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Selective activation or inhibition of the angiotensin II type 2 (AT2) receptor can cause vasodilation, decrease cell proliferation, promote neurite outgrowth and block neuronal excitability. The AT2 receptor can be used as a potential drug target for the treatment of cardiovascular diseases, fibrosis, inflammation, neuronal diseases and tumors. Research and development of new drugs that selectively act on the AT2 receptor and the mechanism of intracellular signal transduction involving the AT2 receptor is a challenging but worthy endeavor. We review research progress on the AT2 receptor and compounds that act on the AT2 receptor, along with structure-activity relationship analysis, to provide reference and guidance for further research in this field.
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@#AIM: To observe the clinical therapeutic efficiency of 1g/L sodium hyaluronate eye drops on ocular surface disorders in patients with proliferative diabetic retinopathy(PDR)after 20G pars plana vitrectomy(PPV). <p>METHODS: Randomized single blind case control study was used. Patients with type 2 diabetes who were admitted to the department of ophthalmology, Xi'an No.4 Hospital for PDR and underwent 20G PPV surgery by the same surgeon were randomly divided into PDR control group(Group A)and sodium hyaluronate treatment group(Group B). Group B received continuous 1g/L sodium hyaluronate eye drops from 1d to 2mo after surgery. Before and 1wk, 1, 3mo after surgery, OSDI, SⅠt, BUT, fluorescein cornea staining(FL)and the tear film and corneal epithelial cell layer under corneal laser scanning confocal microscopy of the two groups were compared. <p>RESULTS:A total of 90 cases and 90 eyes were studied. In preoperative time, the two groups showed obvious dry eye syndrome, and compared with the control subjects, there were no significant difference existed between the two groups(<i>P</i>>0.05). In group A, ocular surface injury was further aggravated after surgery and failed to recover with time extension during the observation period.Some indexes of Group B improved at different observation time after surgery compared with those before surgery, and there were significant differences between group A and Group B after surgery(<i>P</i><0.05). <p>CONCLUSION: Applying 1g/L sodium hyaluronate eye drops could relief the uncomfortable feeling of ocular surface in patients with PDR after 20G vitrectomy and accelerate the recovery of ocular surface disorders.
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Objective Objective To evaluate the efficacy and safety of Reinhartdt and Sea Capsule (RSC) combined with donepezil (experimental group) compared with donepezil (control group) in treatment of Alzheimer's disease.Methods The randomized controlled trials (RCT) of reinhartdt and sea capsule combine with donepezil in treatment of Alzheimer's disease were searched from Pubmed,VIP,CNKI,CBM,and Wangfang detabase by computer.Deadline from January 2000 to February 2017.References of included studies were also retrieved,extracted data,and assessed the methodological quality.Then,Meta-analysis was performed using RevMan 5.0 software.Results A total of eight RCTs were included,including 605 patients with insomnia.Meta-analysis results showed that compared with control group,experimental group MMSE score [P＜0.001,MD=2.69,95％CI(1.46,3.92)],ADAS-Cog score [P＜0.001,MD=-4.54,95％CI(-5.64,-3.43)] and ADL score [P＜0.001,MD=-3.60,95％CI(-4.53,-2.66)],the difference was statistical;There was no signficant difference between two group in the incidences of adverse effect [P=-0.94,OR=1.02,95％CI(0.63,1.66)].Conclusion RSC combined with donepezil showed better efficacy for Alzheimer's disease,yet without increasing adverse effect rate as compared with donepezil alone.
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Objective Objective To evaluate the efficacy and safety of Reinhartdt and Sea Capsule (RSC) combined with donepezil (experimental group) compared with donepezil (control group) in treatment of Alzheimer's disease.Methods The randomized controlled trials (RCT) of reinhartdt and sea capsule combine with donepezil in treatment of Alzheimer's disease were searched from Pubmed,VIP,CNKI,CBM,and Wangfang detabase by computer.Deadline from January 2000 to February 2017.References of included studies were also retrieved,extracted data,and assessed the methodological quality.Then,Meta-analysis was performed using RevMan 5.0 software.Results A total of eight RCTs were included,including 605 patients with insomnia.Meta-analysis results showed that compared with control group,experimental group MMSE score [P＜0.001,MD=2.69,95％CI(1.46,3.92)],ADAS-Cog score [P＜0.001,MD=-4.54,95％CI(-5.64,-3.43)] and ADL score [P＜0.001,MD=-3.60,95％CI(-4.53,-2.66)],the difference was statistical;There was no signficant difference between two group in the incidences of adverse effect [P=-0.94,OR=1.02,95％CI(0.63,1.66)].Conclusion RSC combined with donepezil showed better efficacy for Alzheimer's disease,yet without increasing adverse effect rate as compared with donepezil alone.
