2.Small molecular agents against MERS-CoV infection.
Xiao-yun ZENG ; Lu LU ; Shi-bo JIANG ; Shu-wen LIU
Acta Pharmaceutica Sinica 2015;50(12):1520-1526
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused outbreaks of SARS-like disease with 35% case-fatality rate, mainly in the Middle East. A more severe outbreak of MERS occurred recently in the Republic of Korea, where 186 people contracted the infections, causing great concern worldwide. So far, there has been no clinically available drug for the treatment of MERS-CoV infection. The potential drugs against MERS-CoV mainly consist of monoclonal antibodies, peptides and small molecular agents. Small molecular agents have an advantage of easier synthesis, lower cost in production and relatively higher stability. There is better chance for those candidates to gain a quick development. This article reviews the progress of developing small molecular MERS-CoV agents.
Antibodies, Monoclonal
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pharmacology
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Antiviral Agents
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pharmacology
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Coronavirus Infections
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drug therapy
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Drug Design
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Humans
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Middle East Respiratory Syndrome Coronavirus
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drug effects
3.Identification of constituents in Suanzaoren tang by LC-Q-TOF-MS and LC-IT-MS.
Yun-Xiang ZHU ; Lu-Lin CHEN ; Jing-Ru GONG ; Shu-Fang WANG
China Journal of Chinese Materia Medica 2014;39(3):457-465
LC-Q-TOF-MS and LC-IT-MS in positive and negative ion mode were applied to simultaneously characterize the constituents in Suanzaoren tang. Analysis was performed on an Agilent Zorbax SB-C18, Rapid Resolution HT column(4.6 mmx 50 mm, 1. 8 micro m) with gradient elution of acetonitrile(A) -aqueous solution containing 0. 05% formic acid(B) at a flow rate of 0. 6 mL min(-1) and the column temperature was 30 degreesC. By comparing MS fragmentation, accurate molecular weight, literature date and standard compounds information, a total of48 compounds were successfully identified or speculated. The origins of these compounds were assigned to the corresponding Chinese medicine. Thirty-one compounds were reported in Suanzaoren tang for the first time. LC-Q-TOF-MS combined with LC-IT-MS is a simple and rapid tool for the identification of constituents of Suanzaoren tang, and the results could provide evidence for the research on quality combined and effective constituents of Suanzaoren tang.
Chromatography, Liquid
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Drugs, Chinese Herbal
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chemistry
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Mass Spectrometry
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Organic Chemicals
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analysis
4.Effects of atorvastatin on blood pressure and left ventricular remodeling in patients with both essential hypertension and hypercholesterolemia
Chang-Jiang GE ; Shu-Zheng LU ; Yun-Dai CHEN ; Xin CHEN ; Chun ZHANG ;
Chinese Journal of General Practitioners 2002;0(01):-
Objective To compare the changes in serum levels of high sensitive C-reactive protein (hs-CRP)and uric acid(UA)before and after atorvastatin treatment for the patients with both essential hypertension and hypercholesterolemia,and to evaluate its effects on blood pressure and left ventricular remodeling.Methods One hundred and twenty-six hypertensive patients complicated with hypercholesterolemia were randomized into group A with amlodipine 10 mg/d(n = 65)and group B with amlodipine 10 mg/d plus atorvastatin 20 mg/d(n = 61),for three months continuously.Serum levels of total cholesterol(TC),low-density lipoprotein-cholesterol(LDL-C),high-density lipoprotein-cholesterol (HDL-C),triglyeerides(TG),hs-CRP and UA,as well as blood pressure,were determined for both groups before and after treatment.Left ventricular posterior wall thickness(LPWT)and interventricular septum thickness(IVST)were measured by echocardiography and left ventricle mass index(LVMI)was calculated.Results Serum levels of TC,LDL-C,HDL-C,TG,hs-CRP and UA decreased significantly in gr6up B after three-month treatment with atorvastatin,while serum level of HDL-C increased significantly. And,systolic and diastolic blood pressure reduced in both groups,but significantly lower in group B than those in group A,after treatment(P
