1.Research progresses of Mycobacterium tuberculosis cytochrome P450s as a potential drug target.
Yun LU ; Feng QIAO ; Xue-Fu YOU ; Xin-Yi YANG
Acta Pharmaceutica Sinica 2014;49(4):427-434
Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents
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chemistry
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pharmacology
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Azoles
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chemistry
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pharmacology
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Cytochrome P-450 Enzyme Inhibitors
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chemistry
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pharmacology
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Cytochrome P-450 Enzyme System
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genetics
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metabolism
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Drug Delivery Systems
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methods
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Drug Discovery
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Humans
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Mycobacterium tuberculosis
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drug effects
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enzymology
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genetics
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Phylogeny
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Tuberculosis
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drug therapy
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microbiology
2.Application of saw palmetto fruit extract in the treatment of prostate diseases.
Xu-xin ZHAN ; Xue-jun SHANG ; Yu-feng HUANG
National Journal of Andrology 2015;21(9):841-846
Saw palmetto fruit extract (SPE), as a herbal product, is widely used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Recent studies show that SPE also has some therapeutic effects on chronic prostatitis, prostate cancer, sexual dysfunction, and so on. This article presents an overview on the application of SPE in the treatment of BPH, prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome, with a discussion on its action mechanisms.
Chronic Disease
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Fruit
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chemistry
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Humans
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Lower Urinary Tract Symptoms
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drug therapy
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Male
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Pelvic Pain
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drug therapy
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Plant Extracts
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therapeutic use
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Prostatic Diseases
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drug therapy
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Prostatic Hyperplasia
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drug therapy
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Prostatic Neoplasms
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drug therapy
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Prostatitis
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drug therapy
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Syndrome
4.Ultrasound evaluation of the carotid artery hemodynamics in hypertensive elders
Yu XUE ; Junrong LI ; Feng ZHAO ; Xin ZHANG ; Peijing LIU
Chinese Journal of Tissue Engineering Research 2005;9(27):210-212,封三
BACKGROUND: Non-invasive vascular ultrasound is used to assess in tima-media thickness (IMT) and atheromatous plaque, of which the result is better correlated to that of pathological examination. OBJECTIVE: Non-invasive vascular ultrasound was used to assess the hemodynamical changes of external and internal carotid in hypertensive elders, so as to investigate the relationship between pulse pressures, left ventricular mass index (LVMI), vascular resistance index (VRI) and shearing ratio. DESIGN: Randomized, controlled, correlative analyzedstudy. SETTING: Ultrasound Department of Affiliated Hospital of Jiangshu University. PARTICIPANTS: Totally 54 hypertensive elders, including 33 males and 21 females, were recruited from the Ultrasound Department of Affiliated Hospital of Jiangshu University, from September 30th 2000 to March 30th 2002. Meanwhile 26 normotensive elders (systolic pressure < 130 mm Hg and/or diastolic pressure < 85 mm Hg), including 16 males and 10 females, were selected as controls, METHODS: Color duplex blood flow imaging technique was used to assess the left ventricular end-diastolic diameter (LVEDD) and the interventricular septum thickness (IVST), so as to calculate the LVMI. The insiddiameter of bilateral common carotid artery (CCA) and internal carotid,IMT, the systolic peak flow velocity and resistance index were measured in order to calculate the vascular shearing ratio and atheromatous plaque index,moreover arterial pressure, LVMI, as well as resistance index and shearing ratio were subjected to linear correlative analysis,of which the results were compared with that of control group. MAIN OUTCOME MEASURES: ① Pulse pressure, LVMI and atheromatous plaque index of CCA. ② The inside diameter of bilateral CCA and internal carotid, IMT and the systolic peak flow velocity and resistance index were measured in order to calculate the atheromatous plaque index and maximum vascular shearing ratio. RESULTS: According to the experimental objective,data of all 80 cases were analyzed without loss. ① The pulse pressure and LVMI, the incidence of atheromatous plaque and plaque index of CCA in hypertensive elder group were obviously higher than that of control group [(64.36±7.44) mm Hg,(45.78±8.72) mm Hg; (131.47±18.73) g/m2, (83.28±12.34) g/m2; 5.62 ±1.78,3.44±1.10; 66.7%, 23.1%, (x2=13.37, t=5.730-13.234, P < 0.01)]. ② The inside diameter of bilateral CCA and internal carotid, IMT and resistance index in hypertensive elders were significantly higher than that of control group [CCA: (8.96±1.20) mm, (8.08±0.96) mm; (1.28±0.88) mm, (0.91±0.17) mm;0.75±0.05, 0.69±0.06; ICA: (6.82±1.12) mm, (5.72±0.92) mm; (1.06±0.17) mm,(0.76±0.15) mm; 0.70±0.07, 0.64±0.06, t=2.872-10.850, P < 0.01], but the systolic peak flow velocity and shearing ratio were markedly lower than that of control group [CCA: (47.44±12.85) cm/s, (60.20±14.32) cm/s;(225.78 ±95.76)/s, (300.26 ±110.42)/s. ICA: (41.22 ±10.18) cm/s,(48.64±11.58) cm/s; (268.54±112.56)/s, (324.52±121.42)/s, t=2.872-10.850, P < 0.01]. ③ The pulse pressure, LVMI, the resistance index of CCA and ICA and shearing ratio were linearly correlated (r=0.30-0.36, P < 0.05). CONCLUSION: Pulse pressure and LVMI were found increased in hypertensive elders, together with carotid vessels dilated, IMT and resistance index increased, as well as shearing ratio decreased, atheromatous plaque formed, vascular stiffness increased, which resulted in consequently decrease of vascular compliance.