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Objective:To investigate the effect of Bailing capsule on myocardial fibrosis in mice with viral myocarditis(VMC) and TGF-β1-MAPK/ERK pathway. Methods:Male BALB/c mice ( n=200 ) were randomly divided into model group ( n=180 ) and control group(n=20). The model group mice were infected with Coxsackie virus B3 to prepare VMC myocardial fibrosis. The control group mice were injected with Eagle′s MEM without virus. The model was successful after two months. The survival mice were randomly divided into model group and high,middle and low dose of Bailing capsule was administered consecutively for sixty days,once a day, Cardiac ultrasound was used to test LVEDd,LVEDs,then calculate FS. The expression of type Ⅰ collagen and type Ⅲ collagen in all the mice myocardial tissue was detected by immunohistochemical methods. Masson staining for myocardial fibrosis was used to calculate the collagen volume fraction( CVF) . Western blot was used to detect the protein expression of TGF-β1 and p-ERK1/2. Results:①Compared with the control group,the CVF,typeⅠcollagen and typeⅢcollagen obviously increased,LVEDd,LVEDs increased,FS de-creased,which had statistically significance(P<0. 05).②Compared with the control group,the model group of mice had a statistically significantly higher expression of TGF-β1 and p-ERK1/2(P<0. 05).③Compared with the model group,the expression of CVF,typeⅠcollagen and type Ⅲ collagen of high and middle dose of Bailing capsule was significantly lower,LVEDd,LVEDs decreased,while FS increased(P<0. 05).④Compared with the model group,the high dose of Bailing capsule group of mice had a statistically significantly lower expression of TGF-β1 and p-ERK1/2 ( P<0. 05 ) . Conclusion:①Bailing capsule can prevent myocardial fibrosis of mice with VMC.②The activation of TGF-β1-MAPK/ERK pathway may can promote myocardial fibrosis in VMC.③Bailing capsule could prevent myocardial fibrosis,which may be related to prevention of TGF-β1-MAPK/ERK pathway.
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Twenty phenylpropenamide analogs with structural novelty were designed and synthesized upon pharmacophore-combination strategy. The structures of target compounds were elucidated by IR, 1H NMR, 13C NMR and MS, and all the target compounds were biologically evaluated for the inhibitory activities of platelet aggregation induced by adenosine diphoshate (ADP) and (AA) arachidonic acid via Bron method. As a result, compounds 6b, 9b, 9d and 9h demonstrated potent inhibitory activity against platelet aggregation induced by AA. Meanwhile, compounds 6b, 6d, 6j, 9b and 9g exhibited significant suppression of platelet aggregation induced by ADP.
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Using ligustrazine as the leading compound, we designed and synthesized ten novel ligustrazine derivatives, whose structures were determined by 1H NMR, 13C NMR and MS. Inhibitory effects of the new compounds on the proliferation of A549, A549/DDP and HBE cells were detected by MTT assay. The inhibi-tory activity of the synthesized compounds on migration and invasion of A549 cells were evaluated through scratch assay and transwell assay. Mechanism of the inhibition on migration and invasion was investigated by Western blotting. In addition, the cell cycle was analyzed with flow cytometry. The results showed that, both compounds Z8 and Z10 have an anti-proliferative activity, and the potencies of inhibition of tumor-cell migration and invasion were attributed to the down-regulation of MMP-2 and MMP-9. The compounds Z8 and Z10 could also enhance G2/M arrest in A549 cell as revealed by cell cycle analysis.
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Objective:To investigate the effect of Bailing capsule on myocardial fibrosis in mice with viral myocarditis(VMC) and TGF-β1-MAPK/ERK pathway. Methods:Male BALB/c mice ( n=200 ) were randomly divided into model group ( n=180 ) and control group(n=20). The model group mice were infected with Coxsackie virus B3 to prepare VMC myocardial fibrosis. The control group mice were injected with Eagle′s MEM without virus. The model was successful after two months. The survival mice were randomly divided into model group and high,middle and low dose of Bailing capsule was administered consecutively for sixty days,once a day, Cardiac ultrasound was used to test LVEDd,LVEDs,then calculate FS. The expression of type Ⅰ collagen and type Ⅲ collagen in all the mice myocardial tissue was detected by immunohistochemical methods. Masson staining for myocardial fibrosis was used to calculate the collagen volume fraction( CVF) . Western blot was used to detect the protein expression of TGF-β1 and p-ERK1/2. Results:①Compared with the control group,the CVF,typeⅠcollagen and typeⅢcollagen obviously increased,LVEDd,LVEDs increased,FS de-creased,which had statistically significance(P<0. 05).②Compared with the control group,the model group of mice had a statistically significantly higher expression of TGF-β1 and p-ERK1/2(P<0. 05).③Compared with the model group,the expression of CVF,typeⅠcollagen and type Ⅲ collagen of high and middle dose of Bailing capsule was significantly lower,LVEDd,LVEDs decreased,while FS increased(P<0. 05).④Compared with the model group,the high dose of Bailing capsule group of mice had a statistically significantly lower expression of TGF-β1 and p-ERK1/2 ( P<0. 05 ) . Conclusion:①Bailing capsule can prevent myocardial fibrosis of mice with VMC.②The activation of TGF-β1-MAPK/ERK pathway may can promote myocardial fibrosis in VMC.③Bailing capsule could prevent myocardial fibrosis,which may be related to prevention of TGF-β1-MAPK/ERK pathway.
