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.
4.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.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.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.
7.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.
8.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.
9.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.
10.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.