5.T Endothelial progenitor cells (EPCs) and promote angiogenesis factor levels in peripheral blood in patients with obstructive sleep apnea
Yanchao XUE ; Bei SUN ; Xin WANG ; Jing FENG ; Jie CAO
Tianjin Medical Journal 2016;44(1):19-22
Objective To explore the repair possibilities of endothelial progenitor cells (EPCs)in peripheral blood in patients with different extents of obstructive sleep apnea (OSA) through measuring the levels of pro-angiogenic factors and different subgroups EPCs in peripheral blood in patients with OSA. Methods Ninety adult patients with OSA, 30 healthy controls with matched age and gender were enrolled for this study. The subjects performed Polysomnography, were divided in-to four group based on Apnea Hypopnea Index (AHI). The serum levels of HIF-1α, SDF-1αand VEGF were assessed by ELISA. Mononuclear cells were isolated from peripheral blood with density gradient centrifugation, and flow cytometry was used to detect levels of CD133+KDR+EPC, CD133+CD34+EPC, CD34+KDR+EPC and ALDHloCD34+KDR+EPC based on AL-DH activity, and CD133, CD34, PE-KDR related cell surface markers. Results The levels of CD133+KDR+EPC, CD133+CD34+EPC, CD34+KDR+EPC were higher in OSA groups than those of control group, both of which were higher in severe OSA group than those of in mild and moderate OSA groups. The levels of ALDHloCD34+KDR+EPC were higher in mild and moderate OSA groups than that of the control groups, and the levels of ALDHloCD34+KDR+EPC were significantly lower in se-vere OSA group than those of control, mild and moderate OSA groups. Serum levels of HIF-1α. VEGF were significantly high-er in OSA groups compared to those in control groups, both of which were higher in severe OSA group than those of mild and moderate OSA groups. Serum levels of SDF-1αwere significantly lower in severe OSA groups than those of mild, moderate OSA and control groups (P<0.05). Conclusion The mobilization and recruitment of different subtypes of EPCs are obvious-ly increased in patients with OSA, but ALDHloCD34+KDR+EPC with vascular repair capacity keeps to invariability, even de-creases in patients with severe OSA, which results in endothelial damage, and increases the risk of cardiovascular disease.
6.Arthroscopic prevalence of Ramp lesion of anterior cruciate ligament injury
Xin LIU ; Hui ZHANG ; Hua FENG ; Qingyun XUE
Chinese Journal of Orthopaedics 2011;31(11):1272-1277
ObjectiveTo retrospectively determine the prevalence of Ramp lesion (the peripheral attachment of the posterior horn of the medial meniscus) of the posterior horn of the medial meniscus with concurrent anterior cruciate ligament(ACL) ruptures and analyze the relevant risk factors.MethodsFrom April 2002 to October 2007,868 consecutive knees were diagnosed as ACL injury and received arthroscopic surgery for ACL reconstruction(ACLR).All the patients were verified for the tears of Ramp area under arthroscopy.The prevalence of Ramp lesion was evaluated respectively.Then all cases were divided into different groups depending on the time interval from ACL injury to ACLR (TFI) and other relevant risk factors as age and gender.ResultsAmong 868 knees underwent surgery for ACLR,144 knees were diagnosed as Ramp lesion.The average age was 24.7 years,113 males,31 females.The mean TFI to ACLR was 29.3months.The prevalence of Ramp lesion was 16.59%,which was analyzed as logarithmic correlation with TFI.Patients younger than 30-year old and male patients had significant higher prevalence of Ramp lesion.ConclusionRamp lesion is a common meniscus injury that can occur at the time of ACL rupture or as a result of knee laxity associated with ACL insufficiency.The prevalence of Ramp lesion is 16.59% which increases with time until 24 months after initial injury.Patients younger than 30-year old and male patients have higher prevalence of Ramp lesion.