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Six novel ligustrazine chalcone aromatic oxygen alkyl acids compounds and two pyridine chalcone aromatic oxygen alkyl acids ester compounds were synthesized according to the traditional Chinese medicine theory removing blood stasis. The structures of target compounds were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA) were measured by the liver microsomal incubation method in vitro. Hypolipidemic activities of compounds were tested in vivo for better inhibitory activities of platelet aggregation. Preliminary pharmacological results showed that compounds 7c, 8a and 11a had potent inhibitory activity against platelet aggregation induced by AA, compounds 7c, 7d, 8a and 11b showed significant inhibitory activity against platelet aggregation induced by ADP. Compounds 7c and 8a exhibited good hypolipidemic activities in high-fat-diet (HFD) induced hyperlipidemia C57/BL6 mice and worthy for further investigation.
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<p><b>BACKGROUND</b>Mitochondrial diseases are a group of energy metabolic disorders with multisystem involvements. Variable clinical features present a major challenge in pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in Chinese pediatric patients, to define the common clinical manifestations and study the correlation between heteroplasmic degree of the mutation and clinical severity of the disease.</p><p><b>METHODS</b>Clinical data of one-hundred pediatric patients with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to 2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated. The differences in clinical symptom frequency of patients with low, middle, and high levels of mutation ratio were analyzed by Chi-square test.</p><p><b>RESULTS</b>Sixty-six patients (66%) had suffered a delayed diagnosis for an average of 2 years. The most frequent symptoms were seizures (76%), short stature (73%), elevated plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography (MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%), and muscle weakness (48%). The mutation ratio was correlated negatively with onset age (r = -0.470, P < 0.001). Myopathy was more frequent in patients with a high level of mutation ratio. However, patients with a low or middle level of m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased vision, and gastrointestinal disturbance than patients with a high level of mutation ratio.</p><p><b>CONCLUSIONS</b>Our study showed that half of Chinese pediatric patients with m.3243A>G mutation presented seizures, short stature, abnormal MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric patients with these recurrent symptoms should be considered for screening m.3243A>G mutation. Clinical manifestations and laboratory abnormalities should be carefully monitored in patients with this point mutation.</p>
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Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Age of Onset , Asian People , Chi-Square Distribution , DNA, Mitochondrial , Genetics , Hearing Loss , Pathology , Lactic Acid , Blood , Magnetic Resonance Imaging , Mitochondrial Diseases , Blood , Genetics , Pathology , Mutation , Point Mutation , Genetics , Polymerase Chain Reaction , Retrospective Studies , Seizures , PathologyABSTRACT
OBJECTIVE: To synthesize and evaluate of antihypertensive activity of novel nitric oxide-releasing N-phenyl-1H-pyrrole derivatives. METHODS: By connecting key structural elements present in an AT1 receptor antagonist irbesartan with N-phenyl-1H-pyrrole carboxylic acid, a novel AT1 antagonist compound 4 was designed and synthesized, and a series of novel NO-donating derivatives (IN 1-10) were obtained by introducing NO donor. The amount of NO production in vitro of the target compounds were determined by Greiss assay. And the antagonism of Ang II induced vascular contraction assay was used to value the inhibition rate. RESULTS: The antagonism of Ang II induced vascular contraction assay indicated that the novel compound exhibited similar activity as losartan. The NO derivative, compound IN9, found to release the maximum amount of NO during the NO releasing assay, was more potent than the lead compound 4 and positive control losartan. CONCLUSION: These date indicate that the improved activities of these hybrid molecules contribute to the NO donor and the protection ability of NO donor make them promising candidates as antihypertensive agents.
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A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.
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Humans , Antineoplastic Agents , Chemistry , Pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Design , Esters , Inhibitory Concentration 50 , K562 Cells , Molecular Structure , Prodrugs , Chemistry , Pharmacology , Salicylanilides , Chemistry , Pharmacology , Structure-Activity Relationship , Valproic Acid , Chemistry , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To test the sensitivity and specificity of alpha-fetoprotein (AFP) colloidal gold diagnostic strip as compared with RIA-AFP diagnostic kit.</p><p><b>METHODS</b>Double blind method was used to test sera from 426 healthy people and 1567 patients selected in two general hospitals and a cancer hospital. Each serum was measured by RIA-AFP and AFP colloidal gold diagnostic strip on the same day. RIA-AFP diagnostic results was identified as true positive or negative.</p><p><b>RESULTS</b>Among 426 healthy people, all the RIA-AFP test showed negative result (serum AFP concentration less than 25 IU/ml), but the AFP colloidal gold diagnostic strip had 1.88% false positive. When comparing the result from 1567 patients measured by RIA-AFP, the sensitivity and specificity of AFP colloidal gold diagnostic strip were 99.3%, and 97.2%, respectively. The crude correspondence rate between the two diagnostic regents was 97.6%.</p><p><b>CONCLUSION</b>AFP colloidal gold diagnostic strip showed very good result and could be used as a screening diagnostic kit in clinic and hospital settings.</p>