly identify it's role, highlighting the characteristics of interventions on disease, and as much as possibly avoid the level in soft targets of processing technology to real assess clinical efficacy of TCM.
Drug Therapy
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Drugs, Chinese Herbal
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therapeutic use
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Evaluation Studies as Topic
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Humans
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Medicine, Chinese Traditional
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Research Design
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Treatment Outcome
6.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.
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.Serum microRNA profiles as novel biomarkers for the post-operative evaluation and survival of patients with glioblastoma multiform
Xiujuan GAO ; Xi CHEN ; Wei YAN ; Jingjing YIN ; Yi BA
Chinese Journal of Clinical Oncology 2016;43(13):562-566
Objective:To investigate the differentially expressed miRNAs in serum collected post operation and compared these miR-NAs with those collected pre-surgery among patients suffering from glioblastoma multiform (GBM) and undergoing regular clinical fol-low-up. These miRNAs may be potential biomarkers for the post-operative evaluation of patients with GBM. Methods:Forty-eight pa-tients with GBM and clinical pathological diagnosis were enrolled in this study. In the initial biomarker screening stage, total RNAs were extracted and subjected to Solexa sequencing to select miRNAs with significantly altered expression pre-and post-operation. Some of these differentially expressed miRNAs were chosen and verified through TaqMan probe-based qRT-PCR assay. A t-test was performed to determine the miRNAs that satisfied the two criteria, namely, fold change>2 and P<0.05. All of the patients were fol-lowed-up, and survival data were collected. The patients were then classified into two groups, namely, long-and short-survival groups, on the basis of the median of the miR-30e expression levels in the sera collected post-operation. Kaplan-Meier method and Log-rank test (SPSS version 19.0, IBM) were employed to determine the possible relationships between miR-30e expression levels in the sera collected post-operation and patients' overall survival. Results: Solexa revealed 63 differentially expressed miRNAs. Four miRNAs, namely, miR-26b, miR-30e, miR-129-3p, and miR-206, were selected on the basis of previous and present findings. These miRNAs were then verified in the RT-qPCR phase. Among these miRNAs, only miR-30e was significantly upregulated post-operation. The serum miR-30e expression level post-operation was not significantly associated with the overall survival of the patients. A low miR-30e expression level corresponded to prolonged survival. Conclusion:miR-30e was upregulated in the sera collected post-operation from patients with GBM. This miRNA may be negatively related to the tumor load of these patients. The miR-30e expression level in the serum col-lected post-surgery serum was not significantly associated with overall survival. Therefore, miR-30e may serve as a novel potential non-invasive biomarker for the post-operative evaluation of patients with GBM.
9.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.
10.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