5.The composition of filament in filamentary keratitis eye
Ting, WANG ; Jun-cai, LIU ; Shu-ting, WANG ; Xiu-hai, LU ; Wei-yun, SHI
Chinese Journal of Experimental Ophthalmology 2013;32(11):1061-1064
Background Eyes with filamentary keratitis present with serious clinical symptoms.This disease is easy to relapse and the treatment is tricky.At present,its pathogenesis is still unclear,and few works were done on filamentous composition.Objective This study was to analyze the composition of corneal filament by imageological and histopathological method,and discuss the formation mechanism of filamentary keratitis.Methods Eighty-eight eyes of 82 cases who suffered from filamentary keratitis were collected in Shandong Eye Hospital between January 2008 and January 2011.The etiologies of the patients were classified and the clinical data were recorded.Firstly,the corneal filiform strip was detected by laser scanning confocal microscopy (LSCM),and the corneal structure was examined by high-definition optical coherence tomography (HD-OCT).Then the composition of filamentary strip was analyzed by Giemsa and Masson trichrome staining of stretched preparation of filiform strip.Results Etiological study showed that filamentary keratitis occurred after penetrating keratoplasty in 40 eyes,after cataract surgery and photorefractive keratectomy (PRK) in 18 eyes,dry eye and neural dystrophic corneal disease in 14 eyes,acute conjunctivitis in 10 eyes.HD-OCT revealed that filament lesion developed to Bowman layer.Filament was composed of epithelial cells,inflammatory cells,mucus and the high reflective strip core with spiral arrangement under the LSCM,and epithelial cells,inflammatory cells and fibrous tissue were seen in the strip core.Giemsa staining exhibited that filament contained corneal epithelial cells,inflammatory cells,mucus and dark blued strip core with helical arrangement.Masson trichrome discovered that the strip core was red fibrous tissue surrounding by blue mucus.Conclusions Epithelial cells,inflammatory cells,mucus and the high reflective strip core with spiral arrangement are the main elements of filament in filamentary keratitis.The lesion can reach Bowman layer.The results contribute to reveal the formation mechanism of corneal filament and assist treatment.
6.Effects of advanced glycation end-products on skin keratinocytes by NF-?B activation
Ming TIAN ; Chun QING ; Yi-Wen NIU ; Jiao-Yun DONG ; Shu-Wen JIN ; Fei SONG ; Lan-Nv HUA ; Shu-liang LU
Chinese Journal of Trauma 2003;0(10):-
Objective To investigate the effects of advanced glycation end-products(AGEPs)on the function of normal keratinocytes in vitro so as to explore the role of AGEPs in impaired wound healing. Methods Normal rat keratinocytes were incubated with different concentrations of AGEPs.After 48 hours of culturing,the cell proliferation rates were measured by MTT colorimetric determination.The cell cycle distributions and apoptosis were analyzed with flow cytometry,and the migration was investigated by 24-well fluorimetric cell migration assay kit by exposing to 100?g/ml AGEPs.Nuclear extracts from these cells were examined for binding of nucleotides containing NF-?B consensus by immunocytochemistry and EMSA in vitro.Results The proliferations of normal keratinocytes were significantly arrested and many cells were induced to early apoptosis compared with control ones(P<0.05)by exposing to AGEPs for 48 hours. Meanwhile AGEPs also irritated keratinocytes migration compared with control ones(P<0.05).Inhibiting the activation of NF-?B could partly recover the proliferation of keratinocytes,reverse apoptosis and attenu- ate migration.Conclusion AGEPs are correlated with the migration,proliferation and apoptosis of kera- tinocytes by NF-?B.
7.Effects of intensive antiplatelet therapy in patients with high platelet aggregability after percutaneous coronary intervention.