7.Non-invasive cardiac output measurement in children using bioreactance:a comparison with echocar-diography
Tian SANG ; Ying WANG ; Xue FENG ; Xin ZHANG ; Xueqin LIU
Chinese Pediatric Emergency Medicine 2016;23(2):78-81
Objective To investigate the value of measurement of cardiac output in children by bio-reactance versus echocardiography.Methods Pediatric patients admitted in pediatric department of Peking University First Hospital from September to December 2012 who needed hemodynamic monitoring were enrolled prospectively.Cardiac index(CI)and stroke volume(SV)were measured by echocardiography and non-invasive cardiac output measurement(NICOM)and compared by Spearman correlation and Bland-Alt-man analysis.Results Thirty patients were included.The median age was 7.25 years.CI[M(P5 ,P95 )] measured by NICOM and echocardiography were correlated significantly[3.42(2.28,4.92)L /(min?m2 ) vs.3.51 (2.94,4.85 )L/(min?m2 ),R =0.385,P =0.035 ].Bland-Altman analysis revealed a bias of-0.22 L/(min?m2 )(P =0.051 ),limits of agreement of -1.40 to 0.95 L/(min?m2 ).SV[M(P5 ,P95 )] measured by NICOM and echocardiography were correlated more significantly [36.3 (12.6,87.8 )ml vs.39.4(14.7,86.9)ml,R =0.768,P ﹤0.001 ].Bland-Altman analysis revealed a bias of -3.1 ml(P =0.176),limits of agreement of -27.4 to 21.2 ml.Conclusion There is no significant difference between NICOM and echocardiography for the measurement of CI and SV in pediatric patients.Further validation studies need to be conducted before routine clinical use.
8.Protective effect of antioxidative ?-lipoic acid on kidneys in type 2 diabetic rats
Bo FENG ; Xin-Feng YAN ; Lei XU ; Qiao-Hui QIAN ; Hua WANG ; Jun-Li XUE ;
Chinese Journal of Endocrinology and Metabolism 2001;0(05):-
There were significant increase in urine protein excretion,raised malondialdehyde(MDA) level and expressions of NF-?B,p22phox and p47phox in renal tissue,and significant decrease in reduced glutathione,superoxide dismutase,vitamin C and E levels in type 2 diabetic Goto-Kakisaki rats after 12 weeks. There was obvious histomorphologic change in the kidneys.All the above indices were improved by intraperitoneal injection of?-lipoic acid(35 mg/kg q.o.d).Besides,significant positive correlations were found of MDA level to p22phox,p47phox and NF-?B in the renal tissue,?-lipoic acid seems to protect the diabetic kidney in this diabetic rat model via antioxidative effects.
9.Expression and significance of GOLPH3 in brain glioma
Xue-Yuan LI ; Wei LIU ; Xue-Guang ZHANG ; Xin FENG ; Shuang-Feng CHEN ; Lian-Qun ZHANG ; Xin-Gang LI
Chinese Journal of Neuromedicine 2010;09(9):865-868
Objective To investigate the expression of GOLPH3 in the tumor tissues of patients with gliomas and evaluate its clinical significance. Methods Seventy-six patients with brain gliomas (13 with grade Ⅰ, 27 grade Ⅱ, 25 grade Ⅲ and 11 with glioblastoma) performed surgical excision in our hospitals from July 2008 to December 2009 were chosen and 9 cases of normal brain tissues from patients performed decompression operation resulting from cerebral hernia were selected as the controls in our experiment. RT-PCR and Western-blotting were used to detect the mRNA and protein expressions of GOLPH3. Results The results investigated by RT-PCR and Western-blotting were consistent,revealing that the mRNA and protein expression rate of GOLPH3 in glioma tissues was not significantly different between different grades of tumors (P>0.05), but their expression value was obviously significant between different grades of tumors and increased in a grade-dependent manner (P<0.05). And minimal mRNA and protein expressions of GOLPH3 were found in the tissues of controls. The up-regulative protein expression of GOLPH3 was positively correlated to the malignancy-grade of the gliomas (r,=0.961, P=0.000). Conclusion The mRNA and protein expressions of GOLPH3 are noted with positive correlation to the pathological grades of the gliomas, indicating th at GOLPH3 may play an important role in the generation and development of gliomas.
10.Differential proteomic analysis of total protein of ASMC stimulated by wild and mutant IL-13
Xiao-Feng JIANG ; Xiao-Ying GUO ; Hong-Yan LIANG ; Xue-Fei DU ; Yu XIN ; Li XUE ; Song-Bin FU ;
Chinese Journal of Laboratory Medicine 2001;0(04):-
Objective To analyze the differential proteomics of ASMC stimulated by wild IL-13 and mutant IL-13 and to investigate the relations of protein profiles of ASMC to asthma and possible targets for the treatment of bronchial asthma.Methods The total proteins of ASMC stimulated by wild IL-13 and mutant IL-13 were separated by immobilized pH gradient(IPG)-based 2-DE and the differentially expressed protein spots were identified by matrix assisted laser desorption-time of flight mass spectrometry(MALDI-TOF-MS). Results The 2-DE detected approximately(840?21)spots on wild IL-13 samples and(892?17)spots on mutant IL-13 samples(n=3)and(685?19)spots matched.Six significantly differential proteins were subjected to MALDI-TOF-MS analysis and three of them were identified as stathmin 1,Ribosomal protein p~0 and NADH dehydrogenase.Conclusions ASMCs stimulated by wild IL-13 and mutant IL-13 present different proteomic profiles that may shed some light on the mechanism for the asthma causing effect of wild IL-13 and mutant IL-13.