Yan-ling LU ; Yun-dai CHEN ; Shu-zheng LÜ
Chinese Journal of Cardiology 2007;35(9):793-796
OBJECTIVEPost percutaneous coronary intervention (PCI) major cardiac event rate is high in patients with high platelet aggregability. We observed the effects of intensive antiplatelet therapy in these patients.
METHODSADP-induced platelet inhibition rates were less than 30% after 24 h treatment with Clopidogrel (300 mg) in 402 patients out of 1556 patients who underwent PCI in our institute between January 2004 to June 2006. These patients were randomly divided into control group (Clopidogrel 75 mg/d and aspirin 100 mg/d, n = 201) or treatment group (Clopidogrel 75 mg/d and aspirin 100 mg/d plus cilostazol 200 mg/d, n = 201). Major adverse cardiac events were analyzed after 6 months treatments.
RESULTSPatients with ADP-induced platelet inhibition rates < 30% were significantly lower in treatment group compared to control group after 28 days treatments (9.4% vs. 89.6%, P < 0.05). Thrombosis complication (0.5% vs. 3.0%), death (0 vs. 1.0%), non-fatal myocardial infarction (0.5% vs. 1.5%), hemorrhagic (6% vs. 4%) rates were similar between treatment and control group while target vessel revascularization rate was significantly lower in treatment group compared to control group (6.5% vs. 15.9%, P < 0.05). Total MACE rate was therefore significantly lower in treatment group than that in control group (13.5% vs. 25.4%, P < 0.05).
CONCLUSIONIntensive anti-platelet treatment could significantly reduce major cardiac event rates in patients with high platelet aggregability after percutaneous coronary intervention.
Aged ; Angioplasty, Balloon, Coronary ; Aspirin ; therapeutic use ; Coronary Artery Disease ; drug therapy ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Count ; Ticlopidine ; analogs & derivatives ; therapeutic use
8.Clinical significance of detecting interleukin-2、interleukin-10、interleukin-13 in asthmatic children
xiao-hui, LU ; song-yan, ZHANG ; shu-qiang, QU ; hua, ZHANG ; li-qun, WANG ; yun feng, ZHANG
Journal of Applied Clinical Pediatrics 1986;0(02):-
Objective To evaluate the changes of peripheral blood interleukin(IL) 2, IL 10, IL 13 in the serum of asthmatic children and their effect on the pathogenesis of asthma.Method The serum levels of IL 2,IL 10,II 13 in 16 cases of asthmatic children and 10 cases of healthy controls were measured by ELISA methods.Results The serum levels of IL 2,IL 13 in asthmatic patients were significantly higher than those in healthy controls( P
9.Noninvasive detection and evaluation of coronary atherosclerotic plaques with multi-slice spiral CT:a comparative study with intravascular ultrasonograhy
Wen-Hui WU ; Bin LU ; Shi-Liang JIANG ; Jin-Guo LU ; Shu-Bin QIAO ; Yong-Jian WU ; Ru-Ping DAI ; Yun SHEN ;
Chinese Journal of Radiology 1999;0(10):-
Objective To evaluate the capability and accuracy of multi-shce spiral computed tomography(MSCT)in detecting atherosclerotic plaques in nonstenotic coronary arteries with reference to the findings of intravascular ultrasound(IVUS)in a segment analysis.Methods Both IVUS exams and 16-row MSCT scans were performed on 35 consecutive patients among whom 30 patients had successful MSCT scans.A total of 94 coronary segments without significant coronary stenoses were paired-analyzed both on IVUS and MSCT segment by segment.The plaques were classified as calcified,fibrotic and soft types according to the echogeneity on IVUS.Plaque attenuation on MSCT was measured and expressed by Hounsfield units(HU).Results When referred to IVUS,MSCT had a sensitivity of 82.1%(46/56)and specificity of 89.5% (34/38),respectively in detectiong any plaques.For the detection of calcified plaques,the sensitivity and specificity were 92.1%(35/38)and 96.4%(54/56),respectively.For the detection of mixed and noncalcified plaques,MSCT had sensitivity of 73.2%(30/41)and specificity of 88.7%(47/53).But for the detection of the noncalcified plaque,the sensitivity was 66.7%(12/18). According to the findings On IVUS,the plaques were classified as calcified(n=19),fibrotic(n=19)and soft(n=16).The CT attenuation of calcified plaques was(489?169)HU(196 to 817 HU),fibrotic plaques(69?21)HU(25 to 117 HU)and soft plaques(23?18)HU(-12 to 47 HU).Nonparametric Kruskal-Wallis test revealed a significant difference of plaque attenuation among the three groups(P
10.Effects of advanced glycation end products and its receptor on oxidative stress in diabetic wounds.
Yi-wen NIU ; Ming-yuan MIAO ; Wei DONG ; Jiao-yun DONG ; Xiao-zan CAO ; Shu-liang LU
Chinese Journal of Burns 2012;28(1):32-35
OBJECTIVETo investigate the accumulation of advanced glycation end products (AGE) and the inflammatory response of skin and wound in diabetic patients, and to analyze their relationship in vitro.
METHODSHistological staining and immunohistochemical staining was respectively performed on skin and wound tissue specimens collected from 10 patients with Type II diabetes mellitus (diabetes group) and 12 non-diabetic patients with skin injury (control group) to observe the arrangement of collagen and the distribution of inflammatory cells, and to determine the expression levels of AGE and its receptor (RAGE). Malondialdehyde (MDA) levels in skin and wound tissue homogenates were assayed by enzyme-linked immunosorbent assay. In vitro, human neutrophils were isolated and treated with RPMI-1640 culture medium or that containing AGE-human serum albumin in the concentration of 0.315, 0.625, 1.250 mg/mL, and they were identified as normal control (NC) group, low concentration (L) group, moderate concentration (M) group, and high concentration (H) group. Cell viability in each group was determined by MTT colorimetric assay, and the reactive oxygen species (ROS) in cell was measured with 2', 7'-dichlorofluorescein-diacetate. Data were processed with t test.
RESULTSCompared with those of skin in control group, collagens of skin tissues in diabetes group atrophied and disorderly arranged. Inflammatory cells in wounds in diabetes group were dispersed, in which collagens arranged loosely and irregularly, as compared with those of wounds in control group. Expression levels of AGE and RAGE of skin in diabetes group were higher than those in control group. In diabetes and control groups, especially in diabetes group, the numbers of RAGE-positive cells in wound tissue were more than those in skin tissue. Large amount of inflammatory cells with positive expression of RAGE were observed in diabetes group. MDA level of skin and wound tissue in diabetes group was respectively (6.3 ± 1.0), (7.1 ± 2.4) nmol per milligram protein, which were obviously higher than those in control group [(2.9 ± 1.0), (3.6 ± 1.4) nmol per milligram protein, with t value respectively 8.017, 4.349, P < 0.05 or P < 0.01]. Cell viability and ROS levels in neutrophils were increased in L, M, and H groups [(59 ± 8)%, (77 ± 5)%, (67 ± 6)% and 1.67 ± 0.14, 2.13 ± 0.17, 3.48 ± 0.48] as compared with those in NC group [(34 ± 5)% and 0.58 ± 0.06, with t value respectively 7.195, 14.890, 11.130 and 20.195, 24.905, 16.864, P < 0.05 or P < 0.01].
CONCLUSIONSAbnormal oxidative stress in diabetic skin leads to an atypical origin of wound repair. AGE-RAGE effect is a critical mediator for oxidative stress in diabetic wound tissue during wound healing.
Aged ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; metabolism ; pathology ; Female ; Glycation End Products, Advanced ; metabolism ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Serum Albumin ; metabolism ; Serum Albumin, Human ; Skin ; metabolism ; pathology ; Wound Healing